New organometallic reagents. Use of 2-(trimethylsilyl)thiazole in acyclic stereoselective strategies

Abstract

2-(Trimethylsilyl)thiazole (2-TST) is a member of a set of metalated heterocycles prepared in our laboratory for application as synthetic auxiliaries. 2-TST undergoes rapid and spontaneous carbodesilylation reactions with various C-electrophiles (ketenes, acyl chlorides, aldehydes, heteroaryl cations) producing the corresponding 2-substituted thiazoles in good yields. The addition of 2-TST to chiral aldehydes having a suitably protected asymmetric center adjacent to the carbonyl, occurs with high levels of anti-diastereoselectivity (90-95%) to give adducts which upon thiazole-to-formyl conversion liberate aldehydes having one-more carbon atom. This demonstrates the application of 2-TST as a formyl anion equivalent. The thiazole-addition-unmasking methodology (TH1AZ0LE ROUTE) is applied iteratively for the chain-elongation of D-glyceraldehyde acetonide, 4-0-benzyl-L-threose 2,3-acetonide, a-D-dialdogalactopyranose diacetonide, and N-Boc-L-seri- acetonide into series of higher homologues bearing all anti-1,2-diol units. Aldehyde homologues from protected L-serinal are employed as precursors to sphingosines and phytosphingosines. The synthesis of all possible pentoses and hexoses starting from D-glyceraldehyde acetonide is underway by combination of the anti-addition of 2-TST with an oxidation-reduction sequence providing the syn-adducts. © 1990, IUPAC.