Highly Enantioselective Construction of Strained Spiro[2,3]hexanes through a Michael Addition/Ring Expansion/Cyclization Cascade

We herein report a general organocatalytic enantioselective strategy for the construction of highly strained spiro[2,3]hexane skeletons from methylenecyclopropanes and a broad selection of alpha,beta-unsaturated aldehydes. The reaction proceeds through a Michael addition followed by ring expansion of methylenecyclopropanes and nucleophilic attack of an enamine to realize the construction of spiro[2,3]hexanes. Key to the success of this approach are the utilization of an electron-deficient difluoro-substituted secondary amine catalyst and the intrinsic reactivity of methylenecyclopropanes.