A General, Highly Enantioselective Method for the Synthesis of d and l α-Amino Acids and Allylic Amines

• Published in: Journal of the American Chemical Society Vol. 124; no. 41; pp. 12225 - 12231
• Main Authors: Chen, Young K, Lurain, Alice E, Walsh, Patrick J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.10.2002; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alcohols - chemistry; Amines - chemical synthesis; Amines - chemistry; Amino Acids - chemical synthesis; Amino Acids - chemistry; Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Glycine - analogs & derivatives; Organic chemistry; Oxidation-Reduction; Peptides; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; Vinyl Compounds - chemical synthesis; Vinyl Compounds - chemistry; AMINATION; PRACTICAL SYNTHESIS; ALKYLATION; HYDROGEN-CYANIDE; STEREOSPECIFIC SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; HYDRAZINO ACIDS; INHIBITORS; CATALYTIC ASYMMETRIC-SYNTHESIS; DERIVATIVES; Sigmatropic reaction; α-Aminoacid; Catalytic reaction; Enantioselectivity; Peptidomimetic compound; Asymmetric catalysis; Secondary amine; Allylic compound
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja027271p

Catalytic and enantioselective synthesis of amino acids is a subject of intense interest in the field of asymmetric catalysis. Traditionally, researchers have concentrated their efforts largely on the design and discovery of enantiopure catalysts for the Strecker reaction, alkylation of tert-butyl gylcinate-benzophenone, electrophilic amination of carbonyl compounds, and hydrogenation of N-acyl-aminoacrylic acid; however, the scope of these reactions is limited. In this paper, we report on a different approach to amino acids based on an expeditious route to enantiopure allylic amines. A highly enantioselective and catalytic vinylation of aldehydes leads to allylic alcohols that are then transformed to the allylic amines via Overman's [3,3]-sigmatropic rearrangement of imidates. Oxidative cleavage of the allylic amines furnishes the amino acids in good yields and excellent ee's. The scope and utility of this method are demonstrated by the synthesis of challenging allylic amines and their subsequent transformation to valuable nonproteinogenic amino acids, including both d and l configured (1-adamantyl)glycine.