EDA complex-mediated [3 + 2] cyclization for the synthesis of CF3-oxadiazoles†

Abstract

The diazotrifluoroethyl radical is an essential and prevalent reactive intermediate in the synthesis of fluorine-containing organic molecules. Herein, we report the design and application of an α-diazo sulfonium triflate–dihydropyridine electron donor–acceptor (EDA) complex and its subsequent use in the light-mediated catalyst-free synthesis of CF₃-containing α-heteroatom 1,3,4-oxadiazoles, which was elucidated using a series of spectrometric and mechanistic experiments. This powerful transformation involves a coupling reaction between two different types of radical species and the formation of C–N and C–O bonds. Furthermore, the fundamental innovation of this work relied on an automated experimental platform to determine complementary reaction conditions. Mild conditions and excellent functional group tolerance allowed a diverse range of readily available amines and aldehydes to be efficiently converted into medicinally valuable CF₃-containing 1,3,4-oxadiazoles.