Chiral Amino Siloxy Dienes in the Diels−Alder Reaction:  Applications to the Asymmetric Synthesis of 4-Substituted and 4,5-Disubstituted Cyclohexenones and the Total Synthesis of (−)-α-Elemene

Described is a study of the preparation, reactivity, and diastereoselectivity of chiral 1-amino-3-siloxy-1,3-butadienes in the Diels−Alder reaction. These dienes were easily prepared in good yield from the corresponding enantiomerically pure substituted pyrrolidines. All the dienes described underwent cycloadditions readily with several activated dienophiles under mild reaction conditions. An amino siloxy diene containing a C2-symmetric 2,5-diphenylpyrrolidine auxiliary was found to provide high diastereofacial control, even at or above room temperature. Upon hydrolysis of the cycloadducts, 4-substituted and 4,5-disubstituted cyclohexenones were obtained with ee's ranging from 85% to >98%. A simple model based primarily on steric arguments was developed to rationalize and predict the absolute configurations of final products obtained by this sequence. The synthetic utility of the methodology was illustrated through a concise enantioselective synthesis of (−)-α-elemene. The synthesis also served to establish the absolute stereochemistry of the Diels−Alder product of the chiral amino siloxy diene and methacrolein.