ASAP (As Soon As Publishable)

The total syntheses of the putative structure of serinolipid didemniserinolipids A and C have been achieved in 12 or 13 longest linear steps by divergent strategies starting from chiral pool methyl d-mannopyranoside, respectively. The key transformations include a sequential reaction of Bernet–Vasella-type reductive elimination and Horner–Wadsworth–Emmons in a one-pot process and a cascade reaction of desilylation/deacetalization/selective intramolecular spiroketalization involving the generation of the critical 6,8-dioxabicyclo[3.2.1]octane scaffold. Discrepancies in the spectroscopic data of the synthetic samples and natural products revealed that the original assignments of didemniserinolipids A and C were misassigned and warrant revision.

4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) and its derivatives are highly useful fluorescent dyes employed in myriad applications in chemistry and biology. Here, we revisit a series of dihalogenated (Cl, Br, I) BODIPY derivatives with rare 1,7-regiochemistry. In addition to their synthesis and structural characterization, we fill in a missing piece of the current literature by delineating their photophysical behavior, including the light-driven generation of singlet oxygen (¹O₂) which is mediated with particularly high efficiency by the heavier diiodinated congener.

A multigram synthesis of novel bicyclic α- and β-prolines was achieved via a C(sp³)–H amidation reaction as a key step. This step prepared seven bicyclic γ-lactams in high yield and stereoselective control. The scalable and reproducible protocol allowed the conversion of γ-lactams into α- and β-prolines in amounts up to 45 g under mild conditions, providing access to various isomeric bicyclic proline derivatives for potential use in drug design as medicinal building blocks.

The construction of C(sp³)–C(sp³) bonds through cross-coupling reactions of unactivated alkyl halides and C-radical precursors presents a significant challenge in organic synthesis. Herein, we report a strategy for the formation of C(sp³)–C(sp³) bonds using alkyl halides as alkylation reagents via the 1,5-hydrogen atom transfer (HAT) process. The reactions proceed under mild conditions, demonstrating a remarkable tolerance for a diverse array of functional groups. This method possesses the potential to expand new pathways in organic synthesis.

A biomimetic approach for the synthesis of an advanced intermediate en route to melicolones A and B is described, leading to successful construction of the crucial bicyclo[3.2.1]octane carbon framework of these molecules. Key steps of the strategy include a Wolff rearrangement, a titanium-mediated Giese-type cyclization, and a nitrone acylation/rearrangement process. Our approach enables the reliable assembly of a fully functionalized tricyclic precursor, which in turn provides valuable handles for further elaboration of the target molecules.

Using boronic acid, photoredox, and HAT catalysis, the relative alkylation reactivity of representative alkyl alcohols was evaluated through competition experiments, revealing higher initial reactivity for diols. Electron-poor arylboronic acid catalysts provide increased reaction efficiency for all substrates, which is attributed to a more dynamic and facile equilibrium between boron-containing species. Furthermore, β-carboxyboronic acids resulted in an additional increase in reaction efficiency, and the results from both catalyst classes were compared using kinetic profiles and a select scope of monoalcohols.

Herein, we describe a simple transition-metal-free synthesis of E-α,β-unsaturated β-boryl nitriles by the Horner–Wadsworth–Emmons reaction starting from potassium acyltrifluoroborates. The methodology encompasses a broad range of alkyl and aryl substrates. The reaction conditions are simple, and the reaction products are in most cases isolated with good yields as pure E isomers without column chromatography.

Chiral α-functionalized α-amino ketones are sought-after compounds for drug development; however, their acyclic enantioselective synthesis with amines as nucleophiles remains challenging. The catalytic decarboxylation of propargylic cyclic carbonates through metal–allenylidene intermediates has proven to be an efficient route to chiral quaternary centers, but its enantioselective mechanisms require clarification. Herein, we computationally investigate the Cu(I)-catalyzed decarboxylation of propargyl cyclic carbonates with aniline [Guo, W. J. Am. Chem. Soc. 2021, 143, 7629–7763]. The calculation results elucidate the mechanistic details of the reaction and reveal that enantioselectivity stems from the distinct noncovalent interactions in the (R)- and (S)- transition states, while regioselectivity arises from the lower steric hindrance for aniline attack at C5 versus C1 atom in the zwitterionic metal–allenylidene intermediate. IGMH analysis further validates the enantiocontrol. The theoretical results offer insights into the mechanisms of Cu(I)-catalyzed decarboxylation of propargyl cyclic carbonates with amines as nucleophiles, advancing the understanding of propargylic amination and aiding the development of this research field.

Nitrogen-containing compounds, such as anilines, represent some of the most prevalent and valuable chemical entities within the field of chemistry. However, their high reactivity, which frequently lacks selectivity, has constrained their application in various chemical transformations, including the alkylation of alcohols. In the present study, we successfully accomplished site-selective para and N–H alkylation of anilines by utilizing ortho-quinone methides under mild conditions. The regioselective para-alkylation was conducted with unprotected anilines in a metal-free environment, while N–H alkylations were effectively performed under similarly mild conditions. DFT calculations were carried out to understand the distinctive chemoselectivity of N-alkylation and C-alkylation of unprotected arylamines with different nonpolar (toluene) and polar protic (HFIP) solvents. Furthermore, the different transition state models identified in our calculations shed light on the intricate interplay between solvent effects and reaction selectivity.

In the intramolecular Schmidt reaction of alkyl azides and ketones, stoichiometric acid loading has often been necessary to overcome product inhibition, where the product amide irreversibly binds to the acid and forms a catalytically inactive complex. This limitation has been circumvented by the use of catalytic TiCl₄ or AcCl in HFIP. Despite this advance, several issues and details of product inhibition in the intramolecular Schmidt reaction remain unexplored. Here, we report kinetic studies and a variable time normalization analysis to experimentally determine the rate law and demonstrate the influence of product inhibition on the kinetics of the intramolecular Schmidt reaction. In addition, computational chemistry, basicity parameters, and additive studies were used to establish the relationship between basicity and the reaction rate. The structures of HCl adducts of product lactams were also determined using X-ray crystallography. Overall, this work establishes a more precise theoretical and experimental understanding of the mechanism of product inhibition and its role in the kinetics of the intramolecular Schmidt reaction.

Metalloenamines, generated through the α-deprotonation of N-iminosulfinyl ketimines, can be selectively intercepted at their nitrogen atom by highly fluorinated (hetero)arenes. The interaction leads to the formation of N-polyfluoroarylated enesulfinamidine intermediates, which are capable of undergoing [2,3]-sigmatropic rearrangement to yield α-amino ketimine derivatives. The high enantiopurity of the resulting products is ensured by the precise transfer of chirality from the sulfur atom of the iminosulfinyl group to the α-carbon of the ketimine moiety.

We describe herein the synthesis along with full photophysical and computational studies of three series of boranil complexes (Series I−III), incorporating extended ethynyl substitution, either on the imino side (Series I), on the phenolic side (Series II), or on both sides (Series III), in order to assess the impact of the insertion of electron donors or acceptors on the fluorescence properties. A full photophysical study in solution (various solvents) demonstrated the presence of a strong intramolecular charge transfer process within these boron complexes, with fluorescence colors spanning the entire visible range. Additionally, these compounds are also emissive in the solid state, on a similar wide fluorescence range, thus providing more examples of dual solution- and solid-emissive fluorophores, based on boron complexes. Theoretical calculations on both anil ligands and boranil complexes rationalize the charge transfer nature of the excited states involved in the emissive transitions.

In this investigation, we developed several novel synthetic routes using hydroxynitrile lyase (HNL) from Parafontaria laminata (PlamHNL) to synthesize active pharmaceutical ingredients, specifically Cenobamate (Xcopri), Clopidogrel (Plavix), and Mirabegron (Myrbetriq). Our methods demonstrate higher enantioselectivity, improved regioselectivity, and better yields. Notably, both Xcopri and Clopidogrel are produced from a common intermediate, (R)-methyl-2-chloro mandelate.

Benzoxa- and thienoxaphosphaborinines, a new group of six-membered boron–phosphorus heterocycles, are reported. Their synthesis involved aromatic lithiation of appropriate 2-aryl-6-butyl[1.3.6.2]dioxazaborocans, followed by treatment with PhPCl₂ and subsequent hydrolysis giving rise to (2-(phenylhydrophosphoryl)aryl)boronic acids. These intermediates exhibit nucleophilic character and undergo readily condensation reactions with aldehydes and ketones giving rise to target products. The mechanism of the latter reaction was studied by means of DFT calculations showing that activation of the carbonyl partner occurs through the formation of the hydrogen bond with the B(OH)₂ group rather than through an interaction with the Lewis acid boron atom due to a plausible FLP-like behavior. The molecular structures of a few derivatives were determined by X-ray crystallography showing that in all cases, the molecules assemble through intermolecular BOH···O═P hydrogen bonds.

In this article, a convenient method has been developed for the rapid and expedient diastereoselective synthesis of highly functionalized 3,7a-diazacyclohepta[jk]fluorenes from simple starting materials via a cascade Michael addition/Pictet–Spengler reaction and amidation reaction. In addition, the whole process, losing only one molecule of water and alcohol, has a high atomic economy.

The efficient construction of a C–S bond is one of the important topics in organic synthesis. In this work, a cross-dehydrogenative coupling reaction between ether and thiophenols or thiols under electrochemical conditions was studied, and the acetal-O,S products were obtained in moderate to good yields. A free radical coupling mechanism was proposed. The reaction provided a simple protocol for the formation of C(sp³)–S bonds under transition-metal- and chemical oxidant-free conditions, and will have a good application prospect in organic synthesis and drug synthesis.

Transition-metal-free synthesis of diversely substituted 4-sulfenyl-5-aminopyrazoles was developed under mild conditions through NaI-mediated three-component reaction of β-ketonitriles, disulfides, and hydrazines. The pyrazole products were constructed via consecutive cleavage of C–O and S–S bonds and recombination of C–N and C–S bonds. The methodology features broad substrate scope, mild transition-metal-free conditions, and easy manipulation.

We have introduced a sustainable approach for the photoinduced oxidative formylation of N,N-dimethylanilines using a phenalenyl-based photocatalyst. The methodology exhibits tolerance to a variety of electron-donating and -withdrawing groups as well as to diverse functional groups, specifically offering a selective and efficient pathway for the N-formylation. Using visible light, this photochemical technique proves to be an environmentally friendly, scalable, and milder alternative strategy. The mechanistic insights were gained through a series of spectroscopic techniques, including electron paramagnetic resonance, steady-state fluorescence, and fluorescence lifetime studies. Postfunctionalization was also completed and has the potential to be used in various applications.

A facile method with simple starting materials, including enaminones, α-diazo esters, and nitriles, has been developed for the direct synthesis of N,N-diacyl glycine esters via visible light photocatalysis. The reaction involves a novel carbon–carbon bond cleavage in enaminones, leading to products with high tolerance to the variability of the substructures among all three components.

An efficient and mild Cu(I)-catalyzed Michael-type conjugate addition for 2-nitro glycals to access O-, S-, and C-glycosides with high stereoselectivity is reported. Under optimized conditions, nitrogalactals achieved high α-selectivity, whereas nitroglucal predominantly gave β-selective glycosides. The method is further demonstrated with other Michael-type substrates, including 2-formyl glycals and 3-keto glycals. Initial mechanistic investigations using NMR and supported by DFT calculations suggest that the reaction proceeds via a preorganized complex that positions the nucleophile close to the double bond to promote the Michael-type addition, in a manner analogous to enzyme-catalyzed processes. Moreover, the versatility of this synthetic approach was exemplified in the stereoselective synthesis of a mucin-type glycopeptide and the chemoselective one-pot synthesis of a trisaccharide.

A BINOL-derived chiral phosphoric acid (R)-1 was shown by kinetic profiling to be deactivated during the catalytic bromoesterification of cyclohexene. The products of the deactivation were identified as diastereoisomeric phosphates (R,1R,2R)-3a and (R,1S,2S)-3b and are formed via an alkene bromophosphatation process where the phosphate of 1 behaves as a competitive nucleophile, as confirmed by authentic preparations of 3a and 3b from a stoichiometric bromophosphatation reaction. HPLC separation of the diastereoisomers gave pure 3a whose absolute and relative configurations were proven by single-crystal X-ray diffraction. The ³¹P{¹H} NMR spectrum of phosphate 3a displayed four resonances despite 3a having just one phosphorus atom, and combined VT-NMR and DFT analysis revealed this to be a consequence of rotational isomerism about the 9-phenanthrene (Ar) bearing C3,3′–Ar bonds. Moreover, kinetic studies using variable time normalization analysis (VTNA) of the catalytic cyclohexene bromoesterification showed first order kinetics in all reactants. The amount of phosphates 3a and 3b formed under catalytic bromoesterification conditions was quantified, enabling tracking of the temporal catalyst 1 concentration and hence elucidation of first order kinetics in catalyst 1. A catalytic cycle consistent with these observations is proposed.

The enantioselective, palladium-catalyzed reaction of benzylamine with (E)-1,3-diphenylallyl ethyl carbonate was examined with 12 different chiral ligands across a range of scaffold types. In 8 out of 12 cases, the observed enantiomeric excess was 36–92% higher when DBU or Cs₂CO₃ was added. Nucleophile crossover experiments between the N-benzyl-1,3-diphenylallylamine product and 4-methoxybenzylamine mechanistically linked the changes in enantioselectivity to reformation of the η³-allylpalladium intermediate. In the crossover reactions with 9 out of 12 chiral ligands, 10–75% less elimination to 1-phenylbutadiene was observed with Cs₂CO₃ than with DBU. Analysis of percent crossover vs percent completion of the simultaneous reaction of 1-phenyl-3-methylallyl ethyl carbonate in the crossover experiment revealed that (1) the formation of the 1,3-diphenylallylpalladium intermediate frequently occurred before the reaction of 1-phenyl-3-methylallyl ethyl carbonate was complete, (2) the addition of DBU or Cs₂CO₃ suppressed formation of the 1,3-diphenylallylpalladium intermediate, and (3) the less polar toluene and THF solvents resulted in less or slower formation of the 1,3-diphenylallylpalladium intermediate than the more polar DCM and DMF solvents.

The acid-controlled single-component retro-aldol/Michael addition cascade reaction and [4 + 2] cycloaddition of benzofuran-derived azadienes (BDAs) are reported for the first time. Under the conditions of trifluoromethanesulfonic acid as the catalyst and with the addition of water, BDAs initiate the retro-aldol reaction, followed by a 1,4-Michael addition, yielding (arylmethylene)bis(dibenzofuran) products with excellent yields and broad substrate applicability. This represents the first application of BDAs in a retro-aldol reaction. In contrast, in the absence of water and with boron trifluoride etherate as the catalyst, BDAs undergo a [4 + 2] cycloaddition reaction, constructing the spiro[benzofuran-2,3′-benzofuro[3,2-b]pyridine] framework with high yields and diastereoselectivity. The method features mild conditions and high atom economy, and provides a new approach for constructing benzofuran scaffold derivatives.

Peptides and peptidomimetics have gained increasing interest as therapeutics due to their unique properties as small molecules and proteins. Herein, we report the pyridyloxy-directed Pd (II)-catalyzed C(sp²)–H alkynylation and olefination of tyrosine residues in peptides with high chemo- and site-selectivity. This method achieved the functionalization of tyrosine at any position of the amino acid for alkynylation and olefination. Furthermore, this approach can be used to synthesize peptide–biomolecule conjugates.

We report a ruthenium-catalyzed decarboxylative direct mono-2-pyridination of α,β-unsaturated carboxylic acids, offering a selective method for synthesizing 2-(1-arylalkenyl)pyridines. Under redox-neutral conditions, the reaction demonstrates broad substrate scope, high functional group tolerance, and significant potential for further derivatization. Mechanistic studies reveal that selective activation of the allylic C(sp³)–H bond, directed by the pyridine group, underpins the observed mono-2-pyridination. This work provides an efficient and selective strategy for the catalytic decarboxylative transformation of α,β-unsaturated carboxylic acids, expanding the toolbox for functionalizing pyridine derivatives.

Outlined here are photoelectrocyclization reactions of substituted phenylpyridylcyclohexenones leading to the synthesis of dihydrobenzoquinolines, where the substituents are important in the diastereoselectivity of the products from the reactions. For those substrates that provided mixtures of products, the incorporation of the triplet quenchers 2,3-dimethylbutadiene or Zn(OAc)₂ demonstrated that the mixtures resulted from triplet excited states or mixtures of singlet and triplet excited states. Also demonstrated is that the reductive dearomatization of the dihydrobenzoquinolines gives the corresponding dehydropiperidine scaffold, as are present in members of the ergot alkaloid class of natural products.

A novel and efficient dual-catalysis strategy using nickel and palladium has been developed for the cross-coupling of halostibines with aryl triflates to form C(sp²)–Sb bonds. This approach shows a wide substrate scope and high functional group tolerance and could be conducted on a gram scale. The synthesized arylstibines also could be arylation reagents reacting with alkyl and phenyl alkenes to form olefins and ligands to regulate the hydrogenation of diphenylacetylene. In addition, synthesized arylstibine 3q also shows satisfactory anticancer activity against cancerous MDA-MB-231 cells.

1,2,4-Triazine-3,5(2H,4H)-diones are widely present in various drug molecules and bioactive molecules. A visible-light-driven C–H alkylation of 1,2,4-triazine-3,5(2H,4H)-diones via 1,2-hydrogen-atom transfer (1,2-HAT) of amide radicals is first reported, providing an environmentally friendly and sustainable pathway to enrich the structural and functional diversity of 1,2,4-triazine-3,5(2H,4H)-diones. This novel protocol is characterized by mild and metal-free reaction conditions, an operationally simple method, and good functional group tolerance. To our delight, other heterocycles, such as isoquinoline and coumarin, also undergo alkylation reactions to construct C(sp²)-C(sp³) bonds via infrequent 1,2-HAT under current conditions.

Herein, we present a protocol for the construction of functionalized quinolines, i.e., 3-acyl-4-(2,2,2-trifluoro-ethyl)quinolines (ATFQLs) 4, from ortho-vinyl enaminones and 1-(trifluoromethyl)-1,3-benzo-[d][1,2]-iodaoxol-3(1H)-one, which was catalyzed by FeCp₂ and promoted by FeCl₃ (Lewis acid) additives in solvents (i.e., acetonitrile and toluene). This strategy first utilized the FeCp₂-catalyzed functionalization of alkenes with trifluoromethyl radicals. The intermediate formed was captured by the ortho-iodobenzoate substrate, yielding intermediate 3, which then underwent the FeCl₃-catalyzed elimination of ortho-iodobenzoate at a higher temperature to form an α,β-unsaturated intermediate. The subsequent intramolecular Michael reaction of the intermediate yielded the final target compound 4. In summary, a series of ATFQLs 4 were synthesized through the formation of two bonds (C═C and C–C).

We herein report a dual visible-light photoredox- and copper-catalyzed Z-selective allyl trifluoromethylation reaction of allylamine by using trifluoromethylpyridinium salt (TFSP) as the trifluoromethyl radical precursor. Various thermodynamically disfavorable allyl trifluoromethylated cis-enamides were accessible with moderate to good isolated yields. Cuprous oxide or copper nanoclusters were crucial as the co-catalyst for this transformation.

Here, we reported the synthesis of an ortho-phenylene bridged cyclic tetra(benzo[c][1,2,5]thiadiazole) (3) by stepwise Suzuki–Miyaura couplings. Subsequent oxidation of 3 yielded a two-sided fused product 4, identified as an ortho-phenylene bridged cyclic triphenyleno[1,2-c:7,8-c′]bis([1,2,5]thiadiazole) dimer. The structures of 3 and 4 were confirmed by high-resolution mass spectroscopies (HRMS) and NMR techniques. Their photophysical and electrochemical properties were fully characterized by ultraviolet–visible (UV–vis), fluorescence spectroscopy, cyclic voltammetry, and density functional theory (DFT) calculations.

The Alder-ene reaction of the C–C bond in bicyclo[1.1.0]butanes would provide a unique and efficient synthesis route for cyclobutene frameworks. Herein, we report a regio- and diastereoselective Alder-ene reaction of bicyclo[1.1.0]butanes with β-fluoroalkyl-α,β-unsaturated ketones, giving a wide variety of cyclobutenes with two contiguous centers and diene products. The reaction features atoms and step economies and exhibits broad substrate scope. Several downstream transformations of these cyclobutenes were performed.

Ru-catalyzed stereoselective asymmetric hydrogenation of multifunctionalized ketones has been a formidable challenge, and few related successful works have been reported. Herein, we report our research on Ru-catalyzed asymmetric hydrogenation of chiral δ-hydroxy-β-keto acid derivatives, which achieves excellent diastereoselectivity (up to >99% de). This procedure provides a new route for the synthesis of pure syn- and anti-3,5-dihydroxy acid derivatives, which serve as key intermediates in natural products and drug molecules, such as statins.

Functionalized 3,6-dihydro-2H-thiopyrans are synthesized in moderate to good yields from α-diazo-β-diketones and vinylthiiranes under Cu(hfacac)₂ catalysis and microwave irradiation via [5 + 1] annulation. The reaction mechanism includes a tandem sequence of the Cu-carbenoid generation from α-diazo-β-diketones, nucleophilic attack of vinylthiiranes to the carbenoids, and subsequent [2,3]-sigmatropic rearrangement. The process is a carbene-induced ring expansion of vinylthiiranes.

In this study, we reported the utilization of vinylsulfonium salt as a highly efficient dipolarophile, leveraging the facile leaving ability of its sulfide moiety, to engage in a [3 + 2] cycloaddition with N-amino(iso)quinolinium salts. This approach facilitates the construction of various C₁/C₂-unsubstituted pyrazolo(iso)quinoline skeletons. The transformation is conducted under catalyst- and external oxidant-free conditions. Furthermore, the extended gram-scale reaction demonstrates the practical applicability of the developed protocol.

Herein, we developed a novel radical cascade phosphorylation/cyclization strategy to access phosphorus-containing diazocine-fused carbazoles in moderate to good yields, offering expanded opportunities for the exploration of biologically active molecules. This method features metal-free photochemical tandem, mild conditions, broad substrate scopes, and scale-up ability. Mechanistic experiments implied that this photocatalyzed phosphorylation/cyclization reaction was realized by a sequence of EnT/SET/SET/radical addition/cyclization/SET/deprotonation processes.

Trifluoromethyl ketones (TFMKs) readily form stable hydrates and hemiketals in solution, allowing them to interact with biomolecules as hydrogen-bond donors. This interaction is governed by both the hydration equilibrium and the intrinsic hydrogen-bonding strength for a given compound. The hydrogen-bond-donating abilities for aryl, heterocyclic, and alkyl TFMKs were experimentally determined by using UV–vis titrations with a colorimetric sensor. Values were also adjusted based on the percent hydrate present in solution to provide insight into the hydrogen-bond-donating ability of the hydrate species.

In this article, we provide an extended substrate scope and more detailed mechanistic studies of an operationally simple and generally applicable arene nitration that we previously reported. This method utilizes safe and inexpensive Fe(NO₃)₃•9H₂O as the nitro source in easily recyclable HFIP and obviates the need for corrosive acids (HNO₃ + H₂SO₄). As a result, we speculated that it could serve as an effective substitute for the traditional mixed acid approach under most scenarios due to its operational simplicity. A general guidance for the application of this method was provided.

An efficient strategy for the construction of 3-sulfenylindoles and 3-arylindoles based on a one-pot relay Sc(III)/base-promoted Michael addition/cyclization/aromatization process has been developed. Different types of nucleophiles (thio- and carbon nucleophiles) react with aza-alkynyl o-quinone methides (aza-o-AQMs) generated in situ from 1-(o-aminophenyl)prop-2-ynols to afford the indole derivatives in moderate to excellent yields. This method displays the advantages of mild conditions, simple starting materials, and broad substrate scope.

An organocatalytic cascade reaction of 2-ethylidene 1,3-indandiones and isatylidene-malononitriles has been achieved using quinine as the catalyst. The unexpected vinylogous Michael addition at the β position of isatylidene-malononitriles, followed by aldol cyclization, 1,2-addition of alkoxide to nitrile, and [1,3]-O-to-N rearrangement, leads to the generation of unique spiro-bridged heterocyclic compounds containing amide, indanone, and oxindole moieties in good to excellent yields with high diastereoselectivity.

An efficient bifunctional ionic-liquid-induced electrochemical C–H arylation of quinoxalin(on)es with aryltriazenes has been developed. The reaction utilizes aryltriazenes as stable arylation reagents and ionic liquids as promoter and electrolyte. Various arylated quinoxalin-2(1H)-ones, quinoxaline and 2-methyldibenzo[f,h]quinoxaline were assembled in modest to excellent yields under mild, metal- and oxidant-free conditions. The developed protocol features simple operation, good functional group tolerance, good selectivity, product derivatization, and practical gram-scale synthesis in batch and continuous-flow processes.

A highly effective oxidation/annulation reaction between 2-isocyanoacetates and 2-(3,4-dihydroisoquinolin-2(1H)-yl)malononitriles has been successfully developed to give substituted pyrrolo[2,1-a]isoquinoline derivatives with moderate to good yields in a one-pot manner.

A sustainable, photocatalytic approach for the synthesis of oxindoles and chroman-4-ones was developed using carboxylate salts as radical precursors and FeCl₃ as a catalyst. The reaction proceeds via a decarboxylative radical cyclization mechanism triggered by ligand-to-metal charge transfer under visible light irradiation, operating efficiently at room temperature. This method demonstrates excellent substrate scope, including the use of various alkyl carboxylates, and functional group tolerance and offers a scalable pathway for gram-scale synthesis, highlighting its practical application.

Azobenzenes are proven to be one of the most successful molecular photoswitches applied across different fields such as organic chemistry, materials science, cosmetics, and pharmaceuticals. Such a widespread implementation is possible because of their photochromic properties contingent upon the substitution pattern and aryl-core nature. In recent endeavors of molecular design, replacing one or both phenyl rings with heteroaromatics turned out to be a good strategy to access compounds with improved photoswitching properties, as well as to expand molecular diversity. One of the challenges related to the design of new azobenzene photoswitches is that it often includes the synthesis of large libraries of compounds due to limited methods for prediction of their properties. Herein, we present a computationally driven workflow for the design and synthesis of a novel class of azobenzene photoswitches, heteroaryl azobenzenes with N-bridgehead heterocycles─pyrazolo[1,5-a]pyrimidine and 1,2,4-triazolo[1,5-a]pyrimidine. A small library of heteroaryl photoswitches was synthesized, and their photochemical properties were evaluated. Subsequently, these results were used to validate a computational approach, which included the in silico evaluation of a large library of designed photoswitch candidates leading to the synthesis of a new photoswitch with improved spectral properties, red-shifted λ_max values.

Thianthrenium salts have emerged as one of the most versatile reagents, gaining significant popularity within the synthetic community for their utility in the construction of C–C and C–X (X = N, O, S, P, halogens) bonds. The use of photoredox and transition metal catalysis with thianthrenium salts for C–C and C–heteroatom bond formation is well established. However, most of these methods require elevated temperatures, expensive catalysts, and ligands under stringent conditions for effective execution. In contrast, the photocatalysis- and transition-metal-free approaches for constructing C–C and C–X bonds using thianthrenium salt derivatives have become increasingly sought after. In this regard, electron-donor–acceptor (EDA)-complex reactions have emerged as a powerful strategy in organic synthesis, eliminating the need for photocatalysts under visible light irradiation. EDA-complex photochemistry exploits the electron-acceptor properties of thianthrenium salts, facilitating the rapid generation of radical intermediates via the C–S bond cleavage. These radical intermediates play a pivotal role in enabling a variety of valuable C–C and C–X formations. In this Perspective, we highlight significant advances in the EDA-complex-mediated reactions involving thianthrenium salts with mechanisms, substrate scope, and limitations for constructing C–C and C–heteroatom bonds. For the sake of brevity, the article is organized into five main sections: (1) Nitrogen-based donor reactions, (2) Oxygen-based donor reactions, (3) Sulfur-based donor reactions, (4) Phosphorus-based donor reactions, and (5) π-based donor reactions, with a focus on C–C, C–S, C–B and C–P bond formations.

The ideal deuteration, for organic synthetic chemists, might include the use of a cheap deuterium source, mild operating conditions, and diverse transformations. We developed an umpolung sequence for the reductive deuteration of aldehydes/ketones, affording synthetically useful monodeuterated phosphinates. The further one-pot transformation and plausible mechanism of this reaction were studied.

An efficient photocatalytic method for the synthesis of carbonyl compounds through the oxidation of benzyl C–H bonds was developed. A series of acetophenone derivatives were successfully synthesized by utilizing a bisphosphonium salt catalyst and molecular oxygen as the oxidant. Preliminary mechanistic studies indicated that the reaction mechanism involved a free-radical pathway.

Rhodium(I) promotes a [4 + 1] assembly mode with a vinylallene substrate and CO, leading to the formation of a five-membered ring structure. In striking contrast, palladium(0) catalyzes a more complex [4 + 4 + 1] mode leading to a nine-membered cyclic ketone. The underlying mechanisms that govern this contrast in assembly modes remain unclear, even in today’s date, presenting a major challenge to the further development of efficient reactions. Our computational study reveals that Rh adopts a square pyramidal geometry with CO. This is in contrast to Pd, which prefers a trigonal planar geometry. A stronger metal–CO interaction is detected in Rh than in a Pd intermediate, making the [4 + 1] mode more preferable in Rh than in Pd. The transition state for C–C coupling between two vinylallene has a significantly distorted tetrahedral core in the case of Rh, while Pd retains a stable trigonal planar structure, making the [4 + 4 + 1] reaction less favorable in Rh than in Pd. By conceptualizing and transferring the critical features of Pd to Ni systems, we have rationally designed a Ni-catalyzed [4 + 4 + 1] version that combines the desirable reactivity of Pd with the cost-effectiveness and abundance of Ni, aligning with the growing demand for more sustainable and atom-efficient strategies in synthetic organic chemistry.

In the presence of Hantzsch ester and with JohnPhosAuCl/AgOMs as catalysts, a series of indole-fused iminosugars were obtained in good yields by the intramolecular reductive coupling reaction of iminosugar C-glycoside, in which the terminal alkyne could be coupled with indole and further reduced to methyl. The substrates of iminosugar C-glycosides were conveniently prepared by a three-component reaction of tosylated/mesylated sugar, propargylamine, and indole derivatives. The advantages of this protocol are its simplicity and efficiency in constructing the complex indole-fused iminosugars.

The herbindoles are cyclopent[g]indole alkaloids whose structures incorporate a fully substituted benzenoid ring and, as such, have served as useful platforms for the testing and refinement of methods for the construction of highly substituted indoles. Herein we report efficient and convergent total syntheses of four herbindole alkaloids, including the first enantioselective total synthesis of trans-(+)-herbindole A. The pivotal step in the synthetic strategy is the application of our vinylketene-based benzannulation in which a thermal Wolff rearrangement generates a vinylketene which combines with an ynamide derivative in the first step of a pericyclic cascade that produces a highly substituted aniline intermediate primed for cyclization to form the cyclopent[g]indole ring system. Subsequent cross-coupling reactions allow for the elaboration of a common precursor to herbindoles of the A, B, and C series.

Direct acylation of heteroarenes with aldehydes has been established through a photoinduced hypervalent iodine-mediated cross-dehydrogenative coupling reaction. The reaction proceeds through the in situ generation of nucleophilic acyl radicals from aldehydes via acyl C–H hydrogen atom transfer (HAT), followed by a Minisci-type reaction with heteroarenes. The developed reaction system proved to be suitable for cross-coupling a diverse range of heterocycles and aldehydes.

Fluorination has demonstrated the potential to improve the physicochemical and enzymatic properties of carbohydrates. Hydrotrifluoromethylation is an emerging reaction to introduce trifluoromethyl groups. However, the hydrotrifluoromethylation of glycals has been challenging because of the lack of regioselectivity and stereoselectivity. Herein, we describe an efficient, highly selective, and broadly applicable photoinduced hydrotrifluoromethylation strategy of glycals using cost-effective sodium trifluoromethanesulfonate to give 1,2-dideoxy-2-trifluoromethyl sugars.

An easy approach to the enantioselective synthesis of five-, six-, and seven-membered ring-fused cyclopentadienes (85–99% ee) is based on the Au(I)-catalyzed cycloisomerization of enantiomerically pure or enriched propargyl vinyl ethers, which occurs with complete central-to-axial-to-central chirality transfer. DFT calculations show that the formation of a nonplanar σ-Au(I)-pentadienyl cation intermediate having a helical configuration, which quickly cyclizes to form the target cyclopentadiene, accounts for the lack of erosion of the initial optical purity. From a synthetic point of view, when the cyclopentadienes are subjected to a quick 1,5-H shift and cannot be isolated as pure regioisomers, they can be trapped in situ by suitable dienophiles during or immediately after the gold(I)-catalyzed cycloisomerization to form more complex polycyclic compounds. The synthesis of an enantiomerically pure α-tertiary amine was realized to demonstrate the usefulness of this approach.

Reaction of 2-arylpyridines with α,β-unsaturated imines in the presence of 2.5 mol % of [Cp*RhCl₂]₂ and 10 mol % of AgSbF₆ in acetone affords allylated 2-arylpyridines with an enamine unit located in the allyl segment. This method features ortho-monoallylation selectivity and Z-selectivity of the C–C double bonds, is applicable to a wide range of substrates, and is compatible with air and functional groups such as halides, CF₃, COOMe, OH, MeO, and ketal groups.

A novel and robust deconstructive functionalization reaction of spiro-dihydroquinazolinones with sulfenylating reagents in the presence of base has been realized under visible light irradiation. This reaction enabled the direct ring-opening of unstrained cyclic ring systems, producing skeletally diverse functionalized quinazolinones with moderate to good yields. A range variety of sulfenylating reagents including diaryl disulfide, thiosulfonate, dithiosulfonate and 1-[(trifluoromethyl)thio]-2,5-pyrrolidinedione were compatible for this transformation. In addition, diaryl diselenide and selenosulfonate could also couple with spiro-dihydroquinazolinones to form C–Se Bonds. Mechanistic studies revealed that the reaction proceeds via a radical–radical coupling pathway.

Planar tricyclic aromatics and azaheteroaromatics are of significant interest to organic chemists in the field of materials science owing to their excellent photoconductivity, electroluminescence and fluorescence properties enabled by their rigid extended π-conjugation. Furthermore, tricyclic azaheteroaromatics are effective ligands for organometallic catalysis and a prominent drug discovery framework. Herein, we present the first one-step synthesis of a less-accessible tricyclic fluorophore comprising a 5,6-difluoro-2,9-diarylpyrimido[5,4-h]quinazoline core entailing the regiospecific tandem condensation of tetrafluoroterephthalonitrile and derivatives of benzamidine hydrochloride in the presence of potassium carbonate or cesium carbonate under mild conditions. Single-crystal X-ray diffractometry studies confirmed the structure of the 5,6-difluoro-2,9-diarylpyrimido[5,4-h]quinazolines, and various interactions such as π–π stacking. Spectroscopic measurements, including ultraviolet–visible (UV–vis) and fluorescence spectroscopy, of the synthesized pyrimido[5,4-h]quinazolines revealed that they have excellent fluorescence properties both in the solution and solid states, displaying red-shifted maximum fluorescence wavelengths in the solid state compared to those in the solution state. Density functional theory (DFT) calculations and electrochemical analyses revealed that the introduction of an electron-withdrawing group, such as a halogen, stabilized the energy levels. Thermogravimetric (TG) analysis indicated high decomposition temperatures for 5,6-difluoro-2,9-diarylpyrimido[5,4-h]quinazolines, confirming their favorable thermal stability. Finally, the halochromism of 5,6-difluoro-2,9-diarylpyrimido[5,4-h]quinazolines arising from the protonation of the amino group and/or pyrimidine backbone is described.

An iron-catalyzed ring-opening multicomponent reaction of cyclopropyl alcohols with alkenes and N-heteroarenes involving aryl C(sp²)–H functionalization was developed. This protocol facilitates the regioselective introduction of both the β-carbonyl moiety and an N-heteroarene group across the C═C bond of the alkene, thus allowing a straightforward, efficient, and facile access to 5-heteroarene ketones. In this process, this strategy relies on β-carbonyl alkyl radical formation from the ring-opening of cyclopropyl alcohols, addition across C═C bonds, and heteroaryl C(sp²)–H functionalization cascades. This general approach displays excellent selectivity control and broad functional-group tolerance.

A convenient, visual detection system for environmental monitoring of amines and acyl-transfer reactions is based on the fate of the excited state of photoresponsive dithienylethene derivatives, where the disappearance of color provides a measure of the extent of acyl transfer and, therefore, the amount of amine present.

Here we report a photoinduced [3 + 2] radical cyclization reaction of α-diazodifluoroethane sulfonium reagent with hydrazones to give the corresponding N-amino-4-difluoromethyl-1,2,3-triazoles. This transformation proceeds under simple blue light irradiation conditions without the need of photocatalyst. Preliminary mechanistic studies indicate that the formation of an electron donor–acceptor (EDA) complex between electron-deficient α-diazo sulfonium triflate and electron-rich hydrazone operates as the key mediator.

Direct editing of quaternary carbon remains highly challenging. In this study, we computationally investigated a palladium-catalyzed quaternary carbon-editing strategy using density functional theory (DFT) to elucidate its principal characteristics and address key mechanistic issues. A quaternary carbon-editing mechanism driven by sequential Pd migration was established. The results indicate that the total free energy barrier for the transformation is 29.5 kcal mol⁻¹, which is reasonable under the studied reaction conditions, with 1,3-Pd^IV migration identified as the rate-determining step. Distortion−interaction (D/I) analysis revealed that smaller distortion energy is responsible for the selective palladation. These calculations confirm that 1,3-Pd^IV migration is kinetically more favorable than 1,3-Pd^II migration. Selectfluor can effectively lower the barrier to 1,3-Pd^IV migration, thereby facilitating the conversion. Furthermore, the calculations indicate that the amide bond in the starting reactant (1) plays a critical role in this strategy, particularly in selective palladation and 1,3-Pd migration. Notably, we discovered a novel mechanism involving 1,2-methyl/Pd^IV dyotropic rearrangement and β-hydride elimination. This process exhibits a significantly lower free energy barrier, with methyl migration and HF elimination occurring simultaneously to form a C═C double bond. Thus, these findings enhance the understanding of quaternary carbon-editing strategies and can potentially provide theoretical support for future research.

In this work, we report a gold-catalyzed intramolecular cyclo-isomerization of but-2-yn-1-ols for the construction of 2,3-dihydrofurans under mild reaction conditions. The gold catalysis is enabled by a bifunctional phosphine ligand, and the reaction tolerates a range of substituents and exhibits good efficiencies.

In this study, a series of novel pyrene-based triphenylamine (TPA) and its derivatives (4,4′-dimethoxytriphenylamine, TPA-OMe) were synthesized from a newly developed chemical intermediate, bromopyrene. This approach provides a unique opportunity to systematically investigate the effects of the substituent number and position on their photophysical properties. The results demonstrate that the molar absorption coefficients and fluorescence quantum yields of these pyrene derivatives significantly increase with the number of TPA or TPA-OMe units, exhibiting excellent light-harvesting antenna characteristics. The introduction of TPA or TPA-OMe units at the 1,6-positions induces a blue shift in fluorescence while having minimal impact on the absorption bands in solution. Single-crystal X-ray diffraction analysis and solid-state fluorescence spectroscopy reveal that the steric hindrance effect of TPA-OMe groups suppresses complex intramolecular interactions, thereby preserving the antenna properties of these derivatives. Furthermore, concentration-dependent and time-resolved fluorescence spectra provide insights into the molecular aggregation behavior and energy transfer processes. The findings of this study offer a new molecular strategy for designing efficient artificial light-harvesting antenna systems and lay a theoretical foundation for their applications in energy conversion.

A one-step and facile strategy to synthesize dibenzo[b,f][1,5]diazocine-6,12(5H,11H)-diimine and its analogs via the construction of an eight-membered ring has been established using o-aminobenzonitrile or o-phenylenediamine/phthalonitrile derivatives as raw materials. Twelve compounds, including 9 new compounds, have been synthesized in yields ranging from 62–95%. Five new compounds of 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-diimine derivatives have also been synthesized in yields of 35–52%. Furthermore, the reaction between arylnitriles and various amines was also efficiently established under similar reaction conditions. Finally, a reasonable mechanism involving sodium as a proper base to initiate the cyclization process was proposed.

In this work, we report an electrochemical method for the straightforward preparation of scarcely accessible sulfinimidate esters from readily available sulfonamides, thiophenols, and alcohols. Mechanistic experiments show that sulfur oxidation at the anodic surface generates an electrophilic intermediate, which subsequently undergoes nucleophilic substitution. Moreover, sulfilimines can be obtained in moderate-to-excellent yields when thioethers are used as the S-donor instead of thiophenols via a dehydrogenateive imination process. This method is also characterized by mild reaction condition, operational simplicity, high atomic economic efficiency, easy later drug synthesis, and modification, as well as scaling up to a gram scale.

Aminotriazole is a privileged structural motif in the design of various thermostable and insensitive energetic materials. A series of 3-nitro-1H-pyrazole-5-yl-bridged/fused 4,5-diamino-4H–1,2,4-triazoles was prepared via the cycloaddition of carboxyl pyrazole as a raw material. These newly synthesized compounds and their corresponding salts were fully characterized by chemical analysis (single-crystal X-ray diffraction, infrared, NMR, and mass spectroscopy) as well as experimental tests (thermostability and sensitivities). Their detonation properties (detonation velocity, detonation pressure, etc.) were determined with the EXPLO5 program on the basis of crystal density and calculated heat of formation with the Gaussian 09 suite. These pyrazole-triazoles show very high thermostabilities (T_d > 320 °C) and low mechanical sensitivities (IS ≥ 25 J, FS ≥ 288 N) due to intermolecular hydrogen bonding interactions in polycyclic triazoles. In particular, tricyclic 3a displays an ultrahigh decomposition temperature of 371 °C, surpassing that of 2,2’,4,4’,6,6’-hexanitrostilbene (HNS) and can be used as a candidate for heat-resistant explosives. Dinitroamino compounds 2 (P_CJ = 38.58 GPa, V_det = 9268 m s^–1) and 2d (P_CJ = 36.15 GPa, V_det = 8913 m s^–1) were found to show excellent detonation performance, with 2 being comparable to 1,3,4,7-tetranitro-1,3,5,7-tetrazocane (HMX). Furthermore, compound 1 exhibits desirable detonation properties (P_CJ = 34.74 GPa, V_det = 9284 m s^–1), high thermostability (333 °C), and low sensitivities (IS > 40 J, FS > 360 N), making it a promising HMX replacement. This study supports the superiority of utilizing the polycyclic pyrazole-triazole system in the development of new high-energy insensitive energetic materials.

The stereodirecting effect of various distal benzoyl esters on the anomeric selectivity in galactopyranosylations was investigated. It was found that esters on O-6 of galactosyl donors of the phenyl thioglycoside type had a negligible influence on the anomeric selectivity. Instead, α-selective galactosylations were observed with 4-O-benzoyl, 3,4-di-O-benzoyl, and 4,6-di-O-benzoyl protected galactosyl donors, with the highly electron-withdrawing p-nitrobenzoyl (pNO₂Bz) protecting group providing the most α-selective galactosylations. Furthermore, the α-selectivity was enhanced by replacing the thiophenyl aglycon functionality with the highly reactive cyclohexyl aglycon functionality. These findings enabled the successful synthesis of the biologically relevant α-d-Gal(1→4)Gal linkage. The obtained results do not suggest distal participation as a course for the observed anomeric selectivities.

Polynitrogen-containing scaffolds are of major interest for many applications. To optimize and improve the potential of these scaffolds, it is important to be able to easily introduce and modulate the substituents, regardless of the number and position of the nitrogen atoms in the structure. Therefore, the synthetic approach ideally requires mild experimental conditions and an expanded scope of application. To this end, a versatile and efficient synthesis of [6-5-6] tricyclic derivatives of pyridopyrazolopyrazine, dipyridopyrazole, and pyridopyrazolopyrimidine types was undertaken at room temperature. Against all odds, the key oxidative cyclization step was successfully applied to two electron-poor heteroaromatic partners, and theoretical calculations were performed to rationalize the proposed mechanism for the N–N bond formation. Measurements of the fluorescence properties showed the strong impact of the number and position of nitrogen in the tricyclic scaffold. Among the seven families studied, pyridopyrazolopyrazine offers the best fluorescence properties in terms of brightness.

We herein report a one-pot, three-component coupling of arylhydrazine HCl salts with aryl aldehydes to synthesize a triarylmethane scaffold. This reaction proceeds under simple, mild, and practical conditions without the need for an additional Bro̷nsted or Lewis acid additive, accommodating a broad substrate scope with good to excellent yields. Furthermore, this methodology can be scaled up and allows access to a diverse range of triarylmethane derivatives. Mechanistic studies suggest that the in situ formed hydrazone intermediate is essential for the high efficiency and selectivity of this transformation.

An asymmetric catalytic nucleophilic vinylic substitution (S_NV) reaction of 5H-thiazol-4-ones and nitroolefins has been developed for the synthesis of 3-alkenyl oxindoles. The enantioselective S_NV reaction with a nitro group as the leaving group proceeded smoothly to afford 3-alkenyl oxindoles in good yields with high regio- and enantioselectivity. The reaction showed broad substrate applicability. A quaternary carbon stereocenter, which was substituted by sp² carbon, was constructed under mild reaction conditions.

Computational studies on all proposed possible mechanisms of the annulations of difluorocarbene and enaminones were carried out, providing comprehensive mechanistic insights into the annulations. The results suggest that the asynchronous concerted [4 + 1] cycloaddition is more favorable for the annulation of difluorocarbene and enaminones, leading to 2,2-difluoro-2,3-dihydrofuran-3-amine derivatives and hardly to 3,3-difluoro-2,3-dihydrofuran-2-amine derivatives, which were even documented to be obtained and should be minor products. The calculation results were further verified experimentally. The current studies provide a thorough understanding of the annulation of difluorocarbene and enaminones and correct an unreasonable reported result.

The effect of water on visible-light-driven generation of aryl radicals or aryl cations from colored shelf-stable arylazo sulfonates has been investigated. Photoinduced ionic and radical decomposition of these salts compete, depending on the media used. In organic solvents, light-induced homolysis of the N–S bond occurs, and the resulting aryl radical may be used to some extent for arylation reactions. On the contrary, in neat water, radical chemistry is prevented by an efficient photoheterolysis, and a reactive aryl cation is otherwise generated.

1,2-Thiocyanoamines make up a class of important structural motifs that are found in a number of bioactive molecules and precursors to many more. Despite their synthetic significance, expedient access to this difunctionalization is rare. Herein, the development of a thiocyanoimination reagent is disclosed, taking advantage of photomediated energy transfer phenomena for the facile thiocyanoimination of alkenes. The strategy was found to be viable for σ-bonds as well, providing a generalized strategy for accessing small molecules infused with amine and -SCN.