Chemistry and Chemical Biology ETDs

Xiaobei Chen

Publication Date

6-23-2015

Abstract

One of the central goals in modern organic synthesis is to develop efficient synthetic strategies for the preparation and study of complex molecules possessing interesting structural, biological, and physical properties. Toward this end, my Ph. D. work focuses on the development of novel synthetic methodologies for the facile construction of synthetically and biologically significant molecular architectures. The tert-prenylated indoles and indolines are widely present in a large collection of natural products and biologically active compounds. Although significant efforts have been made on the development of efficient methods to prepare these intriguing molecular architectures, few methods have been explored to introduce the challenging reverse prenyl group (1,1-dimethylallyl) at indolyl C2-position. In this regard, we have uncovered the unprecedented efficient aza-Claisen rearrangement involved the two-step reaction of 3-indolyl bromides with enamines as an effective approach to 2-alkylidene substituted indolines. Furthermore, these versatile products have been explored in a number of new organic transformations to create new organic molecules. A notable example is that we have discovered a divergent Prins cyclization strategy to form indole fused seven-membered cyclic ethers and indoline fused five-membered tetrahydrofurans, respectively. Importantly, a novel variant of the Prins cyclization involving an unprecedented oxygen-participated rearrangement in the formation of the indoline fused five-membered tetrahydrofurans is realized for the first time. It is found that aliphatic aldehydes favor the classic Prins cyclization in the 7-membered ring formation while aromatic and allylic aldehydes for the new non-classic pathway for the formation of the 5-membered ring. The observed experimental results have also been rationalized by the computational studies. Fluoroalkene (C=CF) is widely used in organic synthesis and this functionality is often employed as a bioisostere for replacement of the peptide bond in the field of peptide and peptidomimetic chemistry. Given its broad utilities while the lack of general methods to construct the important functionality, we have developed a novel organocatalytic and direct conjugate addition of HF to alkynals catalyzed by a simple secondary amine. The highly stereoselective (Z)-β-fluoroenals are generated. The versatile (Z)-β-fluoroenal adducts serve as versatile building blocks in a variety of new organic transformations, thus generating highly valued, structurally diverse fluorinated compounds.

Language

English

Keywords

aza-Claisen rearrangement, Prins cyclization, conjugate addition

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Qin, Yang

Second Committee Member

Melancon III, Charles

Third Committee Member

Liang, Fu-Sen

Fourth Committee Member

Feng, Changjian

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