Azolation of Benzylic C–H Bonds via Photoredox-Catalyzed Carbocation Generation

A visible-light photoredox-catalyzed method is reported that enables the coupling between benzylic C–H substrates and N–H azoles. Classically, medicinally relevant N -benzyl azoles are produced via harsh substitution conditions between the azole and a benzyl electrophile in the presence of strong bases at high temperatures. Use of C–H bonds as the alkylating partner streamlines the preparation of these important motifs. In this work, we report the use of N -alkoxypyridinium salts as a critically enabling reagent for the development of a general C(sp 3 )–H azolation. The platform enables the alkylation of electron-deficient, -neutral, and -rich azoles with a range of C–H bonds, most notably secondary and tertiary partners. Moreover, the protocol is mild enough to tolerate benzyl electrophiles, thus offering an orthogonal approach to existing S N 2 and cross-coupling methods.