The ‘off-template’ problem: towards a general solution

Abstract

Wittig reaction of the t-butyldimethylsilylated C-3 ketone methyl 4,6-O-benzylidene-2-O-(t-butyldimethylsilyl)-α-D-ribo-hexopyranosid-3-uloside leads exclusively to C-2 alkenes, providing an efficient synthesis of these potentially useful intermediates. Alternatively, the corresponding t-butyldiphenylsilyl ether, prepared with complete regiospecificity from methyl 4,6-O-benzylidene-α-D-glucopyranoside, gives a C-3 alkene on oxidation and Wittig reaction. Deprotection, hydrogenation and cyclization of this product leads to the cis-fused butyrolactone, methyl 4,6-O-benzylidene-3-deoxy-3-(ethoxycarbonyl)-2,3-butyrolacto-α-D-allopyranoside, which is alkylated stereospecifically to give methyl 4,6-O-benzylidene-3-deoxy-3-(prop-2- yloxycarbonyl)-2,3-butyrolacto-α-D-allopyranoside. This procedure provides a general solution to the ‘off-template’ problem of carbohydrate-based natural product synthesis.