Acylative Redox Dehydration of Carboxylic Acids and Benzoisothiazolones in the Synthesis of Thioesters with Triethylphosphite as a Terminal Reductant Open Access

Abstract

A series of structurally diverse thioesters was synthesized through a redox dehydration reaction with carboxylic acids using a benzoisothiazolone / P(OEt)3 system. Unlike previous systems that utilized various triorganophosphines as the reductant, pure product was typically obtained in good yield after a basic wash and trituration with no need for chromatography. The thioester scope included products derived from amino acids, lipoic acid, and abscisic acid, as well as acids containing oxadiazole or azide functional groups. Acids that possessed steric hindrance around the carbonyl group were found to give lower yields, possibly due to the intermediate thiolate being unable to easily approach the cationic acyl phosphorous intermediate. Though 5-nitro benzoisothiazolones consistently provided good product yields, 2-pyridyl benzoisothiazolones were more troublesome as their thiolate intermediate preferentially tautomerizes into the unreactive thione form. Future work will delve into expanding the library of benzoisothiazolones and optimizing the reaction conditions towards a catalytic system for the formation of amides, peptides, ketones, and esters.

Table of Contents

Introduction. 1

Results / Discussion

Benzoisothiazolone Synthesis. 10

Thioester Synthesis. 12

Expanding the Thioester Library. 18

Large-Scale Thioester Synthesis. 20

Thioester Synthesis from Sterically Hindered Carboxylic Acids. 21

Unsuccessful Thioesters. 23

An Unsuccessful Benzoisothiazolone. 24

Conclusion. 28

Experimental. 29

References. 59

NMR Spectra. 61

About this Master's Thesis

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School	Laney Graduate School
Department	Chemistry
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Chemistry, Organic
Keyword	benzoisothiazolone thioester redox dehydration
Committee Chair / Thesis Advisor	Liebeskind, Lanny S, Emory University
Committee Members	Liotta, Dennis C, Emory University McDonald, Frank, Emory University

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