o‐Cyanobenzoate: A Recyclable and Reusable Stereo‐directing Group for β‐O‐Glycosylation via Pd(0)‐catalyzed Ferrier Rearrangement

• Published in: Chemistry, an Asian journal an Asian journal, 2022-02, Vol.17 (3), p.e202101156-n/a
• Main Authors: Das, Pradip, Rahaman Molla, Mosidur, Kumar, Amit, Thakur, Rima
• Format: Article
• Language: English
• Subjects: Benzoates; Catalysis; Chemical synthesis; Chemistry; Ferrier Rearrangement; Glycosides; Glycosylation; Nucleophiles; Pd catalyzed; Recyclable leaving group; Regeneration; Stereoisomerism; stereoselective glycosylation; Stereoselectivity; Substrates; β-O-glycosylation
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.202101156

Inner sphere Tsuji‐Trost reaction has found recent application for β‐selective Ferrier rearrangement of glycal substrates with alcohol nucleophiles. Herein, we report an efficient and stereoselective synthesis of 2,3‐dideoxy‐β‐O‐glycosides from C3‐(o‐cyanobenzoate) ester protected glycal donors via Ferrier rearrangement under Pd(0)‐catalyzed Tsuji‐Trost conditions. The synthesized donors indeed reacted with a variety of acceptors to afford the corresponding glycosides in good yields and excellent β‐stereoselectivity. The stereochemical outcome of the reactions has been found to be independent of the nature of protecting groups or conformational flexibility of the glycal donors. Furthermore, regeneration of ortho‐cyanobenzoic acid post rearrangement makes it a recyclable and reusable stereodirecting group. A preliminary mechanistic study demonstrates the importance of cyano‐group for the observed rearrangement and stereoselectivity. Incorporation of the directing group on the benzoate ester has altered the reactivity of the ester group as a leaving group for Tsuji‐Trost as well as Ferrier Rearrangement pathway. Stereoselective synthesis of 2,3‐dideoxy‐β‐O‐glycosides has been reported herein. C3‐(o‐cyanobenzoate) ester protected glucal substrates have been efficiently glycosylated under Pd(0) catalyzed Ferrier rearrangement. The reaction was compatible with a large range of alcohol nucleophiles which afforded the rearranged products in high to excellent β‐selectivities. Further, the successful recycling and reusing of the directing group makes the method advantageous for sustainable chemistry.