A highly diastereoselective strain-release Doyle–Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes

Abstract

Difluoro(methylene)cyclopropanes (F2MCPs) show better anti-cancer properties and chemical reactivities compared to their nonfluorinated analogues. However, catalytic stereoselective methods to access these privileged motifs still remain a challenging goal. The Doyle–Kirmse reaction is a powerful strategy for the concomitant formation of carbon–carbon and carbon–sulfur bonds. Although the enantioselective variants of this reaction have been achieved with high levels of selectivity, the methods that control the diastereoselectivity have been only moderately successful. Herein, we report a catalytic, highly diastereoselective strain-release Doyle–Kirmse reaction for synthesizing functionalized F2MCPs using an inexpensive copper catalyst. The transformation proceeds under mild conditions and displays excellent functional group compatibility on both diazo compounds and difluorocyclopropenyl methyl sulfane/selane derivatives. Furthermore, the obtained products were efficiently transformed into valuable building blocks, such as functionalized spiroheterocycles, difluorocyclopropanes, and skipped dienes.