Rhodium(II)-Catalyzed Strain-Enabled Stereoselective Synthesis of Skipped Dienes

Skipped dienes are not only present in fatty acid primary metabolites and natural products but also serve as reactive intermediates in diverse chemical synthesis. Despite this, the regioselective and stereoselective synthesis of skipped dienes remains a challenging goal. Strain release in organic molecules is a powerful tool for creating chemical complexity under mild conditions. The reactivity of strained bicyclo[1.1.0]butane (BCB) systems is mainly dominated by transformations relying on their innate electrophilic reactivity. Herein, we report a rare example of the carbene-type reactivity of the BCB system based on rhodium-carbene chemistry, which enables the highly stereoselective synthesis of skipped dienes through strain release. The reaction is compatible with a diverse range of functional groups on both diazo compounds and BCBs and could be applied successfully to complex structures, providing highly valuable and functionalizable skipped dienes. The functional groups introduced during the reaction served as synthetic handles for downstream manipulations. The high stereoselectivity observed has been rationalized based on DFT calculations, which suggests that the reaction is likely proceeding via a concerted mechanism, and noncovalent interactions between the metallocarbene and BCB mainly control the observed exclusive selectivity.