Search

A visible-light-induced synthesis protocol for silylmonofluoroalkanes is described. The silylation of alkenyl fluorides using (trimethylsilyl)silanes as organosilicon reagents proceeds well under mild conditions via a sequential photoinduced single-electron transfer and protonation process. The protocol shows a broad substrate scope, transition-metal-free conditions, and high functional group tolerance. A wide variety of silylmonofluoroalkanes were obtained in generally good yields (up to 82%).

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

A selective three-component 1,4-difluoroalkylesterification of 1-aryl-1,3-dienes enabled by dual photoredox and copper catalysis is described. This protocol uses commercially available CF 2 -reagents as radical precursors and carboxylic acids as oxygen-based nucleophiles, providing access to difluoroalkylated allylic esters. This protocol could be extended to intramolecular two-component 1,4-difluoroalkylesterification to access 3-substituted benzobutyrolactones. Preliminary mechanistic studies support a radical process.

A three-component 1,2-aminooxygenation reaction of 1,3-dienes by dual photoredox and copper catalysis is described. This protocol uses N -aminopyridinium salts as N-centered radical precursors and nucleophilic alcohols as oxygen sources, providing modular and practical access to 1,2-aminoalkoxylation products with good yields and regioselectivity. Preliminary mechanistic studies support the radical property of the reaction and the involvement of N-centered radical intermediates.

A metal-free, photoredox-catalyzed three-component cyanoalkylfluorination of alkenes under mild and redox-neutral conditions is reported. This protocol features use of readily available alkenes, oxime esters, and cost-effective nucleophilic fluoride reagents, giving diverse cyanoalkylfluorinated products with generally good yields. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for cyanoalkylfluorination of pharmaceutically relevant molecule-derived alkene.

A visible-light-driven photoredox-catalyzed multicomponent reaction of 2-vinylanilines, sulfonyl chlorides, and sulfur ylides is described. This protocol features redox-neutral mild conditions, a broad substrate scope, and good functional group tolerance, providing access to various sulfonated 2,3-disubstituted indolines. The product can be transformed to a diverse range of functionalized indoles by a selective aromatization/nucleophilic substitution process. Mechanistic investigations suggest that both sulfonyl chlorides and sulfur ylides serve as radical sources, and the reaction proceeds through a sequential radical addition/addition/thermal S N 2-substitution process.

A visible-light-driven, copper-catalyzed C(sp 3 )-O coupling of benzylic radicals with phenols is described for the first time. This operationally simple and robust process features mild conditions, broad scope, and high functional-group tolerance, enabling the construction of a diverse range of cyanoalkylated aryl ethers (33 examples). Key to this protocol is the dual role of copper salt that acts not only as a photosensitizer but also as a cross-coupling catalyst.

A visible light photoredox-promoted and nitrogen radical catalyzed [3 + 2] cyclization of vinylcyclopropanes and N -tosyl vinylaziridines with alkenes is developed. Key to the success of this process is the use of the readily tunable hydrazone as a nitrogen radical catalyst. Preliminary mechanism studies suggest that the photogenerated nitrogen radical undergoes reversible radical addition to the vinylcyclopropanes and N -tosyl vinylaziridines to enable their ring-opening C-C and C-N bond cleavage and ensuing cyclization with alkenes.

Catalytic enantioselective chemical reactions involving highly reactive radical species remain largely unexplored. We report herein for the first time a novel enantioselective radical ring-opening cyanation of redox-active oxime esters by dual photoreodox and copper catalysis. This mild protocol shows good functional group tolerance and broad substrate scope, producing a wide range of optically active alkyl dinitriles with high yields and excellent enantioselectivities, which are difficult to access traditionally.

A light-driven, metal-free, and iminyl radical-mediated ring-opening C-C bond cleavage/addition cascade of O -4-methoxybenzyl oxime ethers and alkenes is described for the first time. The reaction shows a broad substrate scope and high functional group compatibility with both components, giving the corresponding valuable oxo nitriles in generally good yields. Key to the success of this protocol is the generation of cyclic iminyl radicals from the O -4-methoxybenzyl oxime ethers via a photocatalytic hydrogen atom transfer (HAT) process. The proposed main pathway is also supported by the preliminary mechanistic studies.

The first cobalt-catalyzed deaminative alkoxycarbonylation reaction was described for the conversion of readily available primary alkyl amines to synthetically versatile esters with moderate to high yields. This transformation shows good functional group compatibility and can serve as a powerful tool for the modification of alkyl amine-containing complex natural products and drug molecules.

A formal [3 + 2]-cycloaddition reaction of 2 H-azirines with nitrosoarenes has been achieved under irradiation by visible light with the assistance of organic dye photoredox catalyst. This method utilizes nitrosoarenes as efficient radical acceptors and provides a green and powerful method for a series of biologically important 1,2,4-oxadiazole derivatives in moderate to good yields.

A photoinduced, copper-catalyzed three-component radical cross-coupling of cycloketone oxime esters, alkenes, and terminal alkynes is described for the first time. Key to the success of this process was the integration of photoinduced iminyl radical-mediated C-C bond cleavage with the conceptual simplicity of copper-catalyzed radical cross-coupling. This protocol provides access to cyanoalkyl-containing propargylic compounds in good yields.

A neutral nitrogen radical-mediation strategy, wherein the existing N-H moiety of substrates serves as a neutral nitrogen radical precursor to enable room-temperature intermolecular radical difunctionalization of styrenes under photoredox catalysis, is reported. The reaction shows high functional group tolerance and substrate scope with respect to both components, giving the corresponding products with generally good yields. Preliminary control experiments and DFT calculations are performed to explain the reaction mechanism.

A catalyst-controlled acylation reaction of β-ketoesters was developed for the first time by combining visible-light photoactivation with Lewis acid or base catalysis. By employing a NiCl 2 ·glyme complex with a bis(oxazoline) ligand as the Lewis acid catalyst, C-acylation products are exclusively achieved, while utilizing pyridine or DABCO as the Lewis base catalyst affords O-acylation products with complete regioselectivity. A range of β-ketoesters with satisfactory structural diversity were suitable for this transformation, demonstrating the functional group compatibility of the method, which was attributed to the mild reaction conditions. This success is heavily built upon the visible-light-induced Wolff rearrangement and the unique catalytic activation modes, and thus, this work significantly expands the applications of ketene chemistry.

A general and efficient Pd/phosphoramidite thioether complex-catalyzed asymmetric N-allylic alkylation of hydrazones with allylic acetates has been developed for the first time. The reaction allows for the preparation of various valuable N-substituted hydrazones with generally good yields and excellent enantioselectivities. Minor structural modification of the ligand resulted in opposite enantiomers, enabling enantiodivergent synthesis of products by the same catalytic system.

The first example of a Pd(OAc) 2 -catalyzed ring-forming alkene aminoaroylation of unsaturated hydrazones and sulfonamides is described. This protocol features the use of diaryliodonium salts as both oxidants and aryl sources, thus enabling mild reaction conditions, good chemoselectivity, a broad substrate scope, and high functional group tolerance. A wide range of synthetically and biologically important functionalized dihydropyrazoles and isoxazolidines have been obtained in good yields.

A copper-catalyzed Friedel-Crafts propargylation/hydroamination/aromatization sequence is described. In the presence of a catalytic amount of CuI, this sequential reaction can convert ethynyl benzoxazinanones and indoles into a diverse set of 3,3'-biindoles with high efficiency and selectivity. Moreover, the synthesis of other indole-heteroaryl molecules and the catalytic asymmetric formation of axially chiral 3,3'-biindoles are demonstrated.

A palladium-catalyzed decarboxylative coupling of enol carbonates with diarylmethyl electrophiles that are derived from secondary benzylic alcohols has been developed. This method allows the generation of a variety of β-diaryl ketones through an efficient and highly stereospecific coupling. In addition, detailed mechanistic insight into the coupling suggests that the reaction is a rare example of an intramolecular decarboxylative coupling that proceeds without crossover between reactants.

Efficient and enantioselective radical difluoroalkylation and perfluoroalkylation reactions of β-ketoesters were successfully developed through an asymmetric photoredox and nickel catalysis cascade. This protocol provides R f -containing quaternary stereocenters in up to 67% yield and 95:5 er with ethyl iododifluoroacetate and perfluoroalkyl iodides (C 3 F 7 I and C 4 F 9 I) as radical sources under extremely mild conditions.

A dual visible light photoredox and nickel-catalyzed cross-coupling reaction of 2-arylaziridines and potassium benzyltrifluoroborates is described for the first time. This strategy features high functional group tolerance, exclusive regioselectivity for reaction at the more hindered C-N bond, easily accessible substrates, and mild redox-neutral reaction conditions. A variety of diversely substituted β-substituted amines are obtained in generally good yields.

A visible-light photocatalytic decarboxylative alkyl radical addition cascade reaction of acrylamide-tethered styrenes for the synthesis of benzazepine derivatives is described. This protocol features broad substrate scope, excellent functional group tolerance, and mild reaction conditions, affording the seven-membered rings in good yields. This method was also applied for efficient grafting of the benzazepine scaffold into the pharmaceutically active ursolic acid scaffold.

A silver(I) and base-mediated [3 + 3]-cycloaddition reaction of in situ generated C,N-cyclic azomethine imines with in situ formed aza-oxyallyl cations is reported. This one-pot cycloaddition process shows broad substrate scope an excellent functional group tolerance and provides the corresponding biologically important isoquinoline-fused triazines in good to excellent yields.

A ligand-free, palladium-catalyzed aminoarylation reaction of the unactivated alkenes in β,γ-unsaturated hydrazones is described. This protocol enables efficient and simultaneous formation of C(sp 3 )-N and C(sp 3 )-C(sp 2 ) bonds under mild conditions, providing a practical and general approach to various diversely substituted dihydropyrazoles in generally good yields, without the use of any stoichiometric external oxidant.

Polycyclic indolines are the common and core structural motif of many indole alkaloids that usually exhibit biological activities. Here, we describe two copper-catalyzed cascade reactions between propargylic carbamates and indoles. By doing so, one-step and divergent synthesis of structurally distinct polycyclic indolines, quinoline-fused indolines, C(3a)-indolyl furoindolines, and pyrroloindolines was achieved in high synthetic efficiency and selectivity.

The palladium-catalyzed branch- and enantioselective allylic amination of vinyl benzoxazinones was accomplished through controlling the hydrogen bond direction. This protocol provides a rapid and efficient route for synthesizing an important building block, chiral amino alkene, from widely available aliphatic amines in 64 → 99% yields with up to 99% ee. Furthermore, this transformation and the accompanying products were utilized to develop one-pot reactions through dual catalysis, affording chiral indolines with good synthetic efficiency and excellent enantiocontrol.

A novel photocatalytic hydrazonyl radical-mediated radical cyclization/allylation cascade reaction of β,γ-unsaturated hydrazones is developed using allyl sulfones and Morita-Baylis-Hillman adduct as allyl sources, which provides an efficient and practical access to various diversely functionalized dihydropyrazoles and tetrahydropyridazines. The reaction is enabled by controllable generation of hydrazonyl radicals via an oxidative deprotonation electron transfer strategy and selective trapping of the resultant C-centered radicals under visible light irradiation.

A general and efficient visible light photocatalytic α-amino carbon radical-based cascade reaction of aroylhydrazones has been described. This protocol tolerates a wide array of α-silylamines and aroylhydrazones to afford the corresponding diversely functionalized hydrazide-containing chroman-2-ones and dihydroquinolin-2-ones in generally good yields with excellent diastereoselectivities.

A general visible light induced photoredox-catalyzed radical trifluoromethylation/cyclization cascade of β-aryl-β,γ-unsaturated hydrazones and oximes is described. The protocol enables an efficient access to various densely functionalized and biologically important CF3-containing dihydropyrazoles and isoxazolines with generally high yields.

A novel [3 + 2] cycloaddition/oxidative aromatization sequence via visible light-induced photoredox catalysis is disclosed. It provides a general synthetic route to 2,4,5-trisubstituted oxazoles from easily accessible 2H-azirines and aldehydes under mild reaction conditions. The potential of this strategy was further demonstrated by the rapid synthesis of a cyclooxygenase-2 inhibitor as well as the success of employing electron-deficient alkenes and imines as the reaction partners.

A general and efficient Pd/sulfoxide-phosphine complex-catalyzed direct asymmetric N-allylic alkylation of indoles has been developed to allow for the preparation of various N-allylated indoles in generally good yields with excellent enantioselectivities. This catalytic system could also be extended to other N-containing heterocycles with good results.

An unprecedented three-component coupling reaction of arynes, α-bromo carbonyl compounds, and DMSO triggered by insertion of arynes into the S═O bond of DMSO has been developed. The reaction can generate a wide range of multisubstituted aryl methyl thioethers in good yields, wherein DMSO serves as both methylthiolation reagent and oxygen source.

A formal [4 + 1]/[3 + 2] cycloaddition sequence of sulfur ylides and alkene-tethered nitroolefins has been developed. The use of (R)-binol-derived chiral sulfide leads to an asymmetric process that allows the construction of oxa- and aza-angular triquinanes in good to excellent diastereo- and enantioselectivities.

A highly efficient approach to indolo [1,2-a]quinoxaline derivatives through a Pd-catalyzed regioselective C-H olefination/cyclization sequence has been developed. This transformation has a wide range of substrates with various functional groups, and the corresponding heterocyclic products were obtained in good yields., (© 2012 American Chemical Society)

An asymmetric nucleophilic addition/protonation reaction of 3-substituted oxindoles and ethyl 2-phthalimidoacrylate has been described. This strategy can give direct access to C(γ)-tetrasubstituted α-amino acid derivatives bearing 1,3-nonadjacent stereocenters with up to 98% yield, 94:6 dr, and >99% ee. Dual activation is proposed in the transition state, and the opposite enantiomers can be obtained simply by changing cinchonidine-derived catalyst to the cinchonine analogue.

A catalytic asymmetric aza-Michael-Michael addition cascade of anilines to nitroolefin enoates in the presence of chiral bifunctional thiourea catalysts has been disclosed. This reaction provides a mild and efficient approach to polysubstituted chiral 4-aminobenzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities.

A highly enantioselective organocatalytic intermolecular conjugate addition of oximes to β-nitroacrylates has been developed. The highly functionalized adducts obtained are valuable precursors for asymmetric synthesis, as demonstrated by the synthesis of β(2,2)-amino acids and oxazolidin-2-ones.

A hydrogen bonding-mediated double Michael addition-aromatization cascade of 2-propenylindoles and nitroolefins has been disclosed. The methodology allows an efficient synthesis of diverse and structurally complex tetrahydrocarbazoles in good to excellent enantioselectivities and diastereoselectivities.

An atom-economic organocatalytic asymmetric Michael reaction of alpha,beta,beta-trisubstituted olefins has been successfully developed. The reaction exhibits excellent enantioselectivities under low loading of catalysts, and the conjugate addition products are valuable for the synthesis of novel beta(2,2)-amino acids and beta-peptides.

Efficient rhodium(I)-catalyzed regioselective direct arylation and alkenylation of aromatic C-H bonds has been realized with aromatic carboxylic and cinnamic anhydrides as the coupling partners via decarbonylation and C-H activation under phosphine-free conditions.

t-BuOK was found to be an effective promoting reagent for tandem ring-opening/closing reactions of various N-Ts aziridines and aryl propargyl alcohols to afford dihydroxazine derivatives in moderate to good yields. A plausible reaction mechanism has been proposed.

An enantioselective organocatalytic intramolecular ring-closing Friedel-Crafts-type alkylation of indolyl alpha,beta-unsaturated aldehydes has been developed. This powerful new strategy allows enantioselective access to THPIs and THBCs in a straightforward and atom-economical manner.

[reaction: see text] A series of new pyrrolidine derivatives were prepared directly in very good yields, from the substrates containing a basic or nucleophilic N atom via ring-closing enyne metathesis reaction under mild reaction conditions. Moreover, the reaction occurs smoothly without the presence of ethylene gas.

[reaction: see text] Readily tunable and bifunctional L-prolinamides as novel organocatalysts have been developed, and their catalytic activities were evaluated in the direct asymmetric Aldol reactions of various aromatic aldehydes and cyclohexanone. High isolated yields (up to 94%), enantioselectivities (up to 99% ee), and anti-diastereoselectivities (up to 99:1) were obtained under the optimal conditions.

Lewis acid assisted ring-closing olefin metathesis (RCM) of chiral diallylamines, using the second generation RCM ruthenium-based catalyst, leads to enantiopure pyrrolidine derivatives in 79-93% yields under very mild conditions. The scope of the olefin metathesis has been expanded. [structure: see text]