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Synthesis of Polycyclic Imidazolidinones via Amine Redox-AnnulationClick to copy article linkArticle link copied!
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† Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States
‡ Department of Chemistry, College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, People’s Republic of China
*E-mail: [email protected]
Abstract
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α-Ketoamides undergo redox-annulations with cyclic secondary amines, such as 1,2,3,4-tetrahydroisoquinoline, pyrrolidine, piperidine, and morpholine. Catalytic amounts of benzoic acid significantly accelerate these transformations. This approach provides polycyclic imidazolidinone derivatives in typically good yields.
Copyright © 2017 American Chemical Society
Imidazolidinones are frequently encountered as substructures of natural products and synthetic, biologically active compounds (Figure 1). (1-3) Among the most common methods used to build the imidazolidinone motif are condensations of α-aminoacetamide derivatives with aldehydes or ketones, various cycloadditions, ring expansions, and others. (1) Methods have also emerged that are particularly suitable for the preparation of ring-fused imidazolidinones (Scheme 1). One such approach involves an oxidative intramolecular coupling of α-aminoacetamide derivatives (eq 1). (4) A decarboxylative strategy involving the condensation of proline with α-ketoamides to build bicyclic imidazolidinones containing a pyrrolidine ring has also been established (eq 2). (5, 6) Here we report a redox-neutral annulation approach to polycyclic imidazolidinones (eq 3).
Figure 1
Figure 1. Selected 4-imidazolidinones.
Scheme 1
Scheme 1. Selected Routes to Polycyclic 4-Imidazolidinones
We (7) and others (8) have developed a range of redox-neutral annulation reactions that proceed via the condensation of a secondary amine with an aldehyde/ketone possessing a pendent (pro)nucleophile. These annulations feature concurrent N-alkylation and the functionalization of an amine α-C–H bond. (9, 10) The majority of these transformations proceed through azomethine ylide intermediates, utilize carboxylic acids as catalysts or promoters, and result in the formation of a new six-membered ring. (11) Although there are examples of redox-neutral amine α-C–H bond functionalizations of secondary amines that give rise to the formation of new five-membered rings, typically via (3 + 2) cycloaddition of azomethine ylide intermediates (12) or 1,5-electrocyclic ring-closure of conjugated azomethine ylides, (13, 14) this chemistry remains underdeveloped and has rarely been applied to C–N bond formation. (13c, 13i) We reasoned that such an annulation could be applied to the synthesis of bi- or polycyclic imidazolidinones via the condensation of cyclic amines with α-ketoamides (Scheme 1, eq 3). (15)
1,2,3,4-Tetrahydroisoquinoline (THIQ) and 2-oxo-N,2-diphenylacetamide (1a) were selected as model substrates in order to evaluate the proposed annulation process (Table 1). A 2:1 mixture of THIQ and 1a, upon heating under reflux in toluene for 2 days, resulted in an incomplete reaction and the isolation of desired product 2a as a single diastereomer in 50% yield (entry 1). Utilization of catalytic amounts of benzoic acid (20 mol %) resulted in a significant improvement (entry 2). Complete consumption of 1a was observed within 7 h, and 2a was obtained in 95% yield. Replacement of benzoic acid with either acetic acid or 2-ethylhexanoic acid (2-EHA) facilitated the formation of 2a in similar yields but required prolonged reaction times (entries 3 and 4). A reaction that was performed at 50 °C remained incomplete after 44 h and led to product in moderate yield (entry 5). A reduction of the amount of THIQ to 1.5 equiv was well tolerated (entry 6), whereas further reduction to 1.2 equiv led to a slight drop in yield (entry 7). Notably, the reaction performed equally well in the absence of molecular sieves (entry 8).
Table 1. Evaluation of Reaction Conditionsa
| entry | THIQ (equiv) | catalyst | time (h) | yield (%) |
|---|---|---|---|---|
| 1 | 2 | 48 | 50 | |
| 2 | 2 | PhCOOH | 7 | 95 |
| 3 | 2 | AcOH | 23 | 92 |
| 4 | 2 | 2-EHA | 21 | 91 |
| 5b | 2 | PhCOOH | 44 | 56 |
| 6 | 1.5 | PhCOOH | 12 | 93 |
| 7 | 1.2 | PhCOOH | 12 | 88 |
| 8c | 1.5 | PhCOOH | 15 | 95 |
a
Reactions were performed on a 0.2 mmol scale. All yields correspond to isolated yields. dr >25:1 in all cases.
b
Reaction was run at 50 °C and remained incomplete.
c
Without 4 Å MS.
The scope of the redox-annulation was explored under the optimized conditions of Table 1 (entry 8). A range of α-ketoamides with different substitution patterns were investigated (Scheme 2). The corresponding 4-imidazolidinone products 2 were isolated in good to excellent yields. Both aromatic and aliphatic substituents on the amide nitrogen were tolerated. Likewise, nonenolizable and enolizable α-ketoamides participated in the annulation reaction. In the case of the primary amide-derived product 2n, which was obtained in 53% yield, a competing pathway was identified. Specifically, the corresponding transamidation product was obtained in 38% yield. (16) An enantiomerically pure α-ketoamide, derived from (S)-1-phenylethan-1-amine, provided product 2o in 86% yield as a 1.3:1 mixture of diastereomers.
Scheme 2
Scheme 2. Ketoamide Scopea
Scheme aReactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.
Scheme bTransamidation product (1-(3,4-dihydroisoquinolin-2(1H)-yl)-2-phenylethane-1,2-dione) was obtained in 38% yield.
The scope of the amine component is summarized in Scheme 3. Benzylic amines other than THIQ, including the sterically hindered 1-phenyl-THIQ, readily formed annulation products upon reaction with α-ketoamide 1a. Amines with attenuated reactivities, such as pyrrolidine and azepane, provided 4-imidazolidinone products in good yields. Particularly challenging substrates such as piperidine, morpholine, and thiomorpholine underwent the title reaction at elevated temperatures.
Scheme 3
Scheme 3. Amine Scopea
Scheme aReactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.
Scheme bReaction was performed in PhMe (0.25 M) under microwave irradiation for 30 min at 220 °C.
Scheme cReaction was performed in PhMe (0.25 M) under microwave irradiation for 1 h at 220 °C.
As shown in Schemes 2 and 3, reactions involving THIQ, related benzylic amines, and pyrrolidine underwent redox-annulations with α-ketoamides in highly diastereoselective fashion. In contrast, reactions with azepane, piperidine, morpholine, and thiomorpholine were poorly diastereoselective. We suspected that the aminal stereogenic center might be configurationally unstable under the reaction conditions. Thus, product ratios may reflect the different thermodynamic stabilities of the two diastereomers. To test this hypothesis, the readily available pure diastereomers of product 3g were exposed to the reaction conditions (eqs 4 and 5). Upon extended heating, both mixtures converged to a final 2.1:1 ratio of diastereomers. These experiments establish that product isomerization can indeed occur under the reaction conditions.
Two plausible mechanistic scenarios are shown in Scheme 4, depicting pyrrolidine and α-ketoamide 1a as prototypical examples. Based on previous investigations, the initial formation of N,O-acetal 4 appears highly likely. Again based on precedent, 4 could lose benzoic acid to form azomethine ylide 5. Following the general mechanism of other redox-annulations, (11)5 could reengage benzoic acid to form N,O-acetal 6. The latter ultimately undergoes ring closure to final product 3e with loss of benzoic acid, possibly via the zwitterionic intermediate 7 (pathway A). In an alternate scenario, conjugated azomethine ylide 8, which represents a tautomer of azomethine ylide 5, undergoes ring closure in what is formally a 1,5-electrocyclization. (14g) The resulting intermediate 9 then undergoes tautomerization to product 3e (pathway B). (17)
Scheme 4
Scheme 4. Mechanistic Considerations
In conclusion, we have achieved high-yielding syntheses of polycyclic imidazolidinones via redox-annulations of cyclic amines with a range of α-ketoamides. These reactions are efficiently catalyzed by benzoic acid and are rare examples of redox-neutral transformations in which an amine α-C–H bond is replaced by a C–N bond in the context of five-membered ring formation.
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b03309.
Experimental procedures and characterization data, including X-ray crystal structures of products 2a and 3d (PDF)
X-ray data for compound 2a (CIF)
X-ray data for compound 3d (CIF)
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Author Information
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- Daniel Seidel - Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, United States;
http://orcid.org/0000-0001-6725-111X;
Z.Z. and X.L. contributed equally.
Acknowledgment
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Financial support from the NIH–NIGMS (R01GM101389) is gratefully acknowledged. We thank Dr. Tom Emge (Rutgers University) for crystallographic analysis and Dr. Wazo Myint (Rutgers University) for assistance with NMR assignments.
References
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This article references 17 other publications.
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Review on the synthetic and medicinal chemistry of 4-imidazolidinones:
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For a general review on the synthesis of aminal-type structures, see:
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Selected reports on natural and synthetic, biologically active 4-imidazolidinones:
(a) Smissman, E.; Inloes, R.; El-Antably, S.; Shaffer, P. J. Med. Chem. 1976, 19, 161 DOI: 10.1021/jm00223a028Google ScholarThere is no corresponding record for this reference.(b) Leysen, J.; Gommeren, W.; Laduron, P. Biochem. Pharmacol. 1978, 27, 307 DOI: 10.1016/0006-2952(78)90233-2Google ScholarThere is no corresponding record for this reference.(c) Nelson, D.; Taylor, E. Eur. J. Pharmacol. 1986, 124, 207 DOI: 10.1016/0014-2999(86)90147-0Google Scholar3chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28XltVyhur8%253D&md5=2993821f8e2086b20ae0b8b004497d25Spiroxatrine: a selective serotonin1A receptor antagonistNelson, David L.; Taylor, Ethan WillEuropean Journal of Pharmacology (1986), 124 (1-2), 207-8CODEN: EJPHAZ; ISSN:0014-2999.In isolated canine cerebral vessels, the Ki's of spiroxatrine (I) [1054-88-2] for 5-HT1A, 5-HT1B, and 5-HT2 receptors were 3.94, 224,000, and 118.5 nM, resp., whereas the corresponding Ki's for spiperone were 110, 50,300, and 0.41 nM. Thus, I is relatively selective for 5-HT1A sites.(d) Nikam, S.; Martin, A.; Nelson, D. J. Med. Chem. 1988, 31, 1965 DOI: 10.1021/jm00118a017Google ScholarThere is no corresponding record for this reference.(e) Rasmussen, G.; Bundgaard, H. Int. J. Pharm. 1991, 71, 45 DOI: 10.1016/0378-5173(91)90066-WGoogle Scholar3ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXkslyksb4%253D&md5=be9449f8c25e908af02186f8d89f72e5Prodrugs of peptides. 10. Protection of di- and tripeptides against aminopeptidase by formation of bioreversible 4-imidazolidinone derivativesRasmussen, Gitte Juel; Bundgaard, HansInternational Journal of Pharmaceutics (1991), 71 (1-2), 45-53CODEN: IJPHDE; ISSN:0378-5173.The kinetics of hydrolysis of a series of 4-imidazolidinones derived from acetone and various di- and tripeptides was studied in aq. soln. and in the presence of enzymes in order to assess their suitability as prodrug forms for the peptides. Whereas the parent di- and tripeptides were readily hydrolyzed by a purified aminopeptidase as well as in human plasma solns. and rabbit intestinal homogenates, the imidazolidinyl peptides were totally resistant to enzymic cleavage in these media. On the other hand, these derivs. are readily bioreversible, being converted to the parent peptide by spontaneous hydrolysis. The rate of hydrolysis is greatly dependent on the structure of the peptide. For the eleven 4-imidazolidinones studied the half-lives of hydrolysis at pH 7.4 and 37° ranged from 18 min to 545 h. The major structural factor influencing the stability was shown to be the steric properties within the α-carbon atom substituents in the amino acid residue next to the N-terminal amino acid. It is concluded that 4-imidazolidinone formation can be a useful prodrug approach to protect the N-terminal amino acid residue of peptides against cleavage by aminopeptidases and related exopeptidases.(f) Pinza, M.; Farina, C.; Cerri, A.; Pfeiffer, U.; Riccaboni, M. T.; Banfi, S.; Biagetti, R.; Pozzi, O.; Magnani, M.; Dorigotti, L. J. Med. Chem. 1993, 36, 4214 DOI: 10.1021/jm00078a011Google Scholar3fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXhvFWlsL8%253D&md5=f8374eb5ac5b086b74b1946dfbd0d24aSynthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancersPinza, Mario; Farina, Carlo; Cerri, Alberto; Pfeiffer, Ugo; Riccaboni, Maria T.; Banfi, Silvano; Biagetti, Raffaella; Pozzi, Ottorino; Magnani, Maurizio; Dorigotti, LucianoJournal of Medicinal Chemistry (1993), 36 (26), 4214-20CODEN: JMCMAR; ISSN:0022-2623.A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, e.g. dimiracetam (I), were synthesized. These bicyclic derivs. contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addn., these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features obsd. are a potent antiamnestic activity after i.p. administration (minimal ED being between 0.3 and 1 mg/kg i.p. for most compds.), the presence of a bell-shaped dose-response curve and, generally, a redn. of biol. activity after po administration. However, the unsubstituted compd. I shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the ref. drug oxiracetam.(g) Thomsen, C.; Hohlweg, R. Br. J. Pharmacol. 2000, 131, 903 DOI: 10.1038/sj.bjp.0703661Google Scholar3ghttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXotFemsLc%253D&md5=6c28da889af05c7b60a6efb9bf2d901b(8-Naphthalen-1-ylmethyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl)acetic acid methyl ester (NNC 63-0532) is a novel potent nociceptin receptor agonistThomsen, Christian; Hohlweg, RolfBritish Journal of Pharmacology (2000), 131 (5), 903-908CODEN: BJPCBM; ISSN:0007-1188. (Nature Publishing Group)Spiroxatrine was identified as a moderately potent (Ki = 118 nM) but non-selective agonist at the human nociceptin/orphanin FQ receptor, ORL1. This compd. was subject to chem. modification and one of the resulting compds., NNC 63-0532 was shown to have high affinity for ORL1 (Ki = 7.3 nM). NNC 63-0532 showed only moderate affinity for the following receptors (Ki values in parentheses): μ-opioid (140 nM), κ-opioid (405 nM), dopamine D2S (209 nM), dopamine D3 (133 nM) and dopamine D4.4 (107 nM) out of 75 different receptors, ion-channels and transporters. In functional assays, NNC 63-0532 was shown to be an agonist at ORL1 (EC50 = 305 nM), a much weaker agonist at the μ-opioid receptor (EC50>10 μM) and an antagonist or weak partial agonist at dopamine D2S (IC50 = 2830 nM). Thus, NNC 63-0532 is a novel non-peptide agonist with ∼ 12 fold selectivity for ORL1 and may be useful for exploring the physiol. roles of this receptor owing to its brain-penetrating properties.(h) Ijzendoorn, D. R.; Botman, P. N. M.; Blaauw, R. H. Org. Lett. 2006, 8, 239 DOI: 10.1021/ol052598rGoogle Scholar3hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlSmtrbF&md5=6f7ce619189d68d57de8997de719f176Diastereoselective Cationic Tandem Cyclizations to N-Heterocyclic Scaffolds: Total Synthesis of (-)-Dysibetaine PPIJzendoorn, Denis R.; Botman, Peter N. M.; Blaauw, Richard H.Organic Letters (2006), 8 (2), 239-242CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)The authors report a short and diastereoselective synthesis of the natural product (-)-dysibetaine PP (I). The key step in the synthetic sequence is a novel diastereoselective tandem-cyclization reaction of an enantiopure dipeptide II in the presence of TsOH in toluene to cyclized product III (92% yield, 10:1 trans:cis ratio). Next, III was converted to I in four steps. This cyclization methodol. is applied in the synthesis of a broader range of N-heterocyclic scaffolds.(i) Toumi, M.; Couty, F.; Marrot, J.; Evano, G. Org. Lett. 2008, 10, 5027 DOI: 10.1021/ol802155nGoogle Scholar3ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht1emtr7O&md5=295ec688457837fe19a15fbc01a001e4Total synthesis of chaetominineToumi, Mathieu; Couty, Francois; Marrot, Jerome; Evano, GwilhermOrganic Letters (2008), 10 (21), 5027-5030CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)An efficient, asym. synthesis of the cytotoxic natural product chaetominine was achieved in 14 steps. The strategy employs a copper(I)-mediated cyclization reaction as a key step to install the abc-tricyclic ring system, which was further elaborated by diastereoselective oxidn. and redn. reactions. This effort also documents the first example of an oxidative rearrangement yielding to homochiral spirocyclic pyrrolidinyloxindoles.(j) Vale, N.; Prudencio, M.; Marques, C.; Collins, M.; Gut, J.; Nogueira, F.; Matos, J.; Rosenthal, P.; Cushion, M.; Rosario, V.; Mota, M.; Moreira, R.; Gomes, P. J. Med. Chem. 2009, 52, 7800 DOI: 10.1021/jm900738cGoogle ScholarThere is no corresponding record for this reference.(k) Vale, N.; Nogueira, F.; Rosario, V.; Gomes, P.; Moreira, R. Eur. J. Med. Chem. 2009, 44, 2506 DOI: 10.1016/j.ejmech.2009.01.018Google ScholarThere is no corresponding record for this reference. - 4(a) Vasvari-Debreczy, L.; Beckett, A.; Vutthikongsirigool, W. Tetrahedron 1981, 37, 4337 DOI: 10.1016/0040-4020(81)85031-4Google ScholarThere is no corresponding record for this reference.(b) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563 DOI: 10.1016/S0040-4020(01)87046-0Google ScholarThere is no corresponding record for this reference.(c) Yu, H.; Shen, J. RSC Adv. 2015, 5, 9815 DOI: 10.1039/C4RA15019HGoogle Scholar4chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjtVylsg%253D%253D&md5=7e7b3ffec1499f1936b18b3705eff5e8Dehydrogenative cyclization of N-acyl dipeptide esters for the synthesis of imidazolidin-4-onesYu, Hui; Shen, JieRSC Advances (2015), 5 (13), 9815-9818CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A dehydrogenative cyclization reaction for the synthesis of imidazolidin-4-ones was developed under mild conditions. Using tert-Bu hydroperoxide as oxidant and potassium iodide as catalyst, N-acyl dipeptide esters were converted to imidazolidin-4-ones in an atom-economical intramol. C-N bond formation process in good yields.(d) Ren, X.; O’Hanlon, J.; Morris, M.; Robertson, J.; Wong, L. ACS Catal. 2016, 6, 6833 DOI: 10.1021/acscatal.6b02189Google Scholar4dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVKjsrjM&md5=a55e23fd9d173a49c76dc6b95231b1c5Synthesis of Imidazolidin-4-ones via a Cytochrome P450-Catalyzed Intramolecular C-H AminationRen, Xinkun; O'Hanlon, Jack A.; Morris, Melloney; Robertson, Jeremy; Wong, Luet LokACS Catalysis (2016), 6 (10), 6833-6837CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Expanding Nature's catalytic repertoire to include reactions important in synthetic chem. opens new opportunities for biocatalysis. An intramol. C-H amination route to imidazolidin-4-ones via α-functionalization of 2-aminoacetamides catalyzed by evolved variants of cytochrome P 450BM3 (CYP102A1) from Bacillus megaterium has been developed. Screening of a library of ca. 100 variants based on four template mutants with enhanced activity for the oxidn. of unnatural substrates and preparative scale reactions in vitro and in vivo show that the enzymes give up to 98% isolated yield of cyclization products for diverse substrates. 2-Aminoacetamides with one- and two-ring cyclic amines bearing substituents and aliph., alicyclic, and substituted arom. amides are cyclized. Regiodivergent C-H amination was achieved at benzylic and nonbenzylic positions in a tetrahydroisoquinolinyl substrate by the use of different mutants. This C-H amination reaction offers a scalable route to imidazolidin-4-ones with varied functionalized substituents that may have desirable biol. activity.
- 5Wu, J.-s.; Jiang, H.-j.; Yang, J.-g.; Jin, Z.-n.; Chen, D.-b. Tetrahedron Lett. 2017, 58, 546 DOI: 10.1016/j.tetlet.2016.12.079Google Scholar5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXotlaktA%253D%253D&md5=ac0724dbda8d84f896515d0bc36d1efeNovel synthesis of tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones via decarboxylative cyclization reaction of α-amino acids and α-ketoamidesWu, Jia-shou; Jiang, Hua-jiang; Yang, Jian-guo; Jin, Zheng-neng; Chen, Ding-benTetrahedron Letters (2017), 58 (6), 546-551CODEN: TELEAY; ISSN:0040-4039. (Elsevier Ltd.)An efficient and practical method was developed for the synthesis of tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones based on the decarboxylative cyclization reaction of α-ketoamides and proline. In most cases, tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones were obtained with perfect diastereoselectivity to give trans-isomer in excellent yield.
- 6
Examples of condensation-based approaches to polycyclic 4-imidazolidinones:
(a) Katritzky, A. R.; He, H.-Y.; Wang, J. J. Org. Chem. 2002, 67, 4951 DOI: 10.1021/jo010842wGoogle ScholarThere is no corresponding record for this reference.(b) Ferraz, R.; Gomes, J. R. B.; de Oliveira, E.; Moreira, R.; Gomes, P. J. Org. Chem. 2007, 72, 4189 DOI: 10.1021/jo0703202Google ScholarThere is no corresponding record for this reference. - 7(a) Zhang, C.; De, C. K.; Mal, R.; Seidel, D. J. Am. Chem. Soc. 2008, 130, 416 DOI: 10.1021/ja077473rGoogle Scholar7ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVehur3P&md5=02ea4c8dbd4684678f08f74bcb17b7c3α-Amination of Nitrogen Heterocycles: Ring-Fused AminalsZhang, Chen; De, Chandra Kanta; Mal, Rudrajit; Seidel, DanielJournal of the American Chemical Society (2008), 130 (2), 416-417CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Arom. aminoaldehydes react with cyclic amines to produce ring-fused aminals under thermal conditions. This process is applied to two-step syntheses of the quinazolinone alkaloids deoxyvasicinone and rutaecarpine.(b) Zhang, C.; Das, D.; Seidel, D. Chem. Sci. 2011, 2, 233 DOI: 10.1039/C0SC00432DGoogle Scholar7bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmsVKqtg%253D%253D&md5=5ea2541ffe14c212a973e3b29fe26eb4Azomethine ylide annulations: facile access to polycyclic ring systemsZhang, Chen; Das, Deepankar; Seidel, DanielChemical Science (2011), 2 (2), 233-236CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)New annulation reactions of azomethine ylides are reported. Amino acids react with aldehydes that are linked to a pronucleophile (e.g. an indole subunit) to provide rapid access to polycyclic ring systems. Simple amines can also be used in place of amino acids.(c) Dieckmann, A.; Richers, M. T.; Platonova, A. Y.; Zhang, C.; Seidel, D.; Houk, K. N. J. Org. Chem. 2013, 78, 4132 DOI: 10.1021/jo400483hGoogle Scholar7chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksFSrurc%253D&md5=ffec985aa582202a64f6075d42f5af30Metal-Free α-Amination of Secondary Amines: Computational and Experimental Evidence for Azaquinone Methide and Azomethine Ylide IntermediatesDieckmann, Arne; Richers, Matthew T.; Platonova, Alena Yu.; Zhang, Chen; Seidel, Daniel; Houk, K. N.Journal of Organic Chemistry (2013), 78 (8), 4132-4144CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The authors have performed a combined computational and exptl. study to elucidate the mechanism of a metal-free α-amination of secondary amines. Calcns. predicted azaquinone methides and azomethine ylides as the reactive intermediates and showed that iminium ions are unlikely to participate in these transformations. These results were confirmed by exptl. deuterium-labeling studies and the successful trapping of the postulated azomethine ylide and azaquinone methide intermediates. Computed barrier heights for the rate-limiting step correlate qual. with exptl. findings.(d) Richers, M. T.; Deb, I.; Platonova, A. Y.; Zhang, C.; Seidel, D. Synthesis 2013, 45, 1730 DOI: 10.1055/s-0033-1338852Google Scholar7dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlSnsLjF&md5=0b9a8971128510fb78aff77c4d2bf096Facile access to ring-fused aminals via direct α-amination of secondary amines with o-aminobenzaldehydes: synthesis of vasicine, deoxyvasicine, deoxyvasicinone, mackinazolinone, and rutaecarpineRichers, Matthew T.; Deb, Indubhusan; Platonova, Alena Yu.; Zhang, Chen; Seidel, DanielSynthesis (2013), 45 (13), 1730-1748CODEN: SYNTBF; ISSN:0039-7881. (Georg Thieme Verlag)Secondary amines undergo redox-neutral reactions with aminobenzaldehydes under conventional and microwave heating to furnish polycyclic aminals, e.g. I [R = Ph, 2-pyridyl, 1-naphthyl, etc.] via amine α-amination/N-alkylation. This unique α-functionalization reaction proceeds without the involvement of transition metals or other additives. The resulting aminal products are precursors for various quinazolinone alkaloids and their analogs.(e) Richers, M. T.; Breugst, M.; Platonova, A. Y.; Ullrich, A.; Dieckmann, A.; Houk, K. N.; Seidel, D. J. Am. Chem. Soc. 2014, 136, 6123 DOI: 10.1021/ja501988bGoogle ScholarThere is no corresponding record for this reference.(f) Jarvis, C. L.; Richers, M. T.; Breugst, M.; Houk, K. N.; Seidel, D. Org. Lett. 2014, 16, 3556 DOI: 10.1021/ol501509bGoogle ScholarThere is no corresponding record for this reference.(g) Kang, Y.; Chen, W.; Breugst, M.; Seidel, D. J. Org. Chem. 2015, 80, 9628 DOI: 10.1021/acs.joc.5b01384Google ScholarThere is no corresponding record for this reference.(h) Ma, L.; Seidel, D. Chem. - Eur. J. 2015, 21, 12908 DOI: 10.1002/chem.201501667Google Scholar7hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1ChtL7L&md5=e0fe2262e2bbaea9d9133a3a8e2ce8ecIntramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine CoreMa, Longle; Seidel, DanielChemistry - A European Journal (2015), 21 (37), 12908-12913CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-C-H bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine (I) and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies.(i) Chen, W.; Seidel, D. Org. Lett. 2016, 18, 1024 DOI: 10.1021/acs.orglett.6b00151Google ScholarThere is no corresponding record for this reference.(j) Zhu, Z.; Seidel, D. Org. Lett. 2017, 19, 2841 DOI: 10.1021/acs.orglett.7b01047Google Scholar7jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXns1yrs78%253D&md5=1a553b958fd87c0bb88c06d013f663f9Acetic Acid Promoted Redox Annulations with Dual C-H FunctionalizationZhu, Zhengbo; Seidel, DanielOrganic Letters (2017), 19 (11), 2841-2844CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)Amines, such as 1,2,3,4-tetrahydroisoquinoline, underwent redox-neutral annulations with 2-alkylquinoline-3-carbaldehydes I (R1 = H, 4-Me, 6-Br, 6-Cl-2-Ph, etc.; R2 = H, Me, Ph) as well as 4-methyl-3-quinolinecarboxaldehyde and pyridine analogs to provide the corresponding polycyclic compds., e.g. II. These processes involve dual C-H bond functionalization. Acetic acid was used as a cosolvent and acted as the sole promoter of these transformations.
- 8(a) Zheng, L.; Yang, F.; Dang, Q.; Bai, X. Org. Lett. 2008, 10, 889 DOI: 10.1021/ol703049jGoogle Scholar8ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhslWjsbc%253D&md5=04416d1001c480165583232075dbfcffA Cascade Reaction with Iminium Ion Isomerization as the Key Step Leading to Tetrahydropyrimido[4,5-d]pyrimidinesZheng, Lianyou; Yang, Fengzhi; Dang, Qun; Bai, XuOrganic Letters (2008), 10 (5), 889-892CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)A novel cascade reaction of aminopyrimidines I (R = allyl, H, Me, Ph) with N-alkyl amino acids or analogs was investigated. The keys to this cascade are the isomerization of an iminium ion formed between the aldehyde group in pyrimidine and the secondary amine of an amino acid, and subsequent cyclization to the neighboring amino group. This sequence could be useful in the synthesis of novel tetrahydropyrimido[4,5-d]pyrimidine libraries. E.g., tetrahydropyrimido[4,5-d]pyrimidine II (R = allyl ) was prepd. from N-benzylglycine and I (R = allyl).(b) Mahato, S.; Haque, M. A.; Dwari, S.; Jana, C. K. RSC Adv. 2014, 4, 46214 DOI: 10.1039/C4RA05045BGoogle Scholar8bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFektb7O&md5=a7f232c6780a5223d0349eab2701cebeDivergent reaction: metal & oxidant free direct C-H aryloxylation and hydride free formal reductive N-benzylation of N-heterocyclesMahato, Sujit; Haque, Md Ashraful; Dwari, Soumita; Jana, Chandan K.RSC Advances (2014), 4 (86), 46214-46217CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Metal, oxidant and other additive-free novel methods for direct C-H aryloxylation of aliph. amines are developed. In the presence of excess amine, the course of the reaction was diverted, producing various arylmethylamines via hydride-free formal reductive amination. Involvement of a quinone methide intermediate was revealed from mechanistic studies.(c) Li, J.; Qin, C.; Yu, Y.; Fan, H.; Fu, Y.; Li, H.; Wang, W. Adv. Synth. Catal. 2017, 359, 2191 DOI: 10.1002/adsc.201601423Google ScholarThere is no corresponding record for this reference.(d) Li, J.; Fu, Y.; Qin, C.; Yu, Y.; Li, H.; Wang, W. Org. Biomol. Chem. 2017, 15, 6474 DOI: 10.1039/C7OB01527EGoogle ScholarThere is no corresponding record for this reference.
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Selected reviews on amine C–H functionalization, including redox-neutral approaches:
(a) Murahashi, S.-I. Angew. Chem., Int. Ed. Engl. 1995, 34, 2443 DOI: 10.1002/anie.199524431Google Scholar9ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXpslOnu70%253D&md5=cf00f40efaca796b993d37c949e93af7Synthetic aspects of metal-catalyzed oxidations of amines and related reactionsMurahashi, Shun-IchiAngewandte Chemie, International Edition in English (1995), 34 (22), 2443-65CODEN: ACIEAY; ISSN:0570-0833. (VCH)A review with 161 refs.(b) Matyus, P.; Elias, O.; Tapolcsanyi, P.; Polonka-Balint, A.; Halasz-Dajka, B. Synthesis 2006, 2006, 2625 DOI: 10.1055/s-2006-942490Google ScholarThere is no corresponding record for this reference.(c) Campos, K. R. Chem. Soc. Rev. 2007, 36, 1069 DOI: 10.1039/B607547AGoogle Scholar9chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsFantLo%253D&md5=42b3862f993380e5724c4f2fdcc8b2e2Direct sp3 C-H bond activation adjacent to nitrogen in heterocyclesCampos, Kevin R.Chemical Society Reviews (2007), 36 (7), 1069-1084CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Activation of sp3 C-H bonds adjacent to nitrogen in heterocycles is an attractive transformation that is emerging as a practical method in org. synthesis. This tutorial review aims to summarize the key examples of direct functionalization of nitrogen-contg. heterocycles via metal-mediated and metal-catalyzed processes, which is meant to serve as a foundation for future investigations into this rapidly developing area of research. The review covers functionalization of N-heterocycles via α-lithiation with alkyllithium/diamine complexes, α-amino radical formation, metal-catalyzed direct C-H activation, C-H oxidns. and oxidative couplings, and metal-catalyzed carbene insertions.(d) Murahashi, S.-I.; Zhang, D. Chem. Soc. Rev. 2008, 37, 1490 DOI: 10.1039/b706709gGoogle Scholar9dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXoslOgtLs%253D&md5=0680a861ea6dd4d3df86a72df8b7e49cRuthenium-catalyzed biomimetic oxidation in organic synthesis inspired by cytochrome P-450Murahashi, Shun-Ichi; Zhang, DazhiChemical Society Reviews (2008), 37 (8), 1490-1501CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Simulation of the function of cytochrome P 450 with low valent ruthenium complex catalysts leads to the discovery of biomimetic, catalytic oxidn. of various substrates selectively under mild conditions. The reactions discussed in this tutorial review are simple, clean, and practical. The principle of these reactions is fundamental and gives wide-scope and environmentally benign future practical methods.(e) Li, C.-J. Acc. Chem. Res. 2009, 42, 335 DOI: 10.1021/ar800164nGoogle Scholar9ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsFSit7vI&md5=82a4256bfc33e2851edcaa64596b32e8Cross-Dehydrogenative Coupling (CDC): Exploring C-C Bond Formations beyond Functional Group TransformationsLi, Chao-JunAccounts of Chemical Research (2009), 42 (2), 335-344CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Synthetic chemists aspire both to develop novel chem. reactions and to improve reaction conditions to maximize resource efficiency, energy efficiency, product selectivity, operational simplicity, and environmental health and safety. Carbon-carbon bond formation is a central part of many chem. syntheses, and innovations in these types of reactions will profoundly improve overall synthetic efficiency. This Account describes our work over the past several years to form carbon-carbon bonds directly from two different C-H bonds under oxidative conditions, cross-dehydrogenative coupling (CDC). We have focused most of our efforts on carbon-carbon bonds formed via the functionalization of sp3 C-H bonds with other C-H bonds. In the presence of simple and cheap catalysts such as copper and iron salts and oxidants such as hydrogen peroxide, dioxygen, tert-butylhydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), we can directly functionalize various sp3 C-H bonds by other C-H bonds without requiring preactivation. We demonstrate (1) reaction of α-C-H bonds of nitrogen in amines, (2) reaction of α-C-H bonds of oxygen in ethers, (3) reaction of allylic and benzylic C-H bonds, and (4) reaction of alkane C-H bonds. These CDC reactions can tolerate a variety of functional groups, and some can occur under aq. conditions. Depending on the specific transformation, we propose the in situ generation of different intermediates. These methods provide an alternative to the sep. steps of prefunctionalization and defunctionalization that have traditionally been part of synthetic design. As a result, these methods will increase synthetic efficiencies at the most fundamental level. On an intellectual level, the development of C-C bond formations based on the reaction of only C-H bonds (possibly in water) challenges us to rethink some of the most fundamental concepts and theories regarding chem. reactivities. A successful reaction requires the conventionally and theor. less reactive C-H bonds to react selectively in the presence of a variety of functional groups. With further investigation, we expect that C-C bond formations based on cross-dehydrogenative coupling will have a pos. economic and ecol. impact on the next generation of chem. syntheses.(f) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem. - Eur. J. 2010, 16, 2654 DOI: 10.1002/chem.200902374Google Scholar9fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXislKgu7Y%253D&md5=91985f8e805c7babf6a1d0682402cd42Functionalization of Organic Molecules by Transition-Metal-Catalyzed C(sp3)-H ActivationJazzar, Rodolphe; Hitce, Julien; Renaudat, Alice; Sofack-Kreutzer, Julien; Baudoin, OlivierChemistry - A European Journal (2010), 16 (9), 2654-2672CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Transition-metal-catalyzed C-H activation has recently emerged as a powerful tool for the functionalization of org. mols. While many efforts have focused on the functionalization of arenes and heteroarenes by this strategy in the past two decades, much less research has been devoted to the activation of non-acidic C-H bonds of alkyl groups. This Minireview highlights recent work in this area, with a particular emphasis on synthetically useful methods.(g) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215 DOI: 10.1021/cr100280dGoogle Scholar9ghttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXivVShtLo%253D&md5=f06ae8207d1e49d5646c35f7afd07012Catalytic Dehydrogenative Cross-Coupling: Forming Carbon-Carbon Bonds by Oxidizing Two Carbon-Hydrogen BondsYeung, Charles S.; Dong, Vy M.Chemical Reviews (Washington, DC, United States) (2011), 111 (3), 1215-1292CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review was given on transformations that can be categorized as catalytic dehydrogenative cross-couplings to highlight the scope and limits of this general strategy. as well as its specific application in asym. catalysis and natural product synthesis. These couplings are arranged by their proposed mechanisms, including those that involve Heck-type processes, direct arylations, ionic intermediates, or radical intermediates. Oxidative C-C bond formation was achieved by various catalysts, including transition metals, organocatalysts, the combined use of metal and organocatalysts, and enzymes.(h) Pan, S. C. Beilstein J. Org. Chem. 2012, 8, 1374 DOI: 10.3762/bjoc.8.159Google Scholar9hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlWrs7rP&md5=5d27b25193150f5950a441a38586d8d2Organocatalytic C-H activation reactionsPan, Subhas ChandraBeilstein Journal of Organic Chemistry (2012), 8 (), 1374-1384, No. 159CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)A review. Organocatalytic C-H activation reactions have recently been developed besides the traditional metal-catalyzed C-H activation reactions. The recent non-asym. and asym. C-H activation reactions mediated by organocatalysts are discussed in this review.(i) Mitchell, E. A.; Peschiulli, A.; Lefevre, N.; Meerpoel, L.; Maes, B. U. W. Chem. - Eur. J. 2012, 18, 10092 DOI: 10.1002/chem.201201539Google Scholar9ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVymtrzK&md5=cc4c815b6114de3dfe9fdb38431f82beDirect α-Functionalization of Saturated Cyclic AminesMitchell, Emily A.; Peschiulli, Aldo; Lefevre, Nicolas; Meerpoel, Lieven; Maes, Bert U. W.Chemistry - A European Journal (2012), 18 (33), 10092-10142CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Recent advances in synthetic methods for the direct α-functionalization of satd. cyclic amines are described. Methods are categorized according to the in situ formed reactive intermediate (α-amino cation, α-amino anion, and α-amino radical). Transition metal-catalyzed reactions involving other intermediates have been treated as a sep. and fourth class.(j) Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3464 DOI: 10.1039/c2cs15323hGoogle Scholar9jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xlt1ynt74%253D&md5=2621d83e4bd5406822434d16673ca947Recent advances in copper-catalyzed dehydrogenative functionalization via a single electron transfer (SET) processZhang, Chun; Tang, Conghui; Jiao, NingChemical Society Reviews (2012), 41 (9), 3464-3484CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Copper salts were developed as versatile catalysts for oxidative coupling reactions in org. synthesis. During these processes, Cu-catalysts are often proposed to serve as a one-electron oxidant to promote the single-electron transfer process. Recently, the transition metal-catalyzed direct dehydrogenative transformation has attracted considerable attention. This tutorial review summarized the recent advances in the copper-catalyzed dehydrogenative functionalization via a single electron transfer (SET) process achieving C-C, C-N, C-O, C-halogen atoms, C-P, and N-N bond formation.(k) Jones, K. M.; Klussmann, M. Synlett 2012, 2012, 159 DOI: 10.1055/s-0031-1290117Google ScholarThere is no corresponding record for this reference.(l) Peng, B.; Maulide, N. Chem. - Eur. J. 2013, 19, 13274 DOI: 10.1002/chem.201301522Google Scholar9lhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVCntrfJ&md5=014e2d7cda182d6d5546b7937bd115e9The Redox-Neutral Approach to C-H FunctionalizationPeng, Bo; Maulide, NunoChemistry - A European Journal (2013), 19 (40), 13274-13287CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The direct functionalization of C-H bonds is an attractive strategy in org. synthesis. Although several advances have been made in this area, the selective activation of inert sp3 C-H bonds remains a daunting challenge. Recently, a new type of sp3 C-H activation mode through internal hydride transfer has demonstrated the potential to activate remote sp3 C-H linkages in an atom-economic manner. This minireview attempts to classify recent advances in this area including the transition to non-activated sp3 C-H bonds and asym. hydride transfers.(m) Platonova, A. Y.; Glukhareva, T. V.; Zimovets, O. A.; Morzherin, Y. Y. Chem. Heterocycl. Compd. 2013, 49, 357 DOI: 10.1007/s10593-013-1257-6Google Scholar9mhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVGktL%252FJ&md5=fb09948c00c061160a7700c808f17ee5tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)Platonova, A. Yu.; Glukhareva, T. V.; Zimovets, O. A.; Morzherin, Yu. Yu.Chemistry of Heterocyclic Compounds (New York, NY, United States) (2013), 49 (3), 357-385CODEN: CHCCAL; ISSN:0009-3122. (Springer)A review. The data published over the last 15-20 years on reactions taking place by the tert-amino effect mechanism have been reviewed.(n) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322 DOI: 10.1021/cr300503rGoogle Scholar9nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFKgtLc%253D&md5=e09e6cf6a4c64fd3e8f21d55e151266eVisible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic SynthesisPrier, Christopher K.; Rankic, Danica A.; MacMillan, David W. C.Chemical Reviews (Washington, DC, United States) (2013), 113 (7), 5322-5363CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This review will highlight the early work on the use of transition metal complexes as photoredox catalysts to promote reactions of org. compds. (prior to 2008), as well as cover the surge of work that has appeared since 2008. We have for the most part grouped reactions according to whether the org. substrate undergoes redn., oxidn., or a redox neutral reaction and throughout have sought to highlight the variety of reactive intermediates that may be accessed via this general reaction manifold.(o) Girard, S. A.; Knauber, T.; Li, C.-J. Angew. Chem., Int. Ed. 2014, 53, 74 DOI: 10.1002/anie.201304268Google Scholar9ohttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslCqsL3J&md5=06a68206aeb4a4912f123cbe86124343The Cross-Dehydrogenative Coupling of Csp3-H Bonds: A Versatile Strategy for C-C Bond FormationsGirard, Simon A.; Knauber, Thomas; Li, Chao-JunAngewandte Chemie, International Edition (2014), 53 (1), 74-100CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Over the last decade, substantial research has led to the introduction of an impressive no. of efficient procedures which allow the selective construction of C-C bonds by directly connecting two different C-H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C-H bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative Csp3-C formations and provides a comprehensive overview on existing procedures and employed methodologies.(p) Haibach, M. C.; Seidel, D. Angew. Chem., Int. Ed. 2014, 53, 5010 DOI: 10.1002/anie.201306489Google Scholar9phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlvVSls7s%253D&md5=5a68fc1857ee1a0433f2e3fe84b54497C-H bond functionalization through intramolecular hydride transferHaibach, Michael C.; Seidel, DanielAngewandte Chemie, International Edition (2014), 53 (20), 5010-5036CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Known for over a century, reactions that involve intramol. hydride transfer events experienced a recent resurgence. Undoubtedly responsible for the increased interest in this research area was the realization that hydride shifts represent an attractive avenue for C-H bond functionalization. The redox-neutral nature of these complexity-enhancing transformations makes them ideal for sustainable reaction development. This review summarized recent progress in this field while highlighting key historical contributions.(q) Wang, L.; Xiao, J. Adv. Synth. Catal. 2014, 356, 1137 DOI: 10.1002/adsc.201301153Google Scholar9qhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFyltrk%253D&md5=5e778e7fcb0e1c6157ce74a5acae160eAdvancement in cascade [1,n]-hydrogen transfer/cyclization: A method for direct functionalization of inactive C(sp3)-H bondsWang, Liang; Xiao, JianAdvanced Synthesis & Catalysis (2014), 356 (6), 1137-1171CODEN: ASCAF7; ISSN:1615-4150. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The cascade [1,n]-hydrogen transfer/cyclization, recognized one century ago, has received considerable interest in recent decades and great achievements were made. This cascade process can functionalize C(sp3)-H bonds directly into C-C, C-N, C-O bonds under the catalysis by Lewis acids, Bronsted acids or organocatalysts, and even under thermal conditions. This methodol. has shown pre-eminent power to construct 5- or 6-membered heterocyclic as well as all-C rings. In this review, various hydrogen donors and hydrogen acceptors are categorized and discussed.(r) Vo, C.-V. T.; Bode, J. W. J. Org. Chem. 2014, 79, 2809 DOI: 10.1021/jo5001252Google Scholar9rhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjvF2qu7k%253D&md5=656a85a09053f529752ebd034ae6138eSynthesis of Saturated N-HeterocyclesVo, Cam-Van T.; Bode, Jeffrey W.Journal of Organic Chemistry (2014), 79 (7), 2809-2815CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)A review discusses recent work in the synthesis of satd. nitrogen heterocycles by potentially general methods with readily available starting materials using lithiation, C-H activation, hydroamination, amination, cyclization, and cyclocondensation reactions; cyclocondensation reactions of tributylstannylated amines and aldehydes developed in the Bode group to give satd. nitrogen heterocycles and benzo-fused nitrogen heterocycles are also discussed.(s) Seidel, D. Org. Chem. Front. 2014, 1, 426 DOI: 10.1039/C4QO00022FGoogle Scholar9shttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXns1Cmtbk%253D&md5=b129fa66adb6ec1229d1c4ad324d0046The redox-A3 reactionSeidel, DanielOrganic Chemistry Frontiers (2014), 1 (4), 426-429CODEN: OCFRA8; ISSN:2052-4129. (Royal Society of Chemistry)A review. This highlight details the recent emergence of a new type of A3 reaction (three-component condensation of an amine, an aldehyde and an alkyne). In contrast to the classic A3 coupling process, the redox-A3 reaction incorporates an iminium isomerization step and leads to amine α-alkynylation. The overall transformation is redox-neutral by virtue of a combined reductive N-alkylation/oxidative C-H bond functionalization.(t) Qin, Y.; Lv, J.; Luo, S. Tetrahedron Lett. 2014, 55, 551 DOI: 10.1016/j.tetlet.2013.11.051Google Scholar9thttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOksrnP&md5=c26f5353dd8bf4892941164437bf8e33Catalytic asymmetric α-C(sp3)-H functionalization of aminesQin, Yan; Lv, Jian; Luo, SanzhongTetrahedron Letters (2014), 55 (2), 551-558CODEN: TELEAY; ISSN:0040-4039. (Elsevier Ltd.)I this review, a brief overview of catalytic asym. α-C(sp3)-H functionalization of amines, mainly via internal tert-aminocyclization, intermol. C-H oxidative couplings, and redox neutral metal insertion C-H bond was presented.(u) Seidel, D. Acc. Chem. Res. 2015, 48, 317 DOI: 10.1021/ar5003768Google Scholar9uhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXks1Kntg%253D%253D&md5=281c6d4cd81ed3a9d123b13543fc62a3The azomethine ylide route to amine C-H functionalization: Redox-versions of classic reactions and a pathway to new transformationsSeidel, DanielAccounts of Chemical Research (2015), 48 (2), 317-328CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Redox-neutral methods for the functionalization of amine α-C-H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C-H bond functionalization are oxidative in nature. While the most efficient variants utilize atm. oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramol. hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic org. transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel-Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C-H bond functionalization. Intramol. versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloaddns. and other pericyclic processes, have been identified as common intermediates. Extension of this chem. to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) satd. cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chem. of amines and carbonyl compds. than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions.(v) Beatty, J. W.; Stephenson, C. R. J. Acc. Chem. Res. 2015, 48, 1474 DOI: 10.1021/acs.accounts.5b00068Google Scholar9vhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnvFCks78%253D&md5=ffbde0361bd2642ddc68f2556d468d31Amine Functionalization via Oxidative Photoredox Catalysis: Methodology Development and Complex Molecule SynthesisBeatty, Joel W.; Stephenson, Corey R. J.Accounts of Chemical Research (2015), 48 (5), 1474-1484CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. While the use of visible light to drive chem. reactivity is of high importance to the development of environmentally benign chem. transformations, the concomitant use of a stoichiometric electron donor or acceptor is often required to steer the desired redox behavior of these systems. The low-cost and ubiquity of tertiary amine bases has led to their widespread use as reductive additives in photoredox catalysis. Early use of trialkylamines in this context was focused on their role as reductive excited state quenchers of the photocatalyst, which in turn provides a more highly reducing catalytic intermediate. In this Account, we discuss some of the observations and thought processes that have led from our use of amines as reductive additives to their use as complex substrates and intermediates for natural product synthesis. Early attempts by our group to construct key carbon-carbon bonds via free-radical intermediates led to the observation that some trialkylamines readily behave as efficient hydrogen atom donors under redox-active photochem. conditions. In the wake of in-depth mechanistic studies published in the 1970s, 1980s and 1990s, this understanding has in turn allowed for a systematic approach to the design of a no. of photochem. methodologies through rational tuning of the amine component. Minimization of the C-H donicity of the amine additive was found to promote desired C-C bond formation in a no. of contexts, and subsequent elucidation of the amine's redox fate has sparked a reevaluation of the amine's role from that of reagent to that of substrate. The reactivity of tertiary amines in these photochem. systems is complex, and allows for a no. of mechanistic possibilities that are not necessarily mutually exclusive. A variety of combinations of single-electron oxidn., C-H abstraction, deprotonation, and β-scission result in the formation of reactive intermediates such as α-amino radicals and iminium ions. These processes have been explored in depth in the photochem. literature and have resulted in a firm mechanistic grasp of the behavior of amine radical cations in fundamental systems. Harnessing the synthetic potential of these transient species represents an ongoing challenge for the controlled functionalization of amine substrates, because these mechanistic possibilities may result in undesired byproduct formation or substrate decompn. The presence of tertiary amines in numerous alkaloids, pharmaceuticals, and agrochem. lends credence to the potential utility of this chem. in natural product synthesis, and herein we will discuss how these transformations might be controlled for synthetic purposes.(w) Mahato, S.; Jana, C. K. Chem. Rec. 2016, 16, 1477 DOI: 10.1002/tcr.201600001Google Scholar9whttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XotFOjtLg%253D&md5=b9561e530dd843c976bfef6baec515f2Classical-Reaction-Driven Stereo- and Regioselective C(sp3)-H Functionalization of Aliphatic AminesMahato, Sujit; Jana, Chandan K.Chemical Record (2016), 16 (3), 1477-1488CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)A large variety of synthetic methods have been developed for the synthesis of functionalized aliph. amines because of their broad spectrum of application. Metallic reagents/catalysts and/or toxic oxidants are involved in most of the cases. Direct C-H functionalization of aliph. amines via their classical condensation reactions with suitable carbonyl compds. is advantageous because this method avoids hazardous metallic reagents, toxic oxidants and pre-activation/pre-functionalization step(s). In this account, the concept of direct C-H functionalization of aliph. amines based on the classical condensation-isomerization-addn. (CIA) strategy followed by recent contributions from our ongoing research in the field along with relevant examples from other groups are described. Successes in stereo- and regioselective C-C and C-O bond formation via direct α- as well as β-C(sp3)-H functionalization are discussed.(x) Qin, Y.; Zhu, L.; Luo, S. Chem. Rev. 2017, 117, 9433 DOI: 10.1021/acs.chemrev.6b00657Google Scholar9xhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVersL0%253D&md5=b0a4596e4582d50b634340130991c227Organocatalysis in Inert C-H Bond FunctionalizationQin, Yan; Zhu, Lihui; Luo, SanzhongChemical Reviews (Washington, DC, United States) (2017), 117 (13), 9433-9520CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. As two coexisting and fast-growing research fields in modern synthetic chem., the merging of organocatalysis and C-H bond functionalization is well foreseeable, and the joint force along this line has been demonstrated to be a powerful approach in making inert C-H bond functionalization more viable, predictable, and selective. In this review, we provide a comprehensive summary of organocatalysis in inert C-H bond functionalization over the past two decades. The review is arranged by types of inert C-H bonds including alkane C-H, arene C-H, and vinyl C-H as well as those activated benzylic C-H, allylic C-H, and C-H bonds alpha to the heteroatom such as nitrogen and oxygen. In each section, the discussion is classified by the explicit organocatalytic mode involved.(y) Cheng, M.-X.; Yang, S.-D. Synlett 2017, 28, 159 DOI: 10.1055/s-0036-1588342Google Scholar9yhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFOgsb%252FF&md5=a5a29e1be97f2fbfc760f159e560866cRecent Advances in the Enantioselective Oxidative α-C-H Functionalization of AminesCheng, Ming-Xing; Yang, Shang-DongSynlett (2017), 28 (2), 159-174CODEN: SYNLES; ISSN:0936-5214. (Georg Thieme Verlag)A review. The recent advances in the enantioselective oxidative α-C(sp3)-H bond functionalization of amines using transition-metal catalysts, organocatalysts or photoredox catalysts were reviewed. - 10
Selected reviews on various types of redox-neutral transformations:
(a) Burns, N. Z.; Baran, P. S.; Hoffmann, R. W. Angew. Chem., Int. Ed. 2009, 48, 2854 DOI: 10.1002/anie.200806086Google Scholar10ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXkvVeht7o%253D&md5=71c2618a333ba2ef4dc2e6a2004d69faRedox economy in organic synthesisBurns, Noah Z.; Baran, Phil S.; Hoffmann, Reinhard W.Angewandte Chemie, International Edition (2009), 48 (16), 2854-2867CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The purpose of this review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep org. synthesis. "Economy" is referred to as the thrifty and efficient use of material resources, as the principle of "min. effort to reach a goal. Redox economy then implies the use of as few redox steps as possible in the synthetic conquest of a target compd. While any sort of economy will help to streamline the effort of total synthesis, redox economy addresses a particularly weak area in present-day total synthesis.(b) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696 DOI: 10.1021/ar400239vGoogle Scholar10bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlslCruw%253D%253D&md5=38a434fd7477a8da6a0a275d6d1ec57fOn the Mechanism of N-Heterocyclic Carbene-Catalyzed Reactions Involving Acyl AzoliumsMahatthananchai, Jessada; Bode, Jeffrey W.Accounts of Chemical Research (2014), 47 (2), 696-707CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. This Account focuses on the discovery and mechanistic investigation of the catalytic generation of acyl azoliums and α,β-unsatd. acyl azoliums. We address the mechanistic inquiries about the characterization of the unsatd. acyl triazolium species and its kinetic profile under catalytically relevant conditions. We also provide explanations for the requirement and effect of the N-mesityl group in NHC catalysis based on detailed exptl. data within given specific reactions or conditions.(c) Ketcham, J. M.; Shin, I.; Montgomery, T. P.; Krische, M. J. Angew. Chem., Int. Ed. 2014, 53, 9142 DOI: 10.1002/anie.201403873Google Scholar10chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1WlsbbF&md5=06a51bafc73c3d9d2a77989a4dfd0020Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: Borrowing hydrogen, returning carbonKetcham, John M.; Shin, Inji; Montgomery, T. Patrick; Krische, Michael J.Angewandte Chemie, International Edition (2014), 53 (35), 9142-9150CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The use of alcs. and unsatd. reactants for the redox-triggered generation of nucleophile-electrophile pairs represents a broad, new approach to carbonyl addn. chem. Discrete redox manipulations that are often required for the generation of carbonyl electrophiles and premetalated carbon-centered nucleophiles are thus avoided. Based on this concept, a broad, new family of enantioselective C-C coupling reactions that are catalyzed by iridium or ruthenium complexes were developed, which are summarized in this Minireview.(d) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Chem. Soc. Rev. 2015, 44, 1155 DOI: 10.1039/C4CS00288AGoogle Scholar10dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvF2ktb3F&md5=9038ede9004e2362282c02b7728e2330Transition metal-catalyzed C-H functionalization of N-oxyenamine internal oxidantsHuang, Huawen; Ji, Xiaochen; Wu, Wanqing; Jiang, HuanfengChemical Society Reviews (2015), 44 (5), 1155-1171CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. The transition metal-catalyzed C-H functionalization with hydroxylamine derivs. serving as both reactants and internal oxidants was highlighted. These reactions obviated the need for external oxidants and therefore resulted in high reactivity and selectivity, as well as excellent functional group tolerance under mild reaction conditions, and moreover, water, methanol or carboxylic acid was generally released as the byproduct, thus leading to reduced waste. The transition metal-catalyzed oxidative C-H functionalization of N-oxyenamine internal oxidants, with an emphasis on the scope and limitations, as well as the mechanisms of these reactions were described. - 11
For detailed discussions on the mechanisms of these transformations, see refs 7c,7e−7g and 9u and the following reports:
(a) Xue, X.; Yu, A.; Cai, Y.; Cheng, J.-P. Org. Lett. 2011, 13, 6054 DOI: 10.1021/ol2025247Google ScholarThere is no corresponding record for this reference.(b) Ma, L.; Paul, A.; Breugst, M.; Seidel, D. Chem. - Eur. J. 2016, 22, 18179 DOI: 10.1002/chem.201603839Google Scholar11bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVGjtrvL&md5=59217d78c011882892a63d2a36268a00Redox-Neutral Aromatization of Cyclic Amines: Mechanistic Insights and Harnessing of Reactive Intermediates for Amine α- and β-C-H FunctionalizationMa, Longle; Paul, Anirudra; Breugst, Martin; Seidel, DanielChemistry - A European Journal (2016), 22 (50), 18179-18189CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Cyclic amines such as pyrrolidine and piperidine are known to undergo condensations with aldehydes to furnish pyrrole and pyridine derivs., resp. A combined exptl. and computational study provides detailed insights into the mechanism of pyrrole formation. A no. of reactive intermediates (e.g., azomethine ylides, conjugated azomethine ylides, enamines) were intercepted, outlining strategies for circumventing aromatization as a valuable pathway for amine C-H functionalization. - 12
Examples of redox-neutral α-C–H functionalizations of secondary amines in the context of (3 + 2) cycloadditions:
(a) Ardill, H.; Grigg, R.; Sridharan, V.; Surendrakumar, S.; Thianpatanagul, S.; Kanajun, S. J. Chem. Soc., Chem. Commun. 1986, 602 DOI: 10.1039/c39860000602Google ScholarThere is no corresponding record for this reference.(b) Ardill, H.; Dorrity, M. J. R.; Grigg, R.; Leon-Ling, M. S.; Malone, J. F.; Sridharan, V.; Thianpatanagul, S. Tetrahedron 1990, 46, 6433 DOI: 10.1016/S0040-4020(01)96013-2Google ScholarThere is no corresponding record for this reference.(c) Ardill, H.; Fontaine, X. L. R.; Grigg, R.; Henderson, D.; Montgomery, J.; Sridharan, V.; Surendrakumar, S. Tetrahedron 1990, 46, 6449 DOI: 10.1016/S0040-4020(01)96014-4Google ScholarThere is no corresponding record for this reference.(d) Wang, B.; Mertes, M. P.; Mertes, K. B.; Takusagawa, F. Tetrahedron Lett. 1990, 31, 5543 DOI: 10.1016/S0040-4039(00)97892-4Google ScholarThere is no corresponding record for this reference.(e) Wittland, C.; Arend, M.; Risch, N. Synthesis 1996, 1996, 367 DOI: 10.1055/s-1996-4208Google ScholarThere is no corresponding record for this reference.(f) Marx, M. A.; Grillot, A.-L.; Louer, C. T.; Beaver, K. A.; Bartlett, P. A. J. Am. Chem. Soc. 1997, 119, 6153 DOI: 10.1021/ja9621051Google ScholarThere is no corresponding record for this reference.(g) Grigg, R.; Sridharan, V.; Thornton-Pett, M.; Wang, J.; Xu, J.; Zhang, J. Tetrahedron 2002, 58, 2627 DOI: 10.1016/S0040-4020(02)00129-1Google ScholarThere is no corresponding record for this reference.(h) Parmar, N. J.; Pansuriya, B. R.; Labana, B. M.; Kant, R.; Gupta, V. K. RSC Adv. 2013, 3, 17527 DOI: 10.1039/c3ra42220hGoogle Scholar12hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVShsL7E&md5=f1f78304e8b9fd8f57e0b581db3c31a3A convenient 1,3-dipolar cycloaddition-reduction synthetic sequence from 2-allyloxy-5-nitro-salicylaldehyde to aminobenzopyran-annulated heterocyclesParmar, Narsidas J.; Pansuriya, Bhavesh R.; Labana, Balvantsingh M.; Kant, Rajni; Gupta, Vivek K.RSC Advances (2013), 3 (38), 17527-17539CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A microwave-assisted, one-pot synthesis of some nitro benzopyran-annulated pyrroles as well as pyrrolo-fused isoquinolines via a 1,3-dipolar cycloaddn., which involves the in-situ generation of azomethine ylide formed from a secondary amines with 2-allyloxy-5-nitro-salicylaldehyde, was achieved in a solvent-free environment. Compared to methods of conventional heating or thermal heating, the present microwave-assisted method is rapid and highly efficient. In addn., amine analogous heterocyclic compds. were successfully accessed after treating the reaction products further with iron in acidic medium, which also highlights a one-pot procedure for a new 1,3-dipolar cycloaddn.-redn. synthetic sequence. All amine products have new bio-profiles and are anticipated to be effective drug-like candidates. All compds. were characterized based on their elemental anal., mass, IR, and 1H and 13C NMR spectroscopic data. The stereochem. of the product was confirmed by 2D NMR COSY and NOESY expts., which, on the basis of single crystal X-ray diffraction data anal., was further confirmed and supported. The title compds. thus formed included (2R,3aS,9bR)-rel-1,2,3,3a,4,9b-hexahydro-8-nitro-1-(phenylmethyl)[1]benzopyrano[4,3-b]pyrrole-2-carboxylic acid Et ester (I) and related substances, such as (2R,3aS,9bR)-rel-8-amino-1,2,3,3a,4,9b-hexahydro-1-(phenylmethyl)[1]benzopyrano[4,3-b]pyrrole-2-carboxylic acid Et ester, [1]benzopyrano[3',4':4,5]pyrrolo[2,1-a]isoquinoline derivs. The synthesis of the target compds. was achieved by a reaction of glycine ester derivs., N-methylglycine, 1,2,3,4-tetrahydroisoquinoline with 5-nitro-2-(2-propen-1-yloxy)benzaldehyde.(i) Rahman, M.; Bagdi, A. K.; Mishra, S.; Hajra, A. Chem. Commun. 2014, 50, 2951 DOI: 10.1039/c4cc00454jGoogle Scholar12ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXis1Churw%253D&md5=01dda3305b2f4647a79e9ad7037405abFunctionalization of an sp3 C-H bond via a redox-neutral domino reaction: diastereoselective synthesis of hexahydropyrrolo[2,1-b]oxazolesRahman, Matiur; Bagdi, Avik Kumar; Mishra, Subhajit; Hajra, AlakanandaChemical Communications (Cambridge, United Kingdom) (2014), 50 (22), 2951-2953CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A diastereoselective synthesis of pyrrolidinooxazolidines, e.g., I, was achieved by a metal-free, base-promoted reaction of pyrrolidine and arom. aldehydes under microwave irradn. The rare functionalization of an sp3 C-H bond probably results from an in situ generated azomethine ylide that undergoes cycloaddn. with aldehydes.(j) Mantelingu, K.; Lin, Y.; Seidel, D. Org. Lett. 2014, 16, 5910 DOI: 10.1021/ol502918gGoogle ScholarThere is no corresponding record for this reference.(k) Pavan Kumar, C. S.; Harsha, K. B.; Mantelingu, K.; Rangappa, K. S. RSC Adv. 2015, 5, 61664 DOI: 10.1039/C5RA10030EGoogle Scholar12khttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtFajs7%252FF&md5=a8842ee9e631e9e1b5b983f04b3ea052Diastereoselective synthesis of fused oxazolidines and highly substituted 1H-pyrrolo[2,1-c][1,4]oxazines via C-H functionalizationPavan Kumar, Chottanahalli. S.; Harsha, Kachigere. B.; Mantelingu, Kempegowda; Rangappa, Kanchugarakoppal. S.RSC Advances (2015), 5 (76), 61664-61670CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The first one pot protocol for the diastereoselective synthesis of oxazolo[2,3-c]isoquinoline e.g., I was achieved by a metal-free, benzoic acid catalyzed reaction of 1,2,3,4-tetrahydroisoquinoline or trypoline with aldehydes under mild conditions via C-H, C-O bond functionalization has been reported. A new approach for the synthesis of highly substituted 1H-pyrrolo[2,1-c][1,4]oxazine, e.g., I was carried out.(l) Safaei-Ghomi, J.; Masoomi, R. RSC Adv. 2015, 5, 15591 DOI: 10.1039/C4RA16020GGoogle Scholar12lhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnvVaitQ%253D%253D&md5=e27de9334ef18984df81127fa8298431Rapid microwave-assisted synthesis of N-benzyl fulleropyrrolidines under solvent free conditionsSafaei-Ghomi, Javad; Masoomi, ReihanehRSC Advances (2015), 5 (20), 15591-15596CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A series of new N-benzyl fulleropyrrolidines I (R = Ph, 2-py, 2-furanyl, etc.) were synthesized in a one-pot via 1,3-dipolar cycloaddn. of C60 with dibenzylamine and aldehyde derivs. using microwave irradn. under solvent-free conditions in good yield. This method provides several advantages involving high yields and rates, decrease in the extent of decompn. of the substrates, as well as environmental friendliness compared to the conventional methods.(m) Yang, H.-T.; Tan, Y.-C.; Ge, J.; Wu, H.; Li, J.-X.; Yang, Y.; Sun, X.-Q.; Miao, C.-B. J. Org. Chem. 2016, 81, 11201 DOI: 10.1021/acs.joc.6b02193Google Scholar12mhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslWjsb3J&md5=d648e2bde5eb3d9c22ce82bfeb19a952Reaction of C60 with inactive secondary amines and aldehydes and the Cu(OAc)2-promoted regioselective intramolecular C-H functionalization of the generated fulleropyrrolidinesYang, Hai-Tao; Tan, Yi-Chen; Ge, Jie; Wu, He; Li, Jia-Xing; Yang, Yang; Sun, Xiao-Qiang; Miao, Chun-BaoJournal of Organic Chemistry (2016), 81 (22), 11201-11209CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The thermal reaction of C60 with arom. aldehydes and inactive secondary amines for the stereoselective synthesis of trans-1,2,5-trisubstituted [6,6]fullero[c]pyrrolidines has been developed. Moreover, when an o-hydroxyl group was located at the Ph ring of the generated fulleropyrrolidines, the Cu(OAc)2-promoted regioselective intramol. C-O coupling reaction occurred to generate unique tricycle-fused fullerene derivs. I.(n) Zheng, K.-L.; Shu, W.-M.; Ma, J.-R.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2016, 18, 3526 DOI: 10.1021/acs.orglett.6b01369Google Scholar12nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFersr7O&md5=a38f0909454ee7e89c142366261fd6ecAcid-Mediated N-H/α,β-C(sp3)-H Trifunctionalization of Pyrrolidine: Intermolecular [3 + 2] Cycloaddition for the Construction of 2,3-Dihydro-1H-Pyrrolizine DerivativesZheng, Kai-Lu; Shu, Wen-Ming; Ma, Jun-Rui; Wu, Yan-Dong; Wu, An-XinOrganic Letters (2016), 18 (15), 3526-3529CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)A 1-pot acid-mediated reaction was developed for the N-H/α,β-C(sp3)-H trifunctionalization of pyrrolidine without any metallic reagents or external oxidants. This reaction involves the intermol. [3+2] cycloaddn. of in situ-generated azomethine ylides with acrylic esters to provide facile access to 2,3-dihydro-1H-pyrrolizine derivs. in high yields under mild conditions.(o) Du, Y.; Yu, A.; Jia, J.; Zhang, Y.; Meng, X. Chem. Commun. 2017, 53, 1684 DOI: 10.1039/C6CC08996HGoogle ScholarThere is no corresponding record for this reference.(p) Zheng, K.-L.; You, M.-Q.; Shu, W.-M.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2017, 19, 2262 DOI: 10.1021/acs.orglett.7b00769Google Scholar12phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtFKlsb4%253D&md5=f182c5f85837425f2dba7a1e7a2945a7Acid-Mediated Intermolecular [3 + 2] Cycloaddition toward Pyrrolo[2,1-a]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G Trimethyl EtherZheng, Kai-Lu; You, Min-Qi; Shu, Wen-Ming; Wu, Yan-Dong; Wu, An-XinOrganic Letters (2017), 19 (9), 2262-2265CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)A novel one-pot reaction was developed for the efficient synthesis of pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2-nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy provides a concise total synthesis of the lamellarin core I and lamellarin G tri-Me ether using electrophilic substitution and palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. - 13
Examples of redox-neutral α-C–H bond annulations of secondary amines that result in the formation of 5-membered rings:
(a) Grigg, R.; Nimal Gunaratne, H. Q.; Henderson, D.; Sridharan, V. Tetrahedron 1990, 46, 1599 DOI: 10.1016/S0040-4020(01)81969-4Google ScholarThere is no corresponding record for this reference.(b) Soeder, R. W.; Bowers, K.; Pegram, L. D.; Cartaya-Marin, C. P. Synth. Commun. 1992, 22, 2737 DOI: 10.1080/00397919208021537Google Scholar13bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XmsFWitbs%253D&md5=cff9638ef9bb2b0a70b737f77fe29e2dA one pot synthesis of 5,7-diphenyl-2,3-dihydro-1H-pyrrolizineSoeder, R. W.; Bowers, K.; Pegram, L. D.; Cartaya-Marin, C. P.Synthetic Communications (1992), 22 (19), 2737-40CODEN: SYNCAV; ISSN:0039-7911.The title compd. (I) was synthesized by reacting dibenzoylmethane with pyrrolidine in C6H6 in one step in 60% yield.(c) Grigg, R.; Kennewell, P.; Savic, V.; Sridharan, V. Tetrahedron 1992, 48, 10423 DOI: 10.1016/S0040-4020(01)88345-9Google ScholarThere is no corresponding record for this reference.(d) Deb, I.; Seidel, D. Tetrahedron Lett. 2010, 51, 2945 DOI: 10.1016/j.tetlet.2010.03.086Google ScholarThere is no corresponding record for this reference.(e) Kang, Y.; Richers, M. T.; Sawicki, C. H.; Seidel, D. Chem. Commun. 2015, 51, 10648 DOI: 10.1039/C5CC03390JGoogle ScholarThere is no corresponding record for this reference.(f) Cheng, Y.-F.; Rong, H.-J.; Yi, C.-B.; Yao, J.-J.; Qu, J. Org. Lett. 2015, 17, 4758 DOI: 10.1021/acs.orglett.5b02298Google ScholarThere is no corresponding record for this reference.(g) Yang, Z.; Lu, N.; Wei, Z.; Cao, J.; Liang, D.; Duan, H.; Lin, Y. J. Org. Chem. 2016, 81, 11950 DOI: 10.1021/acs.joc.6b01781Google ScholarThere is no corresponding record for this reference.(h) Rong, H.-J.; Cheng, Y.-F.; Liu, F.-F.; Ren, S.-J.; Qu, J. J. Org. Chem. 2017, 82, 532 DOI: 10.1021/acs.joc.6b02562Google ScholarThere is no corresponding record for this reference.(i) Purkait, A.; Roy, S. K.; Srivastava, H. K.; Jana, C. K. Org. Lett. 2017, 19, 2540 DOI: 10.1021/acs.orglett.7b00832Google Scholar13ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntFOmsLc%253D&md5=2474160cebee1ab3a53d6d05305ced73Metal-Free Sequential C(sp2)-H/OH and C(sp3)-H Aminations of Nitrosoarenes and N-Heterocycles to Ring-Fused ImidazolesPurkait, Anisha; Roy, Subhra Kanti; Srivastava, Hemant Kumar; Jana, Chandan K.Organic Letters (2017), 19 (10), 2540-2543CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)Hydrogen bond assisted ortho-selective C(sp2)-H amination of nitrosoarenes and subsequent α-C(sp3)-H functionalization of aliph. amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compds. with N-heterocycles provides a facile excess to a wide range of biol. relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, resp. Nucleophilic arom. hydrogen substitution (SNArH) was found to be preferred over classical SNAr reaction during the C(sp2)-H amination of halogenated nitrosoarenes. - 14
Selected reviews on azomethine ylide chemistry:
(a) Padwa, A. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, N. Y., 1984; Vol. 1.Google ScholarThere is no corresponding record for this reference.(b) Padwa, A., Ed. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, 1984; Vol. 2.Google ScholarThere is no corresponding record for this reference.(c) Padwa, A.; Pearson, W. H.. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products; Wiley: Chichester, 2002; Vol. 59.Google ScholarThere is no corresponding record for this reference.(d) Najera, C.; Sansano, J. M. Curr. Org. Chem. 2003, 7, 1105 DOI: 10.2174/1385272033486594Google Scholar14dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFGlsro%253D&md5=8e82a64f549f40d8b74a7fbfbb7db234Azomethine ylides in organic synthesisNajera, Carmen; Sansano, Jose M.Current Organic Chemistry (2003), 7 (11), 1105-1150CODEN: CORCFE; ISSN:1385-2728. (Bentham Science Publishers Ltd.)A review covering the literature from 1988 dealing with cyclic and acyclic azomethine ylides in which a part or the whole of the ylide conjugation is included in a conjugated heterocycle. Special emphasis will be given to the applications of these dipoles in the synthesis of complex structures as well as in key steps of total synthesis.(e) Coldham, I.; Hufton, R. Chem. Rev. 2005, 105, 2765 DOI: 10.1021/cr040004cGoogle Scholar14ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXlsFKrtr8%253D&md5=8b56b4040a6d1fd56845a456bee5e0d1Intramolecular dipolar cycloaddition reactions of azomethine ylidesColdham, Iain; Hufton, RichardChemical Reviews (Washington, DC, United States) (2005), 105 (7), 2765-2809CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on the theor. background and the mechanism of azomethine ylide formation from aldehydes, imines, aziridines, and heterocycles, and their intramol. dipolar cycloaddn. giving access to pyrrolidines and pyrroles in a highly regioselective manner (preferring endo transition state). The use of this methodol. for the synthesis of pyrrolidine- and pyrrole-contg. natural products is emphasized and exemplified.(f) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484 DOI: 10.1021/cr050011gGoogle Scholar14fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFeltrnL&md5=44689d0969948b62cb3f8d0e40397de3Construction of Enantiopure Pyrrolidine Ring System via Asymmetric [3+2]-Cycloaddition of Azomethine YlidesPandey, Ganesh; Banerjee, Prabal; Gadre, Smita R.Chemical Reviews (Washington, DC, United States) (2006), 106 (11), 4484-4517CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review.(g) Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2006, 2006, 2873 DOI: 10.1002/ejoc.200500892Google ScholarThere is no corresponding record for this reference.(h) Bonin, M.; Chauveau, A.; Micouin, L. Synlett 2006, 2006, 2349 DOI: 10.1055/s-2006-949626Google ScholarThere is no corresponding record for this reference.(i) Nair, V.; Suja, T. D. Tetrahedron 2007, 63, 12247 DOI: 10.1016/j.tet.2007.09.065Google Scholar14ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1Oqsb7I&md5=b49dd6f6a02d0046bbdc34c314c9952bIntramolecular 1,3-dipolar cycloaddition reactions in targeted synthesesNair, Vijay; Suja, T. D.Tetrahedron (2007), 63 (50), 12247-12275CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)Review on the use of intramol. 1,3-dipolar cycloaddn. reactions using nitrones, nitrile oxides, carbonyl ylides, azomethine imines and ylides, azides and mesionic dipoles in targeted syntheses of heteroatom contg. cyclic compds. and natural products.(j) Najera, C.; Sansano, J. M. Top. Heterocycl. Chem. 2008, 12, 117 DOI: 10.1007/7081_2007_099Google Scholar14jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXis1eitLc%253D&md5=2b588cf2220640aa6930ec0a411f8218Enantioselective cycloadditions of azomethine ylidesNajera, Carmen; Sansano, Jose M.Topics in Heterocyclic Chemistry (2008), 12 (Synthesis of Heterocycles via Cycloadditions I), 117-145CODEN: THCOA6; ISSN:1861-9282. (Springer GmbH)A review. The asym. 1,3-dipolar cycloaddn. reaction of azomethine ylides, which are generated from the corresponding imino ester and alkenes, is one of the most fascinating transformations because the configuration of the four new stereogenic centers of the finally obtained proline can be absolutely established in only one step with total atom economy. Since 2002, the catalyzed enantioselective 1,3-DCRs have been performed using chiral metal complexes. For example, chiral silver and copper complexes are the most employed catalysts. Silver complexes afforded selectively endo-cycloadducts, however, both exo- and endo-adducts were generated in the presence of several chiral Cu(I) complexes. Although chiral zinc complexes have also been studied in endo-selective processes, the published works are not so numerous. Bidentate ligands, such as bisphosphanes, nitrogenated phosphanes, and sulfur-contg. phosphanes have shown very high enantioselectivity levels. Apart from the employment of chiral Lewis acids, the utilization of chiral bases or organocatalysts are also known, albeit with a large no. of limitations and, in some cases, with lower enantioselections.(k) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887 DOI: 10.1021/cr078371mGoogle Scholar14khttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXotlOmsL8%253D&md5=ff4f4a3a82fe8610b423a67035bbb374Enantioselective Copper-Catalyzed 1,3-Dipolar CycloadditionsStanley, Levi M.; Sibi, Mukund P.Chemical Reviews (Washington, DC, United States) (2008), 108 (8), 2887-2902CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This review summarizes the recent achievements in the development of enantioselective copper-catalyzed 1,3-dipolar cycloaddn. reactions. Topics include reactions with electron-deficient alkenes, reactions with electron-rich alkenes, reactions with alkynes, cycloaddns. with azomethine ylides and misc. cycloaddns.(l) Nyerges, M.; Toth, J.; Groundwater, P. W. Synlett 2008, 2008, 1269 DOI: 10.1055/s-2008-1072743Google ScholarThere is no corresponding record for this reference.(m) Pineiro, M.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2009, 2009, 5287 DOI: 10.1002/ejoc.200900644Google ScholarThere is no corresponding record for this reference.(n) Burrell, A. J. M.; Coldham, I. Curr. Org. Synth. 2010, 7, 312 DOI: 10.2174/157017910791414472Google Scholar14nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXpslSmu7g%253D&md5=946222d8aaa8ac25f6459e6064cd0ddfSynthesis of natural products using intramolecular dipolar cycloaddition reactionsBurrell, Adam J. M.; Coldham, IainCurrent Organic Synthesis (2010), 7 (4), 312-331CODEN: COSUC2; ISSN:1570-1794. (Bentham Science Publishers Ltd.)A review. This review described ylide 1,3-dipoles in cycloaddn. reactions for the synthesis (and formal synthesis) of natural products. Examples using azomethine ylides, carbonyl ylides, nitrones, nitronates, nitrile oxides, and azides were provided. These led to a diverse array of heterocyclic products. Intramol. cycloaddn. provides two new rings in one step and hence an efficient entry to complex target compds.(o) Anac, O.; Gungor, F. S. Tetrahedron 2010, 66, 5931 DOI: 10.1016/j.tet.2010.05.058Google ScholarThere is no corresponding record for this reference.(p) Adrio, J.; Carretero, J. C. Chem. Commun. 2011, 47, 6784 DOI: 10.1039/c1cc10779hGoogle Scholar14phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntlags74%253D&md5=aa0ee768d1e244d622ece481a954110dNovel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylidesAdrio, Javier; Carretero, Juan C.Chemical Communications (Cambridge, United Kingdom) (2011), 47 (24), 6784-6794CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A review. The catalytic asym. 1,3-dipolar cycloaddn. of azomethine ylides constitutes one of the most powerful and atom economical methods for the enantioselective construction of pyrrolidines. This article highlighted the recent developments in this area, with special focus on contributions improving the structural scope at the dipolarophile and azomethine ylide partners.(q) Adrio, J.; Carretero, J. C. Chem. Commun. 2014, 50, 12434 DOI: 10.1039/C4CC04381BGoogle Scholar14qhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCgu7fN&md5=f67669d40970e2109f5767dd84c7d178Recent advances in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylidesAdrio, Javier; Carretero, Juan C.Chemical Communications (Cambridge, United Kingdom) (2014), 50 (83), 12434-12446CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A review. Catalytic asym. 1,3-dipolar cycloaddns. of azomethine ylides have turned out to be one of the most efficient methods for the prepn. of enantioenriched pyrrolidines. The past decade has witnessed the development of a bunch of well-defined catalytic systems capable of affording excellent diastereo and enantioselectivities. Recently, a great effort has been focused on expanding the scope of the cycloaddn. with regard to both reaction partners. In this review, the authors discuss the important advances that have been reported in this area since 2011.(r) Hashimoto, T.; Maruoka, K. Chem. Rev. 2015, 115, 5366 DOI: 10.1021/cr5007182Google Scholar14rhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXot1Sqtr4%253D&md5=ef81ef535549e9697bab054132bc661bRecent Advances of Catalytic Asymmetric 1,3-Dipolar CycloadditionsHashimoto, Takuya; Maruoka, KeijiChemical Reviews (Washington, DC, United States) (2015), 115 (11), 5366-5412CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. An overview is given of the entire field of 1,3-dipolar cycloaddn. (1,3-DC) in the last decade. To directly link this review with the monumental review on asym. 1,3-DC by Joegensen in 1998, seminal works on catalytic asym. 1,3-DCs in early days is also included.(s) Meyer, A.; Ryan, J. 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- 15De Risi, C.; Pollini, G. P.; Zanirato, V. Chem. Rev. 2016, 116, 3241 DOI: 10.1021/acs.chemrev.5b00443
For a review on the chemistry of ketoamides, see:
Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFahsrw%253D&md5=03d7e364ef3c39c3a09830b35933a48fRecent Developments in General Methodologies for the Synthesis of α-KetoamidesDe Risi, Carmela; Pollini, Gian Piero; Zanirato, VinicioChemical Reviews (Washington, DC, United States) (2016), 116 (5), 3241-3305CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. The aim of this review is to give an overview of the diverse methodologies that have emerged since the 1990s up to the present. The different synthetic routes have been grouped according to the way the α-ketoamide moiety has been created. Thus, syntheses of α-ketoamides proceeding via C(2)-oxidn. of amide starting compds. are detailed, as are amidation approaches installing the α-ketoamide residue through C(1)-N bond formation. Also discussed are the methodologies centered on C(1)-C(2) σ-bond construction and C(2)-R/Ar bond-forming processes. Finally, the literature regarding the synthesis of α-ketoamide compds. by palladium-catalyzed double-carbonylative amination reactions has been discussed. - 16Lanigan, R. M.; Sheppard, T. D. Eur. J. Org. Chem. 2013, 2013, 7453 DOI: 10.1002/ejoc.201300573Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1Wrtb7I&md5=3a14f0d90992f8205da733a16f4be466Recent Developments in Amide Synthesis: Direct Amidation of Carboxylic Acids and Transamidation ReactionsLanigan, Rachel M.; Sheppard, Tom D.European Journal of Organic Chemistry (2013), 2013 (33), 7453-7465CODEN: EJOCFK; ISSN:1099-0690. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The synthesis of amides is of huge importance in a wide variety of industrial and academic fields and is of particular significance in the synthesis of pharmaceuticals. Many of the well established methods for amide synthesis involve reagents that are difficult to handle and lead to the generation of large quantities of waste products. As a consequence, there has been a considerable amt. of interest in the development of new approaches to amide synthesis. Over the past few years a wide range of new reagents and catalysts for direct amidation of carboxylic acids have been reported. In addn., the interconversion of amide derivs. through transamidation is emerging as a potential alternative strategy for accessing certain amides. This microreview covers recent developments in the direct amidation of carboxylic acids and the interconversion of amides through transamidation. The advantages and disadvantages of the various methods are discussed, as well as the possible mechanisms of the reactions.
- 17Wang, J.-Y.; Hu, Y.; Wang, D.-X.; Pan, J.; Huang, Z.-T.; Wang, M.-X. Chem. Commun. 2009, 422 DOI: 10.1039/B816007D
An alternative mechanism has also been proposed:
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Abstract
Figure 1
Figure 1. Selected 4-imidazolidinones.
Scheme 1
Scheme 1. Selected Routes to Polycyclic 4-ImidazolidinonesScheme 2
Scheme 2. Ketoamide ScopeaScheme aReactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.
Scheme bTransamidation product (1-(3,4-dihydroisoquinolin-2(1H)-yl)-2-phenylethane-1,2-dione) was obtained in 38% yield.
Scheme 3
Scheme 3. Amine ScopeaScheme aReactions were performed on a 0.5 mmol scale. All yields correspond to isolated yields.
Scheme bReaction was performed in PhMe (0.25 M) under microwave irradiation for 30 min at 220 °C.
Scheme cReaction was performed in PhMe (0.25 M) under microwave irradiation for 1 h at 220 °C.
Scheme 4
Scheme 4. Mechanistic ConsiderationsReferences
This article references 17 other publications.
- 1Blackmore, T.; Thompson, P. Heterocycles 2011, 83, 1953 DOI: 10.3987/REV-11-707
Review on the synthetic and medicinal chemistry of 4-imidazolidinones:
There is no corresponding record for this reference. - 2
For a general review on the synthesis of aminal-type structures, see:
Hiersemann, M. In Comprehensive Organic Functional Group Transformations II; Katritzky, A. R. T.; Richard, J. K., Ed.; Elsevier Ltd.: Oxford, UK, 2005; Vol. 4, p 411.There is no corresponding record for this reference. - 3
Selected reports on natural and synthetic, biologically active 4-imidazolidinones:
(a) Smissman, E.; Inloes, R.; El-Antably, S.; Shaffer, P. J. Med. Chem. 1976, 19, 161 DOI: 10.1021/jm00223a028There is no corresponding record for this reference.(b) Leysen, J.; Gommeren, W.; Laduron, P. Biochem. Pharmacol. 1978, 27, 307 DOI: 10.1016/0006-2952(78)90233-2There is no corresponding record for this reference.(c) Nelson, D.; Taylor, E. Eur. J. Pharmacol. 1986, 124, 207 DOI: 10.1016/0014-2999(86)90147-03chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL28XltVyhur8%253D&md5=2993821f8e2086b20ae0b8b004497d25Spiroxatrine: a selective serotonin1A receptor antagonistNelson, David L.; Taylor, Ethan WillEuropean Journal of Pharmacology (1986), 124 (1-2), 207-8CODEN: EJPHAZ; ISSN:0014-2999.In isolated canine cerebral vessels, the Ki's of spiroxatrine (I) [1054-88-2] for 5-HT1A, 5-HT1B, and 5-HT2 receptors were 3.94, 224,000, and 118.5 nM, resp., whereas the corresponding Ki's for spiperone were 110, 50,300, and 0.41 nM. Thus, I is relatively selective for 5-HT1A sites.(d) Nikam, S.; Martin, A.; Nelson, D. J. Med. Chem. 1988, 31, 1965 DOI: 10.1021/jm00118a017There is no corresponding record for this reference.(e) Rasmussen, G.; Bundgaard, H. Int. J. Pharm. 1991, 71, 45 DOI: 10.1016/0378-5173(91)90066-W3ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXkslyksb4%253D&md5=be9449f8c25e908af02186f8d89f72e5Prodrugs of peptides. 10. Protection of di- and tripeptides against aminopeptidase by formation of bioreversible 4-imidazolidinone derivativesRasmussen, Gitte Juel; Bundgaard, HansInternational Journal of Pharmaceutics (1991), 71 (1-2), 45-53CODEN: IJPHDE; ISSN:0378-5173.The kinetics of hydrolysis of a series of 4-imidazolidinones derived from acetone and various di- and tripeptides was studied in aq. soln. and in the presence of enzymes in order to assess their suitability as prodrug forms for the peptides. Whereas the parent di- and tripeptides were readily hydrolyzed by a purified aminopeptidase as well as in human plasma solns. and rabbit intestinal homogenates, the imidazolidinyl peptides were totally resistant to enzymic cleavage in these media. On the other hand, these derivs. are readily bioreversible, being converted to the parent peptide by spontaneous hydrolysis. The rate of hydrolysis is greatly dependent on the structure of the peptide. For the eleven 4-imidazolidinones studied the half-lives of hydrolysis at pH 7.4 and 37° ranged from 18 min to 545 h. The major structural factor influencing the stability was shown to be the steric properties within the α-carbon atom substituents in the amino acid residue next to the N-terminal amino acid. It is concluded that 4-imidazolidinone formation can be a useful prodrug approach to protect the N-terminal amino acid residue of peptides against cleavage by aminopeptidases and related exopeptidases.(f) Pinza, M.; Farina, C.; Cerri, A.; Pfeiffer, U.; Riccaboni, M. T.; Banfi, S.; Biagetti, R.; Pozzi, O.; Magnani, M.; Dorigotti, L. J. Med. Chem. 1993, 36, 4214 DOI: 10.1021/jm00078a0113fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2cXhvFWlsL8%253D&md5=f8374eb5ac5b086b74b1946dfbd0d24aSynthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancersPinza, Mario; Farina, Carlo; Cerri, Alberto; Pfeiffer, Ugo; Riccaboni, Maria T.; Banfi, Silvano; Biagetti, Raffaella; Pozzi, Ottorino; Magnani, Maurizio; Dorigotti, LucianoJournal of Medicinal Chemistry (1993), 36 (26), 4214-20CODEN: JMCMAR; ISSN:0022-2623.A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones, e.g. dimiracetam (I), were synthesized. These bicyclic derivs. contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addn., these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features obsd. are a potent antiamnestic activity after i.p. administration (minimal ED being between 0.3 and 1 mg/kg i.p. for most compds.), the presence of a bell-shaped dose-response curve and, generally, a redn. of biol. activity after po administration. However, the unsubstituted compd. I shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the ref. drug oxiracetam.(g) Thomsen, C.; Hohlweg, R. Br. J. Pharmacol. 2000, 131, 903 DOI: 10.1038/sj.bjp.07036613ghttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXotFemsLc%253D&md5=6c28da889af05c7b60a6efb9bf2d901b(8-Naphthalen-1-ylmethyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl)acetic acid methyl ester (NNC 63-0532) is a novel potent nociceptin receptor agonistThomsen, Christian; Hohlweg, RolfBritish Journal of Pharmacology (2000), 131 (5), 903-908CODEN: BJPCBM; ISSN:0007-1188. (Nature Publishing Group)Spiroxatrine was identified as a moderately potent (Ki = 118 nM) but non-selective agonist at the human nociceptin/orphanin FQ receptor, ORL1. This compd. was subject to chem. modification and one of the resulting compds., NNC 63-0532 was shown to have high affinity for ORL1 (Ki = 7.3 nM). NNC 63-0532 showed only moderate affinity for the following receptors (Ki values in parentheses): μ-opioid (140 nM), κ-opioid (405 nM), dopamine D2S (209 nM), dopamine D3 (133 nM) and dopamine D4.4 (107 nM) out of 75 different receptors, ion-channels and transporters. In functional assays, NNC 63-0532 was shown to be an agonist at ORL1 (EC50 = 305 nM), a much weaker agonist at the μ-opioid receptor (EC50>10 μM) and an antagonist or weak partial agonist at dopamine D2S (IC50 = 2830 nM). Thus, NNC 63-0532 is a novel non-peptide agonist with ∼ 12 fold selectivity for ORL1 and may be useful for exploring the physiol. roles of this receptor owing to its brain-penetrating properties.(h) Ijzendoorn, D. R.; Botman, P. N. M.; Blaauw, R. H. Org. Lett. 2006, 8, 239 DOI: 10.1021/ol052598r3hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtlSmtrbF&md5=6f7ce619189d68d57de8997de719f176Diastereoselective Cationic Tandem Cyclizations to N-Heterocyclic Scaffolds: Total Synthesis of (-)-Dysibetaine PPIJzendoorn, Denis R.; Botman, Peter N. M.; Blaauw, Richard H.Organic Letters (2006), 8 (2), 239-242CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)The authors report a short and diastereoselective synthesis of the natural product (-)-dysibetaine PP (I). The key step in the synthetic sequence is a novel diastereoselective tandem-cyclization reaction of an enantiopure dipeptide II in the presence of TsOH in toluene to cyclized product III (92% yield, 10:1 trans:cis ratio). Next, III was converted to I in four steps. This cyclization methodol. is applied in the synthesis of a broader range of N-heterocyclic scaffolds.(i) Toumi, M.; Couty, F.; Marrot, J.; Evano, G. Org. Lett. 2008, 10, 5027 DOI: 10.1021/ol802155n3ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht1emtr7O&md5=295ec688457837fe19a15fbc01a001e4Total synthesis of chaetominineToumi, Mathieu; Couty, Francois; Marrot, Jerome; Evano, GwilhermOrganic Letters (2008), 10 (21), 5027-5030CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)An efficient, asym. synthesis of the cytotoxic natural product chaetominine was achieved in 14 steps. The strategy employs a copper(I)-mediated cyclization reaction as a key step to install the abc-tricyclic ring system, which was further elaborated by diastereoselective oxidn. and redn. reactions. This effort also documents the first example of an oxidative rearrangement yielding to homochiral spirocyclic pyrrolidinyloxindoles.(j) Vale, N.; Prudencio, M.; Marques, C.; Collins, M.; Gut, J.; Nogueira, F.; Matos, J.; Rosenthal, P.; Cushion, M.; Rosario, V.; Mota, M.; Moreira, R.; Gomes, P. J. Med. Chem. 2009, 52, 7800 DOI: 10.1021/jm900738cThere is no corresponding record for this reference.(k) Vale, N.; Nogueira, F.; Rosario, V.; Gomes, P.; Moreira, R. Eur. J. Med. Chem. 2009, 44, 2506 DOI: 10.1016/j.ejmech.2009.01.018There is no corresponding record for this reference. - 4(a) Vasvari-Debreczy, L.; Beckett, A.; Vutthikongsirigool, W. Tetrahedron 1981, 37, 4337 DOI: 10.1016/0040-4020(81)85031-4There is no corresponding record for this reference.(b) Papadopoulos, A.; Lewall, B.; Steckhan, E.; Ginzel, K.; Knoch, F.; Nieger, M. Tetrahedron 1991, 47, 563 DOI: 10.1016/S0040-4020(01)87046-0There is no corresponding record for this reference.(c) Yu, H.; Shen, J. RSC Adv. 2015, 5, 9815 DOI: 10.1039/C4RA15019H4chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjtVylsg%253D%253D&md5=7e7b3ffec1499f1936b18b3705eff5e8Dehydrogenative cyclization of N-acyl dipeptide esters for the synthesis of imidazolidin-4-onesYu, Hui; Shen, JieRSC Advances (2015), 5 (13), 9815-9818CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A dehydrogenative cyclization reaction for the synthesis of imidazolidin-4-ones was developed under mild conditions. Using tert-Bu hydroperoxide as oxidant and potassium iodide as catalyst, N-acyl dipeptide esters were converted to imidazolidin-4-ones in an atom-economical intramol. C-N bond formation process in good yields.(d) Ren, X.; O’Hanlon, J.; Morris, M.; Robertson, J.; Wong, L. ACS Catal. 2016, 6, 6833 DOI: 10.1021/acscatal.6b021894dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhsVKjsrjM&md5=a55e23fd9d173a49c76dc6b95231b1c5Synthesis of Imidazolidin-4-ones via a Cytochrome P450-Catalyzed Intramolecular C-H AminationRen, Xinkun; O'Hanlon, Jack A.; Morris, Melloney; Robertson, Jeremy; Wong, Luet LokACS Catalysis (2016), 6 (10), 6833-6837CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)Expanding Nature's catalytic repertoire to include reactions important in synthetic chem. opens new opportunities for biocatalysis. An intramol. C-H amination route to imidazolidin-4-ones via α-functionalization of 2-aminoacetamides catalyzed by evolved variants of cytochrome P 450BM3 (CYP102A1) from Bacillus megaterium has been developed. Screening of a library of ca. 100 variants based on four template mutants with enhanced activity for the oxidn. of unnatural substrates and preparative scale reactions in vitro and in vivo show that the enzymes give up to 98% isolated yield of cyclization products for diverse substrates. 2-Aminoacetamides with one- and two-ring cyclic amines bearing substituents and aliph., alicyclic, and substituted arom. amides are cyclized. Regiodivergent C-H amination was achieved at benzylic and nonbenzylic positions in a tetrahydroisoquinolinyl substrate by the use of different mutants. This C-H amination reaction offers a scalable route to imidazolidin-4-ones with varied functionalized substituents that may have desirable biol. activity.
- 5Wu, J.-s.; Jiang, H.-j.; Yang, J.-g.; Jin, Z.-n.; Chen, D.-b. Tetrahedron Lett. 2017, 58, 546 DOI: 10.1016/j.tetlet.2016.12.0795https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXotlaktA%253D%253D&md5=ac0724dbda8d84f896515d0bc36d1efeNovel synthesis of tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones via decarboxylative cyclization reaction of α-amino acids and α-ketoamidesWu, Jia-shou; Jiang, Hua-jiang; Yang, Jian-guo; Jin, Zheng-neng; Chen, Ding-benTetrahedron Letters (2017), 58 (6), 546-551CODEN: TELEAY; ISSN:0040-4039. (Elsevier Ltd.)An efficient and practical method was developed for the synthesis of tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones based on the decarboxylative cyclization reaction of α-ketoamides and proline. In most cases, tetrahydro-1H-pyrrolo[1,2-a]imidazol-2-ones were obtained with perfect diastereoselectivity to give trans-isomer in excellent yield.
- 6
Examples of condensation-based approaches to polycyclic 4-imidazolidinones:
(a) Katritzky, A. R.; He, H.-Y.; Wang, J. J. Org. Chem. 2002, 67, 4951 DOI: 10.1021/jo010842wThere is no corresponding record for this reference.(b) Ferraz, R.; Gomes, J. R. B.; de Oliveira, E.; Moreira, R.; Gomes, P. J. Org. Chem. 2007, 72, 4189 DOI: 10.1021/jo0703202There is no corresponding record for this reference. - 7(a) Zhang, C.; De, C. K.; Mal, R.; Seidel, D. J. Am. Chem. Soc. 2008, 130, 416 DOI: 10.1021/ja077473r7ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVehur3P&md5=02ea4c8dbd4684678f08f74bcb17b7c3α-Amination of Nitrogen Heterocycles: Ring-Fused AminalsZhang, Chen; De, Chandra Kanta; Mal, Rudrajit; Seidel, DanielJournal of the American Chemical Society (2008), 130 (2), 416-417CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Arom. aminoaldehydes react with cyclic amines to produce ring-fused aminals under thermal conditions. This process is applied to two-step syntheses of the quinazolinone alkaloids deoxyvasicinone and rutaecarpine.(b) Zhang, C.; Das, D.; Seidel, D. Chem. Sci. 2011, 2, 233 DOI: 10.1039/C0SC00432D7bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmsVKqtg%253D%253D&md5=5ea2541ffe14c212a973e3b29fe26eb4Azomethine ylide annulations: facile access to polycyclic ring systemsZhang, Chen; Das, Deepankar; Seidel, DanielChemical Science (2011), 2 (2), 233-236CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)New annulation reactions of azomethine ylides are reported. Amino acids react with aldehydes that are linked to a pronucleophile (e.g. an indole subunit) to provide rapid access to polycyclic ring systems. Simple amines can also be used in place of amino acids.(c) Dieckmann, A.; Richers, M. T.; Platonova, A. Y.; Zhang, C.; Seidel, D.; Houk, K. N. J. Org. Chem. 2013, 78, 4132 DOI: 10.1021/jo400483h7chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXksFSrurc%253D&md5=ffec985aa582202a64f6075d42f5af30Metal-Free α-Amination of Secondary Amines: Computational and Experimental Evidence for Azaquinone Methide and Azomethine Ylide IntermediatesDieckmann, Arne; Richers, Matthew T.; Platonova, Alena Yu.; Zhang, Chen; Seidel, Daniel; Houk, K. N.Journal of Organic Chemistry (2013), 78 (8), 4132-4144CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The authors have performed a combined computational and exptl. study to elucidate the mechanism of a metal-free α-amination of secondary amines. Calcns. predicted azaquinone methides and azomethine ylides as the reactive intermediates and showed that iminium ions are unlikely to participate in these transformations. These results were confirmed by exptl. deuterium-labeling studies and the successful trapping of the postulated azomethine ylide and azaquinone methide intermediates. Computed barrier heights for the rate-limiting step correlate qual. with exptl. findings.(d) Richers, M. T.; Deb, I.; Platonova, A. Y.; Zhang, C.; Seidel, D. Synthesis 2013, 45, 1730 DOI: 10.1055/s-0033-13388527dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlSnsLjF&md5=0b9a8971128510fb78aff77c4d2bf096Facile access to ring-fused aminals via direct α-amination of secondary amines with o-aminobenzaldehydes: synthesis of vasicine, deoxyvasicine, deoxyvasicinone, mackinazolinone, and rutaecarpineRichers, Matthew T.; Deb, Indubhusan; Platonova, Alena Yu.; Zhang, Chen; Seidel, DanielSynthesis (2013), 45 (13), 1730-1748CODEN: SYNTBF; ISSN:0039-7881. (Georg Thieme Verlag)Secondary amines undergo redox-neutral reactions with aminobenzaldehydes under conventional and microwave heating to furnish polycyclic aminals, e.g. I [R = Ph, 2-pyridyl, 1-naphthyl, etc.] via amine α-amination/N-alkylation. This unique α-functionalization reaction proceeds without the involvement of transition metals or other additives. The resulting aminal products are precursors for various quinazolinone alkaloids and their analogs.(e) Richers, M. T.; Breugst, M.; Platonova, A. Y.; Ullrich, A.; Dieckmann, A.; Houk, K. N.; Seidel, D. J. Am. Chem. Soc. 2014, 136, 6123 DOI: 10.1021/ja501988bThere is no corresponding record for this reference.(f) Jarvis, C. L.; Richers, M. T.; Breugst, M.; Houk, K. N.; Seidel, D. Org. Lett. 2014, 16, 3556 DOI: 10.1021/ol501509bThere is no corresponding record for this reference.(g) Kang, Y.; Chen, W.; Breugst, M.; Seidel, D. J. Org. Chem. 2015, 80, 9628 DOI: 10.1021/acs.joc.5b01384There is no corresponding record for this reference.(h) Ma, L.; Seidel, D. Chem. - Eur. J. 2015, 21, 12908 DOI: 10.1002/chem.2015016677hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXht1ChtL7L&md5=e0fe2262e2bbaea9d9133a3a8e2ce8ecIntramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine CoreMa, Longle; Seidel, DanielChemistry - A European Journal (2015), 21 (37), 12908-12913CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-C-H bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine (I) and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies.(i) Chen, W.; Seidel, D. Org. Lett. 2016, 18, 1024 DOI: 10.1021/acs.orglett.6b00151There is no corresponding record for this reference.(j) Zhu, Z.; Seidel, D. Org. Lett. 2017, 19, 2841 DOI: 10.1021/acs.orglett.7b010477jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXns1yrs78%253D&md5=1a553b958fd87c0bb88c06d013f663f9Acetic Acid Promoted Redox Annulations with Dual C-H FunctionalizationZhu, Zhengbo; Seidel, DanielOrganic Letters (2017), 19 (11), 2841-2844CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)Amines, such as 1,2,3,4-tetrahydroisoquinoline, underwent redox-neutral annulations with 2-alkylquinoline-3-carbaldehydes I (R1 = H, 4-Me, 6-Br, 6-Cl-2-Ph, etc.; R2 = H, Me, Ph) as well as 4-methyl-3-quinolinecarboxaldehyde and pyridine analogs to provide the corresponding polycyclic compds., e.g. II. These processes involve dual C-H bond functionalization. Acetic acid was used as a cosolvent and acted as the sole promoter of these transformations.
- 8(a) Zheng, L.; Yang, F.; Dang, Q.; Bai, X. Org. Lett. 2008, 10, 889 DOI: 10.1021/ol703049j8ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhslWjsbc%253D&md5=04416d1001c480165583232075dbfcffA Cascade Reaction with Iminium Ion Isomerization as the Key Step Leading to Tetrahydropyrimido[4,5-d]pyrimidinesZheng, Lianyou; Yang, Fengzhi; Dang, Qun; Bai, XuOrganic Letters (2008), 10 (5), 889-892CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)A novel cascade reaction of aminopyrimidines I (R = allyl, H, Me, Ph) with N-alkyl amino acids or analogs was investigated. The keys to this cascade are the isomerization of an iminium ion formed between the aldehyde group in pyrimidine and the secondary amine of an amino acid, and subsequent cyclization to the neighboring amino group. This sequence could be useful in the synthesis of novel tetrahydropyrimido[4,5-d]pyrimidine libraries. E.g., tetrahydropyrimido[4,5-d]pyrimidine II (R = allyl ) was prepd. from N-benzylglycine and I (R = allyl).(b) Mahato, S.; Haque, M. A.; Dwari, S.; Jana, C. K. RSC Adv. 2014, 4, 46214 DOI: 10.1039/C4RA05045B8bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhsFektb7O&md5=a7f232c6780a5223d0349eab2701cebeDivergent reaction: metal & oxidant free direct C-H aryloxylation and hydride free formal reductive N-benzylation of N-heterocyclesMahato, Sujit; Haque, Md Ashraful; Dwari, Soumita; Jana, Chandan K.RSC Advances (2014), 4 (86), 46214-46217CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)Metal, oxidant and other additive-free novel methods for direct C-H aryloxylation of aliph. amines are developed. In the presence of excess amine, the course of the reaction was diverted, producing various arylmethylamines via hydride-free formal reductive amination. Involvement of a quinone methide intermediate was revealed from mechanistic studies.(c) Li, J.; Qin, C.; Yu, Y.; Fan, H.; Fu, Y.; Li, H.; Wang, W. Adv. Synth. Catal. 2017, 359, 2191 DOI: 10.1002/adsc.201601423There is no corresponding record for this reference.(d) Li, J.; Fu, Y.; Qin, C.; Yu, Y.; Li, H.; Wang, W. Org. Biomol. Chem. 2017, 15, 6474 DOI: 10.1039/C7OB01527EThere is no corresponding record for this reference.
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Selected reviews on amine C–H functionalization, including redox-neutral approaches:
(a) Murahashi, S.-I. Angew. Chem., Int. Ed. Engl. 1995, 34, 2443 DOI: 10.1002/anie.1995244319ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXpslOnu70%253D&md5=cf00f40efaca796b993d37c949e93af7Synthetic aspects of metal-catalyzed oxidations of amines and related reactionsMurahashi, Shun-IchiAngewandte Chemie, International Edition in English (1995), 34 (22), 2443-65CODEN: ACIEAY; ISSN:0570-0833. (VCH)A review with 161 refs.(b) Matyus, P.; Elias, O.; Tapolcsanyi, P.; Polonka-Balint, A.; Halasz-Dajka, B. Synthesis 2006, 2006, 2625 DOI: 10.1055/s-2006-942490There is no corresponding record for this reference.(c) Campos, K. R. Chem. Soc. Rev. 2007, 36, 1069 DOI: 10.1039/B607547A9chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXmsFantLo%253D&md5=42b3862f993380e5724c4f2fdcc8b2e2Direct sp3 C-H bond activation adjacent to nitrogen in heterocyclesCampos, Kevin R.Chemical Society Reviews (2007), 36 (7), 1069-1084CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Activation of sp3 C-H bonds adjacent to nitrogen in heterocycles is an attractive transformation that is emerging as a practical method in org. synthesis. This tutorial review aims to summarize the key examples of direct functionalization of nitrogen-contg. heterocycles via metal-mediated and metal-catalyzed processes, which is meant to serve as a foundation for future investigations into this rapidly developing area of research. The review covers functionalization of N-heterocycles via α-lithiation with alkyllithium/diamine complexes, α-amino radical formation, metal-catalyzed direct C-H activation, C-H oxidns. and oxidative couplings, and metal-catalyzed carbene insertions.(d) Murahashi, S.-I.; Zhang, D. Chem. Soc. Rev. 2008, 37, 1490 DOI: 10.1039/b706709g9dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXoslOgtLs%253D&md5=0680a861ea6dd4d3df86a72df8b7e49cRuthenium-catalyzed biomimetic oxidation in organic synthesis inspired by cytochrome P-450Murahashi, Shun-Ichi; Zhang, DazhiChemical Society Reviews (2008), 37 (8), 1490-1501CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Simulation of the function of cytochrome P 450 with low valent ruthenium complex catalysts leads to the discovery of biomimetic, catalytic oxidn. of various substrates selectively under mild conditions. The reactions discussed in this tutorial review are simple, clean, and practical. The principle of these reactions is fundamental and gives wide-scope and environmentally benign future practical methods.(e) Li, C.-J. Acc. Chem. Res. 2009, 42, 335 DOI: 10.1021/ar800164n9ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsFSit7vI&md5=82a4256bfc33e2851edcaa64596b32e8Cross-Dehydrogenative Coupling (CDC): Exploring C-C Bond Formations beyond Functional Group TransformationsLi, Chao-JunAccounts of Chemical Research (2009), 42 (2), 335-344CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Synthetic chemists aspire both to develop novel chem. reactions and to improve reaction conditions to maximize resource efficiency, energy efficiency, product selectivity, operational simplicity, and environmental health and safety. Carbon-carbon bond formation is a central part of many chem. syntheses, and innovations in these types of reactions will profoundly improve overall synthetic efficiency. This Account describes our work over the past several years to form carbon-carbon bonds directly from two different C-H bonds under oxidative conditions, cross-dehydrogenative coupling (CDC). We have focused most of our efforts on carbon-carbon bonds formed via the functionalization of sp3 C-H bonds with other C-H bonds. In the presence of simple and cheap catalysts such as copper and iron salts and oxidants such as hydrogen peroxide, dioxygen, tert-butylhydroperoxide, and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), we can directly functionalize various sp3 C-H bonds by other C-H bonds without requiring preactivation. We demonstrate (1) reaction of α-C-H bonds of nitrogen in amines, (2) reaction of α-C-H bonds of oxygen in ethers, (3) reaction of allylic and benzylic C-H bonds, and (4) reaction of alkane C-H bonds. These CDC reactions can tolerate a variety of functional groups, and some can occur under aq. conditions. Depending on the specific transformation, we propose the in situ generation of different intermediates. These methods provide an alternative to the sep. steps of prefunctionalization and defunctionalization that have traditionally been part of synthetic design. As a result, these methods will increase synthetic efficiencies at the most fundamental level. On an intellectual level, the development of C-C bond formations based on the reaction of only C-H bonds (possibly in water) challenges us to rethink some of the most fundamental concepts and theories regarding chem. reactivities. A successful reaction requires the conventionally and theor. less reactive C-H bonds to react selectively in the presence of a variety of functional groups. With further investigation, we expect that C-C bond formations based on cross-dehydrogenative coupling will have a pos. economic and ecol. impact on the next generation of chem. syntheses.(f) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem. - Eur. J. 2010, 16, 2654 DOI: 10.1002/chem.2009023749fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXislKgu7Y%253D&md5=91985f8e805c7babf6a1d0682402cd42Functionalization of Organic Molecules by Transition-Metal-Catalyzed C(sp3)-H ActivationJazzar, Rodolphe; Hitce, Julien; Renaudat, Alice; Sofack-Kreutzer, Julien; Baudoin, OlivierChemistry - A European Journal (2010), 16 (9), 2654-2672CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Transition-metal-catalyzed C-H activation has recently emerged as a powerful tool for the functionalization of org. mols. While many efforts have focused on the functionalization of arenes and heteroarenes by this strategy in the past two decades, much less research has been devoted to the activation of non-acidic C-H bonds of alkyl groups. This Minireview highlights recent work in this area, with a particular emphasis on synthetically useful methods.(g) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215 DOI: 10.1021/cr100280d9ghttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXivVShtLo%253D&md5=f06ae8207d1e49d5646c35f7afd07012Catalytic Dehydrogenative Cross-Coupling: Forming Carbon-Carbon Bonds by Oxidizing Two Carbon-Hydrogen BondsYeung, Charles S.; Dong, Vy M.Chemical Reviews (Washington, DC, United States) (2011), 111 (3), 1215-1292CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review was given on transformations that can be categorized as catalytic dehydrogenative cross-couplings to highlight the scope and limits of this general strategy. as well as its specific application in asym. catalysis and natural product synthesis. These couplings are arranged by their proposed mechanisms, including those that involve Heck-type processes, direct arylations, ionic intermediates, or radical intermediates. Oxidative C-C bond formation was achieved by various catalysts, including transition metals, organocatalysts, the combined use of metal and organocatalysts, and enzymes.(h) Pan, S. C. Beilstein J. Org. Chem. 2012, 8, 1374 DOI: 10.3762/bjoc.8.1599hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtlWrs7rP&md5=5d27b25193150f5950a441a38586d8d2Organocatalytic C-H activation reactionsPan, Subhas ChandraBeilstein Journal of Organic Chemistry (2012), 8 (), 1374-1384, No. 159CODEN: BJOCBH; ISSN:1860-5397. (Beilstein-Institut zur Foerderung der Chemischen Wissenschaften)A review. Organocatalytic C-H activation reactions have recently been developed besides the traditional metal-catalyzed C-H activation reactions. The recent non-asym. and asym. C-H activation reactions mediated by organocatalysts are discussed in this review.(i) Mitchell, E. A.; Peschiulli, A.; Lefevre, N.; Meerpoel, L.; Maes, B. U. W. Chem. - Eur. J. 2012, 18, 10092 DOI: 10.1002/chem.2012015399ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVymtrzK&md5=cc4c815b6114de3dfe9fdb38431f82beDirect α-Functionalization of Saturated Cyclic AminesMitchell, Emily A.; Peschiulli, Aldo; Lefevre, Nicolas; Meerpoel, Lieven; Maes, Bert U. W.Chemistry - A European Journal (2012), 18 (33), 10092-10142CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Recent advances in synthetic methods for the direct α-functionalization of satd. cyclic amines are described. Methods are categorized according to the in situ formed reactive intermediate (α-amino cation, α-amino anion, and α-amino radical). Transition metal-catalyzed reactions involving other intermediates have been treated as a sep. and fourth class.(j) Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3464 DOI: 10.1039/c2cs15323h9jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xlt1ynt74%253D&md5=2621d83e4bd5406822434d16673ca947Recent advances in copper-catalyzed dehydrogenative functionalization via a single electron transfer (SET) processZhang, Chun; Tang, Conghui; Jiao, NingChemical Society Reviews (2012), 41 (9), 3464-3484CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Copper salts were developed as versatile catalysts for oxidative coupling reactions in org. synthesis. During these processes, Cu-catalysts are often proposed to serve as a one-electron oxidant to promote the single-electron transfer process. Recently, the transition metal-catalyzed direct dehydrogenative transformation has attracted considerable attention. This tutorial review summarized the recent advances in the copper-catalyzed dehydrogenative functionalization via a single electron transfer (SET) process achieving C-C, C-N, C-O, C-halogen atoms, C-P, and N-N bond formation.(k) Jones, K. M.; Klussmann, M. Synlett 2012, 2012, 159 DOI: 10.1055/s-0031-1290117There is no corresponding record for this reference.(l) Peng, B.; Maulide, N. Chem. - Eur. J. 2013, 19, 13274 DOI: 10.1002/chem.2013015229lhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVCntrfJ&md5=014e2d7cda182d6d5546b7937bd115e9The Redox-Neutral Approach to C-H FunctionalizationPeng, Bo; Maulide, NunoChemistry - A European Journal (2013), 19 (40), 13274-13287CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The direct functionalization of C-H bonds is an attractive strategy in org. synthesis. Although several advances have been made in this area, the selective activation of inert sp3 C-H bonds remains a daunting challenge. Recently, a new type of sp3 C-H activation mode through internal hydride transfer has demonstrated the potential to activate remote sp3 C-H linkages in an atom-economic manner. This minireview attempts to classify recent advances in this area including the transition to non-activated sp3 C-H bonds and asym. hydride transfers.(m) Platonova, A. Y.; Glukhareva, T. V.; Zimovets, O. A.; Morzherin, Y. Y. Chem. Heterocycl. Compd. 2013, 49, 357 DOI: 10.1007/s10593-013-1257-69mhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtVGktL%252FJ&md5=fb09948c00c061160a7700c808f17ee5tert-Amino effect: the Meth-Cohn and Reinhoudt reactions (Review)Platonova, A. Yu.; Glukhareva, T. V.; Zimovets, O. A.; Morzherin, Yu. Yu.Chemistry of Heterocyclic Compounds (New York, NY, United States) (2013), 49 (3), 357-385CODEN: CHCCAL; ISSN:0009-3122. (Springer)A review. The data published over the last 15-20 years on reactions taking place by the tert-amino effect mechanism have been reviewed.(n) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322 DOI: 10.1021/cr300503r9nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXktFKgtLc%253D&md5=e09e6cf6a4c64fd3e8f21d55e151266eVisible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic SynthesisPrier, Christopher K.; Rankic, Danica A.; MacMillan, David W. C.Chemical Reviews (Washington, DC, United States) (2013), 113 (7), 5322-5363CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This review will highlight the early work on the use of transition metal complexes as photoredox catalysts to promote reactions of org. compds. (prior to 2008), as well as cover the surge of work that has appeared since 2008. We have for the most part grouped reactions according to whether the org. substrate undergoes redn., oxidn., or a redox neutral reaction and throughout have sought to highlight the variety of reactive intermediates that may be accessed via this general reaction manifold.(o) Girard, S. A.; Knauber, T.; Li, C.-J. Angew. Chem., Int. Ed. 2014, 53, 74 DOI: 10.1002/anie.2013042689ohttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslCqsL3J&md5=06a68206aeb4a4912f123cbe86124343The Cross-Dehydrogenative Coupling of Csp3-H Bonds: A Versatile Strategy for C-C Bond FormationsGirard, Simon A.; Knauber, Thomas; Li, Chao-JunAngewandte Chemie, International Edition (2014), 53 (1), 74-100CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Over the last decade, substantial research has led to the introduction of an impressive no. of efficient procedures which allow the selective construction of C-C bonds by directly connecting two different C-H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C-H bonds. This strategy was introduced by the group of Li as cross-dehydrogenative coupling (CDC) and discloses waste-minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross-dehydrogenative Csp3-C formations and provides a comprehensive overview on existing procedures and employed methodologies.(p) Haibach, M. C.; Seidel, D. Angew. Chem., Int. Ed. 2014, 53, 5010 DOI: 10.1002/anie.2013064899phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlvVSls7s%253D&md5=5a68fc1857ee1a0433f2e3fe84b54497C-H bond functionalization through intramolecular hydride transferHaibach, Michael C.; Seidel, DanielAngewandte Chemie, International Edition (2014), 53 (20), 5010-5036CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Known for over a century, reactions that involve intramol. hydride transfer events experienced a recent resurgence. Undoubtedly responsible for the increased interest in this research area was the realization that hydride shifts represent an attractive avenue for C-H bond functionalization. The redox-neutral nature of these complexity-enhancing transformations makes them ideal for sustainable reaction development. This review summarized recent progress in this field while highlighting key historical contributions.(q) Wang, L.; Xiao, J. Adv. Synth. Catal. 2014, 356, 1137 DOI: 10.1002/adsc.2013011539qhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXksFyltrk%253D&md5=5e778e7fcb0e1c6157ce74a5acae160eAdvancement in cascade [1,n]-hydrogen transfer/cyclization: A method for direct functionalization of inactive C(sp3)-H bondsWang, Liang; Xiao, JianAdvanced Synthesis & Catalysis (2014), 356 (6), 1137-1171CODEN: ASCAF7; ISSN:1615-4150. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The cascade [1,n]-hydrogen transfer/cyclization, recognized one century ago, has received considerable interest in recent decades and great achievements were made. This cascade process can functionalize C(sp3)-H bonds directly into C-C, C-N, C-O bonds under the catalysis by Lewis acids, Bronsted acids or organocatalysts, and even under thermal conditions. This methodol. has shown pre-eminent power to construct 5- or 6-membered heterocyclic as well as all-C rings. In this review, various hydrogen donors and hydrogen acceptors are categorized and discussed.(r) Vo, C.-V. T.; Bode, J. W. J. Org. Chem. 2014, 79, 2809 DOI: 10.1021/jo50012529rhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXjvF2qu7k%253D&md5=656a85a09053f529752ebd034ae6138eSynthesis of Saturated N-HeterocyclesVo, Cam-Van T.; Bode, Jeffrey W.Journal of Organic Chemistry (2014), 79 (7), 2809-2815CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)A review discusses recent work in the synthesis of satd. nitrogen heterocycles by potentially general methods with readily available starting materials using lithiation, C-H activation, hydroamination, amination, cyclization, and cyclocondensation reactions; cyclocondensation reactions of tributylstannylated amines and aldehydes developed in the Bode group to give satd. nitrogen heterocycles and benzo-fused nitrogen heterocycles are also discussed.(s) Seidel, D. Org. Chem. Front. 2014, 1, 426 DOI: 10.1039/C4QO00022F9shttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXns1Cmtbk%253D&md5=b129fa66adb6ec1229d1c4ad324d0046The redox-A3 reactionSeidel, DanielOrganic Chemistry Frontiers (2014), 1 (4), 426-429CODEN: OCFRA8; ISSN:2052-4129. (Royal Society of Chemistry)A review. This highlight details the recent emergence of a new type of A3 reaction (three-component condensation of an amine, an aldehyde and an alkyne). In contrast to the classic A3 coupling process, the redox-A3 reaction incorporates an iminium isomerization step and leads to amine α-alkynylation. The overall transformation is redox-neutral by virtue of a combined reductive N-alkylation/oxidative C-H bond functionalization.(t) Qin, Y.; Lv, J.; Luo, S. Tetrahedron Lett. 2014, 55, 551 DOI: 10.1016/j.tetlet.2013.11.0519thttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhvFOksrnP&md5=c26f5353dd8bf4892941164437bf8e33Catalytic asymmetric α-C(sp3)-H functionalization of aminesQin, Yan; Lv, Jian; Luo, SanzhongTetrahedron Letters (2014), 55 (2), 551-558CODEN: TELEAY; ISSN:0040-4039. (Elsevier Ltd.)I this review, a brief overview of catalytic asym. α-C(sp3)-H functionalization of amines, mainly via internal tert-aminocyclization, intermol. C-H oxidative couplings, and redox neutral metal insertion C-H bond was presented.(u) Seidel, D. Acc. Chem. Res. 2015, 48, 317 DOI: 10.1021/ar50037689uhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXks1Kntg%253D%253D&md5=281c6d4cd81ed3a9d123b13543fc62a3The azomethine ylide route to amine C-H functionalization: Redox-versions of classic reactions and a pathway to new transformationsSeidel, DanielAccounts of Chemical Research (2015), 48 (2), 317-328CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. Redox-neutral methods for the functionalization of amine α-C-H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C-H bond functionalization are oxidative in nature. While the most efficient variants utilize atm. oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts. Redox-neutral amine α-functionalizations that involve intramol. hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic org. transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet-Spengler, and Kabachnik-Fields reactions, Friedel-Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C-H bond functionalization. Intramol. versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct. Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloaddns. and other pericyclic processes, have been identified as common intermediates. Extension of this chem. to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines. This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) satd. cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chem. of amines and carbonyl compds. than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions.(v) Beatty, J. W.; Stephenson, C. R. J. Acc. Chem. Res. 2015, 48, 1474 DOI: 10.1021/acs.accounts.5b000689vhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnvFCks78%253D&md5=ffbde0361bd2642ddc68f2556d468d31Amine Functionalization via Oxidative Photoredox Catalysis: Methodology Development and Complex Molecule SynthesisBeatty, Joel W.; Stephenson, Corey R. J.Accounts of Chemical Research (2015), 48 (5), 1474-1484CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. While the use of visible light to drive chem. reactivity is of high importance to the development of environmentally benign chem. transformations, the concomitant use of a stoichiometric electron donor or acceptor is often required to steer the desired redox behavior of these systems. The low-cost and ubiquity of tertiary amine bases has led to their widespread use as reductive additives in photoredox catalysis. Early use of trialkylamines in this context was focused on their role as reductive excited state quenchers of the photocatalyst, which in turn provides a more highly reducing catalytic intermediate. In this Account, we discuss some of the observations and thought processes that have led from our use of amines as reductive additives to their use as complex substrates and intermediates for natural product synthesis. Early attempts by our group to construct key carbon-carbon bonds via free-radical intermediates led to the observation that some trialkylamines readily behave as efficient hydrogen atom donors under redox-active photochem. conditions. In the wake of in-depth mechanistic studies published in the 1970s, 1980s and 1990s, this understanding has in turn allowed for a systematic approach to the design of a no. of photochem. methodologies through rational tuning of the amine component. Minimization of the C-H donicity of the amine additive was found to promote desired C-C bond formation in a no. of contexts, and subsequent elucidation of the amine's redox fate has sparked a reevaluation of the amine's role from that of reagent to that of substrate. The reactivity of tertiary amines in these photochem. systems is complex, and allows for a no. of mechanistic possibilities that are not necessarily mutually exclusive. A variety of combinations of single-electron oxidn., C-H abstraction, deprotonation, and β-scission result in the formation of reactive intermediates such as α-amino radicals and iminium ions. These processes have been explored in depth in the photochem. literature and have resulted in a firm mechanistic grasp of the behavior of amine radical cations in fundamental systems. Harnessing the synthetic potential of these transient species represents an ongoing challenge for the controlled functionalization of amine substrates, because these mechanistic possibilities may result in undesired byproduct formation or substrate decompn. The presence of tertiary amines in numerous alkaloids, pharmaceuticals, and agrochem. lends credence to the potential utility of this chem. in natural product synthesis, and herein we will discuss how these transformations might be controlled for synthetic purposes.(w) Mahato, S.; Jana, C. K. Chem. Rec. 2016, 16, 1477 DOI: 10.1002/tcr.2016000019whttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XotFOjtLg%253D&md5=b9561e530dd843c976bfef6baec515f2Classical-Reaction-Driven Stereo- and Regioselective C(sp3)-H Functionalization of Aliphatic AminesMahato, Sujit; Jana, Chandan K.Chemical Record (2016), 16 (3), 1477-1488CODEN: CRHEAK; ISSN:1528-0691. (Wiley-VCH Verlag GmbH & Co. KGaA)A large variety of synthetic methods have been developed for the synthesis of functionalized aliph. amines because of their broad spectrum of application. Metallic reagents/catalysts and/or toxic oxidants are involved in most of the cases. Direct C-H functionalization of aliph. amines via their classical condensation reactions with suitable carbonyl compds. is advantageous because this method avoids hazardous metallic reagents, toxic oxidants and pre-activation/pre-functionalization step(s). In this account, the concept of direct C-H functionalization of aliph. amines based on the classical condensation-isomerization-addn. (CIA) strategy followed by recent contributions from our ongoing research in the field along with relevant examples from other groups are described. Successes in stereo- and regioselective C-C and C-O bond formation via direct α- as well as β-C(sp3)-H functionalization are discussed.(x) Qin, Y.; Zhu, L.; Luo, S. Chem. Rev. 2017, 117, 9433 DOI: 10.1021/acs.chemrev.6b006579xhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXisVersL0%253D&md5=b0a4596e4582d50b634340130991c227Organocatalysis in Inert C-H Bond FunctionalizationQin, Yan; Zhu, Lihui; Luo, SanzhongChemical Reviews (Washington, DC, United States) (2017), 117 (13), 9433-9520CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. As two coexisting and fast-growing research fields in modern synthetic chem., the merging of organocatalysis and C-H bond functionalization is well foreseeable, and the joint force along this line has been demonstrated to be a powerful approach in making inert C-H bond functionalization more viable, predictable, and selective. In this review, we provide a comprehensive summary of organocatalysis in inert C-H bond functionalization over the past two decades. The review is arranged by types of inert C-H bonds including alkane C-H, arene C-H, and vinyl C-H as well as those activated benzylic C-H, allylic C-H, and C-H bonds alpha to the heteroatom such as nitrogen and oxygen. In each section, the discussion is classified by the explicit organocatalytic mode involved.(y) Cheng, M.-X.; Yang, S.-D. Synlett 2017, 28, 159 DOI: 10.1055/s-0036-15883429yhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvFOgsb%252FF&md5=a5a29e1be97f2fbfc760f159e560866cRecent Advances in the Enantioselective Oxidative α-C-H Functionalization of AminesCheng, Ming-Xing; Yang, Shang-DongSynlett (2017), 28 (2), 159-174CODEN: SYNLES; ISSN:0936-5214. (Georg Thieme Verlag)A review. The recent advances in the enantioselective oxidative α-C(sp3)-H bond functionalization of amines using transition-metal catalysts, organocatalysts or photoredox catalysts were reviewed. - 10
Selected reviews on various types of redox-neutral transformations:
(a) Burns, N. Z.; Baran, P. S.; Hoffmann, R. W. Angew. Chem., Int. Ed. 2009, 48, 2854 DOI: 10.1002/anie.20080608610ahttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXkvVeht7o%253D&md5=71c2618a333ba2ef4dc2e6a2004d69faRedox economy in organic synthesisBurns, Noah Z.; Baran, Phil S.; Hoffmann, Reinhard W.Angewandte Chemie, International Edition (2009), 48 (16), 2854-2867CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)The purpose of this review is to serve as a teaching tool for all practitioners of the field by giving and illustrating guidelines to increase redox economy in multistep org. synthesis. "Economy" is referred to as the thrifty and efficient use of material resources, as the principle of "min. effort to reach a goal. Redox economy then implies the use of as few redox steps as possible in the synthetic conquest of a target compd. While any sort of economy will help to streamline the effort of total synthesis, redox economy addresses a particularly weak area in present-day total synthesis.(b) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res. 2014, 47, 696 DOI: 10.1021/ar400239v10bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXlslCruw%253D%253D&md5=38a434fd7477a8da6a0a275d6d1ec57fOn the Mechanism of N-Heterocyclic Carbene-Catalyzed Reactions Involving Acyl AzoliumsMahatthananchai, Jessada; Bode, Jeffrey W.Accounts of Chemical Research (2014), 47 (2), 696-707CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)A review. This Account focuses on the discovery and mechanistic investigation of the catalytic generation of acyl azoliums and α,β-unsatd. acyl azoliums. We address the mechanistic inquiries about the characterization of the unsatd. acyl triazolium species and its kinetic profile under catalytically relevant conditions. We also provide explanations for the requirement and effect of the N-mesityl group in NHC catalysis based on detailed exptl. data within given specific reactions or conditions.(c) Ketcham, J. M.; Shin, I.; Montgomery, T. P.; Krische, M. J. Angew. Chem., Int. Ed. 2014, 53, 9142 DOI: 10.1002/anie.20140387310chttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXht1WlsbbF&md5=06a51bafc73c3d9d2a77989a4dfd0020Catalytic enantioselective C-H functionalization of alcohols by redox-triggered carbonyl addition: Borrowing hydrogen, returning carbonKetcham, John M.; Shin, Inji; Montgomery, T. Patrick; Krische, Michael J.Angewandte Chemie, International Edition (2014), 53 (35), 9142-9150CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The use of alcs. and unsatd. reactants for the redox-triggered generation of nucleophile-electrophile pairs represents a broad, new approach to carbonyl addn. chem. Discrete redox manipulations that are often required for the generation of carbonyl electrophiles and premetalated carbon-centered nucleophiles are thus avoided. Based on this concept, a broad, new family of enantioselective C-C coupling reactions that are catalyzed by iridium or ruthenium complexes were developed, which are summarized in this Minireview.(d) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Chem. Soc. Rev. 2015, 44, 1155 DOI: 10.1039/C4CS00288A10dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvF2ktb3F&md5=9038ede9004e2362282c02b7728e2330Transition metal-catalyzed C-H functionalization of N-oxyenamine internal oxidantsHuang, Huawen; Ji, Xiaochen; Wu, Wanqing; Jiang, HuanfengChemical Society Reviews (2015), 44 (5), 1155-1171CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. The transition metal-catalyzed C-H functionalization with hydroxylamine derivs. serving as both reactants and internal oxidants was highlighted. These reactions obviated the need for external oxidants and therefore resulted in high reactivity and selectivity, as well as excellent functional group tolerance under mild reaction conditions, and moreover, water, methanol or carboxylic acid was generally released as the byproduct, thus leading to reduced waste. The transition metal-catalyzed oxidative C-H functionalization of N-oxyenamine internal oxidants, with an emphasis on the scope and limitations, as well as the mechanisms of these reactions were described. - 11
For detailed discussions on the mechanisms of these transformations, see refs 7c,7e−7g and 9u and the following reports:
(a) Xue, X.; Yu, A.; Cai, Y.; Cheng, J.-P. Org. Lett. 2011, 13, 6054 DOI: 10.1021/ol2025247There is no corresponding record for this reference.(b) Ma, L.; Paul, A.; Breugst, M.; Seidel, D. Chem. - Eur. J. 2016, 22, 18179 DOI: 10.1002/chem.20160383911bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVGjtrvL&md5=59217d78c011882892a63d2a36268a00Redox-Neutral Aromatization of Cyclic Amines: Mechanistic Insights and Harnessing of Reactive Intermediates for Amine α- and β-C-H FunctionalizationMa, Longle; Paul, Anirudra; Breugst, Martin; Seidel, DanielChemistry - A European Journal (2016), 22 (50), 18179-18189CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Cyclic amines such as pyrrolidine and piperidine are known to undergo condensations with aldehydes to furnish pyrrole and pyridine derivs., resp. A combined exptl. and computational study provides detailed insights into the mechanism of pyrrole formation. A no. of reactive intermediates (e.g., azomethine ylides, conjugated azomethine ylides, enamines) were intercepted, outlining strategies for circumventing aromatization as a valuable pathway for amine C-H functionalization. - 12
Examples of redox-neutral α-C–H functionalizations of secondary amines in the context of (3 + 2) cycloadditions:
(a) Ardill, H.; Grigg, R.; Sridharan, V.; Surendrakumar, S.; Thianpatanagul, S.; Kanajun, S. J. Chem. Soc., Chem. Commun. 1986, 602 DOI: 10.1039/c39860000602There is no corresponding record for this reference.(b) Ardill, H.; Dorrity, M. J. R.; Grigg, R.; Leon-Ling, M. S.; Malone, J. F.; Sridharan, V.; Thianpatanagul, S. Tetrahedron 1990, 46, 6433 DOI: 10.1016/S0040-4020(01)96013-2There is no corresponding record for this reference.(c) Ardill, H.; Fontaine, X. L. R.; Grigg, R.; Henderson, D.; Montgomery, J.; Sridharan, V.; Surendrakumar, S. Tetrahedron 1990, 46, 6449 DOI: 10.1016/S0040-4020(01)96014-4There is no corresponding record for this reference.(d) Wang, B.; Mertes, M. P.; Mertes, K. B.; Takusagawa, F. Tetrahedron Lett. 1990, 31, 5543 DOI: 10.1016/S0040-4039(00)97892-4There is no corresponding record for this reference.(e) Wittland, C.; Arend, M.; Risch, N. Synthesis 1996, 1996, 367 DOI: 10.1055/s-1996-4208There is no corresponding record for this reference.(f) Marx, M. A.; Grillot, A.-L.; Louer, C. T.; Beaver, K. A.; Bartlett, P. A. J. Am. Chem. Soc. 1997, 119, 6153 DOI: 10.1021/ja9621051There is no corresponding record for this reference.(g) Grigg, R.; Sridharan, V.; Thornton-Pett, M.; Wang, J.; Xu, J.; Zhang, J. Tetrahedron 2002, 58, 2627 DOI: 10.1016/S0040-4020(02)00129-1There is no corresponding record for this reference.(h) Parmar, N. J.; Pansuriya, B. R.; Labana, B. M.; Kant, R.; Gupta, V. K. RSC Adv. 2013, 3, 17527 DOI: 10.1039/c3ra42220h12hhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhsVShsL7E&md5=f1f78304e8b9fd8f57e0b581db3c31a3A convenient 1,3-dipolar cycloaddition-reduction synthetic sequence from 2-allyloxy-5-nitro-salicylaldehyde to aminobenzopyran-annulated heterocyclesParmar, Narsidas J.; Pansuriya, Bhavesh R.; Labana, Balvantsingh M.; Kant, Rajni; Gupta, Vivek K.RSC Advances (2013), 3 (38), 17527-17539CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A microwave-assisted, one-pot synthesis of some nitro benzopyran-annulated pyrroles as well as pyrrolo-fused isoquinolines via a 1,3-dipolar cycloaddn., which involves the in-situ generation of azomethine ylide formed from a secondary amines with 2-allyloxy-5-nitro-salicylaldehyde, was achieved in a solvent-free environment. Compared to methods of conventional heating or thermal heating, the present microwave-assisted method is rapid and highly efficient. In addn., amine analogous heterocyclic compds. were successfully accessed after treating the reaction products further with iron in acidic medium, which also highlights a one-pot procedure for a new 1,3-dipolar cycloaddn.-redn. synthetic sequence. All amine products have new bio-profiles and are anticipated to be effective drug-like candidates. All compds. were characterized based on their elemental anal., mass, IR, and 1H and 13C NMR spectroscopic data. The stereochem. of the product was confirmed by 2D NMR COSY and NOESY expts., which, on the basis of single crystal X-ray diffraction data anal., was further confirmed and supported. The title compds. thus formed included (2R,3aS,9bR)-rel-1,2,3,3a,4,9b-hexahydro-8-nitro-1-(phenylmethyl)[1]benzopyrano[4,3-b]pyrrole-2-carboxylic acid Et ester (I) and related substances, such as (2R,3aS,9bR)-rel-8-amino-1,2,3,3a,4,9b-hexahydro-1-(phenylmethyl)[1]benzopyrano[4,3-b]pyrrole-2-carboxylic acid Et ester, [1]benzopyrano[3',4':4,5]pyrrolo[2,1-a]isoquinoline derivs. The synthesis of the target compds. was achieved by a reaction of glycine ester derivs., N-methylglycine, 1,2,3,4-tetrahydroisoquinoline with 5-nitro-2-(2-propen-1-yloxy)benzaldehyde.(i) Rahman, M.; Bagdi, A. K.; Mishra, S.; Hajra, A. Chem. Commun. 2014, 50, 2951 DOI: 10.1039/c4cc00454j12ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXis1Churw%253D&md5=01dda3305b2f4647a79e9ad7037405abFunctionalization of an sp3 C-H bond via a redox-neutral domino reaction: diastereoselective synthesis of hexahydropyrrolo[2,1-b]oxazolesRahman, Matiur; Bagdi, Avik Kumar; Mishra, Subhajit; Hajra, AlakanandaChemical Communications (Cambridge, United Kingdom) (2014), 50 (22), 2951-2953CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A diastereoselective synthesis of pyrrolidinooxazolidines, e.g., I, was achieved by a metal-free, base-promoted reaction of pyrrolidine and arom. aldehydes under microwave irradn. The rare functionalization of an sp3 C-H bond probably results from an in situ generated azomethine ylide that undergoes cycloaddn. with aldehydes.(j) Mantelingu, K.; Lin, Y.; Seidel, D. Org. Lett. 2014, 16, 5910 DOI: 10.1021/ol502918gThere is no corresponding record for this reference.(k) Pavan Kumar, C. S.; Harsha, K. B.; Mantelingu, K.; Rangappa, K. S. RSC Adv. 2015, 5, 61664 DOI: 10.1039/C5RA10030E12khttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhtFajs7%252FF&md5=a8842ee9e631e9e1b5b983f04b3ea052Diastereoselective synthesis of fused oxazolidines and highly substituted 1H-pyrrolo[2,1-c][1,4]oxazines via C-H functionalizationPavan Kumar, Chottanahalli. S.; Harsha, Kachigere. B.; Mantelingu, Kempegowda; Rangappa, Kanchugarakoppal. S.RSC Advances (2015), 5 (76), 61664-61670CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)The first one pot protocol for the diastereoselective synthesis of oxazolo[2,3-c]isoquinoline e.g., I was achieved by a metal-free, benzoic acid catalyzed reaction of 1,2,3,4-tetrahydroisoquinoline or trypoline with aldehydes under mild conditions via C-H, C-O bond functionalization has been reported. A new approach for the synthesis of highly substituted 1H-pyrrolo[2,1-c][1,4]oxazine, e.g., I was carried out.(l) Safaei-Ghomi, J.; Masoomi, R. RSC Adv. 2015, 5, 15591 DOI: 10.1039/C4RA16020G12lhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXnvVaitQ%253D%253D&md5=e27de9334ef18984df81127fa8298431Rapid microwave-assisted synthesis of N-benzyl fulleropyrrolidines under solvent free conditionsSafaei-Ghomi, Javad; Masoomi, ReihanehRSC Advances (2015), 5 (20), 15591-15596CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)A series of new N-benzyl fulleropyrrolidines I (R = Ph, 2-py, 2-furanyl, etc.) were synthesized in a one-pot via 1,3-dipolar cycloaddn. of C60 with dibenzylamine and aldehyde derivs. using microwave irradn. under solvent-free conditions in good yield. This method provides several advantages involving high yields and rates, decrease in the extent of decompn. of the substrates, as well as environmental friendliness compared to the conventional methods.(m) Yang, H.-T.; Tan, Y.-C.; Ge, J.; Wu, H.; Li, J.-X.; Yang, Y.; Sun, X.-Q.; Miao, C.-B. J. Org. Chem. 2016, 81, 11201 DOI: 10.1021/acs.joc.6b0219312mhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhslWjsb3J&md5=d648e2bde5eb3d9c22ce82bfeb19a952Reaction of C60 with inactive secondary amines and aldehydes and the Cu(OAc)2-promoted regioselective intramolecular C-H functionalization of the generated fulleropyrrolidinesYang, Hai-Tao; Tan, Yi-Chen; Ge, Jie; Wu, He; Li, Jia-Xing; Yang, Yang; Sun, Xiao-Qiang; Miao, Chun-BaoJournal of Organic Chemistry (2016), 81 (22), 11201-11209CODEN: JOCEAH; ISSN:0022-3263. (American Chemical Society)The thermal reaction of C60 with arom. aldehydes and inactive secondary amines for the stereoselective synthesis of trans-1,2,5-trisubstituted [6,6]fullero[c]pyrrolidines has been developed. Moreover, when an o-hydroxyl group was located at the Ph ring of the generated fulleropyrrolidines, the Cu(OAc)2-promoted regioselective intramol. C-O coupling reaction occurred to generate unique tricycle-fused fullerene derivs. I.(n) Zheng, K.-L.; Shu, W.-M.; Ma, J.-R.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2016, 18, 3526 DOI: 10.1021/acs.orglett.6b0136912nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhtFersr7O&md5=a38f0909454ee7e89c142366261fd6ecAcid-Mediated N-H/α,β-C(sp3)-H Trifunctionalization of Pyrrolidine: Intermolecular [3 + 2] Cycloaddition for the Construction of 2,3-Dihydro-1H-Pyrrolizine DerivativesZheng, Kai-Lu; Shu, Wen-Ming; Ma, Jun-Rui; Wu, Yan-Dong; Wu, An-XinOrganic Letters (2016), 18 (15), 3526-3529CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)A 1-pot acid-mediated reaction was developed for the N-H/α,β-C(sp3)-H trifunctionalization of pyrrolidine without any metallic reagents or external oxidants. This reaction involves the intermol. [3+2] cycloaddn. of in situ-generated azomethine ylides with acrylic esters to provide facile access to 2,3-dihydro-1H-pyrrolizine derivs. in high yields under mild conditions.(o) Du, Y.; Yu, A.; Jia, J.; Zhang, Y.; Meng, X. Chem. Commun. 2017, 53, 1684 DOI: 10.1039/C6CC08996HThere is no corresponding record for this reference.(p) Zheng, K.-L.; You, M.-Q.; Shu, W.-M.; Wu, Y.-D.; Wu, A.-X. Org. Lett. 2017, 19, 2262 DOI: 10.1021/acs.orglett.7b0076912phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXmtFKlsb4%253D&md5=f182c5f85837425f2dba7a1e7a2945a7Acid-Mediated Intermolecular [3 + 2] Cycloaddition toward Pyrrolo[2,1-a]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G Trimethyl EtherZheng, Kai-Lu; You, Min-Qi; Shu, Wen-Ming; Wu, Yan-Dong; Wu, An-XinOrganic Letters (2017), 19 (9), 2262-2265CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)A novel one-pot reaction was developed for the efficient synthesis of pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2-nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy provides a concise total synthesis of the lamellarin core I and lamellarin G tri-Me ether using electrophilic substitution and palladium-catalyzed Suzuki-Miyaura cross-coupling reactions. - 13
Examples of redox-neutral α-C–H bond annulations of secondary amines that result in the formation of 5-membered rings:
(a) Grigg, R.; Nimal Gunaratne, H. Q.; Henderson, D.; Sridharan, V. Tetrahedron 1990, 46, 1599 DOI: 10.1016/S0040-4020(01)81969-4There is no corresponding record for this reference.(b) Soeder, R. W.; Bowers, K.; Pegram, L. D.; Cartaya-Marin, C. P. Synth. Commun. 1992, 22, 2737 DOI: 10.1080/0039791920802153713bhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XmsFWitbs%253D&md5=cff9638ef9bb2b0a70b737f77fe29e2dA one pot synthesis of 5,7-diphenyl-2,3-dihydro-1H-pyrrolizineSoeder, R. W.; Bowers, K.; Pegram, L. D.; Cartaya-Marin, C. P.Synthetic Communications (1992), 22 (19), 2737-40CODEN: SYNCAV; ISSN:0039-7911.The title compd. (I) was synthesized by reacting dibenzoylmethane with pyrrolidine in C6H6 in one step in 60% yield.(c) Grigg, R.; Kennewell, P.; Savic, V.; Sridharan, V. Tetrahedron 1992, 48, 10423 DOI: 10.1016/S0040-4020(01)88345-9There is no corresponding record for this reference.(d) Deb, I.; Seidel, D. Tetrahedron Lett. 2010, 51, 2945 DOI: 10.1016/j.tetlet.2010.03.086There is no corresponding record for this reference.(e) Kang, Y.; Richers, M. T.; Sawicki, C. H.; Seidel, D. Chem. Commun. 2015, 51, 10648 DOI: 10.1039/C5CC03390JThere is no corresponding record for this reference.(f) Cheng, Y.-F.; Rong, H.-J.; Yi, C.-B.; Yao, J.-J.; Qu, J. Org. Lett. 2015, 17, 4758 DOI: 10.1021/acs.orglett.5b02298There is no corresponding record for this reference.(g) Yang, Z.; Lu, N.; Wei, Z.; Cao, J.; Liang, D.; Duan, H.; Lin, Y. J. Org. Chem. 2016, 81, 11950 DOI: 10.1021/acs.joc.6b01781There is no corresponding record for this reference.(h) Rong, H.-J.; Cheng, Y.-F.; Liu, F.-F.; Ren, S.-J.; Qu, J. J. Org. Chem. 2017, 82, 532 DOI: 10.1021/acs.joc.6b02562There is no corresponding record for this reference.(i) Purkait, A.; Roy, S. K.; Srivastava, H. K.; Jana, C. K. Org. Lett. 2017, 19, 2540 DOI: 10.1021/acs.orglett.7b0083213ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXntFOmsLc%253D&md5=2474160cebee1ab3a53d6d05305ced73Metal-Free Sequential C(sp2)-H/OH and C(sp3)-H Aminations of Nitrosoarenes and N-Heterocycles to Ring-Fused ImidazolesPurkait, Anisha; Roy, Subhra Kanti; Srivastava, Hemant Kumar; Jana, Chandan K.Organic Letters (2017), 19 (10), 2540-2543CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)Hydrogen bond assisted ortho-selective C(sp2)-H amination of nitrosoarenes and subsequent α-C(sp3)-H functionalization of aliph. amines is achieved under metal-free conditions. The annulation of nitrosoarenes and 2-hydroxy-C-nitroso compds. with N-heterocycles provides a facile excess to a wide range of biol. relevant ring-fused benzimidazoles and structurally novel polycyclic imidazoles, resp. Nucleophilic arom. hydrogen substitution (SNArH) was found to be preferred over classical SNAr reaction during the C(sp2)-H amination of halogenated nitrosoarenes. - 14
Selected reviews on azomethine ylide chemistry:
(a) Padwa, A. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, N. Y., 1984; Vol. 1.There is no corresponding record for this reference.(b) Padwa, A., Ed. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York, 1984; Vol. 2.There is no corresponding record for this reference.(c) Padwa, A.; Pearson, W. H.. Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products; Wiley: Chichester, 2002; Vol. 59.There is no corresponding record for this reference.(d) Najera, C.; Sansano, J. M. Curr. Org. Chem. 2003, 7, 1105 DOI: 10.2174/138527203348659414dhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3sXksFGlsro%253D&md5=8e82a64f549f40d8b74a7fbfbb7db234Azomethine ylides in organic synthesisNajera, Carmen; Sansano, Jose M.Current Organic Chemistry (2003), 7 (11), 1105-1150CODEN: CORCFE; ISSN:1385-2728. (Bentham Science Publishers Ltd.)A review covering the literature from 1988 dealing with cyclic and acyclic azomethine ylides in which a part or the whole of the ylide conjugation is included in a conjugated heterocycle. Special emphasis will be given to the applications of these dipoles in the synthesis of complex structures as well as in key steps of total synthesis.(e) Coldham, I.; Hufton, R. Chem. Rev. 2005, 105, 2765 DOI: 10.1021/cr040004c14ehttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXlsFKrtr8%253D&md5=8b56b4040a6d1fd56845a456bee5e0d1Intramolecular dipolar cycloaddition reactions of azomethine ylidesColdham, Iain; Hufton, RichardChemical Reviews (Washington, DC, United States) (2005), 105 (7), 2765-2809CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on the theor. background and the mechanism of azomethine ylide formation from aldehydes, imines, aziridines, and heterocycles, and their intramol. dipolar cycloaddn. giving access to pyrrolidines and pyrroles in a highly regioselective manner (preferring endo transition state). The use of this methodol. for the synthesis of pyrrolidine- and pyrrole-contg. natural products is emphasized and exemplified.(f) Pandey, G.; Banerjee, P.; Gadre, S. R. Chem. Rev. 2006, 106, 4484 DOI: 10.1021/cr050011g14fhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtFeltrnL&md5=44689d0969948b62cb3f8d0e40397de3Construction of Enantiopure Pyrrolidine Ring System via Asymmetric [3+2]-Cycloaddition of Azomethine YlidesPandey, Ganesh; Banerjee, Prabal; Gadre, Smita R.Chemical Reviews (Washington, DC, United States) (2006), 106 (11), 4484-4517CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review.(g) Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2006, 2006, 2873 DOI: 10.1002/ejoc.200500892There is no corresponding record for this reference.(h) Bonin, M.; Chauveau, A.; Micouin, L. Synlett 2006, 2006, 2349 DOI: 10.1055/s-2006-949626There is no corresponding record for this reference.(i) Nair, V.; Suja, T. D. Tetrahedron 2007, 63, 12247 DOI: 10.1016/j.tet.2007.09.06514ihttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXht1Oqsb7I&md5=b49dd6f6a02d0046bbdc34c314c9952bIntramolecular 1,3-dipolar cycloaddition reactions in targeted synthesesNair, Vijay; Suja, T. D.Tetrahedron (2007), 63 (50), 12247-12275CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)Review on the use of intramol. 1,3-dipolar cycloaddn. reactions using nitrones, nitrile oxides, carbonyl ylides, azomethine imines and ylides, azides and mesionic dipoles in targeted syntheses of heteroatom contg. cyclic compds. and natural products.(j) Najera, C.; Sansano, J. M. Top. Heterocycl. Chem. 2008, 12, 117 DOI: 10.1007/7081_2007_09914jhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXis1eitLc%253D&md5=2b588cf2220640aa6930ec0a411f8218Enantioselective cycloadditions of azomethine ylidesNajera, Carmen; Sansano, Jose M.Topics in Heterocyclic Chemistry (2008), 12 (Synthesis of Heterocycles via Cycloadditions I), 117-145CODEN: THCOA6; ISSN:1861-9282. (Springer GmbH)A review. The asym. 1,3-dipolar cycloaddn. reaction of azomethine ylides, which are generated from the corresponding imino ester and alkenes, is one of the most fascinating transformations because the configuration of the four new stereogenic centers of the finally obtained proline can be absolutely established in only one step with total atom economy. Since 2002, the catalyzed enantioselective 1,3-DCRs have been performed using chiral metal complexes. For example, chiral silver and copper complexes are the most employed catalysts. Silver complexes afforded selectively endo-cycloadducts, however, both exo- and endo-adducts were generated in the presence of several chiral Cu(I) complexes. Although chiral zinc complexes have also been studied in endo-selective processes, the published works are not so numerous. Bidentate ligands, such as bisphosphanes, nitrogenated phosphanes, and sulfur-contg. phosphanes have shown very high enantioselectivity levels. Apart from the employment of chiral Lewis acids, the utilization of chiral bases or organocatalysts are also known, albeit with a large no. of limitations and, in some cases, with lower enantioselections.(k) Stanley, L. M.; Sibi, M. P. Chem. Rev. 2008, 108, 2887 DOI: 10.1021/cr078371m14khttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXotlOmsL8%253D&md5=ff4f4a3a82fe8610b423a67035bbb374Enantioselective Copper-Catalyzed 1,3-Dipolar CycloadditionsStanley, Levi M.; Sibi, Mukund P.Chemical Reviews (Washington, DC, United States) (2008), 108 (8), 2887-2902CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. This review summarizes the recent achievements in the development of enantioselective copper-catalyzed 1,3-dipolar cycloaddn. reactions. Topics include reactions with electron-deficient alkenes, reactions with electron-rich alkenes, reactions with alkynes, cycloaddns. with azomethine ylides and misc. cycloaddns.(l) Nyerges, M.; Toth, J.; Groundwater, P. W. Synlett 2008, 2008, 1269 DOI: 10.1055/s-2008-1072743There is no corresponding record for this reference.(m) Pineiro, M.; Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2009, 2009, 5287 DOI: 10.1002/ejoc.200900644There is no corresponding record for this reference.(n) Burrell, A. J. M.; Coldham, I. Curr. Org. Synth. 2010, 7, 312 DOI: 10.2174/15701791079141447214nhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXpslSmu7g%253D&md5=946222d8aaa8ac25f6459e6064cd0ddfSynthesis of natural products using intramolecular dipolar cycloaddition reactionsBurrell, Adam J. M.; Coldham, IainCurrent Organic Synthesis (2010), 7 (4), 312-331CODEN: COSUC2; ISSN:1570-1794. (Bentham Science Publishers Ltd.)A review. This review described ylide 1,3-dipoles in cycloaddn. reactions for the synthesis (and formal synthesis) of natural products. Examples using azomethine ylides, carbonyl ylides, nitrones, nitronates, nitrile oxides, and azides were provided. These led to a diverse array of heterocyclic products. Intramol. cycloaddn. provides two new rings in one step and hence an efficient entry to complex target compds.(o) Anac, O.; Gungor, F. S. Tetrahedron 2010, 66, 5931 DOI: 10.1016/j.tet.2010.05.058There is no corresponding record for this reference.(p) Adrio, J.; Carretero, J. C. Chem. Commun. 2011, 47, 6784 DOI: 10.1039/c1cc10779h14phttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXntlags74%253D&md5=aa0ee768d1e244d622ece481a954110dNovel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylidesAdrio, Javier; Carretero, Juan C.Chemical Communications (Cambridge, United Kingdom) (2011), 47 (24), 6784-6794CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A review. The catalytic asym. 1,3-dipolar cycloaddn. of azomethine ylides constitutes one of the most powerful and atom economical methods for the enantioselective construction of pyrrolidines. This article highlighted the recent developments in this area, with special focus on contributions improving the structural scope at the dipolarophile and azomethine ylide partners.(q) Adrio, J.; Carretero, J. C. Chem. Commun. 2014, 50, 12434 DOI: 10.1039/C4CC04381B14qhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhtFCgu7fN&md5=f67669d40970e2109f5767dd84c7d178Recent advances in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylidesAdrio, Javier; Carretero, Juan C.Chemical Communications (Cambridge, United Kingdom) (2014), 50 (83), 12434-12446CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)A review. Catalytic asym. 1,3-dipolar cycloaddns. of azomethine ylides have turned out to be one of the most efficient methods for the prepn. of enantioenriched pyrrolidines. The past decade has witnessed the development of a bunch of well-defined catalytic systems capable of affording excellent diastereo and enantioselectivities. Recently, a great effort has been focused on expanding the scope of the cycloaddn. with regard to both reaction partners. In this review, the authors discuss the important advances that have been reported in this area since 2011.(r) Hashimoto, T.; Maruoka, K. Chem. Rev. 2015, 115, 5366 DOI: 10.1021/cr500718214rhttps://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXot1Sqtr4%253D&md5=ef81ef535549e9697bab054132bc661bRecent Advances of Catalytic Asymmetric 1,3-Dipolar CycloadditionsHashimoto, Takuya; Maruoka, KeijiChemical Reviews (Washington, DC, United States) (2015), 115 (11), 5366-5412CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. An overview is given of the entire field of 1,3-dipolar cycloaddn. (1,3-DC) in the last decade. To directly link this review with the monumental review on asym. 1,3-DC by Joegensen in 1998, seminal works on catalytic asym. 1,3-DCs in early days is also included.(s) Meyer, A.; Ryan, J. Molecules 2016, 21, 935 DOI: 10.3390/molecules21080935There is no corresponding record for this reference.See also ref 9u.
- 15De Risi, C.; Pollini, G. P.; Zanirato, V. Chem. Rev. 2016, 116, 3241 DOI: 10.1021/acs.chemrev.5b00443
For a review on the chemistry of ketoamides, see:
15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XisFahsrw%253D&md5=03d7e364ef3c39c3a09830b35933a48fRecent Developments in General Methodologies for the Synthesis of α-KetoamidesDe Risi, Carmela; Pollini, Gian Piero; Zanirato, VinicioChemical Reviews (Washington, DC, United States) (2016), 116 (5), 3241-3305CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. The aim of this review is to give an overview of the diverse methodologies that have emerged since the 1990s up to the present. The different synthetic routes have been grouped according to the way the α-ketoamide moiety has been created. Thus, syntheses of α-ketoamides proceeding via C(2)-oxidn. of amide starting compds. are detailed, as are amidation approaches installing the α-ketoamide residue through C(1)-N bond formation. Also discussed are the methodologies centered on C(1)-C(2) σ-bond construction and C(2)-R/Ar bond-forming processes. Finally, the literature regarding the synthesis of α-ketoamide compds. by palladium-catalyzed double-carbonylative amination reactions has been discussed. - 16Lanigan, R. M.; Sheppard, T. D. Eur. J. Org. Chem. 2013, 2013, 7453 DOI: 10.1002/ejoc.20130057316https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXht1Wrtb7I&md5=3a14f0d90992f8205da733a16f4be466Recent Developments in Amide Synthesis: Direct Amidation of Carboxylic Acids and Transamidation ReactionsLanigan, Rachel M.; Sheppard, Tom D.European Journal of Organic Chemistry (2013), 2013 (33), 7453-7465CODEN: EJOCFK; ISSN:1099-0690. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The synthesis of amides is of huge importance in a wide variety of industrial and academic fields and is of particular significance in the synthesis of pharmaceuticals. Many of the well established methods for amide synthesis involve reagents that are difficult to handle and lead to the generation of large quantities of waste products. As a consequence, there has been a considerable amt. of interest in the development of new approaches to amide synthesis. Over the past few years a wide range of new reagents and catalysts for direct amidation of carboxylic acids have been reported. In addn., the interconversion of amide derivs. through transamidation is emerging as a potential alternative strategy for accessing certain amides. This microreview covers recent developments in the direct amidation of carboxylic acids and the interconversion of amides through transamidation. The advantages and disadvantages of the various methods are discussed, as well as the possible mechanisms of the reactions.
- 17Wang, J.-Y.; Hu, Y.; Wang, D.-X.; Pan, J.; Huang, Z.-T.; Wang, M.-X. Chem. Commun. 2009, 422 DOI: 10.1039/B816007D
An alternative mechanism has also been proposed:
There is no corresponding record for this reference.
Supporting Information
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b03309.
Experimental procedures and characterization data, including X-ray crystal structures of products 2a and 3d (PDF)
X-ray data for compound 2a (CIF)
X-ray data for compound 3d (CIF)
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