Asymmetric total synthesis of epoxyquinonoid natural products, such as epoxyquinols A, B, and C, epoxytwinol A, and EI-1941-1, -2, and -3, are described. In the first-generation synthesis of epoxyquinols, the HfCl 4-mediated diastereo-selective Diels-Alder reaction of furan with a chiral acrylate ester was 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 were developed. This second-generation synthesis is suitable for large-scale preparation. A biomimetic cascade reaction involving oxidation, 6π-elec-trocyclization, then Diels-Alder dimerization, is the key reaction in the formation of epoxyquinols A-C. Epoxytwinol A was synthesized by the cascade reaction composed of oxidation, 6π-electrocyclization, and formal [4 + 4] cycloaddition. A 2H-pyran, generated by oxidation/6π-electrocyclization, acts as a good diene, reacting with several dienophiles to afford polycyclic compounds in one step. The asymmetric total synthesis of EI-1941s was accomplished, starting from a chiral epoxy iodoquinone, a key intermediate in the total synthesis of epoxyquinols. They were diastereoselectively synthesized via an intramolecular carboxypalladation in a 6-endo cyclization mode, followed by β-hydride elimination, as the key steps.
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