Stereoselective Synthesis of Enantiomerically Pure Piperidine Derivatives by <i>N</i>‐Galactosylation of Pyridones

Abstract

Abstract Stereoselective desymmetrization of 4‐pyridone has been achieved through selective N ‐galactosylation, activation of the N ‐(galactosyl)pyridone by O ‐silylation and immediate addition of Grignard compounds. Chiral piperidine derivatives, e.g. ( S )‐(+)‐coniine and (5 S ,9 S )‐(+)‐indolozidine 167B, were synthesised in enantiomerically pure form using these highly regio‐ and stereoselective reactions. After N ‐galactosylation of 2‐pyridone and O ‐silylation of the N ‐galactosyl‐2‐pyridone, addition of a Grignard compound proceeded with high 1,4‐regioselectivity and complete diastereoselectivity, to furnish 4‐substituted 5,6‐dehydro‐2‐piperidones. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)