Palladium-Catalyzed Amination of Aryl Chlorides and Bromides with Ammonium SaltsClick to copy article linkArticle link copied!
Abstract
We report the palladium-catalyzed coupling of aryl halides with ammonia and gaseous amines as their ammonium salts. The coupling of aryl chlorides and ortho-substituted aryl bromides with ammonium sulfate forms anilines with higher selectivity for the primary arylamine over the diarylamine than couplings with ammonia in dioxane. The resting state for the reactions of aryl chlorides is different from the resting state for the reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes.
The transition-metal-catalyzed amination of aryl electrophiles has become a useful method to construct arylamines. However, the coupling of ammonia is less developed than the coupling of alkylamines, and several properties of ammonia make the coupling of this reagent more challenging than the coupling of alkylamines. Ammonia is a good σ-donor and binds more strongly to metals than do alkylamines, and this binding can lead to catalyst deactivation. In addition, the moderate basicity and low acidity of ammonia disfavor proton exchanges to or from this reagent. Finally, the aniline formed in the reaction of an aryl halide with ammonia is also a reagent for coupling with aryl halides. Therefore, the product of the coupling of ammonia competes with ammonia as the nucleophile, giving rise to mixtures of mono- and diarylamines. (1-3)
In addition to these chemical properties, the physical properties of ammonia make it a challenging coupling partner to use in palladium-catalyzed chemistry. Because it is a gas at ambient temperature and pressure, reactions performed with anhydrous ammonia often require high-pressure reactors.
One approach to avoid the use of gaseous ammonia and the formation of diarylamine side products is to conduct reactions with ammonia surrogates, such as benzophenone imine, (4, 5) amides, (6, 7) bis(trimethylsilyl)amide, (8) or carbamates. (9) However, these ammonia surrogates are much more expensive than ammonia, and these methods require a subsequent hydrolysis or hydrogenolysis step to obtain the aniline.
A few reports have been published on the amination of aryl halides with ammonia that occur with high selectivity for the primary arylamine over the diarylamine side product. In these reactions, either ammonia is charged into the reaction vessel directly as a gas (10) or the reaction is conducted with a commercially available solution of 0.5 M ammonia in dioxane. (11-16) Although a convenient alternative to charging reaction vessels with ammonia, the solution is costly and the concentration of the commercial ammonia solution decreases over time. Ammonium hydroxide and ammonium chloride have been used as alternatives to ammonia in copper-catalyzed coupling reactions. (17) However, the scope of electrophiles that undergo these coupling reactions is limited to aryl iodides and activated aryl bromides. The palladium-catalyzed coupling of aryl halides with ammonium hydroxide or ammonium salts has not been reported.
The combination of an inexpensive ammonium salt and base would be an attractive alternative to anhydrous, gaseous ammonia or solutions of ammonia (Scheme 1). Because ammonium salts are only marginally soluble in organic solvents, we considered that the concentration of ammonia could be fine-tuned by the choice of the counterion of the ammonium salt and the base.
We envisioned multiple benefits to a protocol for the amination of aryl halides involving ammonium salts. A lower concentration of ammonia could reduce catalyst poisoning, leading to lower required loadings of the catalyst. In addition, the low concentration of ammonia at any given time would minimize the safety hazard of heating a sealed vessel containing the reaction. Considering the many benefits of ammonium salts as precursors to ammonia, and to volatile amines, in palladium-catalyzed amination reactions, we sought to develop conditions to conduct palladium-catalyzed amination reactions with ammonium salts.
Scheme 1
We report the coupling of ammonium sulfate in the presence of a base to form monoarylamines with selectivities equal to or greater than those from reactions of anhydrous, gaseous ammonia or solutions of ammonia. Moreover, we show that this approach can be extended to the coupling of methyl and ethylamine, which are gases at room temperature and have rarely been used in palladium-catalyzed cross coupling.
To develop the coupling of ammonium salts, we investigated the reaction of p-chlorotoluene with ammonium salts in the presence of several catalysts previously reported for the arylation of ammonia. Ammonia is not a good reductant of Pd(II) precursors, such as Pd(OAc)2 and PdCl2. Therefore, palladium precursors for the coupling of ammonia are typically limited to Pd(dba)2 or Pd[P(o-tol)3]2, which are air-stable Pd(0) precursors, (18) palladacycles such as Ia,b, or allyl complexes (such as [Pd(cinnamyl)Cl]2, or [Pd(allyl)Cl]2) that can be activated under the reaction conditions. For each catalyst, various ammonium salts were examined. The yields of ArNH2 and selectivity (ArNH2:Ar2NH) with three ammonium salts are shown in comparison to ammonia in dioxane in Scheme 2. The protocols were adapted from those previously reported. (11, 13, 14, 16) The performance of each salt differed with each catalyst system. Ammonium acetate and ammonium sulfate were suitable salts with each catalyst system, and high yields and selectivities were obtained in reactions catalyzed by Pd and tBuBrettPhos, (13) MorDalPhos, (14) and Josiphos ligand CyPF-tBu. (11) Reactions catalyzed by Pd and BippyPhos (16, 19) either did not form any desired product or formed p-toluidine in low yields. Reactions with several ammonium salts catalyzed by Pd[P(o-tol)3]2 and the Josiphos ligand containing one dicyclohexylphosphino and one di-tert-butylphosphino group occurred in high yields and required the lowest catalyst loadings of the systems we studied for this transformation. (11)
These yields and selectivities demonstrate the benefit of maintaining a low effective concentration of ammonia. (20) The concentration of ammonia appears to be affected by the composition of the ammonium salt. Ammonium sulfate is crystalline. Reactions conducted with finely ground ammonium sulfate occurred with lower selectivity (12:1) than those conducted with the salt used as received (20:1).
Scheme 2
Scheme aYields (ArNH2) and selectivities (ArNH2:Ar2NH) determined by GC analysis using dodecane as an internal standard: (a) 100 °C, 12 h; (b) 110 °C, 4 h; (c) 100 °C, 25 h; (d) 80 °C, 5 h; (e) (NH4)2SO4 (1.5 equiv).
Results from the reaction of ammonium sulfate with a series of aryl chlorides catalyzed by Pd[P(o-tol)3]2 and the Josiphos ligand are shown in Scheme 3. Primary arylamines containing ortho substituents of varying size, including smaller groups, such as methyl (2f) and methoxy (2e) groups, and larger groups, such as a phenyl ring (2d), were isolated in high yields (79–98%). Styrenyl functionality (2c), ketals (21) (2g), and silyl-protected alcohols (2h) were tolerated by the reaction. Benzo-fused heterocycles containing nitrogen (2i,j) and sulfur (2k) reacted with the ammonium salt in good yields. The scope of the reaction under these conditions is similar to that of the reaction with the solution of ammonia. (10, 11)
Scheme 3
Scheme aConditions: ArCl (0.600 mmol), ammonium sulfate (0.900 mmol), Pd[P(o-tol)3]2 (1.2–6.0 μmol, 0.2–1.0 mol %), CyPF-tBu (1.2–6.0 μmol, 0.2–1.0 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 100 °C, 12 h. Isolated yields (catalyst loading in parentheses).
The coupling of ammonia with aryl bromides occurs faster and with higher selectivity for the formation of the primary arylamine than does the coupling aryl chlorides. (11) However, we observed that reactions of aryl bromides with ammonium chloride, sulfate, or acetate occurred with lower selectivity (2:1) for the primary arylamine versus the diarylamine than did the reactions of aryl chlorides.
To understand the difference in selectivity between the reactions of aryl chlorides and aryl bromides lacking an ortho substituent, and to understand the impact of using the ammonium salts on the rates of different steps in the catalytic cycle, we studied the mechanism of these amination reactions. The mechanism of the amination of aryl halides with ammonia catalyzed by palladium-Josiphos complexes has been studied. (22) Spectroscopic studies showed that L2Pd(Ar)(NH2) is the resting state of the catalyst, and kinetic experiments indicated that reductive elimination is the turnover-limiting step. (22)
Because the selectivity varies with the identity of the aryl halide, we considered that the catalyst resting state for the reactions of ammonium salts is not the arylpalladium–amido complex. We monitored the reaction of p-chlorotoluene with ammonium sulfate at 80 °C catalyzed by 10 mol % of (CyPF-tBu)Pd(P(o-tol)3), formed in situ, in dioxane. One ligated palladium species was observed by 31P NMR spectroscopy. The chemical shifts and coupling constants of the new complex were different from the reported values for the CyPF-tBu-ligated arylpalladium chloride (23) or amido (22) complexes. Instead, they were consistent with reported values for the CyPF-tBu-ligated arylpalladium tert-butoxide complex. (23) In contrast, a combination of the arylpalladium tert-butoxide complex and the arylpalladium–bromide complex in an 3:4 ratio were observed in solution during the reaction of p-bromotoluene with ammonium sulfate (Figure 1).
Figure 1
Figure 1. Comparison of the resting states for reactions with ammonia and ammonium sulfate.
To understand the effect of the inorganic salts formed in the reaction, we allowed p-chlorotoluene to react with ammonium sulfate in the presence of the palladium catalyst with 1 equiv of added NaBr. A lower selectivity (9:1) was observed for the reaction with the added bromide salt than was observed for the analogous reaction conducted without the bromide salt (20:1). Stoichiometric reactions with isolated complexes suggest that L2Pd(Ar)(OtBu) reacts selectively with ammonia to form the primary arylamine, while L2Pd(Ar)(Br) selectively reacts with aniline to form diarylamine (Figure 1). (20, 24)
Ortho-substituted aryl bromides reacted to provide the primary arylamine in high yields without competing diarylation, presumably due to the large steric difference between the ammonia reagent and an ortho-substituted aniline (Scheme 4).
Scheme 4
Scheme aConditions: ArBr (0.600 mmol), (NH4)2SO4 (0.900 mmol), Pd[P(o-tol)3]2 (3.0 μmol, 0.5 mol %), CyPF-tBu (3.0 μmol, 0.5 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 100 °C, 12 h.
This coupling process provides a convenient method to incorporate 15N into aromatic compounds. The 15N label in anilines is typically installed by nitration and reduction. Such a process is expensive to conduct because it requires solvent quantities of 15N-labeled nitric acid. Ammonium salts are a less expensive and more conveniently handled source of 15N than are nitric acid or 15N-labeled ammonia gas, and our coupling of ammonium salts requires only 3 equiv of solid 15N per mole of substrate. To illustrate this potential application of the coupling of ammonium salts, we prepared 15N-labeled 5-methoxy-2-methylaniline on a 4 mmol scale. This product formed in high yield (eq 1), and the conversion of such products to a range of quinolines (25, 26) and indoles (26-28) is well established.
The coupling of aryl halides with ammonium salts was expanded to include that between aryl halides and the ammonium salts of methylamine (bp = −6.3 °C) and ethylamine (bp = 17 °C) to form the corresponding N-methyl- and N-ethylanilines. There are few reports of the coupling of aryl halides with methylamine, and the source of amine is a commercially available 2.0 M solution in THF. (16, 29-34) The reaction of aryl chlorides and bromides with methylamine and ethylamine hydrochloride yielded the corresponding N-alkylaniline products in moderate to high yields (59–99%), as shown in Scheme 5.
Because the product of the reaction of methylamine and ethylamine are secondary amines, and the Pd-Josiphos system is selective for reaction of primary amines over secondary amines, (35) diarylamines are not observed in these reactions. N-Alkylanilines are less volatile than the corresponding primary arylamines. Therefore, isolated yields from reactions with methyl and ethylamine hydrochloride are slightly higher than those for reactions with ammonium sulfate.
Reactions of ethylamine hydrochloride with aryl halides occur under conditions similar to those previously reported for the coupling of primary alkylamines. In this case, Pd(OAc)2 is a suitable precursor, presumably because of the more facile reduction of the Pd(II) by ethylamine than by methylamine or ammonia. (35) Similarly, aryl halides, including bromopyridines (4l–n), coupled with ethylamine hydrochloride to form the corresponding N-ethylanilines (Scheme 5).
Scheme 5
Scheme aConditions: ArX (0.600 mmol), RNH3Cl (1.80 mmol), [Pd] (0.30–6.0 μmol, 0.05–1.0 mol %), CyPF-tBu (0.30–6.0 μmol, 0.05–1.0 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 12 h.
In summary, we have shown that ammonium salts are practical alternatives to gaseous amines for the aminations of aryl halides and can occur with distinct selectivities, distinct effects of concentration on selectivities, and distinct resting states of the catalyst. We observed a high selectivity for the formation of primary arylamine over diarylamine in reactions of aryl chlorides with ammonium sulfate, but we observed a mixture of mono- and diarylamine in the reactions of aryl bromides with ammonium sulfate. We attribute the difference in selectivity to the difference in resting states in the amination reaction of ammonium sulfate with aryl chlorides and bromides. L2Pd(Ar)(OtBu) was observed as the major ligated palladium species during the reaction of aryl chlorides with ammonium sulfate. However, both L2Pd(Ar)(OtBu) and L2Pd(Ar)(Br) were observed in reactions of aryl bromides with ammonium sulfate. The L2Pd(Ar)(Br) reacts selectively with primary arylamines to afford the diarylamine side product. This method was extended to include other gaseous amines, such as methylamine and ethylamine, to afford N-methyl- and N-ethylanilines.
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Acknowledgment
We thank the Dow Chemical Co. and the NIH (GM-58108) for support and Johnson Matthey for a gift of PdCl2. R.A.G. thanks NSERC for a graduate fellowship, Patrick S. Fier (UCB) and Dr. Andrew T. Brusoe (UCB) for helpful discussions, and Dr. Seung Hwan Cho (UCB) for the synthesis of substrates 1o,q,r,t (Scheme 4).
References
This article references 35 other publications.
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- 2Aubin, Y.; Fischmeister, C.; Thomas, C. M.; Renaud, J.-L. Chem. Soc. Rev. 2010, 39, 4130Google Scholar2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlShtbrJ&md5=fca919906612d8744a769ddd98f049eeDirect amination of aryl halides with ammoniaAubin, Yoann; Fischmeister, Cedric; Thomas, Christophe M.; Renaud, Jean-LucChemical Society Reviews (2010), 39 (11), 4130-4145CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. The traditional homogeneous access to arom. amine derivs. is a nucleophilic arom. substitution of the corresponding aryl halides. The halogen atom is usually relatively inert to amination reaction unless it is activated by the presence of electron withdrawing groups. Consequently, there was particular emphasis over the past decade on the synthesis of metal complexes that are active catalysts for the prepn. of arom. amines. This tutorial review focused on the use of metal-based complexes for the direct amination of aryl halides with ammonia.
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- 9Bhagwanth, S.; Waterson, A. G.; Adjabeng, G. M.; Hornberger, K. R. J. Org. Chem. 2009, 74, 4634Google ScholarThere is no corresponding record for this reference.
- 10Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XmvFaqurw%253D&md5=9d54957b560c21d4ff0e4fc9dff65f96Palladium-catalyzed coupling of ammonia and lithium amide with aryl halidesShen, Qilong; Hartwig, John F.Journal of the American Chemical Society (2006), 128 (31), 10028-10029CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A mild, palladium-catalyzed coupling of aryl halides with ammonia or lithium amide to form primary arylamines as the major product was described. These reactions occurred with excellent selectivity for formation of the primary arylamine over formation of the diarylamine (9.5:1 to over 50:1 ratios of arylamine to diarylamine). In addn., the first organopalladium complex with a terminal -NH2 ligand has been isolated. This complex reductively eliminated to form arylamines.
- 11Vo, G. D.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 11049Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXotl2ht7Y%253D&md5=46ab74c837afdb569423fd1eddea15c7Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides, and Sulfonates: A General Method for the Preparation of Primary ArylaminesVo, Giang D.; Hartwig, John F.Journal of the American Chemical Society (2009), 131 (31), 11049-11061CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)We report that the complex generated from Pd[P(o-tol)3]2 and the alkylbisphosphine CyPF-t-Bu (Josiphos ligand) a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings of ammonia with this catalyst conducted with a soln. of ammonia in dioxane form primary arylamines from a variety of aryl electrophiles in high yields. Catalyst loadings as low as 0.1 mol% were sufficient for reactions of many aryl chlorides and bromides. In the presence of this catalyst, aryl sulfonates also coupled with ammonia for the first time in high yields. A comparison of reactions in the presence of this catalyst vs. those in the presence of existing copper and palladium systems revealed a complementary, if not broader, substrate scope. The utility of this method to generate amides, imides, and carbamates is illustrated by a one-pot synthesis of a small library of these carbonyl compds. from aryl bromides and chlorides, ammonia, and acid chlorides or anhydrides. Mechanistic studies show that reactions conducted with the combination of Pd[P(o-tol)3]2 and CyPF-t-Bu as catalyst occur with faster rates and higher yields than those conducted with CyPF-t-Bu and palladium(II) as catalyst precursors because of the low concn. of active catalyst that is generated from the combination of palladium(II), ammonia, and base.
- 12Surry, D. S.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 10354Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXosVWitLo%253D&md5=c72143368414306026e81db5041752c6Selective Palladium-Catalyzed Arylation of Ammonia: Synthesis of Anilines as Well as Symmetrical and Unsymmetrical Di- and TriarylaminesSurry, David S.; Buchwald, Stephen L.Journal of the American Chemical Society (2007), 129 (34), 10354-10355CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)It is shown that by selection of an appropriate palladium/ligand system, temp., concn., and stoichiometry of reagents, ammonia may be selectively arylated to give either anilines, sym. di-, or triarylamines. Furthermore different aryl halides may be added sequentially to the reaction mixt., allowing the synthesis of unsym. di- and triarylamines (e.g. I) from aryl halides and ammonia in a one-pot protocol.
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- 14Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 4071Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmvFSlu70%253D&md5=27bd995e0a978e95fd394e6da25cd51aA P,N-Ligand for Palladium-Catalyzed Ammonia Arylation: Coupling of Deactivated Aryl Chlorides, Chemoselective Arylations, and Room Temperature ReactionsLundgren, Rylan J.; Peters, Brendan D.; Alsabeh, Pamela G.; Stradiotto, MarkAngewandte Chemie, International Edition (2010), 49 (24), 4071-4074, S4071/1-S4071/99CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)An air-stable P,N-ligand (I), that advances the scope and utility of palladium-catalyzed ammonia cross-coupling reactions, was developed. A variety of aryl chloride and aryl tosylate substrates can be coupled efficiently, most notably electron-rich species lacking ortho-substitution under a range of conditions. The unique preference for ammonia coupling when using Pd/I mixts. can be exploited in unprecedented chemoselective arylations, and for the first time, the room temp. palladium-catalyzed cross-coupling of ammonia has been achieved.
- 15Alsabeh, P. G.; Lundgren, R. J.; McDonald, R.; Johansson Seechurn, C. C. C.; Colacot, T. J.; Stradiotto, M. Chem.—Eur. J. 2013, 19, 2131Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXkvF2rsw%253D%253D&md5=af055740635c93ec27bbd83e19de94f8An Examination of the Palladium/Mor-DalPhos Catalyst System in the Context of Selective Ammonia Monoarylation at Room TemperatureAlsabeh, Pamela G.; Lundgren, Rylan J.; McDonald, Robert; Johansson Seechurn, Carin C. C.; Colacot, Thomas J.; Stradiotto, MarkChemistry - A European Journal (2013), 19 (6), 2131-2141CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)An examn. of the [{Pd(cinnamyl)Cl}2]/Mor-DalPhos (Mor-DalPhos=di(1-adamantyl)-2-morpholinophenylphosphine) catalyst system in Buchwald-Hartwig aminations employing ammonia was conducted to better understand the catalyst formation process and to guide the development of precatalysts for otherwise challenging room-temp. ammonia monoarylations. The combination of [{Pd(cinnamyl)Cl}2] and Mor-DalPhos afforded [(κ2-P,N-Mor-DalPhos)Pd(η1-cinnamyl)Cl] (2), which, in the presence of a base and chlorobenzene, generated [(κ2-P,N-Mor-DalPhos)Pd(Ph)Cl] (1 a). Halide abstraction from 1 a afforded [(κ3-P,N,O-Mor-DalPhos)Pd(Ph)]OTf (5), bringing to light a potential stabilizing interaction that is offered by Mor-DalPhos. An examn. of [(κ2-P,N-Mor-DalPhos)Pd(aryl)Cl] and related precatalysts for the coupling of ammonia and chlorobenzene at room temp. established the suitability of 1 a in such challenging applications. The scope of reactivity for the use of 1 a (5 mol %) encompassed a range of (hetero)aryl (pseudo)halides (X=Cl, Br, I, OTs) with diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro, trifluoromethyl, and nitrile), including chemoselective arylations.
- 16Crawford, S. M.; Lavery, C. B.; Stradiotto, M. Chem.—Eur. J. 2013, 19, 16760Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77F&md5=3e1abc9d0dde72bf9f29217c9f55df76BippyPhos: A Single Ligand With Unprecedented Scope in the Buchwald-Hartwig Amination of (Hetero)aryl ChloridesCrawford, Sarah M.; Lavery, Christopher B.; Stradiotto, MarkChemistry - A European Journal (2013), 19 (49), 16760-16771CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-contg. substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-contg. substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-contg. coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/[Pd(cinnamyl)Cl]2 as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl]2 to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho-alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-contg. coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chem. distinct NH-contg. moieties.
- 17Kim, J.; Chang, S. Chem. Commun. 2008, 3052Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnvFCht7k%253D&md5=01b8787c41b3df2456b2ac52cdcd28dcAmmonium salts as an inexpensive and convenient nitrogen source in the Cu-catalyzed amination of aryl halides at room temperatureKim, Jinho; Chang, SukbokChemical Communications (Cambridge, United Kingdom) (2008), (26), 3052-3054CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Convenient and inexpensive ammonium salts such as NH4Cl and aq. NH3 soln. are found to be readily utilized in the Cu-catalyzed N-arylation of aryl halides, providing N-unprotected aniline derivs. in high yields.
- 18
Pd[P(o-tol)3]2 is stable as a solid in air but must be handled under inert atmosphere in solution.
There is no corresponding record for this reference. - 19Singer, R. A.; Doré, M.; Sieser, J. E.; Berliner, M. A. Tetrahedron Lett. 2006, 47, 3727Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xkt1yitrk%253D&md5=061c51689f0500624fc72020a4645734Development of nonproprietary phosphine ligands for the Pd-catalyzed amination reactionSinger, Robert A.; Dore, Michael; Sieser, Janice E.; Berliner, Martin A.Tetrahedron Letters (2006), 47 (22), 3727-3731CODEN: TELEAY; ISSN:0040-4039. (Elsevier B.V.)A new family of pyrazole and bi-pyrazole phosphine ligands are reported that perform efficiently in the Pd-catalyzed amination reaction. Of the ligands screened, ligand I emerged as the most compatible for couplings involving both primary and secondary amines with typical yields of 84-99%.
- 21
Unprotected enolizable ketones underwent aldol condensation reactions under the basic conditions.
There is no corresponding record for this reference. - 22Klinkenberg, J. L.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 11830Google ScholarThere is no corresponding record for this reference.
- 23Alvaro, E.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 7858Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtVGrsrw%253D&md5=0cb0993aae0cb7c71201d05efabed371Resting State and Elementary Steps of the Coupling of Aryl Halides with Thiols Catalyzed by Alkylbisphosphine Complexes of PalladiumAlvaro, Elsa; Hartwig, John F.Journal of the American Chemical Society (2009), 131 (22), 7858-7868CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Detailed mechanistic studies on the coupling of aryl halides with thiols catalyzed by palladium complexes of the alkylbisphosphine ligand CyPF-tBu (1-dicyclohexylphosphino-2-di-tert-butylphosphinoethylferrocene) are reported. The elementary steps that constitute the catalytic cycle, i.e. oxidative addn., transmetalation and reductive elimination, have been studied, and their relative rates are reported. Each of the steps of the catalytic process occurs at temps. that are much lower than those required for the reactions catalyzed by a combination of palladium precursors and CyPF-tBu. To explain these differences in rates between the catalytic and stoichiometric reactions, studies were conducted to identify the resting state of the catalyst of the reactions catalyzed by a combination of Pd(OAc)2 and CyPF-tBu, a combination of Pd(dba)2 and CyPF-tBu, or the likely intermediate Pd(CyPF-tBu)(Ar)(Br). These data show that the major palladium complex in each case lies off of the catalytic cycle. The resting state of the reactions catalyzed by Pd(OAc)2 and CyPF-tBu was the palladium bis-thiolate complex [Pd(CyPF-tBu)(SR)2] (R = alkyl or aryl). The resting state in reactions catalyzed by Pd2(dba)3 and CyPF-tBu was the binuclear complex [Pd(CyPF-tBu)]2(μ2,η2-dba) (9). The resting states of reactions of both arom. and aliph. thiols catalyzed by [Pd(CyPF-tBu)(p-tolyl)(Br)] (3a) were the hydridopalladium thiolate complexes [Pd(CyPF-tBu)(H)(SR)] (R= alkyl and aryl). All these palladium species have been prepd. independently, and the mechanisms by which they enter the catalytic cycle have been examd. in detail. These features of the reaction catalyzed by palladium and CyPF-tBu have been compared with those of reactions catalyzed by the alkylbisphosphine DiPPF and Pd(OAc)2 or Pd(dba)2. Our data indicate that the resting states of these reactions are similar to each other and that our mechanistic conclusions about reactions catalyzed by palladium and CyPF-tBu can be extrapolated to reactions catalyzed by complexes of other electron-rich bisphosphines.
- 24
A survey of alkoxide and phenoxide bases with various counterions did not improve the selectivity of the reaction.
There is no corresponding record for this reference. - 25Clarke, H. T.; Davis, A. W. Organic Syntheses 1922, 79Google ScholarThere is no corresponding record for this reference.
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- 30Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M. Chem.—Eur. J. 2010, 16, 1983Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVKjtro%253D&md5=6355cdaf090a3c7ccf18b2d44cdd5fe1A Highly Versatile Catalyst System for the Cross-Coupling of Aryl Chlorides and AminesLundgren, Rylan J.; Sappong-Kumankumah, Antonia; Stradiotto, MarkChemistry - A European Journal (2010), 16 (6), 1983-1991, S1983/1-S1983/198CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)The syntheses of 2-(di-tert-butylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74%) and their application in Buchwald-Hartwig amination, are reported. In combination with [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2, these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcs., olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol.% Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)2, PdCl2, [PdCl2(cod)] (cod = 1,5-cyclooctadiene), [PdCl2(MeCN)2], or [Pd2(dba)3] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2 with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho-dimethylamino fragment. Given current limitations assocd. with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross-coupling of aryl chlorides and amines.
- 31Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 15914Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlClur7P&md5=4b2cac129b1462f58dd8ab2ad2619d93A Multiligand Based Pd Catalyst for C-N Cross-Coupling ReactionsFors, Brett P.; Buchwald, Stephen L.Journal of the American Chemical Society (2010), 132 (45), 15914-15917CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An alternative approach to catalyst development, which led to a Pd catalyst based on two biarylphosphine ligands for C-N cross-coupling reactions, is reported. By effectively being able to take the form of multiple catalysts this system manifests the best properties that catalysts based on either of the two ligands exhibit sep. and displays the highest reactivity and substrate scope of any system that has been reported to date for these reactions.
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- 35Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Angew. Chem., Int. Ed. 2005, 44, 1371Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXitVSis70%253D&md5=8df5d549c453e32dee30f1a9c7456626Highly reactive, general, and long-lived catalysts for coupling heteroaryl and aryl chlorides with primary nitrogen nucleophilesShen, Qilong; Shekhar, Shashank; Stambuli, James P.; Hartwig, John F.Angewandte Chemie, International Edition (2005), 44 (9), 1371-1375, S1371/1-S1371/79CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Resisting pathways for decompn. followed by palladium complexes of monodentate ligands was one characteristic of the highly reactive but long-lived catalyst generated from the Josiphos ligand and palladium. It catalyzed, under mild conditions, the coupling of primary amines with chloropyridines and chloroarenes in high yield with low catalyst loadings.
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Abstract
Scheme 1
Scheme 1. Methods for Palladium-Catalyzed Amination of Aryl Halides with AmmoniaScheme 2
Scheme 2. Evaluation of Ammonium Salts and Palladium Catalysts for the Amination of Aryl ChloridesaScheme aYields (ArNH2) and selectivities (ArNH2:Ar2NH) determined by GC analysis using dodecane as an internal standard: (a) 100 °C, 12 h; (b) 110 °C, 4 h; (c) 100 °C, 25 h; (d) 80 °C, 5 h; (e) (NH4)2SO4 (1.5 equiv).
Scheme 3
Scheme 3. Scope of Palladium-Catalyzed Amination of Aryl Chlorides with Ammonium SulfateaScheme aConditions: ArCl (0.600 mmol), ammonium sulfate (0.900 mmol), Pd[P(o-tol)3]2 (1.2–6.0 μmol, 0.2–1.0 mol %), CyPF-tBu (1.2–6.0 μmol, 0.2–1.0 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 100 °C, 12 h. Isolated yields (catalyst loading in parentheses).
Figure 1
Figure 1. Comparison of the resting states for reactions with ammonia and ammonium sulfate.
Scheme 4
Scheme 4. Scope of Palladium-Catalyzed Amination of Ortho-Substituted Aryl Bromides with Ammonium SulfateaScheme aConditions: ArBr (0.600 mmol), (NH4)2SO4 (0.900 mmol), Pd[P(o-tol)3]2 (3.0 μmol, 0.5 mol %), CyPF-tBu (3.0 μmol, 0.5 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 100 °C, 12 h.
Scheme 5
Scheme 5. Pd-Catalyzed Amination of Aryl Chlorides and Bromides with Methylamine and Ethylamine Hydrochloride SaltsaScheme aConditions: ArX (0.600 mmol), RNH3Cl (1.80 mmol), [Pd] (0.30–6.0 μmol, 0.05–1.0 mol %), CyPF-tBu (0.30–6.0 μmol, 0.05–1.0 mol %), NaOtBu (2.70 mmol), 1,4-dioxane (6 mL); 12 h.
References
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- 14Lundgren, R. J.; Peters, B. D.; Alsabeh, P. G.; Stradiotto, M. Angew. Chem., Int. Ed. 2010, 49, 407114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmvFSlu70%253D&md5=27bd995e0a978e95fd394e6da25cd51aA P,N-Ligand for Palladium-Catalyzed Ammonia Arylation: Coupling of Deactivated Aryl Chlorides, Chemoselective Arylations, and Room Temperature ReactionsLundgren, Rylan J.; Peters, Brendan D.; Alsabeh, Pamela G.; Stradiotto, MarkAngewandte Chemie, International Edition (2010), 49 (24), 4071-4074, S4071/1-S4071/99CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)An air-stable P,N-ligand (I), that advances the scope and utility of palladium-catalyzed ammonia cross-coupling reactions, was developed. A variety of aryl chloride and aryl tosylate substrates can be coupled efficiently, most notably electron-rich species lacking ortho-substitution under a range of conditions. The unique preference for ammonia coupling when using Pd/I mixts. can be exploited in unprecedented chemoselective arylations, and for the first time, the room temp. palladium-catalyzed cross-coupling of ammonia has been achieved.
- 15Alsabeh, P. G.; Lundgren, R. J.; McDonald, R.; Johansson Seechurn, C. C. C.; Colacot, T. J.; Stradiotto, M. Chem.—Eur. J. 2013, 19, 213115https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXkvF2rsw%253D%253D&md5=af055740635c93ec27bbd83e19de94f8An Examination of the Palladium/Mor-DalPhos Catalyst System in the Context of Selective Ammonia Monoarylation at Room TemperatureAlsabeh, Pamela G.; Lundgren, Rylan J.; McDonald, Robert; Johansson Seechurn, Carin C. C.; Colacot, Thomas J.; Stradiotto, MarkChemistry - A European Journal (2013), 19 (6), 2131-2141CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)An examn. of the [{Pd(cinnamyl)Cl}2]/Mor-DalPhos (Mor-DalPhos=di(1-adamantyl)-2-morpholinophenylphosphine) catalyst system in Buchwald-Hartwig aminations employing ammonia was conducted to better understand the catalyst formation process and to guide the development of precatalysts for otherwise challenging room-temp. ammonia monoarylations. The combination of [{Pd(cinnamyl)Cl}2] and Mor-DalPhos afforded [(κ2-P,N-Mor-DalPhos)Pd(η1-cinnamyl)Cl] (2), which, in the presence of a base and chlorobenzene, generated [(κ2-P,N-Mor-DalPhos)Pd(Ph)Cl] (1 a). Halide abstraction from 1 a afforded [(κ3-P,N,O-Mor-DalPhos)Pd(Ph)]OTf (5), bringing to light a potential stabilizing interaction that is offered by Mor-DalPhos. An examn. of [(κ2-P,N-Mor-DalPhos)Pd(aryl)Cl] and related precatalysts for the coupling of ammonia and chlorobenzene at room temp. established the suitability of 1 a in such challenging applications. The scope of reactivity for the use of 1 a (5 mol %) encompassed a range of (hetero)aryl (pseudo)halides (X=Cl, Br, I, OTs) with diverse substituents (alkyl, aryl, ether, thioether, ketone, amine, fluoro, trifluoromethyl, and nitrile), including chemoselective arylations.
- 16Crawford, S. M.; Lavery, C. B.; Stradiotto, M. Chem.—Eur. J. 2013, 19, 1676016https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhslaqs77F&md5=3e1abc9d0dde72bf9f29217c9f55df76BippyPhos: A Single Ligand With Unprecedented Scope in the Buchwald-Hartwig Amination of (Hetero)aryl ChloridesCrawford, Sarah M.; Lavery, Christopher B.; Stradiotto, MarkChemistry - A European Journal (2013), 19 (49), 16760-16771CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-contg. substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-contg. substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-contg. coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/[Pd(cinnamyl)Cl]2 as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl]2 to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho-alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-contg. coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chem. distinct NH-contg. moieties.
- 17Kim, J.; Chang, S. Chem. Commun. 2008, 305217https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXnvFCht7k%253D&md5=01b8787c41b3df2456b2ac52cdcd28dcAmmonium salts as an inexpensive and convenient nitrogen source in the Cu-catalyzed amination of aryl halides at room temperatureKim, Jinho; Chang, SukbokChemical Communications (Cambridge, United Kingdom) (2008), (26), 3052-3054CODEN: CHCOFS; ISSN:1359-7345. (Royal Society of Chemistry)Convenient and inexpensive ammonium salts such as NH4Cl and aq. NH3 soln. are found to be readily utilized in the Cu-catalyzed N-arylation of aryl halides, providing N-unprotected aniline derivs. in high yields.
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Pd[P(o-tol)3]2 is stable as a solid in air but must be handled under inert atmosphere in solution.
There is no corresponding record for this reference. - 19Singer, R. A.; Doré, M.; Sieser, J. E.; Berliner, M. A. Tetrahedron Lett. 2006, 47, 372719https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xkt1yitrk%253D&md5=061c51689f0500624fc72020a4645734Development of nonproprietary phosphine ligands for the Pd-catalyzed amination reactionSinger, Robert A.; Dore, Michael; Sieser, Janice E.; Berliner, Martin A.Tetrahedron Letters (2006), 47 (22), 3727-3731CODEN: TELEAY; ISSN:0040-4039. (Elsevier B.V.)A new family of pyrazole and bi-pyrazole phosphine ligands are reported that perform efficiently in the Pd-catalyzed amination reaction. Of the ligands screened, ligand I emerged as the most compatible for couplings involving both primary and secondary amines with typical yields of 84-99%.
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Unprotected enolizable ketones underwent aldol condensation reactions under the basic conditions.
There is no corresponding record for this reference. - 22Klinkenberg, J. L.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 11830There is no corresponding record for this reference.
- 23Alvaro, E.; Hartwig, J. F. J. Am. Chem. Soc. 2009, 131, 785823https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmtVGrsrw%253D&md5=0cb0993aae0cb7c71201d05efabed371Resting State and Elementary Steps of the Coupling of Aryl Halides with Thiols Catalyzed by Alkylbisphosphine Complexes of PalladiumAlvaro, Elsa; Hartwig, John F.Journal of the American Chemical Society (2009), 131 (22), 7858-7868CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Detailed mechanistic studies on the coupling of aryl halides with thiols catalyzed by palladium complexes of the alkylbisphosphine ligand CyPF-tBu (1-dicyclohexylphosphino-2-di-tert-butylphosphinoethylferrocene) are reported. The elementary steps that constitute the catalytic cycle, i.e. oxidative addn., transmetalation and reductive elimination, have been studied, and their relative rates are reported. Each of the steps of the catalytic process occurs at temps. that are much lower than those required for the reactions catalyzed by a combination of palladium precursors and CyPF-tBu. To explain these differences in rates between the catalytic and stoichiometric reactions, studies were conducted to identify the resting state of the catalyst of the reactions catalyzed by a combination of Pd(OAc)2 and CyPF-tBu, a combination of Pd(dba)2 and CyPF-tBu, or the likely intermediate Pd(CyPF-tBu)(Ar)(Br). These data show that the major palladium complex in each case lies off of the catalytic cycle. The resting state of the reactions catalyzed by Pd(OAc)2 and CyPF-tBu was the palladium bis-thiolate complex [Pd(CyPF-tBu)(SR)2] (R = alkyl or aryl). The resting state in reactions catalyzed by Pd2(dba)3 and CyPF-tBu was the binuclear complex [Pd(CyPF-tBu)]2(μ2,η2-dba) (9). The resting states of reactions of both arom. and aliph. thiols catalyzed by [Pd(CyPF-tBu)(p-tolyl)(Br)] (3a) were the hydridopalladium thiolate complexes [Pd(CyPF-tBu)(H)(SR)] (R= alkyl and aryl). All these palladium species have been prepd. independently, and the mechanisms by which they enter the catalytic cycle have been examd. in detail. These features of the reaction catalyzed by palladium and CyPF-tBu have been compared with those of reactions catalyzed by the alkylbisphosphine DiPPF and Pd(OAc)2 or Pd(dba)2. Our data indicate that the resting states of these reactions are similar to each other and that our mechanistic conclusions about reactions catalyzed by palladium and CyPF-tBu can be extrapolated to reactions catalyzed by complexes of other electron-rich bisphosphines.
- 24
A survey of alkoxide and phenoxide bases with various counterions did not improve the selectivity of the reaction.
There is no corresponding record for this reference. - 25Clarke, H. T.; Davis, A. W. Organic Syntheses 1922, 79There is no corresponding record for this reference.
- 26Alvarez-Builla, J.; Vaquero, J. J.; Barluenga, J. Modern Heterocyclic Chemistry, 4th ed.; John Wiley & Sons: Weinheim, 2011.There is no corresponding record for this reference.
- 27Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 287527https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XltlCitbg%253D&md5=ed3275cc7c57303254010e695c1a5a8ePractical methodologies for the synthesis of IndolesHumphrey, Guy R.; Kuethe, Jeffrey T.Chemical Reviews (Washington, DC, United States) (2006), 106 (7), 2875-2911CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review on prepn. of indole derivs. A lot of procedures which have either been successfully demonstrated or are potentially useful for the large scale prepn. of indoles is presented with indication of reagents, reaction conditions, and yields. The review focuses on the literature of the last decade.
- 28Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045There is no corresponding record for this reference.
- 29Fors, B. P.; Watson, D. A.; Biscoe, M. R.; Buchwald, S. L. J. Am. Chem. Soc. 2008, 130, 13552There is no corresponding record for this reference.
- 30Lundgren, R. J.; Sappong-Kumankumah, A.; Stradiotto, M. Chem.—Eur. J. 2010, 16, 198330https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhsVKjtro%253D&md5=6355cdaf090a3c7ccf18b2d44cdd5fe1A Highly Versatile Catalyst System for the Cross-Coupling of Aryl Chlorides and AminesLundgren, Rylan J.; Sappong-Kumankumah, Antonia; Stradiotto, MarkChemistry - A European Journal (2010), 16 (6), 1983-1991, S1983/1-S1983/198CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)The syntheses of 2-(di-tert-butylphosphino)-N,N-dimethylaniline (L1, 71%) and 2-(di-1-adamantylphosphino)-N,N-dimethylaniline (L2, 74%) and their application in Buchwald-Hartwig amination, are reported. In combination with [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2, these structurally simple and air-stable P,N ligands enable the cross-coupling of aryl and heteroaryl chlorides, including those bearing as substituents enolizable ketones, ethers, esters, carboxylic acids, phenols, alcs., olefins, amides, and halogens, to a diverse range of amine and related substrates that includes primary alkyl- and arylamines, cyclic and acyclic secondary amines, N-H imines, hydrazones, lithium amide, and ammonia. In many cases, the reactions can be performed at low catalyst loadings (0.5-0.02 mol.% Pd) with excellent functional group tolerance and chemoselectivity. Examples of cross-coupling reactions involving 1,4-bromochlorobenzene and iodobenzene are also reported. Under similar conditions, inferior catalytic performance was achieved when using Pd(OAc)2, PdCl2, [PdCl2(cod)] (cod = 1,5-cyclooctadiene), [PdCl2(MeCN)2], or [Pd2(dba)3] (dba = dibenzylideneacetone) in combination with L1 or L2, or by use of [Pd(allyl)Cl]2 or [Pd(cinnamyl)Cl]2 with variants of L1 and L2 bearing less basic or less sterically demanding substituents on phosphorus or lacking an ortho-dimethylamino fragment. Given current limitations assocd. with established ligand classes with regard to maintaining high activity across the diverse possible range of C-N coupling applications, L1 and L2 represent unusually versatile ligand systems for the cross-coupling of aryl chlorides and amines.
- 31Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 1591431https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlClur7P&md5=4b2cac129b1462f58dd8ab2ad2619d93A Multiligand Based Pd Catalyst for C-N Cross-Coupling ReactionsFors, Brett P.; Buchwald, Stephen L.Journal of the American Chemical Society (2010), 132 (45), 15914-15917CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)An alternative approach to catalyst development, which led to a Pd catalyst based on two biarylphosphine ligands for C-N cross-coupling reactions, is reported. By effectively being able to take the form of multiple catalysts this system manifests the best properties that catalysts based on either of the two ligands exhibit sep. and displays the highest reactivity and substrate scope of any system that has been reported to date for these reactions.
- 32Li, J. J.; Wang, Z.; Mitchell, L. H. J. Org. Chem. 2007, 72, 3606There is no corresponding record for this reference.
- 33Alsabeh, P. G.; Lundgren, R. J.; Longobardi, L. E.; Stradiotto, M. Chem. Commun. 2011, 47, 6936There is no corresponding record for this reference.
- 34Tardiff, B. J.; McDonald, R.; Ferguson, M. J.; Stradiotto, M. J. Org. Chem. 2012, 77, 1056There is no corresponding record for this reference.
- 35Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Angew. Chem., Int. Ed. 2005, 44, 137135https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXitVSis70%253D&md5=8df5d549c453e32dee30f1a9c7456626Highly reactive, general, and long-lived catalysts for coupling heteroaryl and aryl chlorides with primary nitrogen nucleophilesShen, Qilong; Shekhar, Shashank; Stambuli, James P.; Hartwig, John F.Angewandte Chemie, International Edition (2005), 44 (9), 1371-1375, S1371/1-S1371/79CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Resisting pathways for decompn. followed by palladium complexes of monodentate ligands was one characteristic of the highly reactive but long-lived catalyst generated from the Josiphos ligand and palladium. It catalyzed, under mild conditions, the coupling of primary amines with chloropyridines and chloroarenes in high yield with low catalyst loadings.
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