The thiazole aldehyde synthesis

Aldehydes with diverse structural arrays are prepared by construction of carbon chains at C-2 of the thiazole ring and conversion of the heterocycle into the formyl group. Various methods are described that differ depending on the type of thiazole-based reagent employed in the initial carbon-carbon bond forming reaction leading to 2-substituted thiazole intermediates. The most common reagents are metalated thiazoles, phosphoranes, and carbonyl derivatives. On the other hand the unmasking of the formyl group from the thiazole ring is carried out by a general protocol involving a sequence of three reactions: N-methylation, reduction, and hydrolysis. The essential neutral conditions under which these reactions take place are tolerated by various hydroxy and amino protective groups and compatible with unprotected functional groups (azido, phosphonate). Some applications of these methods are illustrated by the synthesis of natural carbohydrates and carbon-linked analogues. Also, the viabili...