A Photochemical Strategy towards Michael Addition Reactions of Cyclopropenes
Yaseen Hussain, R. Prasanna, Claire Empel, Deepak Sharma, Lennard Kloene, Wenyong Zhu, Astrid Kaiser, Lilia Weizel, Ewgenij Proschak, René M. Koenigs, Pankaj Chauhan
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.