Date of Degree

6-2021

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Yu Chen

Committee Members

William H. Hersh

Shengping Zheng

Subject Categories

Organic Chemistry

Keywords

ring-opening of isoxazoles and isoxazolines, aged NMP, iron-catalyzed transfer hydrogenation, iodine-mediated C-N bond cross-coupling, formylation of amides, ICl-mediated functionalization of β-alkoxy alkynes

Abstract

This thesis work focuses on developing facile, low-cost, and environmentally friendly reactions, specifically the iron and iodine-mediated reactions, including (1) iron-catalyzed reductive ring-opening of 3,5-disubstituted isoxazoles and isoxazolines in aged N-methyl-2-pyrrolidone (NMP*), (2) iodine-mediated C-N bond cross-coupling reactions between amides and aldehydes, and (3) ICl-mediated functionalization of β-alkoxy alkynes – synthesis of α-iodo-γ-chloro-ketones.

Chapter I provides a background introduction on previous synthesis and applications of β-enaminones and 1,3-diketones that play as synthons or ligands. Ring-openings of heterocycles, such as isoxazoles and isoxazolines have attracted great attentions. A newly developed iron-catalyzed reductive system was established upon our previous palladium-catalyzed research. 3,5-Disubstituted isoxazoles and isoxazolines as starting materials undergo an iron-catalyzed reductive ring-opening in aged N-methyl-2-pyrrolidone (NMP*). 5-Hydroxy-N-methyl-2-pyrrolidone that is generated in situ via a simple activation of commercial NMP acts as the hydrogen donor in the iron-catalyzed transfer hydrogenation reaction. This is the first attempt employing a combination of an iron catalyst and 5-hydroxy-N-methyl-2-pyrrolidone as reducing agents in a transfer hydrogenation reaction. The protocol was highly efficient for the synthesis of β-enaminones and 1,3-diketones, providing a versatile route for the preparation of these 1,3-difunctional compounds bearing diversified substitution patterns.

Chapter II presents the introduction about general synthetic methods for iodine-mediated C-N bond cross-coupling reactions. Our work employs TBAI and K2S2O8 as catalysts to tackle the challenge of C-N bond cross-coupling between amides and aldehydes. An oxidative N-acylation occurred between amides and aldehydes. However, another unexpected N-formylation was observed between amides and p-anisaldehyde. It was processed through a phenyl group migration of the peroxosulfate intermediate. The reaction was catalyzed by tetrabutylammonium peroxydisulfate which is the active peroxide. The tetrabutylammonium peroxydisulfate was generated from the combination of TBAI and K2S2O8 and was readily soluble in various organic solvents. These reactions feature several advantages, including the facile and mild conditions, various substrate scopes, and high compatibility for the formation of imides and formyl imides. In addition, the formation of quinazolinones between 2-aminobenzaimdes and aldehydes in the presence of TBAI and K2S2O8 was reported as well.

Chapter III describes a brief introduction about α-halogenated carbonyl compounds and 1,3-dihalogenation. ICl-mediated functionalization of β-alkoxy alkynes is first reported and provides much more chemistry opportunities. The α-iodo-γ-chloro-ketones were formed from alkoxy alkynes at low temperature. In addition, the corresponding cyclization products, i.e., furans, were obtained when mixing alkoxy alkynes with ICl at room temperature.

Share

COinS