Oral Presentation Royal Australian Chemical Institute National Congress 2026

Visible Light-Induced Synthesis of 2-Deoxy Sugars (136707)

Guoqing Zhang 1 , Elizabeth H. Krenske 1 , Vito Ferro 1
  1. The University of Queensland, St Lucia, QLD, Australia

The 2-deoxy sugars play pivotal roles in natural products, pharmaceutical agents and biological processes.[1] Since the seminal report by Giese in 1988,[2] extensive efforts have been devoted to modernizing the synthesis of 2-deoxy sugars. However, widespread application remains restricted by reliance on toxic stannane reagents (e.g., Bu3SnH) under forcing thermal conditions, hazardous hydrogenation setups, or exotic and costly photocatalysts.[3,4]

Herein, we describe the establishment of a contemporary platform utilizing (TMS)3SiH under purple LED irradiation to efficiently generate anomeric carbon radicals from glycosyl bromides. Elevated temperatures (≥80 °C) and dilution promotes a rapid 1,2-spin centre shift to furnish 2-deoxy sugars with excellent regio- and stereoselectivity.

The mechanistic underpinnings of the requisite 1,2-acyloxy migration have remained the subject of intense debate while a concerted, five-membered delocalized cyclic transition state is frequently invoked.[5,6] We were inspired by a proposal by Crich regarding β-(phosphatoxy)alkyl radical rearrangements, which postulated a highly polarized transition state.[7] Through comprehensive mechanistic investigations, we propose that the 1,2-acyloxy migration in carbohydrates proceeds via a highly polarized and loose transition state, resembling an alkene radical cation electrostatically bound to an acyloxy anion.

We observed that migration efficiency is critically dependent on the nature of the migrating group, saccharide type and solvent polarity. Notably, intermolecular acyloxy transfer was detected in crossover experiments, providing strong evidence for a charge-separated transition state. This loose ion-pair mechanism was further corroborated by extensive computational studies, including natural bond orbital (NBO) analysis, evolution of spin densities, non-covalent interaction (NCI) and topological analysis (atoms in molecules, AIM).[8]

 

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