Protocol Features Mild Conditions Research Articles

Photoredox-Catalyzed Multicomponent α-Sulfonylation of Terminal Alkynes.

A generality-oriented and adaptive α-sulfonylation of alkynes via photoinduced multicomponent radical cross-coupling of terminal alkynes with sulfinates and a variety of alcohols, thiophenols, or selenophenols has been explored. This protocol features mild conditions, good functional group tolerability, broad substrate scope, excellent chemo-, site-, and stereoselectivity, and applicability to late-stage functionalization. It provides a modular platform for the synthesis of value-added structurally diverse α-sulfonyl-containing multisubstituted alkenes from simple precursors.

Additive‐Free and Diastereoselective Synthesis for Trans‐Disubstituted‐2,3‐Dihydro‐Benzofurans via [4+1] Annulation between p‐QMs and TFISYs

AbstractAn additive‐free and diastereoselective [4+1] annulation between ortho‐hydroxyphenyl‐substituted para‐quinone methides and CF3‐substituted imidoyl sulfoxonium ylides is developed, providing a facile and practical route to diverse trans‐2,3‐dihydrobenzofurans with high efficiency. This protocol features mild conditions, broad substrate scope and easy to operate.

Light-promoted AIBN-catalyzed oxidative cleavage of aryl olefins to aryl ketones

A convenient light-promoted 2,2-azobis(isobutyronitrile) (AIBN)-catalyzed synthesis of aryl ketone from aryl alkenes with molecular oxygen as the oxidant was developed. A series of aryl ketone were obtained in moderate to good yields. The new protocol features mild conditions and relatively broad substrate scope. The reaction was successfully applied for the synthesis of Fenofibrate in good yield. Based on previous documents and current experimental results, a plausible mechanism is proposed.

Light-Induced 1,3-Thiosulfonylation of β,γ-Unsaturated Ketones with Thiosulfonates.

Sulfur-containing compounds exhibit potent significance in drug molecules. Thiosulfonates as 1,3-thiosulfonylation reactants to olefins have yet to be investigated. Herein, we report photoinduced 1,3-difunctionalization of β,γ-unsaturated ketones with thiosulfonates, which undergo a radical 1,2-acyl shift. The protocol features mild conditions, high regioselectivity, and 100% atom economy.

Synthesis of N-N Axially Chiral Pyrrolyl-oxoisoindolin via Isothiourea-Catalyzed Acylative Dynamic Kinetic Resolution.

The development of methods for the asymmetric synthesis of N-N axial chirality remains elusive and challenging. Here, we disclose a method for the construction of N-N axially chiral pyrrolyl-oxoisoindolins along with central chirality via the isothiourea (ITU)-catalyzed acylative dynamic kinetic resolution (DKR). Axial chirality was introduced into the acylative DKR of hemiaminals for the first time. This protocol features mild conditions with excellent yields and enantioselectivities.

Synthesis of Sulfonyl‐Containing spiro[5,5]trienones from Sodium Metabisulfite

AbstractAn efficient three‐component reaction of biaryl ynones, sodium metabisulfite and aryldiazonium tetrafluoroborates is developed. The reaction occurs at room temperature without any additives, thus offering a sustainable approach to access sulfonyl‐containing spiro[5,5]trienones. This protocol features mild conditions, broad substrate scope and high functional group compatibility, furnishing the target products in moderate to good yields. Mechanistic studies indicate that the reaction undergoes a 6‐exo‐trig dearomative spirocyclization process which is initated by an aryl radical with the insertion of sulfur dioxide.

Visible-Light-Induced Regioselective Radical-Polar Crossover 1,4-Hydrophosphinylation of 1,3-Enynes: Access to Trisubstituted Allenes Bearing a Phosphine Oxide Group.

The radical 1,4-functionalizations of 1,3-enynes have emerged as a powerful strategy for the synthesis of multisubstituted allenes. However, the phosphorus-centered radical-initiated transformations remain largely elusive. Herein, visible-light photoredox catalytic regioselective radical hydrophosphinylation of 1,3-enynes with diaryl phosphine oxides as phosphinoyl radical precursors has been realized. This protocol features mild conditions, a wide substrate scope, and good functional group tolerance, producing a diverse range of phosphinoyl-substituted allenes in moderate to good yields with high atom economy. Detailed mechanistic experiments revealed a radical-polar crossover process in the reaction.

Catalytic Kinetic Resolution of Monohydrosilanes via Rhodium-Catalyzed Enantioselective Intramolecular Hydrosilylation.

The catalytic access of silicon-stereogenic organosilanes remains a big challenge, and largely depends on the desymmetrization of the symmetric precursors with two identical substitutes attached to silicon atom. Here we report the construction of silicon-stereogenic organosilanes via catalytic kinetic resolution of racemic monohydrosilanes with good to excellent selectivity factors. Both Si-stereogenic dihydrobenzosiloles and Si-stereogenic monohydrosilanes could be efficiently accessed in one single operation via Rh-catalyzed enantioselective intramolecular hydrosilylation, employing (R,R)-Et-DuPhos as the optimal ligand. This catalytic protocol features mild conditions, a low catalyst loading (0.1 mol % [Rh(cod)Cl]2), high stereoinduction (S factor up to 152), and excellent scalability. Moreover, further derivatizations led to the efficient synthesis of uncommon middle-size (7- and 8-membered) Si-stereogenic silacycles. Preliminary mechanistic study indicates this reaction might undergo a modified Chalk-Harrod mechanism.

Catalytic Kinetic Resolution of Monohydrosilanes via Rhodium‐Catalyzed Enantioselective Intramolecular Hydrosilylation

AbstractThe catalytic access of silicon‐stereogenic organosilanes remains a big challenge, and largely depends on the desymmetrization of the symmetric precursors with two identical substitutes attached to silicon atom. Here we report the construction of silicon‐stereogenic organosilanes via catalytic kinetic resolution of racemic monohydrosilanes with good to excellent selectivity factors. Both Si‐stereogenic dihydrobenzosiloles and Si‐stereogenic monohydrosilanes could be efficiently accessed in one single operation via Rh‐catalyzed enantioselective intramolecular hydrosilylation, employing (R,R)‐Et‐DuPhos as the optimal ligand. This catalytic protocol features mild conditions, a low catalyst loading (0.1 mol % [Rh(cod)Cl]2), high stereoinduction (S factor up to 152), and excellent scalability. Moreover, further derivatizations led to the efficient synthesis of uncommon middle‐size (7‐ and 8‐membered) Si‐stereogenic silacycles. Preliminary mechanistic study indicates this reaction might undergo a modified Chalk–Harrod mechanism.

Phosphonylacylation of Alkenes Enabled by Visible-Light-Induced N-Heterocyclic Carbene Catalysis.

Herein, we report the phosphonylacylation of alkenes via visible-light-induced N-heterocyclic carbene (NHC) catalysis to afford a series of γ-ketophosphonates in moderate to good yields. This protocol features mild conditions, free of photocatalyst, and good compatibility of functional groups. The excited Breslow enolate intermediate was proposed to undergo single-electron transfer with oxime phosphonate to generate the corresponding ketyl radical and phosphonyl radical.

Transition-Metal-Free Anti-Markovnikov Hydroarylation of Alkenes with Aryl Chlorides through Consecutive Photoinduced Electron Transfer.

The hydroarylation of alkenes has emerged as a powerful strategy for arene functionalization. However, aryl chlorides remain a large challenge in this type of reaction due to the chemical inertness of the C(sp2)-Cl bond and high negative reduction potential. Herein, we report an anti-Markovnikov radical hydroarylation of alkenes with aryl chlorides via visible-light photoredox catalysis. The key reactive aryl radicals can be efficiently achieved from aryl chlorides by consecutive photoinduced electron transfer. This transition-metal-free protocol features mild conditions, a wide substrate scope, and functional group tolerance, producing a diverse range of linear alkylarenes in moderate to good yields. The reaction is proposed to proceed through a radical-polar crossover pathway.

Visible light-promoted C3-H alkoxycarbonylation of quinoxalin-2(1H)-ones or coumarins with alkyloxalyl chlorides.

Herein, we describe a green and efficient photoredox catalytic C3-H alkoxycarbonylation between quinoxalin-2(1H)-ones or coumarins and readily available alkyloxalyl chlorides under ambient conditions. A series of quinoxaline-3-carbonyl and coumarin-3-carbonyl compounds are prepared through the radical addition of in situ-generated alkoxycarbonyl radicals. Notably, this protocol features mild conditions, operational simplicity, and excellent functional group tolerance. More importantly, the carboxylated products can be readily derivatized into other important compounds that would be of great potential for the exploitation of pharmaceutically active compounds.

Synthesis of axially chiral diaryl ethers via NHC-catalyzed atroposelective esterification.

Axially chiral diaryl ethers bearing two potential axes find unique applications in bioactive molecules and catalysis. However, only very few catalytic methods have been developed to construct structurally diverse diaryl ethers. We herein describe an NHC-catalyzed atroposelective esterification of prochiral dialdehydes, leading to the construction of enantioenriched axially chiral diaryl ethers. Mechanistic studies indicate that the matched kinetic resolutions play an essential role in the challenging chiral induction of flexible dual-axial chirality by removing minor enantiomers via over-functionalization. This protocol features mild conditions, excellent enantioselectivity, broad substrate scope, and applicability to late-stage functionalization, and provides a modular platform for the synthesis of axially chiral diaryl ethers and their derivatives.

An aryl-to-alkyl radical relay arylation reaction of a remote C(sp3)–H bond using 1,4-dicyanobenzene as an electrochemical redox-mediator

In this paper, we developed an electro-reductive aryl-to-alkyl radical relay arylation reaction of a remote C(sp3)–H bond via a 1,5-HAT process. This protocol features mild conditions, simple operation, and a broad substrate scope.

Metal‐Free Arylation of Pyridine/Quinoline N‐Oxides with Indoles

AbstractWe achieved metal‐free pyridine arylations via O‐triflated pyridine N‐oxides and N‐alkylated indoles. The reactions proceeded through reactive intermediates, obtained upon treatment of pyridine N‐oxides with Tf2O, which were sufficiently activated for preferentially installing various indoles at the nitrogen‐adjacent positions of pyridine. This protocol features mild conditions, short reaction times, and ease of handling under stirring and air at room temperature. Furthermore, no transition metal is required, which renders our procedure an environmentally benign approach to pyridine arylation.

A green one-pot process for the synthesis of 1,2,4-triazole-fused heterocycles using FeBr3 catalyst and hydrogen peroxide

An environmentally benign oxidative cyclization utilizing FeBr3 catalyst and hydrogen peroxide as terminal oxidant is devised for one-pot synthesis of 1,2,4-triazole-fused heterocycles from commercially available aliphatic or (hetero)aromatic aldehydes and 2-hydrazinopyridine derivatives. The protocol features mild conditions, simple operation, air/water tolerance, short reaction time, and waste prevention, and has been demonstrated by the synthesis of 32 examples of 1,2,4-triazole-fused heterocycles bearing different substituents in moderate to excellent yields.

Visible Light‐Induced Benzylic C(sp3)−C(sp2) Defluorinative Coupling between Indole Derivatives and Polyfluoroarenes

AbstractA visible light‐induced transition metal‐free benzylic C(sp3)−C(sp2) defluorinative coupling between indole derivatives and polyfluoroarenes via the sequential electron transfer‐proton transfer (ET/PT) process has been developed, affording various polyfluorinated diarylmethanes. This protocol features mild conditions and good functional group tolerance.

Thianthrene Radical Cation as a TransientSETMediator: Photoinduced Thiocyanation and Selenocyanation of Arylthianthrenium Salts†

Comprehensive SummaryA novel transient SET mediator approach has been developed for the photoinduced radical‐radical cross coupling reaction. Using thein‐situgenerated thianthrene radical cation as the transient SET mediator, the thiocyanation and selenocyanation of aryl thianthrenium salts have been realized under the mild conditions without the need for photocatalyst or single electron donor. In comparison with the photocatalyst enabled process, the protocol features mild conditions, simple manipulation, a broad substrate scope, excellent functional group and heterocycle tolerance. Due to the feasible accessibility of aryl thianthrenium salts, this method has also been applied in the efficient synthesis of a bioactive molecule, and the late‐stage functionalization of complex arenes.

Synthesis of E-Dienyl Esters Using Acetylene as C2 Synthon

The stereoselective synthesis of dienyl esters with high atom- and step-economy has been largely unexplored. Herein, we report an efficient approach for the synthesis of E-dienyl esters via rhodium catalysis using carboxylic acid and acetylene as C2 synthon through the cascade of cyclometalation and C-O coupling. This protocol features mild conditions, excellent functional group tolerance, and exclusive E-stereoselectivity and utility in the late-stage modification of pharmaceuticals and natural products.

Visible-Light-Driven Photocatalyst-Free Deoxygenative Radical Transformation of Alcohols to Oxime Ethers.

A visible-light-driven deoxygenative cross-coupling of alcohols with sulfonyl oxime ethers has been developed by using xanthate salts as alcohol-activating groups. Upon convenient generation and direct photoexcitation of xanthate anions, a broad range of alcohols including primary ones can efficiently undergo this transformation to afford diverse oxime ethers and derivatives. This one-pot protocol features mild conditions, broad substrate scope, and late-stage applicability, without the need for any external photocatalysts or electron donor-acceptor complex formation.