title: Combined Lewis acid and Brønsted acid-mediated reactivity of glycosyl trichloroacetimidate donors.
abstract: Biomimetic conditions for a synthetic glycosylation reaction, inspired by the highly conserved functionality of carbohydrate active enzymes, were explored. At the outset, we sought to generate proof of principle for this approach to developing catalytic systems for glycosylation. However, control reactions and subsequent kinetic studies showed that a stoichiometric, irreversible reaction of the catalyst and glycosyl donor was occurring, with a remarkable rate variance depending upon the structure of the carboxylic acid. It was subsequently found that a combination of Brønsted acid (carboxylic acid) and Lewis acid (MgBr2) was unique in catalyzing the desired glycosylation reaction. Thus, it was concluded that the two acids act synergistically to catalyze the desired transformation. The role of the catalytic components was tested with a number of control reactions and based on these studies a mechanism is proposed herein.
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Gould
authors.forename: C
authors.initials: C
authors.lastname: Liana Allen
authors.forename: Brandon C
authors.initials: BC
authors.lastname: Nam
authors.forename: Alanna
authors.initials: A
authors.lastname: Schepartz
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D032701:Biomimetics; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D062845:Chloroacetates / Q000737:chemistry*; D006031:Glycosylation; D007700:Kinetics; D058116:Lewis Acids / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry
chemical_list: D000081:Acetamides; D062845:Chloroacetates; D058116:Lewis Acids; D008274:Magnesium; C009528:trichloroacetamide
keywords: Biomimetic; Catalytic; Glycosylation; Magnesium; Schmidt