Visible-light enabled synthesis of cyclopropane-fused indolines via dearomatization of indoles

Abstract

An efficient synthesis of methylene-unsubstituted cyclopropane-fused indolines via photoredox catalyzed dearomative cyclopropanation of indole derivatives was developed. A broad range of indoles bearing a variety of functional groups were compatible...

Visible Light‐Mediated Cyclopropanation: Recent Progress

“…Recently, You and Cheng developed a radical‐involved photocatalytic cyclopropanation of N‐protected indoles bearing an electron deficient group at C‐3 position using a similar strategy (Scheme 21c) [60] . Some cyclopropane‐fused indolines were produced under conditions where iodomethylsilicate was used as a methylene transfer reagent.…”

“…Recently, You and Cheng developed a radical-involved photocatalytic cyclopropanation of N-protected indoles bearing an electron deficient group at C-3 position using a similar strategy (Scheme 21c). [60] Some cyclopropane-fused indolines were produced under conditions where iodomethylsilicate was used as a methylene transfer reagent. During the entire process of the addition of halomethyl radical species to alkenes and subsequently ring closure to form cyclopropane, either the radical 3-exo-tet cyclization or anionic 3-exo-tet cyclization is inevitably accompanied by the departure of the halogen leaving group.…”

Copper/Chiral Phosphoric-Acid-Catalyzed Intramolecular Reductive Isocyanide-Alkene (1 + 2) Cycloaddition: Enantioselective Construction of 2-Azabicyclo[3.1.0]hexanes

“…2-Azabicyclo­[3.1.0]­hexane is a key structural motif in a number of marked drugs or drug candidates with a wide range of bioactivities (Scheme a). − The unique cyclopropano-annelated architecture could reduce the lipophilicity of the parent pyrrolines and regulate the N -centered basicity. , Retrosynthetic analysis of this azabicyclo scaffold leads to basically two strategies, monoring formation and double-ring formation. Among them, intermolecular cyclopropanation of pyrrole and indole derivatives with free carbene or carbenoids represents the most straightforward approach to this scaffold; however, it often suffers from regio- and stereoselectivity, limited substrate scope, and harsh reaction conditions. − Alternatively, forming the pyrroline ring was realized through Pd-catalyzed enantioselective C–H functionalization developed by Pedroni and Cramer and Peng et al Aza-palladation of an alkene and intramolecular C­(sp 3 )–H functionalization was developed by Yang et al and Bower et al, and gold-catalyzed cycloisomerizations of ene-ynamides and Kulinkovich cyclopropanation of ene-amides also proved efficient double-ring-forming approaches to construct the scaffold. Although featuring a high bond-forming efficiency, these tandem processes could only provide racemic products.…”

Cyclopropanation ofN-vinylimidesviaa redox-neutral photocatalysed radical addition/anionic cyclisation process

“…15 Inspired by the continuing interest in radical chemistry, 16,17 we envision that cyclopropanation could proceed well via reaction of N -vinylimides with halomethyl radicals enabled by photoredox catalysis. As for the CH 2 transfer reactions via a redox-neutral “radical addition–anionic cyclopropanation” process, 18,19 the generation of Zn-waste encountered in the Simmons–Smith reactions and the application of hazardous methylene transfer reagents (diazomethane) could be nicely excluded. Herein, using N -vinylimides as the radial acceptor and halomethyl silicates as the methylene transfer reagent, cyclopropanation reactions have been realized via the visible-light-driven redox-neutral photocatalysed reductive RPC process (Scheme 2).…”

“…Next, we set out to investigate the generality via using various groups as substituents at the nitrogen atom. Notably, by taking advantage of the high efficiency of iodomethylsilicate, 19 the contamination of the non-cyclized Giese-type addition product could be alleviated. As shown in Table 3, along with N -Boc- N -acetyl enamides, N -Boc- N -propionyl enamide is amenable to affording the desired product 9a in 86% yield.…”