Structure and Reactivity of Lithiated α-Amino Nitriles

Investigations aimed at elucidating the structure of lithiated α-amino nitriles B have led to the identification of N-lithio α-amino nitrile anions as characteristic structural features. Their preparations, crystal structures, and solution structures under the reaction conditions, are described. X-ray crystal structure analyses of crystalline 3 and (S, S)-4 reveal the presence of dimeric aggregates B4 with Ci symmetry, held together by four-membered NLiNLi rings, coordinatively saturated at lithium by four THF ligands. The crystal structure of (S, S)-6 shows polymeric aggregation with dimeric subunits similar to those of 3 and (S, S)-4. The solution structure has been investigated by IR and Raman spectroscopy of 2, (S, S)-4 and (S, S)-6, by NMR spectroscopy of 3, (S, S)-5 and (S, S)-6, and by cryoscopic measurements of (S, S)-6 in THF. Trapping experiments complement the results. In THF, which constitutes the principal reaction medium, the lithiated amino nitriles B are found to exist as monomeric species B6 between −110 and +25°C. In less polar solvents, higher aggregation is presumed. NMR spectroscopic studies of 3 show that the favored orientations of the amine and phenyl groups are similar to their conformations in the solid state. In the light of the results obtained, a transition state is proposed to account for the relative topicity observed in the 1,4-additions of enantiopure lithiated α-amino nitriles (S, S)-4, (S, S)-5, and (S, S)-6 to Michael acceptors.