Studies On Semipinacol Rearrangement Reaction And Its Application To The Total Synthesis Of Galanthamine

Base on the study of the semipinacol rearrangement reactions, this dissertation had developed a novel semipinacol rearrangement/alkylation tandem reaction of 2,3-epoxy alcohols, and achieved high-stereoselectivily the construction of a type of multifuctional and multi-stereocenteral quaternary carbon unit. And then based on the semipinacol rearrangement of allyic alcohol, the total synthesis of Galanthamine was efficiently achieved. The major content include two parts shown as below:1. The semipinacol rearrangement/alkylation tandem reaction of 2,3-epoxy alcohols promoted by allylboronic acid and allenylboronic acid respectivelyIn this reaction, allylboronic acid displayed two pivotal characters: acidity and nucleophilicity. This is the first report of the dual characters of allylboronic acid in one reaction system. We also had observed an interesting stereochemistry in the reaction. Meanwhile, this tandem reaction efficiently constructed three continued stereocenters, and afforded a kind of 2-quaternary-l,3-diol unit processing an allyl or a progargyl, which could have great value in organic synthesis. Starting from a containing allyl 2-quaternary-l,3-diol, we further constructed compactly and efficiently a tricycle skeleton, which exists in many natural products.2. The total synthesis of GalanthamineStarting from the commercially available materials and based on the key steps of the semipinacol rearrangement of allylic alcohol promoted by NBS and the Saegusa-Ito oxidation, we compactly and efficiently achieved the total synthesis of the alkaloid, galanthamine, in 13 steps and an overall yield of 12%. At the same time, we afforded a novel possible approach to the manufacture of this important biological activity natural product in large scale.