Total Synthesis of Epoxyquinols A,B,and C and Epoxytwinol A and the Reactivity of a 2H-Pyran Derivative as the Diene Component in the Diels-Alder Reaction

摘要

Full details of two versions of the total synthesis of epoxyquinols A,B,and C and epoxytwinol A(RKB-3564D)are described.In the first-generation synthesis,the HfCl_4-mediated diastereoselective Diels-Alder reaction of furan with Corey's chiral auxiliary 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.This second-generation synthesis is suitable for large-scale preparation.A biomimetic cascade reaction involving oxidation,6pi-electrocyclization,and then Diels-Alder dimerization is the key reaction in the formation of the complex heptacyclic structure of epoxyquinols A,B,and C.Epoxytwinol A is synthesized by the cascade reaction composed of oxidation,6pi-electrocyclization,and formal [4 + 4] cycloaddition reactions.A 2H-pyran,generated by oxidation/6pi-electrocyclization,acts as a good diene,reacting with several dienophiles to afford polycyclic compounds in one step.An azapentacyclic compound is synthesized by a similar cascade reaction composed of the four successive steps:oxidation,imine formation,6pi-azaelectrocyclization,and Diels-Alder dimerization.