Practical synthesis of enantiomerically pure beta2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes.
Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides alpha-substituted-beta-amino aldehydes with 85:15 to 90:10 dr. The alpha-substituted-beta-amino aldehydes can be reduced to beta-substituted-gamma-amino alcohols, the major diastereomer of which can be isolated via crystallization or column chromatography. The amino alcohols are efficiently transformed to protected beta2-amino acids, which are valuable building blocks for beta-peptides, natural products, and other interesting molecules. Because conditions for the aminomethylation and subsequent reactions are mild, beta2-amino acid derivatives with protected functional groups in the side chain, such as beta2-homoglutamic acid, beta2-homotyrosine, and beta2-homolysine, can be prepared in this way. The synthetic route is short, and purifications are simple; therefore, this method enables the preparation of protected beta2-amino acids in useful quantities.
Chi
Yonggui
Y
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
English
Emily P
EP
Pomerantz
William C
WC
Horne
W Seth
WS
Joyce
Leo A
LA
Alexander
Lane R
LR
Fleming
William S
WS
Hopkins
Elizabeth A
EA
Gellman
Samuel H
SH
D000447:Aldehydes / Q000737:chemistry*; D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D002384:Catalysis; D002853:Chromatography, Liquid; D003460:Crystallization; D008745:Methylation; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D000588:Amines; D000596:Amino Acids; D011392:Proline