Total synthesis of epoxyquinols: Oxidative dimerization and its theoretical analysis

The asymmetric total synthesis of epoxyquinols A, B, and C, and epoxytwinol A, and computational analysis of the key biomimetic oxidative dimerization, are described. In the first-generation synthesis, the HfC_l4-mediated diastereoselective Diels-Alder reaction of furan with chiral acrylate has been developed. In the second-generation synthesis, a chromatography-free preparation of an iodolactone by using acryloyl chloride as the dienophile in the Diels-Alder reaction of furan, and the lipase-mediated kinetic resolution of a cyclohexenol derivative have been developed. A biomimetic cascade reaction involving oxidation, 6π-electrocyclization, and Diels-Alder dimerization or formal [4 + 4] cycloaddition, is the key reaction in the formation of heptacyclic structure of epoxyquinols A, B, and C, and epoxytwinol A. Intermolecular hydrogen-bonding is found to be the key, causing formation of both epoxyquinols A and B. In the dimerization of epoxyquinol monomer, two monomeric 2H-pyrans interact each other to afford pre-associated complexes stabilized by hydrogen-bonding, then Diels-Alder reaction proceeds.