Mechanistic insight into stereoselective carbolithiation.

This article addresses the mechanistic features of asymmetric carbolithiation of β-methylstyrenes. While often the presence of functional groups is required to obtain high enantioselectivities in carbolithiation reactions, simple β-methylstyrene also gives high selectivities in (-)-sparteine-mediated addition of alkyl lithium compounds. Computational studies on the carbolithiation of β-methylstyrene with (-)-sparteine show that the observed selectivities are the result of repulsion effects in the diastereomeric transition states between the (-)-sparteine⋅alkyl lithium adduct and the β-methylstyrene, upon approximation of the two reactants. In contrast, for the ortho-amino β-methylstyrene (E)-benzyl(2-propenylphenyl)amine (4) X-ray structure analyses of intermediate lithium amides indicate a carbolithiation mechanism in which one side of the double bond is shielded by the amide moiety, leaving only one side free for approach of the chiral alkyl lithium adduct.