Enantioselective Alkylation\nof Primary C(<i>sp</i><sup>3</sup>)–H Bonds in <i>N</i>‑Methyl\nTertiary Amine Enabled by Iridium Complex of Axially Chiral β‑Aryl\nPorphyrins

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