Stereochemistry associated with the addition of 2-trimethylsilylthiazole to differentially protected ?-amino aldehydes. Applications toward the synthesis of amino sugars and sphingosines

The stereochemistry and synthetic utility of the addition of 2-(trimethylsily1)thiazole (2-TST, 1) to various N-protected a-amino aldehydes is described. The reactions of 1 with N-Boc-L-serinal acetonide (2) and NBoc- L-threoninal acetonide (3) are essentially anti diastereoselective (ds = 85-90%) in agreement with the Felkin-Anh model for asymmetric induction, whereas the reactions with 0-benzyl-NH-Boc-L-serinal (4) and NH-Boc-L-phenylalaninal(5a)r e syn diestereoselective( ds = 80%). The reversal of diasteremelectivity is interpreted on the basis of a proton-bridged cyclic Cram model for asymmetric induction. The anti adduct derived from the N-Boc-L-serinal acetonide (2) was subjected to thiazole-to-formyl unmasking to give a one-carbon higher homologue (Le., the 0,N-protected 8-amino-a-hydroxy aldehyde 6a). This material serves as a precursor to riboand arabino-4-amin~4-deoxn~veias a further one-carbon-chain elongation with 2-TST and to a Cm sphingosine via Wittig olefination. The above ribo-amino sugar was transformed via sequential Wittig olefiiation and reduction into a C, phytosphingosine.