Titanium-mediated methylene transfer reactions on sugar esters, lactones, and uloses

Abstract

The titanium alkylidene 1, a versatile methylenating agent readily derived’ from the rather costly Tebbe compound 2, has been used in Wittig-type reactions to convert ketones into olefins and esters into vinyl ethers’. We now reportt its application to a variety of sugar derivatives that contain carbonyl and/or ester functions, with the aim of delineating the scope of the reaction with respect to blocking groups and the structure of the ketone, ester, or lactone. In order to simplify the procedure and increase the value of the method, the unpurified form of 2 was used (see Experimental). Pure, crystalline Tebbe reagent has been used by others3t4 on some aldonolactones and, where comparisons can be made, both similarities and differences were found. Reaction of the ulose 3 (X = 0) and the aldehyde 5 (R = H) with 2 gave, after chromatography, 70% and 35%, respectively, of the olefins 4’*(’ and 6 (R = H)7 in experiments that were easier to execute than the customary Wittig procedure5. Mono-esters of sugars were converted smoothly into vinyl ethers. Thus, 1,2:5,6di-0-isopropylidene-u-D-glucofuranose 3-acetate, 3-benzoate, and 3-p-chlorobenzoate gave, in good yields, the respective substituted vinyl ethers 7 (R = Me, or Ph, or ClC6H4). Each of the vinyl ethers 7 was susceptible to hydrolysis and gave methyl ketones uiu hemiacetals. The stability of these compounds towards hydrolysis increased in the order cited. Esters of glycuronic acids reacted readily with the crude 2, thereby affording a route to chain-extended sugars. The methyl glucoronate derivative 8 gave the methylene compound 9, and the methyl galacturonate derivative 5 (R = OMe) gave compound 6 (R = OMe), which needed more careful handling than 9 because it was rapidly hydrolysed on silica gel with neutral eluants to give the useful ketone 5 (R = Me). The &lactones 2,3,4,6-tetra-O-methyl-p-glucono-1,5-lactone (10, R = Me) and