Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Chemistry

Language

English (en)

Date of Award

6-26-2012

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Vladimir Birman

Abstract

Neutral Lewis bases, such as 4-(dimethylamino)pyridine and N-methylimidazole, are widely used as acyl transfer catalysts. In contrast, anionic nucleophiles have been little explored in acyl transfer catalysis, although their high nucleophilicity may enable unique applications. In the course of my studies, 1,2,4-triazole anion was found to be an effective acyl transfer catalyst in both aminolysis and transesterification reactions. These findings pave the way to designing asymmetric anionic acyl transfer catalysts, which may be useful, e.g., for catalytic kinetic resolution of chiral amines.

From 2003 to 2009, our group developed four generations of amidine-based enantioselective acyl transfer catalysts(ABCs) and applied them successfully to the kinetic resolution of chiral alcohols. Compared with chiral alcohols, the kinetic resolution of chiral acyl donors is more complicated and far less developed. In my study, a new method for the catalytic kinetic resolution of racemic &alpha-substituted carboxylic acids was devised by using ABCs. Subsequently, we developed related methods that proved to be suitable for the dynamic kinetic resolution of azlactones and &alpha-thiosubstituted carboxylic acids. The transition-state models were proposed and studied by computational methods.

As an extension of our group's earlier studies on ABC-catalyzed enantioselective N-acylation reactions, we undertook a systematic study of different types of lactams and thiolactams. The substrate structure-reactivity relationship was studied both experimentally and computationally. A transition state model proposed to explain the origin of the enantioselectivity was supported by computational studies.

Comments

Permanent URL: http://dx.doi.org/10.7936/K7T43R43

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