Manganese Porphyrins Catalyze Selective C−H Bond Halogenations

Abstract

We report a manganese porphyrin mediated aliphatic C−H bond chlorination using sodium hypochlorite as the chlorine source. In the presence of catalytic amounts of phase transfer catalyst and manganese porphyrin Mn(TPP)Cl 1, reaction of sodium hypochlorite with different unactivated alkanes afforded alkyl chlorides as the major products with only trace amounts of oxygenation products. Substrates with strong C−H bonds, such as neopentane (BDE =∼100 kcal/mol) can be also chlorinated with moderate yield. Chlorination of a diagnostic substrate, norcarane, afforded rearranged products indicating a long-lived carbon radical intermediate. Moreover, regioselective chlorination was achieved by using a hindered catalyst, Mn(TMP)Cl, 2. Chlorination of trans-decalin with 2 provided 95% selectivity for methylene-chlorinated products as well as a preference for the C2 position. This novel chlorination system was also applied to complex substrates. With 5α-cholestane as the substrate, we observed chlorination only at the C2 and C3 positions in a net 55% yield, corresponding to the least sterically hindered methylene positions in the A-ring. Similarly, chlorination of sclareolide afforded the equatorial C2 chloride in a 42% isolated yield. Regarding the mechanism, reaction of sodium hypochlorite with the Mn^III porphyrin is expected to afford a reactive Mn^V═O complex that abstracts a hydrogen atom from the substrate, resulting in a free alkyl radical and a Mn^IV—OH complex. We suggest that this carbon radical then reacts with a Mn^IV—OCl species, providing the alkyl chloride and regenerating the reactive Mn^V═O complex. The regioselectivity and the preference for CH₂ groups can be attributed to nonbonded interactions between the alkyl groups on the substrates and the aryl groups of the manganese porphyrin. The results are indicative of a bent [Mn^v═O---H---C] geometry due to the C—H approach to the Mn^v═O (dπ−pπ)* frontier orbital.