Abstract
Thiol esters derived from N-substituted and aryl substituted thiosalicylamides were synthesized. Their aerobic coupling with one equivalent of aryl boronic acids
to give ketones was investigated in the presence of catalytic palladium(0) bis(tricyclohexylphosphine) and copper(I) methyl salicylate. The byproducts of the reaction were found to be mixtures
S-arylation of the thiosalicylamide pendant and ring closure of the thiosalicylamide to form a benzoisothiazolinone. A novel, aerobic ketone synthesis from simple
and complex thiol esters and commercially available boronic acids catalyzed by copper (I) methyl salicylate (CuMeSal) is reported. The reaction is highly chemoselective for thiol esters containing
an N-tert-butyl or N-iso-propyl -2-mercaptobenzamide pendant. The reaction occurs under very mild reaction conditions (ambient temperature, aerobic,
neutral conditions, and in the presence of a broad range of functional groups). The application of this chemistry may prove useful for selective carbon-carbon bond forming reactions on complex
biomolecules. Thiol esters bearing ortho-chelating groups that did not react with copper alone were found to undergo cross-coupling with catalytic amounts of added
Pd(PCy3)2. A new ketone synthesis from simple thiol esters and organic halides using copper (I) carboxylates is reported. The reaction
requires the use of thiol esters containing an N-isopropyl -2-mercaptobenzamide pendant. The reaction occurs under mild reaction conditions (ambient temperature, neutral conditions, under argon). A
preliminary study of the reaction is presented.
Table of Contents
Chapter 1 Aerobic Palladium and Copper Catalyzed Coupling of Boronic Acids and Thiol Esters Derived from Thiosalicylamide: Benzoisothiazolinone Formation versus
S-Arylation..3 1.1
Introduction.......4 1.2 Results and
Discussion......7 1.2.1 Pyridyl Thiol Esters and Their
Reactivity....10 1.2.2 Extending the
Thiol Ester
Library....16 1.2.3 Ketone
Synthesis.......18 1.2.4 Imidazole and Thiazole Derived Thiol Esters and Their Couplings.20 1.2.5 Sterically Hindered Boronic
Acids.......22
1.3
Conclusion...23 1.4 References....................................................................................................................23 1.5
Experimental....26 Chapter 2 An Aerobic, Chemoselective Copper-Templated Coupling of Thiol Esters and Boronic
Acids.77 2.1
Introduction........78 2.2 Results and
Discussion.......79 2.2.1 Reaction
Optimization.....81 2.2.2 Cross-Coupling
Examples...84 2.2.3
Mechanism...86 2.3
Conclusion..88 2.4 References...................................................................................................................89 2.5
Experimental...93 Chapter 3 An Aerobic, Chemoselective, Palladium-Templated Coupling of Thiol Esters and Boronic
acids.120 3.1 Introduction and Initial
Studies.......121 3.1.1 Probing
Catalysis..121 3.1.2 Summary of Work Completed by Dr. Jiri Srogl and Silvia Cabrera123 3.2 Results and
Discussion....125 3.2.1 A Thorough Study of Thiol Ester Pendants.....125
3.2.2 Mechanistic
Insights.....128 3.3
Conclusion.......132 3.4 References................................................................................................................132 3.5
Experimental....134 Chapter 4 The Copper Mediated Coupling of Thiol Esters with Aryl and Heteroaryl Iodides.144 4.1 Introduction and
Background.....145 4.2 Results and
Discussion.......146 4.3
Mechanism..147 4.4
Conclusion......151 4.5 References...............................................................................................................151 4.6
Experimental...152
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