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.