Radicals in Carbohydrate Chemistry

Abstract

Radical methods are of central importance in organic synthesis [ 11. These reactions are performed under mild and neutral conditions, which usually avoids competing ionic side reactions. Carbon-centered radicals are compatible with a range of functional groups (e.g. aliphatic alcohols, amines, ketones, esters) and also show high chemoselectivity under carefully controlled reaction conditions. Furthermore, reactions involving loss of stereochemistry at the non-radical center are not problematic, and hence radical methods are emerging as a powerful synthetic tool in the field of carbohydrate chemistry.In this article we provide a broad overview of the application of radical methods in carbohydrate chemistry, including typical examples classified by the type of bond formed. The factors controlling the stereoselectivity of inter-and intramolecular C-C bond formation are now well understood and have been exploited in the synthesis of C-glycosides [2]. Intramolecular C-C bond formation using carbohydratebased chiral templates also provides a powerful route to branched-chain sugars [ 3 ] and carbocycles [4]. Finally, we include synthetically useful processes involving key carbon-heteroatom and C-H bond formation. Intermolecular Carbon-Carbon Bond Formation Synthesis of C-GlycosidesA powerful strategy for the formation of C-glycosides is the intermolecular addition of an anomeric radical to n-systems [2]. Anomeric pyranosyl radicals are readily generated by a variety of standard methods and are nucleophilic in character because of interaction of the SOMO with the non-bonding electron pair of the adjacent ring oxygen. Anomeric radicals therefore undergo addition to n-systems when the high-lying SOMO can interact with a low-lying LUMO as in electron-deficient Radicals in Organic Synthesis Edited

Influence of the O3 Protecting Group on Stereoselectivity in the Preparation ofC-Mannopyranosides with 4,6-O-Benzylidene Protected Donors

“…We have also very briefly investigated the formation of 4,6- O -benzylidene-protected C -mannosides by radical reactions employing allyltributylstannane as reagent. As expected on the basis of literature precedent for similarly protected systems, radicals generated from thioglycosides 26 and 27 obey the general rule of α-selectivity in the quenching of pyranosyl radicals and gave the α-allyl C -glycosides 28 and 29 in good yield irrespective of the protecting group at the 3-position (Scheme ). As 4,6- O -benzylidene-protected glucopyransoyl radicals are known to adopt either B 2,5 or 4 H 5 conformations that closely approximate the calculated conformations of similarly protected oxocarbenium ions, the α-selectivity observed in the 3- O -benzyl series strongly supports the involvement of the counterion (in the CIP) in the β-selective formation of C - and O -glycosides under the typical ionic conditions.…”

Stereoselective Synthesis of C,C-Glycosides from exo-Glycals Enabled by Iron-Mediated Hydrogen Atom Transfer

“…Indeed, in the common d - gluco , d - galacto , and d - manno series, reactions of pseudoanomeric radicals often display high α-selectivity due to their innate preference for an axial conformation. , Furthermore, very small energetic changes in the conformation of glycopyranosyl radicals have been predicted when replacing an anomeric hydrogen with a methyl substituent, hinting at a predictable stereochemical outcome for the addition of sought-after tertiary pseudoanomeric radicals. However, these reactive intermediates are hardly accessible given the low availability/stability of C- substituted anomeric bromide, sulfide, or selenide precursors, notwithstanding Suárez’s alternative approach involving intramolecular 1, n -hydrogen abstraction which employs specific substrates. , When considering alternative manifolds, catalytically generated transition metal hydrides have emerged as outstanding tools for the hydrofunctionalization of electron-rich alkenes with Marknovnikov-like selectivity . Baran et al have developed an iron-mediated Michael–Giese hydroalkylation of olefins that covers a broad substrate scope and whose mechanism was recently deciphered. , Under such conditions, exo -glycals could thus be viewed as precursors to C , C -glycosides.…”

Stereoselective Formation of Eight-Membered Rings by Radical Cyclization of Silylenedioxy-Tethered Bis-methacrylate Derivatives

“…Like many other cyclization reactions where germinal substituents on the tether may facilitate the reactions, known as the Thorpe–Ingold effect, similar behavior has been observed in radical cyclization . Silicon tethers has also been extensively used in cyclization reactions, , particularly in radical cyclization, , and the silicon tethers can readily be removed afterward. This strategy offers versatile entries for the selective synthesis of products with fascinating structural complexities.…”