Asymmetric Amination of Unstrained C(sp3)–C(sp3) Bonds

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.