Stereoselective Homologation–Amination of Aldehydes by Addition of Their Nitrones to C‐2 Metalated Thiazoles—A General Entry to α‐Amino Aldehydes and Amino Sugars

Abstract

AbstractA general method for the homologation of aldehydes to α‐amino aldehydes (aminohomologation) has been developed, which employs nitrones as iminium derivatives of the aldehydes. Key operations include a) the addition of a thiazole metalated at C‐2 to the N‐benzylnitrone derived from the aldehyde, b) the reductive dehydroxylation of the resultant thiazolyl N‐benzylhydroxylamine, and c) the unmasking of the formyl group from the thiazole ring. The homologation sequence was studied by employing nitrones derived from various chiral polyalkoxy aldehydes and dialdoses. The addition of 2‐lithiothiazole to these nitrones was syn‐selective, whereas the reaction with the same nitrones precomplexed with Lewis acids was anti‐selective. Hence, from each nitrone a pair of diastereoisomeric hydroxylamines was obtained. These compounds were then converted by the above sequence into α‐epimeric α‐amino aldehydes. Model elaborations of some of these products afforded the amino sugars D‐glucosamine, D‐mannosamine, D‐nojirimycin, and advanced intermediates for the synthesis of destomic acid and lincosamine.