Reactive azolyl intermediates: Generation via photocatalysis and synthetic utility

Abstract

We have conducted a systematic study of photocatalyst-mediated electron transfer from amines to 2-haloazoles with a particular interest in the nature, reactivity, and utility of the intermediates that can be generated. Electron transfer converts these stable molecules into reactive intermediates, whose behavior often depends entirely on the identity of the halogen that undergoes substitution. The result is both diverse chemistry and an alternative way of thinking about the chemical reactivity of these motifs. The divergent pathway is illustrated by 2-bromoazoles as well as 2-diazonium benzothiazole, which yield azolyl radicals that can be added to π-bonds. In contrast, 2-chloroazole substrates give an entirely different reaction profile, and we believe that bond formation takes place with a radical anion, rather than a radical. Under the appropriate reaction conditions, the transient reactive intermediates can be coupled with various partners to provide rapid access to new chemical methods such as alkylation, arylation and alkenylation as well as iterative synthesis of azoles and other arenes. Furthermore, since the reaction is mediated by electron transfer, minimal prefunctionalization of the coupling partners is needed, making this strategy attractive for synthesis.