Efficient Copper‐Catalyzed Highly Stereoselective Synthesis of Unprotected C‐Acyl Manno‐, Rhamno‐ and Lyxopyranosides. Issue 71 (26th October 2022)

• Record Type: Journal Article
• Authors: Boehlich, Gordon Jacob; Sterzel, Hannes; Rehbein, Julia; Schützenmeister, Nina
• Is Part Of: Chemistry. Volume 28:Issue 71(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-26
• Subjects: carbohydrates -- C-glycosylation -- corey-seebach reaction -- copper catalysis -- reaction mechanism; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202202619
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Due to their high stability towards enzymatic hydrolysis C ‐acyl glycosidic compounds are useful synthetic intermediates for potential candidates in drug discovery. Syntheses for C ‐acyl mannosides have remained scarce and usually employ donors obtained from lengthy syntheses. Furthermore, syntheses of unprotected C ‐acyl mannosides have not been reported so far, due to the incapability of the C ‐acyl mannoside motif with deprotection conditions for protective groups commonly used in carbohydrate chemistry. Herein, we report an efficient and highly α‐selective four‐step one‐pot method for the synthesis of C ‐acyl α‐d ‐manno‐, l ‐rhamno‐ and d ‐lyxopyranosides from easily accessible persilylated monosaccharides and dithianes requiring only trace amounts of a copper source as catalyst and explain the crucial role of the catalyst by mechanistic studies. Furthermore, the C ‐acyl α‐glycosides were easily isomerized to give rapid access to their β‐anomers. Abstract : Just a pinch of copper iodide promotes the reaction of manno‐type glycosyl iodides with lithiated dithianes. Herein, we report an efficient and highly α‐selective four‐step one‐pot method for the synthesis of unprotected manno‐type C ‐acyl pyranosides. The crucial role of the catalyst was proven by mechanistic studies and DFT calculations, suggesting a copper‐radical mechanism over a SN ‐type mechanism.