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

Abstract

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.