Asymmetric hetero-Michael addition to α,β-unsaturated carboxylic acids using thiourea–boronic acid hybrid catalysts

• Published in: Tetrahedron Vol. 89; p. 132089
• Main Authors: Hayama, Noboru, Kobayashi, Yusuke, Takemoto, Yoshiji
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 04-06-2021
• Subjects: Arylboronic acid; Asymmetric catalyst; Michael addition; Thiourea; α,β-unsaturated carboxylic acid; Michael addition; Thiourea; α,β-unsaturated carboxylic acid; Asymmetric catalyst; Arylboronic acid
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2021.132089

The first catalytic asymmetric Michael addition of heteroatomic nucleophiles to α,β-unsaturated carboxylic acids is summarized. Direct Michael addition is one of the most straightforward and atom-economical methods for constructing pharmaceutically beneficial building blocks and intermediates, although unsaturated carboxylic acids are known to be inactive Michael acceptors. We designed hybrid catalysts comprising arylboronic acid, thiourea, and tertiary amine to activate the unsaturated carboxylic acids. This review describes the aza- and thia-Michael additions using chiral multifunctional hybrid catalysts, their synthetic applications to biologically active compounds, and the mechanistic consideration of multicomponent borate complexes.
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