Synthesis of Chiral Pyrrolidines by Palladium-Catalyzed Carboamination

Abstract

Reported is the asymmetric synthesis of 2-(arylmethyl)- and 2-(alkenylmethyl)-­pyrrolidines 3 via the palladium-catalyzed carbo­amination of N-Boc-pent-4-enylamines 1 with aryl and alkenyl halides 2. EDGs and moderate EWGs are tolerated on the aryl halide, although a more electron-poor substrate (4-NCC6H4Br) proved unreactive. Aryl chlorides were also found to be unreactive under the reaction conditions, whilst aryl triflates suffer from competing base-mediated cleavage of the sulfonate ester. The utility of this efficient process was illustrated by the enantio­selective synthesis of the natural product (-)-tylophorine.