The stereoselective synthesis of β-branched α-amino acid derivatives via organoboranes

Jeremy Todd Cooper, Purdue University

Abstract

The stereoselective synthesis of β-branched α-amino acids is an important area in asymmetric synthesis due to the increased demand for non-proteinogenic amino acids of high isomeric purity. This research combines methodology developed recently in our laboratories for α-stereocontrol during the preparation of non-proteinogenic amino acid derivatives with reactions of chiral, non-racemic organoboranes to achieve the stereoselective synthesis of β-branched α-amino acid derivatives. The reaction of trialkylboranes with a stabilized nucleophile bearing a good leaving group, the Brown boron alkylation reaction, is the key reaction sequence of this methodology. Two methods for the preparation of organoboranes of high isomeric purity were employed. The Matteson asymmetric homologation route and the rhodium-catalyzed asymmetric hydroboration first reported by Hayashi and co-workers were used to prepare the necessary chiral, non-racemic organoboranes. Boron alkylation of a Schiff base ester in the presence of a chiral, non-racemic alcohol and base provided the desired products with high stereoselectivity. Two specific targets, each representative of a class of β-branched α-amino acids, were chosen to demonstrate the methodology. Isoleucine, a commercially available natural β,β-dialkyl amino acid, was chosen as the first target. β-Methylphenylalanine, a non-proteinogenic β-alkyl-β-aryl amino acid, was chosen as the second target. Using the chiral, non-racemic organoboranes prepared by the routes described above, and the boron alkylation with α-stereocontrol, each of the four possible stereoisomers of the two targets was prepared in high stereochemical purity.

Degree

Ph.D.

Advisors

O'Donnell, Purdue University.

Subject Area

Organic chemistry

COinS