Installing Axial Chirality by Atroposelective C(sp³)-H Bond Oxidation

The synthesis of optically enriched multifunctionalized biaryl compounds by a non-directed atroposelective C(sp³)-H bond oxidation of 2,6-dimethyl-1,1'-biaryls is reported. The reaction is catalyzed by a novel family of manganese complexes bearing a highly structured oxidation site, which is shown to be the key factor controlling the excellent chemo- and enantioselectivity of the reaction. The system operates under mild conditions, using low catalyst loading and H₂O₂ as oxidant, enabling compatibility with configurationally labile substrates and tolerance toward a wide variety of functional groups that are typically sensitive in organometallic catalysis. The devoid of directing groups on the substrate core allows access to axially chiral biaryls (42 examples) decorated with a plethora of functionalities in high yields (up to 88%) and outstanding enantioselectivity ratios (up to >99% ee). Furthermore, the exquisite site- and enantioselective C-H oxidation activity of the catalysts enables subsequent site- and chemoselective oxidation of the second methyl group, offering a novel and versatile platform for elaboration of the biaryl core. Overall, the catalysts' activity enables recognition of methyl groups as functional groups for synthetic manipulations, showcasing the strategic use of C-H bond functionalization reactions as a powerful approach for stereoselective synthesis.