‘meso-Selective’ functionalisation of N-benzyl-α-methylbenzylamine derivatives by α-lithiation and alkylation

Lithiation and methylation of amide and carbamate derivatives of α-methylbenzylamine proceeds with high diastereoselectivity in favour of meso bis-α-methylbenzylamine derivatives. Carboxylation of the intermediate organolithium is also diastereoselective, and with N-Boc p-methoxy-α-methylbenzylamine as starting material, oxidative cleavage provides a new asymmetric route to phenylglycine. Other electrophiles give a range of stereochemical outcomes, apparently depending on the stereospecificity of their reactions with a pair of diastereoisomeric organolithiums of low to moderate configurational stability.