Formal [3 + 3]-Cyclization of β-Trifluoromethyl Enones and Amidines: Synthesis of 1,4-Dihydropyrimidines Featuring a CF3-Tetrasubstituted Carbon Center

Abstract

The introduction of a privileged trifluoromethyl group into targeted molecules typically exerts a profound physicochemical impact. Efficient methods for the synthesis of trifluoromethylated 1,4-dihydropyrimidines remain challenging. Herein, a base-promoted formal [3 + 3]-cyclization of β-trifluoromethyl enones with readily available amidines for accessing structurally unique 1,4-dihydropyrimidines featuring a CF3-tetrasubstituted carbon center was developed. The mild reaction, integrating heterocycle assembly and precisely regioselective trifluoromethyl group installation in a one-pot, simple, and efficient manner, demonstrates advantages including broad substrate scope, excellent functional group compatibility, good scalability, and the modification of complex molecules.