A new "Mitsunobu homocoupling" reaction using aldol adducts of kojic acid. (13th August 2021)

• Record Type: Journal Article
• Authors: Azuma, Hideki; Morishima, Yasuhito; Nakaguro, Keijin; Kato, Reiko; Nagasaki, Takeshi
• Is Part Of: Tetrahedron. Volume 94(2021)
• Publication Date: 2021-08-13
• Subjects: Kojic acid -- Mitsunobu reaction -- Homocoupling -- Quinone methide -- Michael acceptor; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2021.132314
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: In this study, we attempted to carry out the Mitsunobu 1, 4-elimination using the kojic acid analog 3, which carries a hydroxymethyl group on C-6 introduced by aldol condensation, to obtain an effective Michael acceptor 4 . To the ethyl acetate solution of 3 and Ph3 P, diisopropyl azodicarboxylate was added quickly at 0 °C, resulting in the immediate generation of a yellow precipitate. NMR, mass spectrometry, and X-ray crystal structure analyses allowed to identify the precipitate as a diastereomeric/racemic mixture of dimeric compounds of 4 . The dimerization reaction was hypothesized to occur through two major steps: (i) intramolecular dehydration of 3 by Mitsunobu reagents and (ii) homocoupling of the dehydration product 4 to form a new trans- carbon–carbon double bond. Presumably, the enol ether moiety of 4 acts as an electron donor and immediately attacks the α, β-unsaturated carbonyl group of another molecule via a reaction that can be dubbed "Mitsunobu homocoupling." Graphical abstract: Image 1 Highlights: Mitsunobu dehydration of a kojic acid analog with a hydroxymethyl group on the C-6 carbon yields the homocoupling product. The dimerization, the so-called "Mitsunobu homocoupling, " may occur via generation of a quinone methide-like intermediate. Presumably, the enol ether moiety of the intermediate acts as an electron donor and attacks another molecule.