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. 2024 Dec 20;89(24):18684-18688.
doi: 10.1021/acs.joc.4c02176. Epub 2024 Nov 26.

Nontraditional Synthesis of Disaccharides via Acyclic Vinylic Ether Intermediates: Catalytic C-O Cross-Coupling as the Enabling Link

Taehee Kim  1 , Eric J Meindl  1 , Frank E McDonald  1
Affiliations

Nontraditional Synthesis of Disaccharides via Acyclic Vinylic Ether Intermediates: Catalytic C-O Cross-Coupling as the Enabling Link

Taehee Kim et al. J Org Chem. .

Abstract

We describe complementary methods for synthesizing acyclic vinylic ethers from two carbohydrate-derived synthons. We compare a nonstereoselective olefination approach with a stereoselective catalytic C-O cross-coupling method, preparing 1,2-disubstituted vinylic ethers with complexity on both sides of the ether linkage. Upon epoxidation/in situ oxacyclization of acyclic vinylic ethers, we synthesized disaccharides with α-d-galacto-, α-d-talo-, β-d-allo-, and α-d-altropyranoside stereochemistry, from d-lyxose and d-ribose precursors. Stereoselective CuI/CyDMEDA-catalyzed C-O cross-couplings offer considerable potential for broadly implementing this nontraditional strategy for glycoside synthesis.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Nontraditional Disaccharide Synthesis from Oxacyclization of Vinylic Ether Intermediates
Scheme 2
Scheme 2. Modified Julia Olefination with Carbohydrate-Derived Synthons 7 and 9
Figure 1
Figure 1
Stereochemical assignments from coupling constants for disaccharides 14 and 15, compared with coupling constants for methyl glycosides 16 and 17, respectively.
Scheme 3
Scheme 3. Synthesis of (E)-Vinylic Iodides from d-Lyxose and d-Ribose Acetonides
Scheme 4
Scheme 4. Synthesis of (E)-Vinylic Ethers from Catalytic C–O Cross-Coupling with Galactose Bis-Acetonide (6)
Scheme 5
Scheme 5. Epoxidations–Oxacyclizations of (E)-12 and (E)-25 to Novel Disaccharides
Figure 2
Figure 2
Stereochemical assignments for disaccharide diacetates 30 and 31.
See this image and copyright information in PMC

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