Asymmetric Synthesis of Vicinally Bis(trifluoromethyl)-Substituted 3,3′-Pyrrolidinyl Spirooxindoles via Organocatalytic 1,3-Dipolar Cycloaddition Reactions

Abstract

Under bifunctional squaramide and thiourea organocatalysis, a series of vicinally bis(trifluoromethyl)-substituted 3,3′-pyrrolidinyl spirooxindoles were successfully synthesized via 1,3-dipolar cycloaddition reactions of 3-(trifluoroethylidene)oxindoles with diethyl 2-((2,2,2-trifluoroethyl)imino)malonate and N-(2,2,2-trifluoroethyl)isatin ketimines. The highlight of this protocol is the efficient construction of the vicinally bis(trifluoromethyl)-substituted pyrrolidine unit of spirooxindoles, including multiple contiguous stereogenic centres, in excellent yields and stereoselectivities.