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 α,β‐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. Round, like a circle in a spiral: Highly strained spiro[2,3]hexane skeletons are accessed from readily prepared starting materials through a Michael addition/ring expansion/cycloaddition cascade. The process does not require metals, proceeds through organocatalysis, can be carried out on a gram scale, and gives three continuous carbon stereocenters with good enantioselectivity and diastereoselectivity.