Regioselective Acetolysis of Highly O‐Benzylated Carbohydrates Promoted by Iodine or an Iodine/Silane Combined Reagent: Use of Isopropenyl Acetate as an Alternative to Acetic Anhydride

Abstract Regioselective acetolytic de‐O‐benzylation of poly‐O‐benzylated sugars can be triggered by the activation of isopropenyl acetate (IPA) with either an iodine/silane combined reagent or iodine alone. Unlike other known acetolysis procedures, the protocols presented here do not suffer from the use of harsh acidic reagents and excess amounts of high‐boiling acetic anhydride. The activation of IPA with iodine and triethylsilane (or the cheaper polymethylhydrosiloxane, PMHS) usually results in shorter reaction times, with the acetolysis occurring preferentially (with some exceptions) at primary benzyloxy groups. With anomerically armed sugars, anomeric iodination can be a concomitant process to give highly reactive intermediates which can be converted in situ into workable and useful building blocks upon suitable quenching conditions. On the other hand, IPA activation with iodine alone allows the reactions to occur under milder conditions, albeit over longer times. In almost all reported examples, IPA can be used in moderate excess (5 equiv.), but its employment as the solvent is crucial with an amino sugar model compound otherwise recalcitrant to any acetolytic modification. An additional advantage of these conditions lies in the unprecedented possibility of incorporating the acetolysis step into one‐pot synthetic sequences leading to multiple functional modifications of saccharidic substrates. As to the regioselectivity, most reactions seem to be controlled by steric factors, as the most accessible primary benzyloxy groups are commonly acetolyzed. However, a couple of disclosed examples display that under suitable structural conditions, strain relief effects might be a ruling factor for the regiocontrol of the processes. Overall, the reported protocols offer complementary options for experimentally easy access to a wide range of useful saccharide building blocks featuring a varied profile of protecting groups.