Highly Enantioselective Oxidation of Nonactivated Aliphatic C–H Bonds with Hydrogen Peroxide Catalyzed by Manganese Complexes

[Image: see text] Monosubstituted cycloalkanes undergo regio- and enantioselective aliphatic C–H oxidation with H(2)O(2) catalyzed by biologically inspired manganese catalysts. The reaction furnishes the corresponding ketones resulting from oxidation at C3 and C4 methylenic sites (K(3) and K(4), respectively) leading to a chiral desymmetrization that proceeds with remarkable enantioselectivity (64% ee) but modest regioselectivity at C3 (K(3)/K(4) ≈ 2) for tert-butylcyclohexane, and with up to 96% ee and exquisite regioselectity toward C3 (up to K(3)/K(4) > 99) when N-cyclohexylalkanamides are employed as substrates. Efficient H(2)O(2) activation, high yield, and highly enantioselective C–H oxidation rely on the synergistic cooperation of a sterically bulky manganese catalyst and an oxidatively robust alkanoic acid. This represents the first example of nonenzymatic highly enantioselective oxidation of nonactivated methylenic sites. Furthermore, the principles of catalyst design disclosed in this work constitute a unique platform for further development of stereoselective C–H oxidation reactions.