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An electrochemical Reformatsky‐type reaction of bromodifluoroamides with aldehydes/ketones via electron reductive umpolung is reported, leading to the generation of a series of β‐hydroxy‐α,α‐difluoro amides in moderate to good yields. This protocol tolerated a variety of commercially available alkyl ketone, alkyl and aromatic aldehydes, featuring broad substrate scope and good functional group tolerance under transition metal‐free conditions without metal reduction reagents. Control experiment indicated that the reaction proceeded via an electron reductive umpolung pathway. [ABSTRACT FROM AUTHOR]

A direct electrochemical phosphine-mediated deoxygenative [3 + 2] cycloaddition strategy for oxazole synthesis is described, employing naturally abundant and inexpensive carboxylic acids as starting materials. This method is performed in a green and sustainable catalytic system, and avoids the use of transition metals and toxic oxidants. Good functional group tolerance, the success of gram-scale experiments and the late-stage modification of drug molecules greatly highlight the potential applicability of our method. Mechanistic studies suggest that an acyloxyphosphonium ion is generated as a key intermediate via anodic oxidation, followed by nucleophilic substitution and cycloaddition with isocyanide. [ABSTRACT FROM AUTHOR]

(Deuterium‐labeled) CF2H‐ and CFH2‐moieties are of high interest in drug discovery. The high demand for the incorporation of these fluoroalkyl moieties into molecular structures has witnessed significant synthetic progress, particularly in the (deutero)hydrodefluorination of CF3‐containing compounds. However, the controllable replacement of fluorine atoms while maintaining high chemoselectivity remains challenging. Herein, we describe the development of a selective (deutero)hydrodefluorination reaction via electrolysis. The reaction exhibits a remarkable chemoselectivity control, which is enabled by the addition of different organoboron sources. The procedure is operationally simple and scalable, and provides access in one step to high‐value building blocks for application in medicinal chemistry. Furthermore, density functional theory (DFT) calculations have been carried out to investigate the reaction mechanism and to rationalize the chemoselectivity observed. [ABSTRACT FROM AUTHOR]

(Deuterium‐labeled) CF2H‐ and CFH2‐moieties are of high interest in drug discovery. The high demand for the incorporation of these fluoroalkyl moieties into molecular structures has witnessed significant synthetic progress, particularly in the (deutero)hydrodefluorination of CF3‐containing compounds. However, the controllable replacement of fluorine atoms while maintaining high chemoselectivity remains challenging. Herein, we describe the development of a selective (deutero)hydrodefluorination reaction via electrolysis. The reaction exhibits a remarkable chemoselectivity control, which is enabled by the addition of different organoboron sources. The procedure is operationally simple and scalable, and provides access in one step to high‐value building blocks for application in medicinal chemistry. Furthermore, density functional theory (DFT) calculations have been carried out to investigate the reaction mechanism and to rationalize the chemoselectivity observed. [ABSTRACT FROM AUTHOR]

A new copper/silver-co-mediated three-component bicyclization of benzene-linked 1,6-enynes with ICF2CO2Et with TMSN3 was reported, and used to produce a wide range of hitherto unreported difluorinated tetrahydroindeno[1,2-c]azepine-3,6-diones with moderate to good yields. The mechanistic pathway consists of radical-induced 1,6-addition–cyclization, oxidative addition, reductive elimination, nitrene insertion and N–O cleavage, resulting in continuous multiple bond-forming events including C–C and C–N bonds to build up a 6/5/7 tricyclic framework. [ABSTRACT FROM AUTHOR]

A tunable electrosynthesis of sulfonyl‐ and bromo‐substituted indolo[2,1‐α]isoquinoline derivatives has been disclosed. In this reaction, a variety of easily available 2‐aryl‐N‐acryloyl indoles can readily react with sulfonyl and/or bromine radicals, which are generated from arylsulfonyl hydrazides and potassium bromide respectively, to furnish the valuable sulfonyl‐ and bromo‐substituted benzindolo‐fused polycyclic compounds in moderate to good yields. Control experiment indicated that the reaction proceeds via a radical cascade cyclization pathway. This protocol features broad substrate scope and good functional group tolerance under transition metal‐free and oxidant‐free conditions. [ABSTRACT FROM AUTHOR]

Tunable halofluoroalkylation and hydrofluoroalkylation of 1,6‐enynes were first reported by switching between copper‐catalysis and photocatalysis, leading to the atom‐economic and highly stereoselective protocols toward functionalized 1‐indenones with moderate to good yields. Copper‐catalysis enabled the concomitant incorporation of two important fluoroalkyl and halo functionalities into 1‐indenone skeleton, in which fluoroalkyl bromides were transformed into (E)‐1‐indenones as a major stereoisomer while fluoroalkyl iodides oriented complete Z‐selectivity to access (Z)‐1‐indenones. Specifically, photocatalysis allowed hydrofluoroalkylation of 1,6‐enynes to access fluoroalkylated (Z)‐1‐indenones under mild conditions, in which THF behaved as a hydrogen source. These two approaches feature remarkable compatibility with a wide variety of 1,6‐enynes and fluoroalkyl halides and excellent atomic utilization. [ABSTRACT FROM AUTHOR]

A novel visible-light photocatalytic bicyclization of β-alkynyl propenones with α-bromocarbonyls for highly diastereoselective synthesis of richly decorated syn-fluoren-9-ones is described. The reaction proceeds via a radical-triggered 5-exo-dig cyclization/1,6-H-abstraction/6-endo-trig cyclization cascade and offers a new and practical method for the assembly of 6/5/6 carbocyclic skeletons via C(sp3)–H alkenylation. [ABSTRACT FROM AUTHOR]

New radical-triggered multi-component cyclizations of β-alkynyl propenones have been developed, leading to 50 examples of sulfonated 1-indenones with generally good yields and high levels of stereoselectivity. The oxidant-free azosulfonylation of β-alkynyl propenones with aryldiazonium salts and DABSO was realized under the neutral–redox conditions where TBHP enabled the direct selenosulfonylation of β-alkynyl propenones by combining sulfinic acids and diphenyl diselenide. This protocol features a broad substrate scope, high functional group tolerance and mild reaction conditions. [ABSTRACT FROM AUTHOR]