Single electron/energy transfer photocatalysis: α-/β-switchable synthesis of 3-deoxy-d-manno-oct-2-ulosonic acid O-glycosides

TL;DR

This paper presents a new photocatalytic method to efficiently synthesize both α- and β-Kdo O-glycosides with high yields using a dual pathway mechanism.

Contribution

The study introduces a dual mediated photocatalytic system for switchable α-/β-Kdo O-glycoside synthesis with a novel SET and EnT mechanism.

Findings

β-Kdo O-glycosides were synthesized in excellent yields (up to 99%) at −78 °C via glycosyl nitrilium ion.

α-Kdo O-glycosides were produced in good yields (57–99%) at −30 °C via oxosulfonium ion.

The dual pathway (SET & EnT) mechanism was confirmed using experimental and computational methods.

Abstract

Stereoselective glycosidation of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) has emerged as a focal point in glycoscience, attributed to the burgeoning identification of naturally occurring α- or β-Kdo glycosides within the glycoconjugate structures of various organisms. Nonetheless, advancements in α-/β-switchable stereoselective Kdo O-glycosidation remain scarce due to the complicated synthesis of Kdo donors and the complex chemical environment at the anomeric carbon of Kdo. Herein, inspired by the property that the conditions of the photocatalytic reaction can be facilely controlled and mediated, we report an efficient photocatalytic IrIII/CuII-catalysed Kdo O-glycosidation for the stereoselective synthesis of both α- and β-Kdo O-glycosides with the dual mediation of MeCN and (p-Tol)2SO. Within a facile photoreactor, the glycosidation reactions were carried out at −78 °C to generate β-Kdo O-glycosides in excellent yields (up to 99%) via the glycosyl nitrilium ion, and at −30 °C to generate α-Kdo O-glycosides in good yields (57–99%) via the oxosulfonium ion. Two crystals of α-Kdo O-glycosides were cultivated to assess the stereochemical configurations. Subsequently, laser flash photolysis, steady-state measurement and ESR spectral measurement were conducted to first reveal a single electron transfer (SET) together with the Dexter energy transfer (EnT) process of the photocatalytic activation by monitoring the trifluoromethyl radical, the cation radical of dibenzothiophene and the cation radical of 4,5,7,8-tetra-O-acetyl-Kdo p-toluenethioglycoside. (TD)-DFT calculations further supported this process and illustrated a SN2-like mechanism for the attack of hydroxyl acceptors.

An acetonitrile/(p-Tol)2SO dual mediated photocatalytic IrIII/CuII-catalysed Kdo O-glycosidation was developed to synthesize α-/β-Kdo O-glycosides in good to excellent yields via a dual pathway (SET & EnT) photoactivation and a SN2-like mechanism.

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