Stereoselectivity in reactions of atropisomeric lactams and imides

A range of reactions of cyclic lactam systems is described in which an atropisomeric C-N axis controls the stereochemical outcome of ring substitution or addition. In the case of enantiopure menthol adducts, substitution via N-acyliminium intermediates occurred with essentially complete control. However, the range of nucleophiles that participate in the reaction is very limited and at present the removal of the N-aryl substituent is problematic. A six-membered enamide is of moderate configurational stability and the axis exerts synthetically useful levels of control over enolate alkylations of the system. A novel Lewis acid mediated enamide arylation process was identified.