Enantioconvergent vinylcyclopropane-cyclopentene rearrangement with vessel-controlled chemodivergence

The vinylcyclopropane-cyclopentene (VCP-CPent) rearrangement serves as a fundamental method for constructing five-membered carbocycles from vinylcyclopropanes. However, achieving enantioconvergent rearrangement of less activated VCPs remains a formidable challenge. Here we report a strategy to achieve enantioconvergent VCP-CPent rearrangement of vinyl gem-difluorocyclopropanes. Our strategy proceeds through a key vinyl fluoroallyl rhodium intermediate that is mechanistically distinct from those in previously reported pathways. Furthermore, we discovered a vessel-controlled chemodivergence in this rearrangement: the reaction forms gem-difluorocyclopentenes in plastic tubes and cyclopentenones in glass vials. This protocol demonstrates excellent chemoselectivity and enantioselectivity, delivering both products in high yields with excellent e.e. values. These products, which are difficult to synthesize by conventional methods, represent privileged scaffolds in synthetic and medicinal chemistry. Mechanistic investigations offer insights into this enantioconvergent rearrangement pathway and vessel-effected chemodivergence. In addition, preliminary biological activity study shows potential of gem-difluorocyclopentene as cyclopentenone bioisostere in medicinal chemistry.