Enantioselective Synthesis-3

Alkylation of lithiated dimethyl hydrazones forms the basis of asymmetric alkylation of aldehydes and ketones. The following steps are involved.

• Formation of hydrazones of the ketone/aldehydes with a chiral auxiliary group, an amine, ((S)-1-amino-2-(methoxymethyl)-pyrrolidine (SAMP) and its enantiomer (RAMP).
• Formation of an anion using LDA.
• Alkylation.
• Removal of the auxiliary group through hydrolysis of the N-methyl quaternary salt. The following example is an illustration of the procedure.

 Alkylation of α-amino acids without loss of chirality, or using chiral auxiliary reagents have been effected as follows.

• Proline with pivaldehyde gave a single stereoisomer.
• The product was deprotonated using LDA to the chiral non racemic enolate.
• Attack on the enolate with asymmetric induction by the acetal center takes place 
  entirely on the same side of the bicyclic system.
• The product then readily hydrolyses to optically pure α-methyl proline.