Direct, stereoselective thioglycosylation enabled by an organophotoredox radical strategy.

Peng Ji,Fangchao Bi,Yueteng Zhang,Feng Gao,Wei Wang

doi:10.1039/d0sc04136j

Peng Ji, Fangchao Bi + Show 3 more

Open Access

https://doi.org/10.1039/d0sc04136j

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Abstract

While strategies involving a 2e− transfer pathway have dictated glycosylation development, the direct glycosylation of readily accessible glycosyl donors as radical precursors is particularly appealing because of high radical anomeric selectivity and atom- and step-economy. However, the development of the radical process has been challenging owing to notorious competing reduction, elimination and/or SN side reactions of commonly used, labile glycosyl donors. Here we introduce an organophotocatalytic strategy through which glycosyl bromides can be efficiently converted into corresponding anomeric radicals by photoredox mediated HAT catalysis without a transition metal or a directing group and achieve highly anomeric selectivity. The power of this platform has been demonstrated by the mild reaction conditions enabling the synthesis of challenging α-1,2-cis-thioglycosides, the tolerance of various functional groups and the broad substrate scope for both common pentoses and hexoses. Furthermore, this general approach is compatible with both sp2 and sp3 sulfur electrophiles and late-stage glycodiversification for a total of 50 substrates probed.

Highlights

Despite the fact that O-linked glycosides are a dominant form in biologically important glycoconjugates,[1] the replacement of “O” by C, N- and S-linked glycosides offers the merits of improved hydrolytic stability and/or bioactivity while maintaining similar conformational preferences. 2 In particular, thioglycosides have emerged as a privileged class of structures owing to their broad spectrum of biological activities.[2,3,4,5] they are widely used as glycosyl donors in glycosylation reactions.[6]
This general approach is compatible with both sp[2] and sp[3] sulfur electrophiles and latestage glycodiversification for a total of 50 substrates probed
A Standard conditions: unless speci ed, a mixture of glycosyl bromide (0.2 mmol), sulfur electrophile (0.1 mmol), 4ClCzIPN (0.005 mmol), K3PO4 (0.4 mmol), and (TMS)3SiOH (0.15 mmol) in DCE/DMSO (1 mL, 1 : 1, v/v) or DCE/H2O (1.5 mL, 2 : 1, v/v) was irradiated with 40 W Kessil blue LEDs in a N2 atmosphere at À5 C for 24 h. b Yield determined by 1H NMR using 1,1,2,2-tetrachloroethane as an internal reference. c Ratio determined by crude 1H NMR. d Isolated yield

Summary

Introduction

Despite the fact that O-linked glycosides are a dominant form in biologically important glycoconjugates,[1] the replacement of “O” by C-, N- and S-linked glycosides offers the merits of improved hydrolytic stability and/or bioactivity while maintaining similar conformational preferences. 2 In particular, thioglycosides have emerged as a privileged class of structures owing to their broad spectrum of biological activities (see representative examples in Scheme 1).[2,3,4,5] they are widely used as glycosyl donors in glycosylation reactions.[6]. While strategies involving a 2eÀ transfer pathway have dictated glycosylation development, the direct glycosylation of readily accessible glycosyl donors as radical precursors is appealing because of high radical anomeric selectivity and atom- and step-economy.

Results

Conclusion