A Photochemical Strategy towards Michael Addition Reactions of Cyclopropenes

Abstract

The development of Michael addition reactions to conjugated cyclopropenes is a challenge in organic synthesis due to the fleeting and reactive nature of such strained Michael acceptor systems. Herein, the development of a photochemical approach towards such conjugated cyclopropenes is reported that serves as a strategic entry point to densely functionalized cyclopropanes in a diastereoselective fashion. The process involves the light-mediated generation of transient cyclopropenyl α,β-unsaturated esters from vinyl diazo esters, followed by an organic base catalyzed nucleophilic addition of N-heterocycles to directly access β-N-heterocyclic cyclopropanoic esters. With this synergistic approach, various trisubstituted cyclopropanes bearing N-heteroaryl and N-heterocyclic rings such as indole, pyrrole, benzimidazole, isatin, pyridinone, and quinolinone were accessed efficiently in good yield and decent to good diastereoselectivities. Further, β-indolyl cyclopropanoic acids have been synthesized and were successfully evaluated as FABP-4 inhibitors. Theoretical calculations have been performed to elucidate the mechanism, which was further supported by experimental findings.