New methodologies for the synthesis of chiral phosphorus acids and related compounds

Abstract

Organocatalysis has become a major subdiscipline in (asymmetric) organic synthesis. Among chiral organocatalysts, C2-symmetrical chiral phosphorus acids (CPAs) occupy a rather special place because they can catalyze numerous transformations as Brønsted acids, however, they suffer from serious limitations such as: extremely high cost (they are much too expensive for use on an industrial scale, and often too expensive even on much smaller academic scales), very high molecular weight, inability to access both enantiomers without a significant and separate synthetic effort, difficulty in catalyst-immobilization, etc. In order to solve these problems, which hamper the broader uses and applications of CPAs, our proposed approach is to rely on compounds in which the phosphorus atom is chiral (called P-stereogenic, P-chiral, or P-chirogenic) but the rest of the molecule is not. This dissertation presents our development and research findings for the synthesis of chiral phosphorus acids as well as their application in asymmetric organocatalysis.