Stereoselective Protection-Free Modification of 3-Keto-saccharides

Abstract

Unprotected 3-keto-saccharides have become readily accessible via site-selective oxidation, but their protection-free functionalization is relatively unexplored. Here we show that protecting groups are obsolete in a variety of stereoselective modifications of our model substrate methyl α-glucopyranoside. This allows the preparation of rare sugars and the installation of click handles and reactive groups. To showcase the applicability of the methodology, maltoheptaose has been converted into a chemical probe, and the rare sugar evalose has been synthesized.

On the Origin of Regioselectivity in Palladium‐Catalyzed Oxidation of Glucosides

“…These reactions are well‐developed to suit a variety of monosaccharides with different stereochemical configuration and with controllable selectivity for the desired transformation [3] and include, but are not limited to, acylation, [4,5] alkylation, [6] silylation, [7] and oxidation. While the utility of acylation, alkylation and silylation is clear in protecting‐group chemistry, and acylation allows for limited subsequent modifications, [8] oxidation, on the other hand, allows further modifications such as epimerization, reductive amination, nucleophilic addition [9] and epoxidation [10] without further protection. One of the most well‐studied oxidation reactions is the selective oxidation of pyranosides at C6 with TEMPO [11] or transition metal catalysts such as rhodium [12] .…”

Selective Transformations of Carbohydrates Inspired by Radical-Based Enzymatic Mechanisms

“…Outside a well-defined active site, the diastereoselectivity of the bond forming step in alkylation reactions is often substrate controlled. , While synthetic C–C bond forming reactions with sugar radicals have not been widely explored, the addition of nucleophiles to sugar ketone intermediates has been shown to be substrate controlled, with reactants approaching the least sterically hindered face to deliver kinetically controlled products. ,, Substrate-controlled selectivity is also observed in Minnaard’s radical alkylation reaction, with radical addition preferentially occurring with net stereochemical inversion (Figure D) . Analogous to the “conformational locking” mechanism observed in the methylation by GenK, Taylor’s method uses transient diphenylborinate·diol coordination to enforce overall retention of configuration at the alkylated position (Figure E) …”

Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis

“…[58e] However, the ring-opening of 1,6-anhydrosugars by simple alcohols -mainly methanol -is a tactic that has been used in numerous syntheses to protect the anomeric position while releasing the hydroxyl group at C-6 (Scheme 27). [80][81][82][83][84][85] Based on this approach, the group of Skrydstrup reported the convergent synthesis of a branched C-trisaccharide. This stable glycomimetic related to the core structure of asparaginelinked oligosaccharides was obtained by methanolysis of a 3-Cvinyl-1,6-anhydromannose derivative (Scheme 28).…”

“…However, the ring‐opening of 1,6‐anhydrosugars by simple alcohols – mainly methanol – is a tactic that has been used in numerous syntheses to protect the anomeric position while releasing the hydroxyl group at C‐6 (Scheme 27). [80–85] …”