The merger of vinyl-N-triftosylhydrazones and silver catalysis to enable stereoselective vinylcyclopropanation of alkenes

Abstract

Despite extensive synthetic efforts, the application of vinyl- N -sulfonylhydrazones as a vinylcarbene precursor remains a persistent challenge in carbene chemistry, owing to the competitive formation of pyrazoles through [1,5] self-cyclization. Here, we report a strategy to address this long-term issue by combining vinyl- N -triftosylhydrazones and silver catalysis. This strategy inhibited the formation of pyrazoles and offered a highly electrophilic silver vinylcarbenoid species, thereby establishing a powerful silver-catalyzed stereoselective vinylcyclopropanation of alkenes. We found that diverse alkenes and vinyl- N -triftosylhydrazones are well suited for this protocol, affording a variety of vinylcyclopropanes in high yield with excellent stereoselectivity. The usefulness of this method was further showcased in gram-scale synthesis, late-stage modification, and total synthesis of bioactive molecules. DFT calculations disclosed that both the easy decomposition of vinyl- N -triftosylhydrazones and the weak coordination of silver play a crucial role during the vinylcyclopropanation of alkenes. • Electrophilic silver vinylcarbenes generated in situ from vinyl- N -sulfonylhydrazones • Highly cis -stereoselective vinylcyclopropanation of alkenes • Detailed mechanistic investigations Vinyl- N -sulfonylhydrazones are the most ideal and highly desirable vinylcarbene precursors due to their ready availability, great stability, and operational safety. However, their application in organic synthesis remains a long-standing challenge because they easily undergo the self-cyclization to form pyrazoles as the main side reaction. Here, we report a strategy to address this long-term issue by combining easily decomposable vinyl- N -triftosylhydrazones and silver catalysis. This strategy offered a highly electrophilic silver vinylcarbenoid species, thereby establishing a powerful stereoselective vinylcyclopropanation of alkenes. The usefulness of this method was further showcased in gram-scale synthesis, late-stage modification, and total synthesis of bioactive molecules. More important, the undesired reactivity of vinyl- N -sulfonylhydrazones was completely bypassed, which should seed the creation of new catalytic transforms based on metal vinylcarbenes. A powerful stereoselective vinylcyclopropanation of alkenes was achieved by the merger of easily decomposable vinyl- N -triftosylhydrazones and weakly coordinated silver catalysis, in which the inherent propensity of vinyl- N -sulfonylhydrazones to undergo intramolecular cyclization to form pyrazoles was totally suppressed. The usefulness of this methodology has been demonstrated by broad substrate scope, high product yields, and excellent cis -diastereoselectivity, as well as the successful applications in the late-stage modification and the total synthesis of bioactive molecules.