Role of the nitrogen atom in the complex metal hydride reduction of unhindered γ-azacyclohexanones

Abstract

Preferential hydride attack has been found to occur at the en face, which is the opposite side to the γ-nitrogen atom, of the carbonyl group in the LiAlH₄ reduction of 1-azaadamantan-4-one, whose n_N orbital is in an equatorial position. On the other hand, hydride attack occurred predominantly from the axial side of 1,2-dimethylpiperidin-4-one and 2-ketoquinolizidine whose n_N orbitals are in the axial position. The appreciable solvent effect apparent in the NaBH₄ reduction of 1-azaadamantan-4-one may be responsible for the hydrogen bond formation of the n_N orbital with the protic solvent. The stereochemistry of the complex metal hydride reduction of γ-azacyclohexanones could be explained by the difference in the non-bonding two electron stabilisation between the incipient σ_‡* bond and the antiperiplanar allylic σ_i bonds which were perturbed by the through-space and/or through-bond interaction with the remote heteroatom.