Construction of enantiopure imine bridged benzo[c]azepinones by a silver(i) and chiral N-heterocyclic carbene multicatalytic reaction sequence of N′-(2-alkynylbenzylidene)hydrazides and cyclopropanecarbaldehydes

Abstract

A novel and efficient method for the synthesis of enantiopure bridged benzo[c]azepinone compounds has been developed by metal/N-heterocyclic carbene multicatalysis. Catalyzed by CF₃CO₂Ag and a triazolium-derived chiral N-heterocyclic carbene in a cascade, the reaction between N′-(2-alkynylbenzylidene)hydrazides and cyclopropanecarbaldehydes proceeded efficiently under mild conditions to produce enantioselectively and diastereoselectively bridged heterocyclic compounds, (1R,4R,5S)-4-(acylethyl)-11-aryl-2-tosyl-1,2,4,5-tetrahydro-5,1-(azenometheno)benzo[c]azepin-3-ones, generally in good yields with 99–99.9% ee and 11 : 1–>50 : 1 dr.