title: A highly enantioselective route to either enantiomer of both alpha- and beta-amino acid derivatives.
abstract: This report describes the unprecedented use of unmodified aldehydes as donors in a catalytic asymmetric Mannich-type reaction. The proline-catalyzed reaction of N-PMP-protected alpha-imino ethyl glyoxylate with unmodified aliphatic aldehydes provided a general and very mild entry to either enantiomer of beta-amino and alpha-amino acids and derivatives in high yield and stereoselectivity. Six of the seven aldehydes studied yielded products with ee values of 99% or greater. The diastereoselectivity of the reaction increased with the bulkiness of the substituents of the aldehyde donor in the order R = Me < Et < i-Pr < n-Pent. In five of the cases studied, excellent syn stereoselectivities were achieved. In addition, the corresponding chiral beta-amino aldehyde adducts can be readily converted to the corresponding amino acid derivatives. Most significantly, this approach provides facile access to substituted beta-lactams.
authors.affiliation: The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Córdova
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Fujie
authors.initials: F
authors.lastname: Tanaka
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Notz
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Barbas
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis*; D006038:Glyoxylates / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D006038:Glyoxylates; D011392:Proline