Trifluoromethyl-2-Isoxazoles via Phase-Transfer Catalysis

Significance

Shibata and co-workers report a catalytic asymmetric synthesis of trifluoromethyl-substituted 2-isoxazoles 3, an industrially important compound class which includes powerful agrochemicals and promising drug candidates. Cognizant of the difficulty in synthesizing 1 via the traditional approaches, such as 1,3-dipolar cyclo-additions, the authors developed a highly efficient and enantioselective cinchona alkaloid catalyzed cascade reaction of hydroxylamine and enones under phase-transfer conditions. The reaction is proposed to be initiated by the hydroxylamine addition to the enone, and the origin of stereoselectivity was rationalized with model A obtained by computational analysis.