Chiral Phosphorif Acid Catalyzed Asymmrtrlc Semipinacol Rearrangement And Formal Synthesis Of (-)-Cephalotaxine

Organocatalysts including chiral amine (cinchona alkaloids derivatives and proline),(thio)urea, chiral phosphoric acid, phase transfer catalyst etc. have attracted numerous attention since2000. As a brand new area, which is distinct from enzyme and (transition) metal catalyzed asymmetric reactions, new activation mode and new reactions have been extensively disclosed. In the past ten years, our group has been engaged in the development of various types of semipinacol reactions and tandem reactions based on which the total syntheses of a variety of alkaloids and Pharmaceuticals have been accomplished. The dissertation developed a novel catalytic asymmetric semipinacol rearrangement for the synthesis of spiro ethers taking advantage of the recent advances of organocatalysis. The synthesis of azaspirocycle based on tandem intramolecular hydroamination/asymmetric semipinacol rearrangement has also been accomplished and was then applied to the chiral synthesis of related natural products. The following two parts are mainly discussed.1. Catalytic asymmetric semipinacol rearrangement reaction of2-oxa-allylic alcohols in the presence of a catalytic amount of chiral phosphoric acid or its silver salt was explored, affording enantiomerically pure spiro ethers in moderate to high yields with good to excellent enantiomeric excess. In this section, the mechanism of the reaction including the activation mode and Ag-H exchange are discussed.2. Catalytic asymmetric formal synthesis of (-)-cephalotaxine has been accomplished based on an efficient tandem intramolecular hydroamination/asymmetric semipinacol rearrangement reaction catalyzed by chiral silver phosphate. During the course, an interesting self-disproportionation phenomenon on achiral silica gel of the advanced intermediate was observed.