Synthesis of an optically pure 3-unsubstituted β-lactam using an asymmetric Reformatsky reaction and its conversion to cholesterol absorption inhibitors

• Published in: Tetrahedron letters 1996-06, Vol.37 (24), p.4095-4098
• Main Authors: Shankar, B.B., Kirkup, M.P., McCombie, S.W., Clader, J.W., Ganguly, A.K.
• Format: Article
• Language: English
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/0040-4039(96)00764-2

Asymmetric induction by several chiral alcohols in the reaction of their bromoaceates with imines in the presence of activated Zn (Reformatsky reaction) was studied. Trans -2-phenylcyclohexanol and phenyl menthol gave β-lactam 9, obtained by cyclizing the diastereoisomeric β-aminoesters 8, in > 99%ee. The resulting chiral 3-unsubstituted azetidin-2-one 9 was converted to 3-substituted products 11, 12, and 13 which exhibit cholesterol absorption inhibitory activity. Asymmetric induction by several chiral alcohols in the reaction of their bromoacetates with imines under Reformatsky conditions was studied. Trans-2-phenylcyclohexanol and phenylmenthol gave >99% induction. The resulting diastereoisomeric β-aminoesters 8 were cyclized to β-lactam 9 which was then converted to 3-substituted products.