Regioselective 2‐Imino‐1,3‐thiazolidine vs. 2‐Imino‐1,3‐oxazolidine Formation from the Vicinal sec‐Amino Alcohol of Desosamine

In order to optimize Mukaiyama reagent-induced cyclization of vicinal sec-amino alcohols of desosamine origin towards exclusive formation of N-substituted-2-imino-1,3-thiazolidines via a thiocarbamoyl intermediate, the influence of reaction conditions was studied. A novel, mild, one-pot, two-step method was developed, and the formation of N-substituted-2-imino-1,3-oxazolidines as side products was minimized. The inversion of configuration at C-2 was unambiguously established using NMR-based conformational analysis. A reaction mechanism was proposed. A test series of novel desosamine-modified 14- and 15-membered macrolides, bearing N-alkyl-2-imino-1,3-thiazolidines fused to the desosamine sugar were prepared.