title: Investigations of scope and mechanism of nickel-catalyzed transformations of glycosyl trichloroacetimidates to glycosyl trichloroacetamides and subsequent, atom-economical, one-step conversion to α-urea-glycosides.
abstract: The development and mechanistic investigation of a highly stereoselective methodology for preparing α-linked-urea neo-glycoconjugates and pseudo-oligosaccharides is described. This two-step procedure begins with the selective nickel-catalyzed conversion of glycosyl trichloroacetimidates to the corresponding α-trichloroacetamides. The α-selective nature of the conversion is controlled with a cationic nickel(II) catalyst, [Ni(dppe)(OTf)2 ] (dppe=1,2-bis(diphenylphosphino)ethane, OTf=triflate). Mechanistic studies have identified the coordination of the nickel catalyst with the equatorial C2 -ether functionality of the α-glycosyl trichloroacetimidate to be paramount for achieving an α-stereoselective transformation. A cross-over experiment has indicated that the reaction does not proceed in an exclusively intramolecular fashion. The second step in this sequence is the direct conversion of α-glycosyl trichloroacetamide products into the corresponding α-urea glycosides by reacting them with a wide variety of amine nucleophiles in presence of cesium carbonate. Only α-urea-product formation is observed, as the reaction proceeds with complete retention of stereochemical integrity at the anomeric CN bond.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, Iowa, 52242 (USA), Fax: (+1) 319-335-1270.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McKay
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Park
authors.forename: Hien M
authors.initials: HM
authors.lastname: Nguyen
mesh_terms: D000081:Acetamides; D002384:Catalysis; D062845:Chloroacetates; D006027:Glycosides / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D013237:Stereoisomerism; D014508:Urea / Q000737:chemistry*
chemical_list: D000081:Acetamides; D062845:Chloroacetates; D006027:Glycosides; D009532:Nickel; D014508:Urea; C009528:trichloroacetamide
keywords: carbohydrates; glycosyl trichloroacetimidates; stereoselectivity; trichloroacetamides; urea glycosides