Catalytic enantioselective synthesis of alpha-amino acids and alpha,alpha-dialkyl amino acids by phase-transfer catalysis. (Volumes I and II)

Shengde Wu, Purdue University

Abstract

A new method for a catalytic asymmetric synthesis of $\alpha$-amino acids using phase-transfer catalysis has been developed. The methodology developed to date allows preparation of either enantiomer of a variety of types of target amino acids in up to 66% ee by a simple and straightforward procedure at room temperature from readily available starting materials. The ability to scale the reaction up and the possibility of preparing $\alpha$-amino acids in high optical purity have been demonstrated by synthesis of 6.5 g of 4-chloro-D-phenylalanine in $>$99% ee from 19.2 g of starting substrate. This has resulted the first practical asymmetrical synthesis of $\alpha$-amino acids using phase-transfer catalysis. This method has been extended to the preparation of $\alpha$,$\alpha$-dialkyl amino acids from the starting material aldimine ester by solid-liquid phase-transfer catalysis. The alkylation of aldimine ester with less active alkyl halides in up to 70% ee has been successfully carried out under the condition of high concentration of substrate or in the absence of organic solvent. A mild, safe and economical method has been developed for the synthesis of various novel chiral phase-transfer catalysts. Alternative approaches to preparation of either O-alkyl N-alkyl or O-alkyl N-benzyl as well as dimer cinchona quaternary catalysts were developed. Most of these novel catalysts have shown good optical induction (up to 70% ee) in the alkylation reaction. A key finding is the first direct evidence for the O-alkyl N-benzyl cinchona quaternary catalysts as the active chiral phase-transfer catalyst in our alkylation system. The discovery of this result is inconsistent with the current mechanistic concept of chiral phase-transfer catalysis. Additionally, systematic studies of the pathways of formation of racemic products, the nature of the catalyst in the reaction process and the isolation and identification of the various by-products formed from the reaction process has resulted in a new mechanistic proposal for the reaction.

Degree

Ph.D.

Advisors

O'Donnell, Purdue University.

Subject Area

Organic chemistry

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