Palladium-Catalyzed Stereoselective C–2 Arylation of 2,3-Pseudoglycals Using Aryl Diazonium Salts at Room Temperature
Aryl C-glycosides are an important class of carbohydrate derivatives known for their exceptional stability and significant biological relevance; however, C–2 aryl glycosides remain rare and synthetically challenging targets. Herein, we report a mild and efficient palladium-catalyzed protocol for the stereoselective synthesis of 2-aryl-4-ketoglycosides from protected and unprotected 2,3- d -pseudoglycals using aryl diazonium salts. The transformation proceeds smoothly at room temperature under ligand and base-free conditions, affording the desired products in good to excellent yields with high stereocontrol. The methodology exhibits a broad substrate scope, tolerating aryl diazonium salts bearing electron-donating, electron-withdrawing, and halogen substituents, as well as a variety of benzyl-, alkyl-, silyl-protected and unprotected pseudoglycals. Notably, halogen substituents are retained, enabling further downstream functionalization. The protocol is also applicable to unprotected 2,3-pseudorhamnal and can be extended to a one-pot process from anilines via in situ diazonium formation. Gram-scale synthesis and postfunctionalization highlight the robustness and synthetic utility of the method. Overall, this operationally simple and practical strategy provides a general and stereoselective route to C–2 aryl glycosides, expanding access to valuable carbohydrate scaffolds for applications in medicinal chemistry and chemical biology.
Authors
- Rapelly Venkatesh (ORCID: https://orcid.org/0000-0001-6998-2653)
- Jeyakumar Kandasamy (ORCID: https://orcid.org/0000-0003-3285-971X)
- Rubesh Kumar Perumal
Institutions
- Pondicherry University (IN)
Publication Details
- Journal
- The Journal of Organic Chemistry
- Published
- 2026-06-18
- DOI
- https://doi.org/10.1021/acs.joc.6c00734
- Primary Topic
- Carbohydrate Chemistry and Synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00