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Über dieses Buch

This thesis presents the latest developments in new catalytic C–C bond formation methods using easily accessible carboxylate salts through catalytic decarboxylation with good atom economy, and employing the sustainable element iron as the catalyst to directly activate C–H bonds with high step efficiency. In this regard, it explores a mechanistic understanding of the newly discovered decarboxylative couplings and the catalytic reactivity of the iron catalyst with the help of density functional theory calculation.

The thesis is divided into two parts, the first of which focuses on the development of a series of previously unexplored, inexpensive carboxylate salts as useful building blocks for the formation of various C–C bonds to access valuable chemicals. In turn, the second part is devoted to several new C–C bond formation methodologies using the most ubiquitous transition metal, iron, as a catalyst, and using the ubiquitous C–H bond as the coupling partner.

Inhaltsverzeichnis

Frontmatter

New Carbon–Carbon Coupling Reactions Based on Decarboxylation

Frontmatter

Chapter 1. Transition Metal-Catalyzed Decarboxylation and Decarboxylative Cross-Couplings

Transition metal-catalyzed decarboxylative cross-coupling reactions have recently emerged as a new and important category of organic transformations that find versatile applications in the construction of carbon–carbon and carbon–heteroatom bonds. The use of relatively cheap and stable carboxylic acids to replace organometallic reagents enables the decarboxylative cross-coupling reactions to proceed with good selectivities and functional group tolerance. In the present review, we summarize the various types of decarboxylative cross-coupling reactions catalyzed by different transition metal complexes. The scope and applications of these reactions are described. The challenges and opportunities in the field are discussed.

Rui Shang

Chapter 2. Palladium-Catalyzed Decarboxylative Coupling of Potassium Oxalate Monoester with Aryl and Alkenyl Halides

Abstract
Pd-catalyzed decarboxylative cross-couplings of aryl iodides, bromides, and chlorides with potassium oxalate monoesters have been discovered. This reaction is potentially useful for laboratory-scale synthesis of aryl and alkenyl esters. Pd catalyst with bidentate phosphine ligands was found as the optimal catalyst, and unlike other reported decarboxylative couplings, copper is not needed as support catalyst in this reaction. The theoretical calculation shows that the decarboxylation on Pd(II) is the rate-determining step, with a transition state where Pd(II) has a five-coordination state. The calculated energy barrier of rate-determining step is about ∼30 kcal/mol, which is in accordance with the optimized reaction temperature.
Rui Shang

Chapter 3. Synthesis of Polyfluorobiaryls via Copper-Catalyzed Decarboxylative Couplings of Potassium Polyfluorobenzoates with Aryl Bromides and Iodides

In this chapter, we report a copper-catalyzed decarboxylative cross-coupling of potassium polyfluorobenzoates with aryl iodides and bromides. This reaction can be used for the preparation of polyfluoroaromatic compounds and polyfluorostilbene. The reactants used in the reaction are easily accessible nonvolatile polyfluorobenzoate salts. Mechanistic studies suggest that decarboxylation occurs at first on copper(I) to generate a polyfluorophenylcopper(I) intermediate, which then undergoes oxidative addition with aryl halides and reductive elimination to produce the coupling products.

Rui Shang

Chapter 4. Palladium-Catalyzed Decarboxylative Couplings of Potassium Polyfluorobenzoates with Aryl Bromides, Chlorides, and Triflates

Abstract
Pd-catalyzed decarboxylative cross-coupling of potassium polyfluorobenzoates with aryl bromides, chlorides, and triflates is achieved using diglyme as the solvent. The reaction is useful for synthesis of polyfluorobiaryls from readily accessible and nonvolatile polyfluorobenzoate salts. Different from the Cu-catalyzed decarboxylation cross-coupling where oxidative addition is the rate-limiting step, in the Pd-catalyzed version decarboxylation is the rate-limiting step.
Rui Shang

Chapter 5. Construction of C(sp3)–C(sp2) Bonds Via Palladium-Catalyzed Decarboxylative Couplings of 2-(2-Azaaryl)Acetate Salts with Aryl Halides

Abstract
Pd-catalyzed decarboxylative cross-couplings of 2-(2-azaaryl)acetates with aryl halides and triflates have been discovered. This reaction is potentially useful for the synthesis of some functionalized pyridines, quinolines, pyrazines, benzoxazoles, and benzothiazoles. Theoretical analysis shows that the nitrogen atom at the 2-position of the heteroaromatics directly coordinates to Pd(II) in the decarboxylation transition state.
Rui Shang

Chapter 6. Synthesis of α-Aryl Nitriles and α-Aryl Acetate Esters Via Palladium-Catalyzed Decarboxylative Couplings of α-Cyano Aliphatic Carboxylate Salts and Malonate Monoester Salts with Aryl Halides

Palladium-catalyzed decarboxylation coupling reaction between α-cyano aliphatic carboxylate salts with aryl chlorides, aryl bromides, or aryl triflates has been discovered. The reaction is competent for the synthesis of secondary, tertiary, and quaternary α-aryl nitriles utilizing cheap and low-toxic starting materials. This reaction is demonstrated to be useful to synthesize two drug molecules, Flurbiprofen and Anastrozole in gram scale, showcasing its applicability as an alternative choice of the Buchwald–Hartwig α-arylation reaction. The concept of decarboxylative α-arylation reaction was also extended to the synthesis of α-aryl acetate from malonate monoester salt.

Rui Shang

Chapter 7. Palladium-Catalyzed Decarboxylative Couplings of Nitrophenyl Acetate Salts and Its Derivatives with Aryl Halides

Abstract
In this chapter, we report the palladium-catalyzed decarboxylative cross-coupling of 2-nitrophenyl acetates and 4-nitrophenyl acetates with aryl bromides and chlorides. Because the nitro group can be easily converted to many other functional groups in synthetic organic chemistry, this reaction provides a new path for the synthesis of diverse functionalized 1,1-diaryl methanes and their derivatives.
Rui Shang

Chapter 8. Palladium-Catalyzed Decarboxylative Benzylation of α-Cyano Aliphatic Carboxylate Salts with Benzyl Electrophiles

Abstract
The palladium-catalyzed decarboxylative benzylation of α-cyano aliphatic carboxylate salts with benzyl electrophiles was discovered. This reaction exhibits good functional group compatibility and proceeds under relatively mild conditions. A diverse range of quaternary, tertiary, and secondary β-aryl nitriles can be conveniently prepared by this method with good to excellent yield, and many of them are difficult to be synthesized by strong base-mediated nucleophilic substitution.
Rui Shang

New Carbon–Carbon Coupling Reactions Based on Iron-Catalyzed C–H Activation

Frontmatter

Chapter 9. Recent Developments of Iron-Catalyzed Directed C–H Activation/C–C Bond Formation Reactions

Abstract
Driven by the interest in chemical utilization of ubiquitous metals that are abundant and non-toxic, iron catalysis has become a rapidly growing area of research, and iron-catalyzed C–H activation is actively explored in recent years. In this chapter, I summarize the developments of iron-catalyzed C–H activation that emerged recently.
Rui Shang

Chapter 10. β-Arylation of Carboxamides Via Iron-Catalyzed C(sp3)–H Bond Activation

Abstract
Directed C(sp3)–H bond functionalization has been studied mainly by using precious metal catalysts, such as Pd, Ru, Rh, and Ir under harsh conditions. Generally, these metal-catalyzed C–H functionalization reactions are based on the formation of a C(sp3)-metallacycle. Iron-catalyzed C(sp3)–H functionalization has been studied mainly using radical processes. Functionalization of an unactivated C(sp3)–H bond via formation of a ferracycle intermediate is limited to stoichiometric reactions. We report here an iron/biphosphine-catalyzed directed arylation of a C(sp3)–H bond in an aliphatic carboxamide with an organozinc reagent in high yield under mild oxidative conditions. The choice of the directing group and of the biphosphine ligand was crucial for the success of this reaction. This reaction shows selectivity for a primary C–H over a secondary one and is sensitive to steric factors on both the amide and the Grignard reagent. Various β-arylated aliphatic carboxamides can be readily prepared by using this method.
Rui Shang

Chapter 11. Iron-Catalyzed Directed C(sp2)–H Bond Functionalization with Organoboron Compounds

Abstract
Iron, the most abundant transition metal on earth, has so far not received enough attention in catalytic organic synthesis because the catalytic activity of organoiron species is often difficult to control, resulting in narrow applicability. We report here that an iron-catalyzed C–H functionalization reaction allows the coupling of a wide variety of combinations of aromatic, heteroaromatic and olefinic substrates, and alkenyl, alkyl and aryl boron compounds among the reactions catalyzed by precious metals such as palladium. We rationalize these results by the involvement of an organoiron(III) reactive intermediate that is responsible for the C–H bond activation process, and a metal-to-ligand charge transfer that enables smooth catalytic turnover via an iron(I) intermediate.
Rui Shang
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