Li ⁺ Promoted the Cyanation of Unactivated C–H Bonds Catalyzed by the Manganese Porphyrin Complex through Biomimetic Oxidation

Heme and nonheme oxygenases have been known to catalyze the oxidation of unactivated C-H bonds. In most cases, hydroxylated products are formed predominantly via the "oxygen rebound" pathway. Alternatively, under certain conditions where the "oxygen rebound" pathway is inhibited, nonhydroxylated products could be obtained. Consequently, bioinspired oxidative functionalization of unactivated C-H bond is considered as a potential application to introduce various functional groups. The cyano group is widely found in bioactive molecules and serves as a versatile building block in organic synthesis. However, direct cyanation of unactivated C-H bonds under mild conditions still remains challenging. No cyanation of hydrocarbons through biomimetic oxidative reactions has been reported yet. In this study, LiOAc acting as Lewis acid was introduced into the manganese-porphyrin-catalyzed oxidation of hydrocarbons in the presence of a cyanation source. In all cases, nitrile products were obtained as the major products (>90%) with satisfying turnover numbers, indicating the effective suppression of the "oxygen rebound" pathway in the presence of LiOAc. Mechanistic studies combined with theoretical calculations suggested that the reactive intermediate manganese(IV)-oxo porphyrin π-cation radical interacted with Li⁺, significantly inhibiting the "oxygen rebound" step. This led to the formation of a carbocation intermediate, which ultimately yielded nitrile products with a cyanation source. These findings demonstrate that redox-inactive metal ions, such as Li⁺, can modulate the reactivity of high-valent metal-oxo species, diverting the pathway from "oxygen rebound" to nonrebound processes. This strategy offers a potential route for the synthesis of nitriles from simple hydrocarbons under mild conditions.