Buchwald–Hartwig amination

About: Buchwald–Hartwig amination is a research topic. Over the lifetime, 222 publications have been published within this topic receiving 13961 citations. The topic is also known as: Buchwald-Hartwig reaction & Buchwald-Hartwig amination.

Biaryl Phosphane Ligands in Palladium‐Catalyzed Amination

Abstract: Palladium-catalyzed amination reactions of aryl halides have undergone rapid development in the last 12 years, largely driven by the implementation of new classes of ligands. Biaryl phosphanes have proven to provide especially active catalysts in this context. This Review discusses the application of these catalysts in C-N cross-coupling reactions in the synthesis of heterocycles and pharmaceuticals, in materials science, and in natural product synthesis.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Abstract: Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

Transition Metal Catalyzed Synthesis of Arylamines and Aryl Ethers from Aryl Halides and Triflates: Scope and Mechanism.

Abstract: Oxidative addition and reductive elimination are the central steps in new palladium-catalyzed chemistry that forms C–N and C–O bonds in arylamines and ethers. In the potential mechanism shown on the right the amine is formed by reductive elimination from a four-coordinate, 16-electron amido aryl complex. The use of a chelating ligand such as 1,1′-bis(diphenylphosphanyl)ferrocene (DPPF) reduces the occurrence of the competing β-hydrogen elimination. X=Br, I; R, R′=alkyl, aryl.

Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides.

Abstract: Many active pharmaceuticals, herbicides, conducting polymers, and components of organic light-emitting diodes contain arylamines. For many years, this class of compound was prepared via classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. However, during the past decade, palladium-catalyzed coupling reactions of amines with aryl halides have largely supplanted these earlier methods. Successive generations of catalysts have gradually improved the scope and efficiency of the palladium-catalyzed reaction. This Account describes the conceptual basis and utility of our latest, "fourth-generation" palladium catalyst for the coupling of amines and related reagents with aryl halides. In the past five years, we have developed these catalysts using the lessons learned from previous generations of catalysts developed in our group and in other laboratories. The ligands on the fourth-generation catalyst combine the chelating properties of the aromatic bisphosphines of the second-generation systems with the steric properties and strong electron donation of the hindered alkylphosphines of the third-generation systems. The currently most reactive catalyst in this class is generated from palladium and a sterically hindered version of the Josiphos family of ligands that possesses a ferrocenyl-1-ethyl backbone, a hindered di-tert-butylphosphino group, and a hindered dicyclohexylphosphino group. This system catalyzes the coupling of aryl chlorides, bromides, and iodides with primary amines, N-H imines, and hydrazones in high yield. The reaction has broad scope, high functional group tolerance, and nearly perfect selectivity for monoarylation. It also requires the lowest levels of palladium that have been used for C-N coupling. In addition, this latest catalyst has dramatically improved the coupling of thiols with haloarenes to form C-S bonds. Using ligands that lacked one or more of the structural elements of the most active catalyst, we examined the effects of individual structural elements of the Josiphos ligand on catalyst activity. This set of studies showed that each one of these elements contributes to the high reactivity and selectivity of the catalyst containing the hindered, bidentate Josiphos ligand. Finally, we examined the effect of electronic properties on the rates of reductive elimination to distinguish between the effect of the properties of the M-N sigma-bond and the nitrogen electron pair. We have found that the effects of electronic properties on C-C and C-N bond-forming reductive elimination are similar. Because the amido ligands contain an electron pair, while the alkyl ligands do not, we have concluded that the major electronic effect is transmitted through the sigma-bond.

Practical Palladium Catalysts for C-N and C-O Bond Formation

Abstract: The development of new palladium catalysts for the arylation of amines and alcohols with aryl halides and sulfonates is reviewed. Initial systems as well as mechanistic issues are discussed briefly, while subsequent generations of catalysts are described in greater detail. For these later generations of catalysts, substrate scope and limitations are also discussed. The review is organized by substrate class. Modifications and improvements in technical aspects of reaction development are described where appropriate. In addition, applications of this technology toward natural product synthesis, new synthetic methodology, and medicinal chemistry are chronicled. This review is organized in a manner that is designed to be useful to the synthetic organic chemist.