STEREOSELECTIVE HOMOLOGATION - AMINATION OF ALDEHYDES BY ADDITION OF THEIR NITRONES TO C-2 METALATED THIAZOLES - A GENERAL ENTRY TO ALPHA-AMINO ALDEHYDES AND AMINO-SUGARS

A general method for the homologation of aldehydes to alpha-amino alde hydes (aminohomologation) has been developed, which employs nitrones a s 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 gr oup from the thiazole ring. The homologation sequence was studied by e mploying 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 w ith Lewis acids was anti-selective. Hence, from each nitrone a pair of diastereoisomeric hydroxylamines was obtained. These compounds were t hen converted by the above sequence into alpha-epimeric alpha-amino al dehydes. Model elaborations of some of these products afforded the ami no sugars D-glucosamine, D-mannosamine, D-nojurimycin, and advanced in termediates for the synthesis of destomic acid and lincosamine.