Enantioselective deprotonation of 4-tert-butylcyclohexanone by conformationally constrained chiral lithium amide bases

Conformationally rigid chiral lithium amides based on a tetrahydroisoquinoline motif have been prepared bearing a range of substituents at C1 and C3. These bases were tested in the asymmetric deprotonation reaction of 4-tert-butylcyclohexanone. Although the 1-substituted tetrahydroisoquinolines gave low enantioselectivity, the chiral bases containing a nitrogen heterocycle at C3 were found to induce high enantioselectivity (81% ee) in the presence of HMPA.