Succinct Synthesis of β-Amino Acids via Chiral Isoxazolines

• Published in: Journal of the American Chemical Society Vol. 127; no. 15; pp. 5376 - 5383
• Main Authors: Fuller, Amelia A, Chen, Bin, Minter, Aaron R, Mapp, Anna K
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.04.2005; Amer Chemical Soc
• Subjects: Amino Acids - chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Isoxazoles - chemistry; Molecular Conformation; Organic chemistry; Physical Sciences; Proline - chemical synthesis; Science & Technology; Stereoisomerism; PHYSICOCHEMICAL PROPERTIES; 1,3-DIPOLAR CYCLOADDITIONS; DE-NOVO DESIGN; ASYMMETRIC CONJUGATE ADDITION; ENANTIOSELECTIVE SYNTHESIS; ORGANOMETALLIC REAGENTS; MANNICH-TYPE REACTIONS; STEREOSELECTIVE-SYNTHESIS; ORGANOLITHIUM REAGENTS; BIOLOGICAL STABILITY; Chemical reduction; Five membered ring; Isoxazole derivatives; Chiral compound; Experimental study; Diastereoselectivity; Nucleophilic addition; Oxygen nitrogen heterocycle
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0431713

β-Amino acids are important synthetic targets due to their presence in a wide variety of natural products, pharmaceutical agents, and mimics of protein structural motifs. While β-amino acids containing geminal substitution patterns have enormous potential for application in these contexts, synthetic challenges to the stereoselective preparation of this class of compound have thus far limited more complete studies. We present here a straightforward method employing chiral isoxazolines as key intermediates to access five different β-amino acid structural types with excellent selectivity. Of particular note is the use of this approach to prepare highly substituted cis-β-proline analogues. The ready access to these diversely substituted compounds is expected to facilitate future studies of the structure and function of this important class of molecules.