Rhodium‐Catalyzed Enantio‐ and Regioselective Allylation of Indoles with gem‐Difluorinated Cyclopropanes

Abstract

The use of gem‐difluorinated cyclopropanes (gem‐DFCPs) as fluoroallyl surrogates under transition‐metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono‐fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem‐DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem‐DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

Palladium/Amine Dual-Catalyzed Tsuji–Trost Fluoroallylation of Aldehydes with gem-Difluorinated Cyclopropanes

“…gem -Difluorinated cyclopropanes ( gem -F 2 CPs) are specifically valuable surrogates for fluorallylation reactions, and recent years have witnessed the significant progress in the development of transition-metal-catalyzed ring-opening transformations of gem -F 2 CPs (Scheme a). , Indeed, the Fu group pioneered the first palladium-catalyzed cross-coupling of gem -F 2 CPs with a wide range of nucleophiles to furnish 2-fluoroallylic skeletons with a high stereoselectivity . The Xia group elegantly disclosed the Rh catalytic system for the functionalization of gem -F 2 CPs, while the Li group nicely reported the Pd/NHC catalytic system to afford the 2-fluoroallylic products with branched selectivity. Despite such significant progress having been made, only relatively strong nucleophiles, such as amines, alcohols, diethyl malonates, aryl boronic acids, etc., could be used.…”

Palladium-Catalyzed Regioselective Monofluoroallylation of Indoles with gem-Difluorocyclopropanes

“…However, the base was necessary for the reaction to proceed smoothly, and a limitation in the scope of the use of C3-substituted indoles was observed. Very recently, Xia and co-workers reported an efficient strategy for the highly branched and enantioselective monofluoroallylation of indoles with gem -DFCPs using rhodium catalysis (Scheme b) . This reaction exhibited a broad substrate scope, and a wide range of substituted indoles could provide the corresponding C2 and C3 vinylation products.…”