Synthesis of 2-C-Branched Sugars

Abstract

<p>A range of unnatural carbohydrates (sugars) with an unusual 2-C-bromomethylene branch have been synthesised by reaction of the 1,2-cyclopropanated carbohydrate 52 with different nucleophiles. Initial work to optimise the cyclopropane ring opening in the presence of sodium allyloxide/allyl alcohol provided anomers 140 and 141 in up to 75% yield. Use of sodium thiophenolate/thiophenol provided anomeric thioglycosides 181 and 182 (76% yield, 7:2 ratio), while sodium diethylamide/ diethylamine provided anomeric glycosylamines 183 and 184 (50% yield, 1:1 ratio). Further functionalisation of the 2-C-branch of 141 was performed using various palladium-catalysed cross-coupling reactions, providing a series of products. Reaction of 140 and 141 under acidic conditions caused E-Z isomerisation of the bromoalkene forming a single anomer, 194. Efforts to obtain mechanistic information about the cyclopropane ring opening were made through attempted trapping of a cyclopropene intermediate, deuterium labelling experiments, synthesis of possible stable intermediates and reactions with internal nucleophiles.</p>