Catalysis-Enabled 13-Step Total Synthesis of (−)-Peyssonnoside A

We report a 13-step enantioselective and stereoselective total synthesis of (−)-peyssonnoside A, a unique diterpene glucoside with a rare and highly congested pentasubstituted cyclopropane and promising antimicrobial activity. Among the 10 steps to synthesize (−)-peyssonnosol, the aglycone of (−)-peyssonnoside A, eight transition-metal-catalyzed transformations enabled the construction of all new C–C bonds and stereocenters without involving any protecting groups. Notably, a palladium-catalyzed dearomative cyclization was used to build the C-6 spiro all-carbon quaternary center, and a counterintuitive hydrogen atom transfer (HAT)-initiated reductive olefin cross-coupling was realized to forge the pentasubstituted cyclopropane ring with excellent stereoselectivity.