Fluoroalkyl N-Triftosylhydrazones as Easily Decomposable Diazo Surrogates for Asymmetric [2 + 1] Cycloaddition: Synthesis of Chiral Fluoroalkyl Cyclopropenes and Cyclopropanes

Abstract

The development of asymmetric carbene transfer reactions using N-sulfonylhydrazones as the diazo surrogate is a long-term issue in organic synthesis since N-sulfonylhydrazones commonly require high temperatures for their decomposition to release reactive diazo compounds. We report on the use of fluoroalkyl-aryl ketone N-triftosylhydrazones as a class of N-sulfonylhydrazone capable of decomposing below 0 °C (to −40 °C). Their application in asymmetric [2 + 1] cycloadditions with alkynes and alkenes catalyzed by a chiral rhodium catalyst is described. This protocol affords a wide variety of fluoroalkylated cyclopropenes and cyclopropanes in high yields and high enantioselectivity and demonstrates broad functional group tolerance. It is noteworthy that these small-ring products feature a fluoroalkyl chiral quaternary carbon center. The origin of enantioselectivity for the cyclopropenation reaction of N-triftosylhydrazones with alkynes was rationalized by density functional theory calculations.