Highly stereoselective cycloadditions of Danishefsky's diene to (−)-8-phenylmenthyl and (+)-8-phenylneomenthyl glyoxylate N-phenylethylimines

Abstract

Enantiopure 4-oxo-pipecolic acid derivatives were obtained by double asymmetric induction aza-Diels–Alder reactions between chiral glyoxylate N-phenylethylimines and Danishefsky's diene mediated by zinc iodide. The key to success was the use of iminoacetates possessing two chiral auxiliaries, N-(S)- or N-(R)-1-phenylethyl and (−)-8-phenylmenthyl or (+)-8-phenylneomenthyl. Adducts were formed in good yields (78–81%), with complete regioselectivity and high diastereoselectivity (87–96%). The absolute configuration of the adducts formed was unequivocally assigned through NMR, specific optical rotation and X-ray data of appropriated derivatives. These cycloadducts can serve as precursors for bioactive piperidinic azasugars and pipecolic acid derivatives.