C−C Bond-Forming Strategy by Manganese-Catalyzed Oxidative Ring-Opening Cyanation and Ethynylation of Cyclobutanol Derivatives

Despite the growing importance of fluorinated organic compounds in drug development, there are no direct protocols for the fluorination of aliphatic C-H bonds using conveniently handled fluoride salts. We have discovered that a manganese porphyrin complex catalyzes alkyl fluorination by fluoride ion under mild conditions in conjunction with stoichiometric oxidation by iodosylbenzene. Simple alkanes, terpenoids, and even steroids were selectively fluorinated at otherwise inaccessible sites in 50 to 60% yield. Decalin was fluorinated predominantly at the C2 and C3 methylene positions. Bornyl acetate was converted to exo-5-fluoro-bornyl acetate, and 5α-androstan-17-one was fluorinated selectively in the A ring. Mechanistic analysis suggests that the regioselectivity for C-H bond cleavage is directed by an oxomanganese(V) catalytic intermediate followed by F delivery via an unusual manganese(IV) fluoride that has been isolated and structurally characterized.

A simple and effective catalytic method to construct propargylamine was developed by using copper bromide and tert-BuOOH via a combination of sp3 C-H bond and sp C-H bond activations followed by C-C bond formation.