Despite the significant synthetic potential of C—H oxidation, the development of small molecule catalysts that can selectively oxidize inert C(sp3)—H bonds while tolerating more reactive π-functionality remains an unsolved problem. A novel manganese catalyst, [Mn(tBuPc)], has been developed to intramolecularly aminate all types of C(sp3)—H bonds without oxidizing more reactive π-functionality, demonstrating an unprecedented balance between reactivity and selectivity for a C—H oxidation reaction. Catalyst [Mn(tBuPc)] effects the chemoselective, intramolecular amination of all types of C(sp3)—H bonds (aliphatic, allylic, propargylic, benzylic, ethereal), including strong 1° aliphatic C—H bonds and propargylic C—H bonds, while maintaining stereospecificity and high functional group tolerance. Mechanistic studies suggest that the unique reactivity and selectivity of [Mn(tBuPc)] can be attributed to its mechanism of metallonitrene C—H insertion that lies between stepwise radical C—H abstraction/rebound, observed with chemoselective base metals (e.g. iron), and concerted C—H insertion, observed with reactive noble metals (e.g. rhodium). The high reactivity of this catalyst and its application to late-stage diversification is showcased by the amination of 1° C—H bonds in pleuromutilin and betulinic acid derivatives, transformations inaccessible with previous C—H amination methods.

Highly reactive and chemoselective manganese catalyst for intramolecular C(sp3)-H amination

251st National Meeting (2016)

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