Chemistry and Chemical Biology ETDs

Chenguang Yu

Publication Date

7-1-2016

Abstract

Development of efficient organocatalytic reactions for the facile assembly of synthetically and medicinally useful molecules is an important task in modern organic synthesis. Towards this end, my Ph. D. study focuses on the development of novel organocatalytic reactions for the construction of structurally diverse molecular architectures. A chiral bifunctional amine thiourea as promoter has been developed as an efficient solution to a long standing challenging issue in atropo-enantioselective transesterification of the Bringmann lactones. This organocatalytic approach delivers the first highly enantioselective, high yielding dynamic kinetic resolution process for the preparation of axially chiral biaryl compounds with a broad substrate scope under mild reaction conditions. The higher reaction efficiency attributes to a distinct synergistic activation by bifunctional amine and thiourea groups from previous reported methods relying on mono activation. The new reactivity of N, O-acetals in an aminocatalytic fashion is harnessed for organic synthesis. Unlike widely used strategies requiring the use of acids and/or elevated temperatures, direct replacement of the amine component of the N, O-acetals by carbon-centered nucleophiles for C-C bond formation is realized under mild reaction conditions. Furthermore, without preformation of the N, O-acetals, amine catalyzed in situ formations of N, O-acetals are developed. Coupling both reactions into one-pot operation enables to achieve a catalytic process. We demonstrate the employment of simple anilines as promoters for the cyclization-substitution cascade reactions. The process offers an alternative approach to structurally diverse, ‘privileged’ 2-substituted 2H-chromenes, 1,3-dihydroisobenzofurans and isochromans. The synthetic power of the new process is furthermore shown by its application in the synthesis of natural products and biologically active molecules. Finally, a chiral amine/Lewis acid synergistically catalyzed cyclization-Michael cascade reaction has also been developed for the construction of chiral γ,γ-disubstituted butenolides. More significantly, the binary catalytic system promoted cyclization-Michael-aldol cascade reactions is also applied for the synthesis of (-)-aromdendranediol. The merits of this strategy are not only the employment of simple and cost-effective starting materials but also the enhancement of yields by the synergistic catalysis effect.

Language

English

Keywords

Organic synthesis, Organocatalysis, Cascade reaction, Metal catalysis

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Feng, Changjian

Second Committee Member

Liang, Fu-Sen

Third Committee Member

Melancon, Charles E. (Chad) III

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