An Easy and Versatile Approach for the Regioselective De‐O‐benzylation of Protected Sugars Based on the I₂/Et₃SiH Combined System

Abstract

The use of cheap and easy to handle reagents, such as I(2) and Et(3) SiH, at low temperature allows the regioselective removal of benzyl protecting groups from highly O-benzylated carbohydrates. The observed regioselectivity is dependent on the nature of the precursor, the least accessible carbinol often being liberated. A mechanistic investigation reveals that in situ generated HI is the promoter of the process, whereas the regioselectivity appears to be mainly controlled by steric effects. However, the presence of an electron withdrawing acyl protecting group can switch the regioselectivity to favour deprotection of the carbinol position farthest from the ester group. The protocol is experimentally simple and provides straightforward access in useful yields to a wide range of partially protected mono- and disaccharide building blocks that are valuable for the synthesis of either biologically useful oligosaccharides or highly functionalised chiral compounds. Partially protected sugars thus obtained can also be coupled in situ with a glycosyl donor, as illustrated by the one-pot synthesis of a Lewis X mimic from fully protected precursors.

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

“…It should be recalled at this stage that a previous investigation demonstrated that under similar conditions to entries 1–2, but in the absence of any acetylating reagent, debenzylation at O ‐4 occurs predominantly, as a consequence of an HI‐promoted benzyl ether cleavage (see comparison of results in Scheme ) 4. The different regioselective outcome of these reactions, only dependent on the presence of an acetylating agent (IPA or acetic anhydride), points to the preferential interaction of HI with the acetylating agent rather than with the benzyloxy groups of the substrate.…”

“…Spurred by our long‐term interest towards the development of practical procedures for regioselective modifications of carbohydrates,4,18 we have explored the possible development of experimentally less‐demanding protocols for acetolytic de‐ O ‐benzylation of sugars. In an initial test reaction, model mannose derivative 1 was treated in DCM with a slight excess of both I 2 and triethylsilane (1.25 equiv.)…”

“…Very recently we also reported that polymethylhydrosiloxane (PMHS) can be an effective, cheaper alternative to triethylsilane in many of these transformations 3. In addition, the iodine/triethylsilane system also proved effective in the regioselective removal of especially hindered benzyl protecting groups from highly O ‐benzylated sugars 4. In all these applications, the reagents were used in anhydrous solvents but without resorting to inert atmosphere 5.…”

Reductive Amination of Acetals by Anilines in the Presence of Triethylsilane and Iodine

“…31 In most cases, reductive N-alkylation of aniline with either five-or six-membered-ring acetals was not observed at room temperature. Under reflux conditions, the expected secondary amines were produced at moderate to high yields ( Table 2, entries 9-17, 65-89% yields).…”

“…The I 2 -Et 3 SiH combination has been used as catalyst for a wide range of reactions. 31,32 However, its application in reductive N-alkylation has not been reported.…”