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.

Cyanomethyl (CNMe) ether: an orthogonal protecting group for saccharides

“…In continuation to our efforts to discover sustainable glycosylation methods, 26–29 we have recently reported cyanomethyl ether (CNMe) as a participating group for stereocontrolled trans -1,2-β- O -glycosylation when present at the C2-position of thioglycosides. During our earlier work a facile synthetic method for CNMe ether formation from C2-hydroxy allowed us to circumvent the well-documented difficulties of low yield and conversion associated with it.…”

Amino-Acid-Derived Amides as Stereodirecting Leaving Groups for Ferrier Rearrangement via Pd(0)-Catalyzed Tsuji–Trost Reactions

“…It was thus concluded that the reaction necessitated coordination of the amide group with the metal center. On the basis of these observations and earlier literature precedence, ,, we propose that amidyl O at the equatorial C3-ester of glycals enables Pd(0) coordination from the β face of substituted glycal I with subsequent π-allyl formation from above the plane of the sugar ring II (Scheme c). An approaching hard alcohol nucleophile coordinates to the hard metal center III followed by syn -facial attack at the C-1 position to afford β- O -glycosides.…”

“…Conventional Pd(0) co-ordinating groups, ethyl carbonate and picoloyl ester, have thus been reported by Liu’s group as suitable LGs for Ferrier rearrangements of glucal substrates 1 (Figure a). With our continued interest in design and development of efficient synthetic methods in glycochemistry, including stereoselective glycosylations, we have recently reported the β-directing ability of o -cyanobenzoate ( o -CNBz) ester 2 (Figure b). The presence of a nitrile moiety on the Bz ester enabled metal co-ordination for the stereoselective rearrangement, which is in stark contrast to the unreactive nature of the parent benzoate group in the same reaction.…”