Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

• Published in: Chemical & pharmaceutical bulletin Vol. 64; no. 7; pp. 704 - 717
• Main Authors: Hayama, Noboru, Azuma, Takumi, Kobayashi, Yusuke, Takemoto, Yoshiji
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2016
• Subjects: Amino Acids - chemical synthesis; Amino Acids - chemistry; arylboronic acid; Aza Compounds - chemistry; aza-Michael addition; Boronic Acids - chemistry; Carboxylic Acids - chemistry; Catalysis; integrated catalyst; Molecular Structure; O-benzylhydroxylamine; Stereoisomerism; thiourea; Thiourea - chemistry; α,β-unsaturated carboxylic acid
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c15-00983

The first intermolecular asymmetric Michael addition of nitrogen-nucleophiles to α,β-unsaturated carboxylic acids was achieved through a new type of arylboronic acid equipped with chiral aminothiourea. The use of BnONH2 as a nucleophile gives a range of enantioenriched β-(benzyloxy)amino acid derivatives in good yields and with high enantioselectivity (up to 90% yield, 97% enantiomeric excess (ee)). The obtained products are efficiently converted to optically active β-amino acid and 1,2-diamine derivatives.