Harnessing the Reactivity of Cyclopropenes in the Synthesis of Spiroketals via Putative Generation of Donor–Acceptor Cyclopropanes

Abstract

TMSOTf-mediated 5/6-exo-trig hydroalkoxylation followed by the (3 + 2) cycloaddition cascade reaction of hydroxy cyclopropenes with aldehydes gave an expedient, stereoselective synthesis of [5.5]-and [6.5]-spiroketal derivatives. The developed protocol provides a new approach toward the synthesis of spiroketals from hydroxy cyclopropenes via a transiently generated donor–acceptor cyclopropane intermediate. These spirocyclic derivatives could be transformed to facilitate the access of intricate polycyclic heterocycles via a metal halogen exchange reaction and a copper-catalyzed C–O cross coupling reaction. The decarboxylation of the diester diastereoselectively sets the fourth chiral center of the spiroketal product.