A highly enantioselective route to either enantiomer of both alpha- and beta-amino acid derivatives.
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.
Córdova
Armando
A
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.
Watanabe
Shin-ichi
S
Tanaka
Fujie
F
Notz
Wolfgang
W
Barbas
Carlos F
CF
D000596:Amino Acids / Q000138:chemical synthesis*; D006038:Glyoxylates / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D006038:Glyoxylates; D011392:Proline