title: Bifunctional Lewis acid-nucleophile-based asymmetric catalysis: mechanistic evidence for imine activation working in tandem with chiral enolate formation in the synthesis of beta-lactams.
abstract: We report a mechanistically based study of bifunctional catalyst systems in which chiral nucleophiles work in conjunction with Lewis acids to produce beta-lactams in high chemical yield, diastereoselectivity, and enantioselectivity. Chiral cinchona alkaloid derivatives work best when paired with Lewis acids based on Al(III), Zn(II), Sc(III), and, most notably, In(III). Homogeneous bifunctional catalysts, in which the catalyst contains both Lewis acidic and Lewis basic sites, were also studied in detail. Mechanistic evidence allows us to conclude that the chiral nucleophiles form zwitterionic enolates that react with metal-coordinated imines. Alternative scenarios, which postulated metal-bound enolates, were disfavored on the basis of our observations.
authors.affiliation: Department of Chemistry, New Chemistry Building, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: France
authors.forename: Meha H
authors.initials: MH
authors.lastname: Shah
authors.forename: Anthony
authors.initials: A
authors.lastname: Weatherwax
authors.forename: Harald
authors.initials: H
authors.lastname: Wack
authors.forename: Justine P
authors.initials: JP
authors.lastname: Roth
authors.forename: Thomas
authors.initials: T
authors.lastname: Lectka
mesh_terms: D000535:Aluminum / Q000737:chemistry; D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D007204:Indium / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D012538:Scandium / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry; D047090:beta-Lactams / Q000138:chemical synthesis*
chemical_list: D002930:Cinchona Alkaloids; D007097:Imines; D008670:Metals; D047090:beta-Lactams; D007204:Indium; D000535:Aluminum; D015032:Zinc; D012538:Scandium