Mn-Catalyzed Regio- and Stereoselective C(sp3)–H Lactonization of Carboxylic Acids with H2O2

Recently, nonheme manganese complexes with bis-amino-bis-pyridylmethyl and structurally related ligands have been reported to efficiently catalyze the intramolecular C–H acyloxylation of readily available linear carboxylic (fatty) acids, directly converting those to lactones. Herein, we present the general oxidation protocol, employing H2O2 as the terminal oxidant, which allows deliberately switching the reaction selectivity between γ-lactonization, δ-lactonization, or ω-1 hydroxylation of the fatty acid in synthetically useful yields. γ-Lactonization of carboxylic acids with a linear main chain has been found to proceed enantioselectively in up to 67% ee; in addition, the activation of primary C–H sites can be efficiently performed, to yield γ-butyrolactones in up to 86% yield. The molecular mechanisms responsible for the observed γ-regioselectivity are discussed on the basis of combined experimental (reaction outcome and isotopic labeling) and quantum-chemical (DFT, DLPNO–CCSD(T)) data. The overall picture is formally consistent with the intramolecular 1,7-H abstraction at the triplet potential energy surface, followed by spin crossing to the lower-lying quintet PES, to end up with intramolecular carboxylate rebound.