Direct, stereoselective thioglycosylation enabled by an organophotoredox radical strategy

Abstract

While strategies involved 2e- transfer pathway have dictated glycosylation development, direct glycosylation of readily accessible glycosyl donors as radical precursors is particularly appealing because of high radical anomeric selectivity and...

Diastereoselective Synthesis of Thioglycosides via Pd-Catalyzed Allylic Rearrangement

“…Various methods of thioglycoside synthesis have mainly focused on two aspects: ionic and radical reactions (Figure B). Although ionic reactions have been developed for many years, they generate a mixture of α/β anomers in most cases. − Because of the efficient stereoselectivity of anomeric radicals, − chemists have developed a series of radical reactions to construct thioglycosides to compensate for the defects of ionic reactions. ,, Since the first glycosylation reaction of glycal donor was reported in 1964, building a stereoselective glycosideis a persistent aim with diverse biological and pharmaceutical goals. − Although axial glycosides can be obtained via anomeric effects, they are indispensable for stoichiometric Lewis − or Brønsted , acids, dramatically restricting the functional group compatibility. Equatorial glycosides can be generated via the gauche effect, limited to a structure by ortho-hydroxyl groups protected with acyl groups.…”

“…9−12 Because of the efficient stereoselectivity of anomeric radicals, 13−16 chemists have developed a series of radical reactions to construct thioglycosides to compensate for the defects of ionic reactions. 12,17,18 Since the first glycosylation reaction of glycal donor was reported in 1964, 19 building a stereoselective glycosideis a persistent aim with diverse biological and pharmaceutical goals. 20−25 Although axial glycosides can be obtained via anomeric effects, they are indispensable for stoichiometric Lewis 26−28 or Brønsted 29,30 acids, dramatically restricting the functional group compatibility.…”

Desulfonylation via Radical Process: Recent Developments in Organic Synthesis

“…An earlier method reported by Wang’s group mainly focused on stereoselective construction of glycosidic bonds (Scheme A, 3) . This strategy employed glycosyl bromides 156 - 6 , which could be efficiently converted into the corresponding anomeric radicals by photoredox-mediated HAT catalysis in the presence of 4ClCzIPN, K 3 PO 4 , and (TMS) 3 SiOH to achieve high anomeric selectivity while minimizing the side reactions.…”

“…An earlier method reported by Wang's group mainly focused on stereoselective construction of glycosidic bonds (Scheme 156A, 3). 557 This strategy employed glycosyl bromides 156-6, which could be efficiently converted into the corresponding anomeric radicals by photoredox-mediated HAT catalysis in the presence of 4ClCzIPN, K 3 PO 4 , and (TMS) 3 SiOH to achieve high anomeric selectivity while minimizing the side reactions. Furthermore, both C(sp 2 ) and C(sp 3 ) sulfur electrophiles were suitable substrates for the synthesis of challenging α-1,2-cisthioglycosides 156-7, entailing their potential application for late-stage glycodiversification (Scheme 156B).…”

Nonenzymatic StereoselectiveS-Glycosylation of Polypeptides and Proteins

“…Interestingly, the use of glycosyl radicals to build glycosyl-peptide bonds remains an underdeveloped area, presumably due to the lack of methods to generate glycosyl radicals under biorelevant conditions. The Walczak group and the Wang group reported generation of S -glycosides from glycosyl stannanes and glycosyl bromides, respectively. However, these methods need to use protected substrates and require conditions that may not be tolerated by biomolecules.…”