Solvophobic Effect-Driven C4-Selective C-H Oxidation of Diverse Alkyl Substrates by a Macrocyclic Supramolecular Catalyst.

The selective oxidation of inert aliphatic C-H bonds remains a formidable challenge in organic synthesis, particularly at medial positions in substrates lacking directing groups. We report a macrocyclic supramolecular manganese catalyst that achieves C4-site-selective C-H oxidation across a broad substrate range by harnessing the solvophobic effect for substrate binding. It is effective on alkanes as well as more complex molecules containing functional groups such as chlorides, nitriles, esters, and protected amines, underscoring its potential for late-stage functionalization. Notably, the catalyst also provides moderate enantioselectivity, a rare feat on unfunctionalized alkanes. This macrocyclic platform offers a blueprint for the rational design of next-generation supramolecular catalysts with tunable site selectivity for C-H functionalization.