Atropisomeric diastereoisomers from nucleophilic attack on 8-acyl-1-naphthamides

Restricted rotation about the Ar-CO bond means that 1-naphthamides bearing chiral 8-substituents may exist as pairs of diastereoisomeric atropisomers. These atropisomers are formed with good to excellent stereoselectivity for the syn-diastereoisomer by the reaction of 8-formyl-1-naphthamides with organolithiums and Grignard reagents. The reduction of 8-acyl-l-naphthamides also proceeds with syn-selectivity. The product alcohols are prone to lactonisation and also to epimerisatiori, and some of the apparent diastereoselectivities may be the result of thermodynamic, rather than kinetic, control.