Reactions of ketosulfoxonium ylides with allylic carbocations: stereoselective and direct access to highly-substituted cyclo-propanes and α-alkylated ylides

Abstract

Despite the well-documented use of sulfur ylides in organic synthesis, the reactivity of α-carbonyl sulfoxonium ylides with carbocations remains largely unexplored. Herein, we report the first reaction between sulfoxonium ylides and allylic carbocations. As a starting point, we investigated the reaction of trans-1,3-diphenyl-2-propen-1-ol with a α-carbonyl sulfoxonium ylide under various conditions aimed at generating the corresponding carbocation. We found that hexafluoroisopropanol (HFIP) efficiently promotes carbocation formation. Upon nucleophilic attack by the sulfoxonium ylide, two divergent pathways were observed: (i) intramolecular cyclization to afford a highly substituted cyclopropane as a single diastereomer, and (ii) simple deprotonation leading to α-alkylated sulfoxonium ylides. This method was successfully extended to a wide range of allylic alcohols and sulfoxonium ylides, enabling the synthesis of various highly substituted cyclopropanes. Furthermore, the developed protocol proved to be robust and broadly applicable for the synthesis of α-alkylated sulfoxonium ylides. DFT calculations were performed to gain insight into the observed diastereoselectivity, thereby providing a rationale for stereochemical control.