Metal Mediated Cross-Coupling Reactions for Carbon-Carbon andCarbon-Nitrogen Bonds Formation under Neutral pH Conditions Open Access
Zhang, Zhihui (2009)
Abstract
Metal Mediated Cross-Coupling Reactions for Carbon-Carbon and Carbon-Nitrogen Bonds Formation under Neutral pH Conditions By Zhihui Zhang
The transition metal-catalyzed cross-coupling of thioorganics with boronic acids or organostannanes under neutral conditions for the construction of C-C bond has found various applications in modern organic synthesis. As an extension of this strategy, a novel cyanide-free cyanation reaction through the palladium(0)-catalyzed, copper(I)-mediated coupling of boronic acids with thiocyanates was developed. This non-basic desulfitative process provides a useful complement to the traditional synthesis of nitriles through metal-catalyzed cross-coupling of aryl halides with cyanide sources.
Based on the extensive study on previous thioorganic-boronic acid cross-couplings, a mechanistically unprecedented desulfitative protocol was developed which was completely catalytic in copper or palladium. A general ketone synthesis through the copper(I)-catalyzed cross-coupling of thiol esters with organoborons or organostannanes was reported. The application of this mechanism to the palladium-catalyzed desulfitative reaction of more thioorganic substrates was proven promising. Present results demonstrated the efficient coupling of heteroaromatic thioethers with boronic acids.
In addition to the selective functionalization of C-S bonds, a novel N-O bond cleavage to give C-N bond products was investigated. Under non-basic and non-oxidative conditions, O-acetyl hydroxamic acids couple efficiently with a variety of organostannanes or boronic acids in the presence of copper(I) sources to generate N-substituted amides and enamides in good yields.
Table of Contents
Chapter 1
Palladium-Catalyzed, Copper-Mediated Coupling of Boronic Acids and Thiocyanates. A Cyanide-Free Cyanation of Boronic Acids
1.1. Introduction and Background...2
1.2. Results and Discussion...6
1.2.1 Preparation of Starting Materials...6
1.2.2 Thiocyanates/Boronic Acid Coupling...7
1.2.3 Mechanistic Consideration...14
1.3. Conclusions...14
1.4. Experimental...15
Chapter 2
Metal-Catalyzed Desulfitative Cross-Coupling Reactions for Carbon-Carbon Bond Formation
2.1 Introduction and Background...26
2.2 Results and Discussion...32
2.2.1 Preparation of Starting Materials...32
2.2.2 Cu-Catalyzed Cross-Coupling of Thiol Esters with Organostannanes...34
2.2.3 Cu-Catalyzed Cross-Coupling of Thiol Esters with Boronic Acids...37
2.2.4 Synthesis of High Enantiopurity Peptidyl Ketones...38
2.2.5 Cu-Catalyzed Cross-Coupling of Thiol Esters with Alkyl Boron Reagents...39
2.2.6 Cu-Catalyzed Cross-Coupling of Thiol Esters with Alkyl Tin Reagents...40
2.2.7 Mechanistic Study...42
2.2.8 Pd-Catalyzed Coupling of Thiol Esters with Boronic Acids...46
2.2.9 Pd-Catalyzed Coupling of Heteroaromatic Thioether with Boronic Acids...50
2.2.10 Mechanistic Speculation...51
2.3 Conclusions...52
2.4 Experimental...52
Chapter 3
New Amidation Reaction by the Copper-Mediated Cross-coupling of Organostannanes and Boronic Acids with O-Acetyl Hydroxamic Acids
3.1 Introduction and Background...81
3.2 Results and Discussion...87
3.2.1 Preparation of O-Substituted Benzohydroxamic Acids...87
3.2.2 N-Amidation of Organostannanes with O-Acyl Hydroxamic Acids...89
3.2.3 Mechanistic Consideration...92
3.2.4 Chemoselectivity Study...94
3.3 Conclusions...94
3.4 Experimental...95
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