UC Berkeley

The asymmetric functionalization of unstrained C(sp3)-C(sp3) bonds could be a powerful strategy to stereoselectively reconstruct the backbone of an organic compound, but such reactions are rare. Although allylic substitutions have been used frequently to construct C-C bonds by the cleavage of more reactive C-X bonds (X is usually an O atom of an ester) by transition metals, the reverse process that involves the replacement of a C-C bond with a C-heteroatom bond is rare and generally considered thermodynamically unfavorable. We show that an unstrained, inert allylic C-C σ bond can be converted to a C-N bond stereoselectively via a designed solubility-control strategy, which makes the thermodynamically unfavorable process possible. The C-C bond amination occurs with a range of amine nucleophiles and cleaves multiple classes of alkyl C-C bonds in good yields with high enantioselectivity. A novel resolution strategy is also reported that transforms racemic allylic amines to the corresponding optically active allylic amine by the sequential conversion of a C-N bond to a C-C bond and back to a C-N bond. Mechanistic studies show that formation of the C-N bond is the rate-limiting step and is driven by the low solubility of the salt formed from the cleaved alkyl group in a nonpolar solvent.