Diastereoisomeric atropisomers of peri-substituted naphthamides:: synthesis, stereoselectivity and stability

8-Formyl-1-naphthamides can be made by perilithiation of 1-(dimethylaminomethyl)-naphthalene, quenching the organolithium with a carbamoyl chloride and subjecting the product amine to a Polonovski reaction. The naphthamides react stereoselectively with nucleophiles to give predominantly the syn atropisomers of the product alcohols. Oxidation gives ketones which also give mainly the syn atropisonner on reduction. The rate of thermal epimerisation of the products is high relative to 2-substituted 1-naphthamides: the barrier to Ar-CO rotation is ca. 90 kJ mol(-1). (C) 1999 Elsevier Science Ltd. All rights reserved.