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

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 alpha-diazo sulfonium triflate-dihydropyridine electron donor-acceptor (EDA) complex and its subsequent use in the light-mediated catalyst-free synthesis of CF3-containing alpha-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.