Download or read book Challenging Nickel Catalyzed Cross Couplings Enabled by Ligand Design written by Ryan McGuire and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Carbon-nitrogen linkages are highly prevalent in bioactive molecules, and as such, the development of sustainable methodologies for their formation is of immense importance to both the pharmaceutical and agricultural industries. Within this realm, the advent of homogeneous transition metal catalysis has allowed significant progress to be made in the development of routes toward the formation of these linkages, encompassing a wide range of different carbon and nitrogen-containing organic reagents. Specifically, the development of Pd-catalyzed C(sp2)-N (herein, C-N) cross-coupling (i.e. Buchwald-Hartwig-Amination, BHA) has transformed the way chemists approach solving synthetic problems. Indeed, research efforts in BHA over the past 25 years have allowed for the development of several catalytic systems, encompassing a large array of both (hetero)aryl (pseudo)halide and NH-bearing substrates. Successes in BHA can be largely attributed to the rational design of ancillary ligands, which are able to dramatically influence the reactive properties of Pd through a combination of steric and electronic effects. Despite the utility of BHA, researchers have now turned to more Earth-abundant sources for effecting these transformations, including the implementation of Cu for improved versions of well-known Ullmann-coupling, and the implementation of Ni, both as alternatives to precious Pd. In this thesis, my contributions toward the rational design, syntheses and use of appropriate ancillary ligands for enabling Ni-catalyzed C-N cross-coupling are described. Included are the development of new phosphonite/phosphine ligands such as Phen-DalPhos and related variants, along with the application of Ni-based pre-catalysts for the cross-coupling of ammonia, (hetero)anilines, indoles, sulfonamides, fluoroalkylamines and amides with (hetero)aryl (pseudo)halides under unprecedently mild conditions in Ni-based catalysis.

Download or read book Advances in Nickel Catalyzed C N Cross Coupling Enabled by Tailored Ancillary Ligand Design written by Christopher Lavoie and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The nickel-catalyzed Csp2-N cross-coupling of NH substrates and (hetero)aryl (pseudo)halides for the synthesis of (hetero)anilines is in the midst of a resurgence. Reactivity breakthroughs that have been achieved in this field within the past five years have served to establish Ni catalysis as being competitive with, and in some cases superior to, more well-established Pd- or Cu-based protocols. Whereas the repurposing of useful ancillary ligands from the Pd domain has been the most frequently employed approach in the quest to develop effective Ni-based catalysts for such transformations, considerable progress has been made as of late in the design of ancillary ligands tailored specifically for use with Ni. Bisphosphine ancillary ligands have proven to be well-suited for such an approach, given their modular and facile syntheses. As part of this thesis research, several new bidentate phosphine ancillary ligands were developed that are particularly effective in enabling a range of otherwise challenging Nicatalyzed Csp2-N cross-couplings. Presented herein is a comprehensive summary of my contributions to the field of Ni-catalyzed Csp2-N cross-coupling, achieved by the application of a newly developed PAd-DalPhos ancillary ligand class. It is anticipated that the discussion of key ancillary ligand design concepts and mechanistic considerations presented herein will provide a useful platform for researchers to initiate ancillary ligand design efforts for the continued development of high-performing Ni cross-coupling catalysts.

Download or read book Exploring Ligand Enabled Nickel Catalyzed Cross Coupling of Sulfur Based Nucleophiles written by Connor Simon and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The catalytic synthesis of C(sp2)-N linkages is of utmost significance in modern synthetic chemistry, predominantly due to their prevalence in active pharmaceutical ingredients and natural products. Pd-catalyzed cross-couplings of this type, known colloquially as Buchwald-Hartwig amination (BHA), represent a tremendously important class of reactions in research and industrial settings. The success achieved by BHA can largely be attributed to the rational design of ancillary ligands specifically configured to exploit the natural electronic characteristics of the Pd metal centre. Research efforts surrounding the BHA reaction have enabled the scope of suitable coupling partners to grow rapidly, encompassing a vast array of (hetero)aryl (pseudo)halides and NH couplings partners. Notwithstanding the value of the BHA reaction, concerns over the rising costs of Pd and subsequent sustainability issues have prompted researchers to seek economical methods for accessing these linkages. One of the most promising alternatives to Pd-catalysis is the developing field of its 3d congener, Ni. However, given the relatively underdeveloped nature of Ni-catalyzed C-N bond formation, many questions regarding the mechanistic underpinnings and scope limitations remain unanswered. In this thesis, my contributions include experimental investigations into the elementary steps of a successful Ni-catalyzed cross-coupling. The successful synthesis and characterization of primary Ni-NHR catalytic intermediates reveal previously undocumented C-N bond-forming pathways, and the implementation of the mechanistic lessons learned from these studies allow for the discovery of new ligand-enabled Ni-catalyzed C-N cross-couplings.

Download or read book Investigating the Design of Bisphosphine Ligands for Use in Nickel catalyzed C sp2 N Cross Coupling written by Jillian Clark and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Notwithstanding the matured protocol of palladium-catalyzed C(sp2)-N cross-coupling (Buchwald Hartwig Amination, BHA), the development of nickel-based catalysts that carry out analogous transformations is motivated both by the benefits of employing Earth-abundant, cost-effective first-row transition-metals, and the potential for nickel catalysts to unveil new modes of reactivity. Over the past five years, significant advances in nickel-catalyzed amination chemistry have led to a widespread interest and expansion of this methodology. Although nickel catalysts are highly effective in the cross-coupling of ammonia, alkylamine, indole, and primary amide nucleophiles with (hetero)aryl electrophiles, these catalytic systems have yet to contend with palladium analogs in terms of exceedingly low catalyst loadings and the turnover of increasingly challenging substrate classes. Whereas BHA benefits from an unambiguous set of criteria that defines optimal ancillary ligand properties for this palladium-catalyzed transformation, structure-reactivity trends for nickel counterparts are ill-defined. Additionally, complex mechanistic details exist for nickel-catalyzed C(sp2)-N cross-coupling, which may be responsible for the vague guidelines for optimizing ancillary ligands, and the need for higher catalyst loadings. My thesis work explores ancillary ligand design criteria for nickel-catalyzed C(sp2)-N cross-coupling by cross-examining top-tier bisphosphine ligand classes with aims of clarifying the apparently divergent properties that exist among state-of-the-art ancillary ligands. Information gathered from the systematic comparisons of these ligand classes results in the development of the new bisphosphine ligand, PAd2-DalPhos, which enables the hitherto unknown nickel-catalyzed C(sp2)-N cross-coupling of primary heteroarylamines with (hetero)aryl chlorides. This chemical transformation is highly sought-after by pharmaceutical chemists for the synthesis of heteroatom-dense molecular structures, and reveals a new mode of reactivity involving challenging substrates in the context of nickel catalysis.

Download or read book N Heterocyclic Bisphosphine Ligands For Use In Nickel Catalyzed C sp2 N Cross Coupling written by Alexandre Gatien and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Notwithstanding the utility of Buchwald-Hartwig Amination (BHA) technology, the cost and scarcity of palladium has prompted a move to base metal catalysis in recent years. Nickel has emerged as a prime candidate in this chemistry to compete with palladium, being both cheap and abundant. Amination chemistry with nickel is relatively unexplored, and the distinct electronic properties of nickel offer reactivity benefits over palladium when employing challenging phenol derived electrophiles. While ligand design requirements for BHA chemistry are well-understood, structure-reactivity trends for nickel counterparts are ill-defined, with few ligands capable of promoting these nickel-catalyzed cross-couplings. Following the establishment of PAd-DalPhos as the state-of-the-art ligand in challenging nickel-catalyzed amination reactions, we sought to build on this ortho phenylene bridged motif and explore new architectures encompassing a bulky, modestly electron-donating bisphosphine framework which would favour reductive elimination, the presumed rate-limiting step in the catalytic cycle.

Download or read book Catalysis without Precious Metals written by R. Morris Bullock and published by John Wiley & Sons. This book was released on 2011-08-02 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written for chemists in industry and academia, this ready reference and handbook summarizes recent progress in the development of new catalysts that do not require precious metals. The research thus presented points the way to how new catalysts may ultimately supplant the use of precious metals in some types of reactions, while highlighting the remaining challenges. An essential copanion for organic and catalytic chemists, as well as those working with/on organometallics and graduate students. From the contents: * Catalysis Involving the H' Transfer Reactions of First-Row Transition Metals * Catalytic Reduction of Dinitrogen to Ammonia by Molybdenum Complexes * Molybdenum and Tungsten Catalysts for Hydrogenation, Hydrosilylation and Hydrolysis * Iron in Catalytic Alkene and Carbonyl Hydrogenation Reactions * Olefin Oligomerizations and Polymerizations Catalyzed by Iron and Cobalt Complexes * Cobalt and Nickel Catalyzed Reactions Involving C-H and C-N Activation Reactions * Development of Molecular Electrocatalysts for H2 Oxidation and Production Based on Inexpensive Metals * Nickel-Catalyzed Reductinve Couplings and Cyclizations * Copper-Catalyzed Ligand Promoted Ullmann-Type Coupling Reactions * Copper-Catalyzed Azide-Alkyne Cycloaddition * "Frustrated Lewis Pairs": A Metal-Free Strategy for Hydrogenation Catalysis

Download or read book A Systematic Investigation Into Bisphosphine Ligands for Nickel Catalyzed C sp2 N Cross Coupling written by Nicole Martinek and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Research into transition metal-catalyzed C-N cross-coupling reactions has been driven by a need for robust and facile synthetic routes towards bioactive molecules which are rich in C-N linkages. The use of Pd-based catalysts in Buchwald-Hartwig Amination (BHA) protocols are the most well studied and utilized within industry. The choice of Pd source, ancillary ligand, base, solvent, and the use of additives have been thoroughly investigated aiding in the selection and optimization of reaction conditions. However, research has refocused towards finding more Earth-abundant and cost-effective transition metals capable of comparable reactivity. Ni has proven to be a competitor with the development of new ancillary ligands after efforts to repurpose well-known ligands in Pd-catalysis had limited success. In particular, bisphosphines within the DalPhos ligand family have enabled the Ni-catalyzed N-arylation of challenging substrates including ammonia, alkylamines, heteroarylamines, indole, and amides with (hetero)aryl electrophiles prompting the commercialization of several ligand variants. The effects of varying experimental parameters within these ligand/Ni systems are less established and prompt further investigation in order to determine trends in reactivity and limitations. A systematic evaluation of selected bases and solvents on the effectiveness of leading DalPhos ligand variants in the C-N cross-coupling of structurally varied (hetero)aryl electrophiles with primary and secondary amines is reported herein.

Download or read book Applications of Transition Metal Catalysis in Drug Discovery and Development written by Matthew L. Crawley and published by John Wiley & Sons. This book was released on 2012-05-14 with total page 386 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs. The authors pay particular attention to the challenges of transitioning academically-developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development – it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.

Download or read book Ni and Fe Based Cross Coupling Reactions written by Arkaitz Correa and published by Springer. This book was released on 2016-11-26 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: The series Topics in Current Chemistry Collections presents critical reviews from the journal Topics in Current Chemistry organized in topical volumes. The scope of coverage is all areas of chemical science including the interfaces with related disciplines such as biology, medicine and materials science. The goal of each thematic volume is to give the non-specialist reader, whether in academia or industry, a comprehensive insight into an area where new research is emerging which is of interest to a larger scientific audience. Each review within the volume critically surveys one aspect of that topic and places it within the context of the volume as a whole. The most significant developments of the last 5 to 10 years are presented using selected examples to illustrate the principles discussed. The coverage is not intended to be an exhaustive summary of the field or include large quantities of data, but should rather be conceptual, concentrating on the methodological thinking that will allow the non-specialist reader to understand the information presented. Contributions also offer an outlook on potential future developments in the field.

Download or read book Metal Catalyzed Cross Coupling Reactions and More written by Armin de Meijere and published by John Wiley & Sons. This book was released on 2013-12-04 with total page 1640 pages. Available in PDF, EPUB and Kindle. Book excerpt: This three volume book is the follow-up handbook to the bestselling volume "Metal-Catalyzed Cross-Coupling Reactions", the definitive reference in the field. In line with the enormous developments in this area, this is not a new edition, but rather a new book in three volumes with over 50% more content. This new content includes C-H activation, shifting the focus away from typical cross-coupling reactions, while those topics and chapters found in de Meijere/Diederich's book have been updated and expanded. With its highly experienced editor team and the list of authors reading like an international Who's-Who in the field, this work will be of great interest to every synthetic chemist working in academia and industry.

Download or read book Development of Nickel catalyzed Cross electrophile Coupling of Aryl Chlorides and Triflates with Alkyl Halides written by Seoyoung Kim (Ph.D.) and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cross-coupling is one of the most commonly used reactions in synthetic chemistry. While palladium-catalyzed cross-coupling is well-developed and established, cross-electrophile coupling is significantly younger field of study. In this approach two carbon electrophiles are directly coupled under reductive conditions, avoiding the need to prepare organometallic reagents. This is an attractive strategy because these reactions proceed through mild conditions, have high functional group tolerance, and employ readily available coupling partners. Nickel-catalyzed cross-electrophile couplings have seen considerable success in the past decade, initially in the coupling of organic iodides and later organic bromides. Despite these advances, the cross-coupling with the more abundant and inexpensive organic chlorides remain elusive due to their low reactivity. Furthermore the nickel-catalyzed cross-coupling of aryl triflates presents analogous challenges due to their differential reactivity. This thesis presents our studies to address these limitations. Through a combination of: (1) new ligand application, (2) fine tuning of alkyl electrophile reactivity through in situ halide exchange, (3) detailed mechanistic investigation of elementary steps, we demonstrate the nickel-catalyzed cross-electrophile coupling of these traditionally inert organic coupling partner. This dissertation is presented as follows: Chapter 1 is an introduction to cross-coupling strategies. Common palladium-catalyzed cross-coupling methods are discussed and their origin of cross-selectivity is highlighted. This is contrasted to cross-electrophile approaches of which mechanism is less well-understood. Early reports on nickel-catalyzed cross-electrophile coupling are presented and how mechanistic studies have elucidated the origin of cross-selectivity in these processes. Finally, the challenges of applying aryl chlorides in these first generation approaches are briefly discussed. Chapter 2 describes the development of nickel-catalyzed cross-electrophile coupling of aryl chlorides with primary alkyl chlorides to form C(sp2)-C(sp3) bonds. Investigation of ligands on selectivity and in situ halide exchange on the activation of C(sp3)-Cl bonds are detailed. Chapter 3 discusses a strategy for nickel-catalyzed cross-electrophile coupling of aryl triflates with alkyl halides. The development of reaction conditions for differing aryl electronics and mechanistic insights are described in detail. Mechanistically driven optimization and the extent of halide exchange to modulate alkyl halide reactivity are also discussed.

Download or read book Modern Organonickel Chemistry written by Yoshinao Tamaru and published by John Wiley & Sons. This book was released on 2006-03-06 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: Organonickel chemistry plays an increasingly important role in organic chemistry, and interest in this topic is now just as keen as in organopalladium chemistry. While there are numerous, very successful books on the latter, a book specializing in organonickel chemistry is long overdue. Edited by one of the leading experts in the field, this volume covers the many discoveries made over the past 30 years, and previously scattered throughout the literature. Active researchers working at the forefront of organonickel chemistry provide a comprehensive review of the topic, including cross-coupling reactions, asymmetric synthesis and heterogeneous catalysis reaction types. A must-have for both organometallic chemists and synthetic organic chemists.

Download or read book Advances in Cross Coupling Reactions written by José Pérez Sestelo and published by MDPI. This book was released on 2020-12-03 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this Special Issue, recent advances in cross-coupling reactions are presented in the form of original research articles, reviews, and short communications. These contributions cover different topics in this area, including novel coupling reactions, reaction conditions, synthetic alternatives, metal ligands, and applications for new pharmaceutical compounds and organic materials. In particular, the reviews deal with methodologies such as the synthesis of diarylketones through palladium catalysis and the most relevant examples of Suzuki–Miyaura and Buchwald–Hartwig coupling reactions in the synthesis of bioactive compounds. The synthetic utility of cross-coupling reactions for the synthesis of medium-size rings and the utility of Stille and Suzuki coupling reactions for the synthesis of new molecular machines based on sterically hindered anthracenyl trypticenyl units are also summarized. The original research articles present the synthesis of 2-alkynylpyrrols by inverse Sonogashira coupling and the synthesis of indoles under oxidative dearomative cross-dehydrogenative conditions. The efficient combination of iridium-catalyzed C–H borylation of aryl halides with the Sonogashira coupling and a sequential iridium-catalyzed borylation of NH-free pyrroles followed by a Suzuki–Miyaura reaction are included. The synthesis of aryl propionic acids, a common structural motif in medicinal chemistry, and the synthesis of new organic dyes are also covered.

Download or read book Development of New Transition Metal Catalysts for C N Bond Formation and Continuous Flow Processes for C F Bond Formation written by Nathaniel Hamilton Park and published by . This book was released on 2015 with total page 391 pages. Available in PDF, EPUB and Kindle. Book excerpt: The work presented in this dissertation addresses the development of new methodologies and processes to form carbon-nitrogen (C-N) and carbon-fluorine (C-F) bonds. The development of methods for the formation of C-N and C-F bonds are highly important to chemistry in general and find broad application in many different areas of research. With regard to C-N bond formation, the development of new nickel and palladium catalyst for C-N cross-coupling is presented. Finally, the development of a new process to enable the rapid preparation of aryl fluorides via the Balz-Schiemann reaction is explored. Chapter 1. Development of an Air-Stable Nickel Precatalyst for the Amination of Aryl Chlorides, Sulfamates, Mesylates, and Triflates. A new air-stable nickel precatalyst for C-N cross-coupling is reported. The developed catalyst system displays a greatly improved substrate scope for C-N bond formation to include both a wide range of aryl and heteroaryl electrophiles and aryl, heteroaryl, and alkyl amines. The catalyst system is also compatible with weak base, allowing for the amination of substrates containing base-sensitive functional groups. Chapter 2. Design of New Ligands for the Palladium-Catalyzed Arylation of a- Branched Secondary Amines. In Pd-catalyzed C-N cross-coupling reactions, a-branched secondary amines are difficult coupling partners and often produce low yields of the desired product. To provide a robust method for accessing N-aryl a-branched tertiary amines, new catalysts have been designed to suppress undesired side reactions often encountered when these amine nucleophiles are used. These advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions. Chapter 3. Rapid Synthesis of Aryl Fluorides in Continuous Flow via the Balz- Schiemann Reaction. The synthesis of aryl fluorides (ArF) is of critical importance for the development of new and potent pharmaceuticals and agrochemicals. While there have been numerous and intense research efforts focused on developing new fluorination methods, the Balz-Schiemann reaction remains a valuable and efficient means of aryl C-F bond construction from a vast pool of available aryl amines. However, the harsh reaction conditions, modest yields, and often prohibitive safety concerns have limited the general application of this methodology. Here, we have developed a semi-flow process that enables safe handling of the potentially explosive aryl diazonium salt intermediates as well as improved yields of the desired aryl fluoride products. This process has been demonstrated on an array of different aryl and heteroaryl amine substrates containing a variety of different functional groups.

Download or read book New Trends in Cross Coupling written by Thomas Colacot and published by Royal Society of Chemistry. This book was released on 2015 with total page 914 pages. Available in PDF, EPUB and Kindle. Book excerpt: Following on from its recognition in the 2010 Nobel Prize for Chemistry, contributors from across the globe present the latest cross-coupling trends in both academia and industry.

Download or read book Applied Cross Coupling Reactions written by Yasushi Nishihara and published by Springer Science & Business Media. This book was released on 2012-12-14 with total page 247 pages. Available in PDF, EPUB and Kindle. Book excerpt: “Applied Cross-Coupling Reactions” provides students and teachers of advanced organic chemistry with an overview of the history, mechanisms and applications of cross-coupling reactions. Since the discovery of the transition-metal-catalyzed cross-coupling reactions in 1972, numerous synthetic uses and industrial applications have been developed. The mechanistic studies of the cross-coupling reactions have disclosed that three fundamental reactions: oxidative addition, transmetalation, and reductive elimination, are involved in a catalytic cycle. Cross-coupling reactions have allowed us to produce a variety of compounds for industrial purposes, such as natural products, pharmaceuticals, liquid crystals and conjugate polymers for use in electronic devices. Indeed, the Nobel Prize for Chemistry in 2010 was awarded for work on cross-coupling reactions. In this book, the recent trends in cross-coupling reactions are also introduced from the point of view of synthesis design and catalytic activities of transition-metal catalysts.

Download or read book Cross Coupling Reactions written by Norio Miyaura and published by Springer. This book was released on 2003-07-01 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 1972, a very powerful catalytic cycle for carbon-carbon bond formation was 2 first discovered by the coupling reaction of Grignard reagents at the sp -carbon. Over the past 30 years, the protocol has been substantially improved and expanded to other coupling reactions of Li,B,N,O,Al,Si,P,S,Cu,Mn,Zn,In,Sn, and Hg compounds. These reactions provided an indispensable and simple methodology for preparative organic chemists. Due to the simplicity and rel- bility in the carbon-carbon, carbon-heteroatom, and carbon-metalloid bo- formations,as well as high efficiency of the catalytic process,the reactions have been widely employed by organic chemists in various fields. Application of the protocol ranges from various syntheses of complex natural products to the preparation of biologically relevant molecules including drugs, and of sup- molecules, and to functional materials. The reactions on solid surfaces allow robot synthesis and combinatorial synthesis. Now, many organic chemists do not hesitate to use transition metal complexes for the transformation of org- ic molecules. Indeed, innumerable organic syntheses have been realized by the catalyzed reactions of transition metal complexes that are not achievable by t- ditional synthetic methods. Among these, the metal-catalyzed cross-coupling reactions have undoubtedly contributed greatly to the development of such a new area of “metal-catalyzed organic syntheses”. An excellent monograph for the cross-coupling reactions and other met- catalyzed C-C bond-forming reactions recently appeared in Metal-catalyzed Cross-coupling Reactions (Wiley-VCH,1998).