A Unified Strategy to Access 2- and 4-Deoxygenated Sugars Enabled by Manganese-Promoted 1,2-Radical Migration

Abstract

The selective manipulation of carbohydrate scaffolds is challenging due to the presence of multiple, nearly chemically indistinguishable O–H and C–H bonds. As a result, protecting-group-based synthetic strategies are typically necessary for carbohydrate modification. Here we report a concise semisynthetic strategy to access diverse 2- and 4-deoxygenated carbohydrates without relying on the exhaustive use of protecting groups to achieve site-selective reaction outcomes. Our approach leverages a Mn2+-promoted redox isomerization step, which proceeds via sugar radical intermediates accessed by neutral hydrogen atom abstraction under visible light-mediated photoredox conditions. The resulting deoxyketopyranosides feature chemically distinguishable functional groups and are readily transformed into diverse carbohydrate structures. To showcase the versatility of this method, we report expedient syntheses of the rare sugars l-ristosamine, l-olivose, l-mycarose, and l-digitoxose from commercial l-rhamnose. The findings presented here validate the potential for radical intermediates to facilitate the selective transformation of carbohydrates and showcase the step and efficiency advantages attendant to synthetic strategies that minimize a reliance upon protecting groups.

Application of the Spin-Center Shift in Organic Synthesis

“…Recently, another representative dehydration of monosaccharides was disclosed by using manganese catalyst under photoredox conditions, allowing for the concise synthesis of various deoxygenated sugars from readily available biomass-derived monosaccharides ( Scheme 5 ). 30 In this reaction, the SCS process is facilitated by the Mn 2+ catalyst, although the detailed mechanism remains unclear. The authors surmised that Mn 2+ may act as a Lewis acid to induce the elimination of H 2 O to give Int-12 , or it undergoes inner-sphere electron transfer as well as promotes the SCS process to deliver Int-13 .…”

Deoxy sugars. General methods for carbohydrate deoxygenation and glycosidation

“…7D). 173 After an extensive study of reaction conditions, they concluded that the use of a metal with redox activity could facilitate the formation of deoxyketo products. Other tested metals, such as Cu( ii ), have the disadvantage of producing overoxidation.…”

α-C–H Photoalkylation of a Glucose Derivative in Continuous Flow

“…This type of photocatalysis is not limited to alkylations: in more recent reports, Wendlandt et al have used the HAT reaction for isomerization, providing access to rare monosaccharides from commonly available monosaccharides (15), (16) , whilst the group of Taylor employed the system for oxidations. (17) Redox isomerization, a strategy that combines the two, gives rise to ketodeoxysugars, with examples of both furanosides (18) and pyranosides (19), (20) having been investigated. The photocatalytic system has also seen success in chiral resolutions: with a chiral phosphate, racemic ureas could be enantiomerically enriched.…”