Enantioselective Alkylation of Primary C(<i>sp</i>³)–H Bonds in <i>N</i>-Methyl Tertiary Amine Enabled by Iridium Complex of Axially Chiral β-Aryl Porphyrins

A fine-tuning of enantioselective carbene insertion into primary C(<i>sp</i>³)-H bonds has been realized in challenging substrates, such as <i>N</i>-methyl unblocked aromatic and non-deactivated aliphatic tertiary amines, in which sterically demanding β-axially chiral iridium porphyrin catalysts play a crucial role. This primary C(<i>sp</i>³)-H alkylation with diazo compounds affords a series of β-chiral tertiary amines in high yields with excellent enantioselectivities. Notably, the protocol was successfully applied to the postmodification of chiral bicuculline, yielding the desired derivative with high diastereoselectivity. This approach paves a facile way for the stereodivergent derivation of chiral alkaloid natural products featuring an <i>N</i>-methyl handle. In addition, a mechanism for the reaction was proposed based on deuterium experiments and an identified cationic iridium species via HRMS analysis.