A new “Mitsunobu homocoupling” reaction using aldol adducts of kojic acid

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 Ph3P, 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.”