Enantioselective Synthesis of Trifluoromethyl-Substituted Cyclopropanes

Significance

Trifluoromethyl-substituted, enantioenriched cyclopropanes can provide access to chiral building blocks for new drug candidates; however, only a few synthetic approaches towards these compounds have been reported so far. In this paper, a highly enantio- and diastereoselective cobalt-catalyzed cyclopropanation of alkenes with F₃CCHN₂ is reported. Importantly, the reaction was carried out in aqueous media. The methodology tolerates a wide range of styrenes, including 1,1-disubstituted derivatives. ­Diastereoselectivities up to 180:1 in favor of the trans adduct were observed, accompanied with enantioselectivities of 86-94% ee.