Concise and practical synthesis of C-glycosyl ketones from sugar benzothiazoles and their transformation into chiral tertiary alcohols

[Reaction: see text]. A collection of 13 unsymmetrical ketones, each one featuring a sugar (d-glucosyl, d-galactosyl, d-mannosyl, and l-fucosyl) and an aglycone moiety (phenyl, 2-thiazolyl, TMS-ethynyl, allyl, and 1-propenyl) was prepared by a uniform route based on the use of benzothiazole as a carbonyl group equivalent. Succinctly, C-glycosylbenzothiazoles readily prepared by addition of 2-lithiobenzothiazole to sugar lactones and deoxygenation, were subjected to a one-pot reaction sequence involving N-methylation of the heterocyclic ring by MeOTf, treatment of the N-methylbenzothiazolium salt with a Grignard reagent, and HgCl(2)-promoted hydrolysis of the benzothiazoline thus formed. The resulting ketones were isolated in yields varying from 35 to 80%. Treatment of the sugar ketones with various organometals containing the phenyl, 2-thiazolyl, TMS-ethynyl, or ethynyl group as a substituent afforded chiral tertiary alcohols. These addition reactions were highly stereoselective as observed by crude NMR analysis and isolation of a single epimer in high yield in each case examined. However, because of the complexity of the reagents involved, the stereochemical outcome of these reactions appears to be difficult to rationalize by simple classical steric models, thus, ab initio studies taking into account the role of the sugar fragment are advisable. An interesting synthetic elaboration of a propargylic alcohol containing the thiazole ring into a propargylic alcohol bearing the formyl and carboxylate groups is reported.