Aryl nitriles serve as important functional groups within a variety of pharmaceuticals and agrochemicals, thus the development of new methods for the synthesis of benzonitriles is valuable. Typically, these scaffolds are constructed using the Sandmeyer reaction or transition metal catalysis, but catalyst deactivation by cyanide is a major limiting factor in the scope of these methodologies. Herein we report the development of a novel transition metal-free cyanation of alkoxy arenes via photoredox catalysis. This method utilizes a highly oxidizing acridinium photoredox catalyst to perform a cation radical accelerated nucleophilic aromatic substitution (CRA-S<sub>N</sub>Ar) reaction. This cyanation is selective for carbon-oxygen (C–O) bond functionalization utilizing acetone cyanohydrin, an inexpensive and commercially available cyanide source, and is applicable to a range of methoxyarenes and dimethoxyarenes. Initial rate and fluorescence quenching data provide mechanistic insight into the CRA-S<sub>N</sub>Ar functionalization pathway. Furthermore, computational studies provide a model for predicting regioselectivity and chemoselectivity in competitive C–H and C–O cyanation of methoxyarene cation radicals.

Arene cyanation via cation radical accelerated nucleophilic aromatic substitution

2019 Fall National Meeting

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