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Bifunctional Lewis Acid-Nucleophile-Based Asymmetric Catalysis: Mechanistic Evidence for Imine Activation Working in Tandem with Chiral Enolate Formation in the Synthesis of β-Lactams
journal contribution
posted on 2005-02-02, 00:00 authored by Stefan France, Meha H. Shah, Anthony Weatherwax, Harald Wack, Justine P. Roth, Thomas LectkaWe report a mechanistically based study of bifunctional catalyst systems in which chiral
nucleophiles work in conjunction with Lewis acids to produce β-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.