Download or read book Development of Novel Cross Coupling Reactions Via Nickel Catalyzed C O C N Bond Activation and Nickel Photoredox Dual Catalysis written by Huifeng Yue and published by . This book was released on 2018 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Nickel Catalysis in Organic Synthesis written by Sensuke Ogoshi and published by John Wiley & Sons. This book was released on 2020-03-09 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive reference to nickel chemistry for every scientist working with organometallic catalysts Written by one of the world?s leading reseachers in the field, Nickel Catalysis in Organic Synthesis presents a comprehensive review of the high potential of modern nickel catalysis and its application in synthesis. Structured in a clear and assessible manner, the book offers a collection of various reaction types, such as cross-coupling reactions, reactions for the activation of unreactive bonds, carbon dioxide fixation, and many more. Nickel has been recognized as one of the most interesting transition metals for homogeneous catalysis. This book offers an overview to the recently developed new ligands, new reaction conditions, and new apparatus to control the reactivity of nickel catalysts, allowing scientists to apply nickel catalysts to a variety of bond-forming reactions. A must-read for anyone working with organometallic compounds and their application in organic synthesis, this important guide: -Reviews the numerous applications of nickel catalysis in synthesis -Explores the use of nickel as a relatively cheap and earth-abundant metal -Examines the versatility of nickel catalysis in reactions like cross-coupling reactions and CH activations -Offers a resource for academics and industry professionals Written for catalytic chemists, organic chemists, inorganic chemists, structural chemists, and chemists in industry, Nickel Catalysis in Organic Synthesis provides a much-needed overview of the most recent developments in modern nickel catalysis and its application in synthesis.

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 Development of Nickel Catalyzed Cross Coupling Reactions written by Liana Hie and published by . This book was released on 2016 with total page 620 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition metal-catalyzed cross-couplings provide a powerful means to assemble carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. Although Pd catalysis is most commonly used in these transformations, Ni catalysis offers a valuable alternative due to the low cost and high reactivity of Ni. More importantly, Ni catalysis has proven effective for the activation of traditionally inert carbon-heteroatom bonds and therefore provides exciting opportunities with regard to chemical reactivity and synthetic applications. Chapter one, two, and three describe the development of practical cross-coupling methodologies. Chapter one explains the amination of aryl sulfamates and carbamates that relies on an air-stable Ni(II) precatalyst. Chapter two introduces the development of green cross-couplings of phenolic derivatives and aryl halides to form biaryls. Subsequently, the couplings of heterocycles, which are commonly encountered in natural product synthesis and in the pharmaceutical sector, are described. Chapter three describes the development of green cross-couplings of aryl sulfamates and chlorides to form aryl amines. Chapter four and seven concern the utility of amides as electrophilic cross-coupling partners. These traditionally unreactive moieties are activated by nickel and coupled to alcohols to form acyl C-O bonds. This study suggests that amides may serve as useful building blocks to construct carbon-carbon and carbon-heteroatom bonds. Chapter four describes the development of nickel-catalyzed activation of benzamides and chapter seven introduces the development of nickel-catalyzed activation of aliphatic amide derivatives. Chapter five describes the nickel-catalyzed activation of the acyl carbon-oxygen bonds of methyl esters through an oxidative addition process. The oxidative addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and Al(OtBu)3 additive on the kinetics and thermodynamics of the reaction. Chapter six focus on the nickel-catalyzed Heck cyclization for the construction of quaternary stereocenters. This transformation is demonstrated in the synthesis of 3,3-disubstituted oxindoles, which are prevalent motifs seen in bioactive molecules.

Download or read book Reaction Development and Mechanistic Analysis in Nickel Photoredox Catalysis written by Nicholas A. Till and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition metal-catalyzed cross-coupling has had a significant impact onpharmaceutical, agrochemical, and materials science research. This broad class of synthetic reactions has dramatically streamlined the synthesis of molecules at the center of research in these areas and others. The development of cross-coupling reactions for such applications continues to occupy a central role in the synthetic organic chemistry community. The advent of photoredox catalysis and its merger with transition metal catalysis has further elevated this broader reaction platform by expanding the scope of accessible bond-forming and bond-breaking events. These advances in cross-coupling technology have seen widespread adoption in academic and industrial settings, but we are just beginning to understand how these processes function on a mechanistic level.This thesis describes the discovery of new reactivity within the broader context of nickel/photoredox dual-catalysis as well as studies into the mechanisms underlying multiple cross-coupling reactions within this regime. Chapter 2 details the discovery of a stereoselective approach to alkyne radical addition using carboxylic acids to effect an overall alkyne hydroalkylation process. In chapter 3, a nickel C-O reductive elimination process is studied in detail using transient absorption spectroscopy and stoichiometric organometallic experiments. Chapter 4 covers the use of multiple spectroscopic, kinetic, and organometallic studies to uncover the mechanism of a Ni/photoredox aryl amination reaction. Finally, the use of pulse radiolysis and spectroelectrochemistry to generate and study short-lived Ni(I) intermediates relevant to Ni/photoredox cross-coupling is disclosed in chapter 5.

Download or read book Development and Mechanistic Understanding of Nickel catalyzed Cross couplings Via C N and C O Bond Activation written by Olivia Bercher and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation is focused on developing methods through activation of C-N bonds to form new C(sp3)-C(sp3) bonds as well as understanding the mechanism behind these transformations. In addition to gaining understanding of the mechanism via C-N bond activation, it also focuses on gaining insight on the mechanism of a Suzuki arylation via C-O bond activation.

Download or read book Development of Novel Synthetic Approaches in Nickel catalyzed Cross coupling Reactions written by Takashi Tomioka and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Development of Stereospecific Nickel Catalyzed Cross Coupling and Reductive Cross Electrophile Coupling Reactions written by Lucas William Erickson and published by . This book was released on 2017 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, the Jarvo lab has developed the field of stereospecific nickel-catalyzed cross-coupling reactions of benzylic electrophiles. This chemistry allows for straightforward synthesis of asymmetric C--C bonds. The focus of this dissertation is on the study of the mechanism of these transformations, and the development of reductive cross-electrophile coupling reactions.First, the mechanism of the nickel-catalyzed Kumada cross-coupling reaction was studied via a 13C kinetic isotope effect experiment. This experiment indicated that oxidative addition of the nickel catalyst into the C--O sigma bond was the rate limiting step. Combining this data with a rate law allowed us to propose a catalytic cycle for this reaction. Additionally, the nickel-catalyzed deoxygenation of benzylic ethers was optimized for the formation of diaryl methanes. Deoxygenation performed best with a proton-rich Grignard reagent. We demonstrated that these Grignard reagents act as the hydride source for the reduction reaction.Next, an intramolecular nickel-catalyzed reductive cross-electrophile coupling reaction of benzylic ethers and alkyl chlorides was developed. This reaction proceeds with a variety of extended aromatic and heteroaromatic groups to produce cyclopropane rings in great yields and diastereoselectivity. This is the first example of a stereospecific reductive cross-electrophile coupling reaction, as well as the first to employ alkyl ethers and alkyl halides as the electrophiles.Finally, the work on nickel-catalyzed reductive cross-electrophile coupling reactions was expanded to synthesize vinylcyclopropanes from allylic ethers and alkyl halides. This reaction occurs with both alkyl fluorides and alkyl chlorides. To the best of our knowledge, this is the first reported cross-electrophile coupling reaction of an alkyl fluoride. Ring contraction proceeds with high stereospecificity, providing selective synthesis of either diastereomer of di- and tri-substituted cyclopropanes. The utility of this methodology is demonstrated by several synthetic applications including the synthesis of the natural product dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific ring contractions, providing access to synthetically useful hydroxymethyl cyclopropanes.

Download or read book Development of Nickel catalyzed Stereospecific Cross coupling Reactions written by Buck L. H. Taylor and published by . This book was released on 2012 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition-metal catalyzed cross-coupling reactions are powerful methods for the synthesis of natural products and medicinal compounds. Cross-coupling reactions of secondary alkyl electrophiles are currently more challenging than those of aryl or vinyl halides, but these reactions enable the construction of tertiary stereogenic centers with control of configuration. Several methods have been reported for the stereoconvergent cross-coupling of alkyl halides using chiral nickel catalysts. Herein, we report the development of a stereospecific cross-coupling reaction of enantioenriched benzylic ethers using achiral nickel catalysts. We initially performed mechanistic studies to determine the stereochemical course of established nickel-catalyzed cross-coupling reactions. A deuterium-labeled alkylborane reagent was used to establish that transmetalation from boron to nickel occurs with retention of configuration. In addition, these studies establish that alkylnickel intermediates are stereochemically stable under these cross-coupling conditions. A stereospecific cross-coupling reaction of benzylic ethers with alkyl Grignard reagents has been developed. Enantioenriched benzylic ethers, derivatives of easily synthesized chiral secondary alcohols, undergo cross-coupling with high enantiospecificity using an achiral nickel catalyst. The method was applied to the asymmetric synthesis of a biologically active diarylethane, a common structural motif in medicinally relevant compounds. Initial mechanistic studies are consistent with a rate-limiting oxidative addition that is facilitated by a magnesium Lewis-acid. The cross-coupling method has been extended to include aryl Grignard reagents for the asymmetric synthesis of triarylmethanes. The reaction proceeds in high enantiospecificity and employs an ether leaving group capable of chelating to magnesium ions. The method was applied to the asymmetric synthesis of an anti-breast-cancer agent.

Download or read book Advances in Palladium and Nickel Catalyzed Cross Coupling Reactions written by Ryan Sawatzky and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Homogeneous organometallic complexes have become an indispensable tool as they are employed as catalysts for a large number of chemical transformations. Ancillary ligands, organic molecules that bind to the metal center, are critical for fine tuning the performance of these catalysts. The initial portion of this thesis describes a comparative survey of several state-of-the-art ligands for Pd catalyzed C-O cross-coupling reactions. As part of this survey two sets of conditions are employed: reactions carried out at 90 °C, using 1 mol % Pd, and room temperature reactions, using 7 mol % Pd. In these comparisons, it was found that Rockphos was the ligand of choice for reactions at room temperature, as well for electron rich electrophiles. The Josiphos variant, CyPF-tBu, was the optimal ligand for reactions at elevated temperatures, as well as for activated electrophiles. Many ligands that have found use in Pd chemistry have been repurposed for use in Ni catalysis. While this an effective strategy, it is not necessarily ideal. The bisphosphine PAd-Dalphos has been tailored for Ni catalyzed monoarylation of ammonia, and primary amines. Here, ammonium, methylamine, and ethylamine salts are successfully used as cross-coupling partners employing microwave heating. High yielding reactions, utilizing as little as 1 mol % Ni can be completed in as little as 5 minutes under these conditions. In an effort to establish trends of reactivity in Ni catalysis, the complex (DPEphos)Ni(mesityl)Br was developed for both C-N, C-C cross-coupling reactions. This complex was first established in the cross-coupling of secondary amines, and azoles with activated aryl chlorides. The observation of PhB(OH)2 required as a catalyst activator lead to the development of this complex as a catalyst for C-C cross-coupling using unstable 5-membered heterocyclic boronic acids for challenging biheteroaryl formation. Here reactions conducted at room temperature were found to be comparable to the previous state-of-the-art Ni catalysis. In addition, 3-pyridinyl-boronic acids were also successfully employed. While the scope of reactivity with such challenging substrates was modest, the work herein represents a step forward as only a small handful of examples exist for Ni catalyzed reactions.

Download or read book Oxidative Cross Coupling Reactions written by Aiwen Lei and published by John Wiley & Sons. This book was released on 2016-11-14 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first handbook on this emerging field provides a comprehensive overview of transition metal-catalyzed coupling reactions in the presence of an oxidant. Following an introduction to the general concept and mechanism of this reaction class, the team of authors presents chapters on C-C cross-coupling reactions using organometallic partners, C-Heteroatom bond forming reactions via oxidative couplings, and C-H couplings via C-H activation. The text also covers such groundbreaking topics as recent achievements in the fields of C-C and C-X bond formation reactions as well as C-H activation involving oxidative couplings. With its novel and concise approach towards important building blocks in organic chemistry and its focus on synthetic applications, this handbook is of great interest to all synthetic chemists in academia and industry alike.

Download or read book Single electron Transmetalation Enabling C sp3 Cross coupling Via Photoredox nickel Dual Catalysis written by John C. Tellis and published by . This book was released on 2016 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition metal-catalyzed cross-coupling has afforded synthetic chemists a remarkable variety of effective protocols for the construction of C-C bonds. However, despite the widespread application of these methods in both academic and industrial settings, there remains a notable dearth of protocols for the cross-coupling of secondary sp3-hybridized organometallic reagents. The ramifications of this prominent methodological gap are widespread, limiting the efforts of chemists involved in the development of small molecule therapeutics, agrochemicals, and advanced materials. We recognized that these limitations of conventional cross-coupling were inherent to the mechanistic underpinnings of the reaction manifold itself. Specifically, the two-electron nature of the transmetalation step establishes a reactivity hierarchy wherein C sp3 organometallics are least reactive. Whereas previous strategies had focused on overcoming the high energetic barrier associated with the two-electron transmetalation event, we sought to develop a new manifold for transmetalation that would invert the conventional reactivity hierarchy, thereby rendering sp3-hybridized organometallic reagents most reactive. Realization of this ideal, which he have termed single-electron transmetalation, was achieved through the application of a novel dual catalytic system based on the cooperative functions of an Ir-based photoredox catalyst and a nickel cross-coupling catalyst.

Download or read book Nickel and Palladium Catalyzed Cross Coupling Reactions written by Rebecca Green and published by . This book was released on 2016 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: The following dissertation discusses the development of a nickel catalyst for the synthesis of Csp2-Csp bonds in addition to the development and mechanistic studies of nickel and palladium catalysts for the synthesis of Csp2-N bonds. The first chapter is a review of the cross-coupling reactions discussed in this dissertation. Nickel and palladium will be compared with respect to physical properties and reactivity differences. The challenges associated with nickel-catalyzed cross coupling will be illustrated, while drawing analogies to analogous palladium-catalyzed reactions. The literature background for the synthesis of Csp2-Csp bonds, catalyzed by palladium and palladium/copper catalytic systems, will be reviewed, while highlighting the challenges and limitations of the field. The field of Csp2-N bond-forming reactions will be examined, as the differences in reactivity between nickel and palladium will be emphasized. Chapter 2 discusses our efforts towards the development of a nickel catalyst for the development of a Csp2-Csp bond forming reaction, performed in the absence of a copper co-catalyst. Chapter 3 describes the development of a single-component nickel complex that catalyzes the coupling of aryl chlorides with primary alkylamines. A series of mechanistic experiments, including synthesis of catalytic intermediates and kinetic experiments, were performed to elucidate the mechanism of the reaction. Chapter 4 discusses our report the palladium-catalyzed coupling of aryl halides withammonia and gaseous amines as their ammonium salts. A difference in selectivity between reactions of aryl chlorides and aryl bromides was discovered and investigated. Chapter 5 describes the development of a single-component nickel catalyst for the coupling of aryl chlorides with ammonia and ammonium sulfate to form the corresponding primary arylamines. The application of ammonium salts was extended to the coupling of gaseous amines, such as methylamine and ethylamine, which were subjected to the reaction conditions as their hydrochloride salt.

Download or read book Transition Metal Catalyzed Oxidative Cross Coupling Reactions written by Aiwen Lei and published by Springer. This book was released on 2018-12-14 with total page 192 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive text covering the research and development trends in the booming field of transition metal catalyzed oxidative cross-coupling reactions. Oxidative cross-coupling reaction is a new method to forming chemical bonds besides the traditional cross-coupling reactions. This book provides the answers to how this coupling reaction occurs and what its advantages are. The palladium, copper and iron catalyzed oxidative cross-coupling reactions as the main focuses of interest are described in detail. The oxidative cross-coupling reactions catalyzed by other metals and transition-metal-free oxidative coupling reactions are also introduced.This book provides a useful reference source for researchers and graduates in the field of transition metal catalyzed coupling reactions. It is also valuable to researchers working in pharmaceutical companies, fine organic chemical companies, and etc.

Download or read book Novel Platforms for Cross Coupling and Decarboxylative Functionalization Via Metallaphotocatalysis written by Tiffany Q. Chen and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Access to novel molecular scaffolds in organic synthesis relies on the exploration of new chemical space. Consequently, the development of new methods to rapidly construct diverse, complex molecules has become of increasing importance in the field of synthetic organic chemistry in recent decades. To address these needs, our group leverages the merger of transition metal catalysis and photocatalysis (i.e., metallaphotocatalysis) toward the development of new coupling and activation platforms. The ability of photocatalysis to selectively activate organic substrates via single electron transfer pathways to generate open-shell species under mild conditions, coupled with transition metal cross-coupling, has led to the development of a diverse and powerful array of synthetic manifolds that enable previously elusive bond disconnections and streamline the synthesis of molecules. Although this field has advanced rapidly in the past decade, the development of novel metallaphotocatalytic methods that broadly enable the coupling of diverse fragments continues to be in high demand. This thesis details several efforts that employ metallaphotocatalysis in the development of novel cross-coupling methods and activation modes. First, Chapter 2 describes a new approach for nickel/photoredox-catalyzed cross-electrophile coupling of activated alkyl chlorides and aryl halides, facilitated by silyl radical-mediated halogen atom abstraction as a key design element. Chapter 3 extends this design element to the activation of C(sp2)-Br bonds which, in combination with dual copper/photoredox catalysis, enables a general protocol for trifluoromethylation of aryl bromides. Finally, Chapter 4 describes a novel ligand-to-copper charge transfer platform that promotes the decarboxylative functionalization of aryl carboxylic acids (a modular and abundant yet recalcitrant class of substrates), rendering a previously inaccessible range of aryl carboxylic acids broadly accessible as adaptive functional handles.

Download or read book Nickel Catalyzed Cross Coupling Reactions written by Luke Edward Hanna and published by . This book was released on 2016 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cross-coupling technology has become an indispensable tool for the rapid and efficient synthesis of complex molecules. Over the past few decades a foundational understanding of organometallic chemistry has been laid using palladium and other precious metals. Recent research on first row base metal catalysts such as nickel, cobalt and iron has uncovered new and complementary modes of reactivity compared to their more well-studied precious metal counterparts. While nickel sits one row above palladium on the periodic table, ongoing research has illustrated that nickel possesses a unique reactivity profile. Thus, while nickel is commonly thought of as a cheaper alternative to palladium, research in the field of nickel catalysis has demonstrated far more potential than this. The unique propensity of nickel to undergo single electron chemistry as well as its ability to break strong carbon oxygen bonds make research into nickel reactivity an immensely beneficial endeavor to the fields of inorganic, organometallic and synthetic organic chemistry.Chapter 1 describes the development of a stereospecific Suzuki coupling of benzylic carbamates and pivalates with aryl- and heteroarylboronic esters. The reaction proceeds with selective inversion or retention at the electrophilic carbon, depending on the identity of the ligand used. Tricyclohexylphosphine ligand provides products with retention of configuration at the electrophilic carbon, while an N-heterocyclic carbene ligand SIMes provides products with inversion.Chapter 2 discusses the development of a regio- and stereoselective nickel-catalyzed hydroarylation of alkynes using propargylic carbamates as directing groups. The reaction proceeds under mild reaction conditions using arylboronic acids in the absence of base. A range of heterocycles and functional groups are tolerated under the reaction conditions. Additionally, the method is applied to the synthesis of tamoxifen.Chapter 3 details a nickel-catalyzed cross-electrophile coupling reaction of benzylic esters and aryl halides. Both inter- and intramolecular variants proceed under mild reaction conditions. A range of heterocycles and functional groups are tolerated under the reaction conditions. Additionally, the first example of a stereospecific cross-electrophile coupling of a secondary benzylic ester is described.Chapter 4 presents secondary benzylzinc reagents generated from 2-pyridylcarbinols using a nickel catalyst and diethylzinc. Substrates are activated in situ using a chlorophosphate reagent. Quenching the organozinc reagents allows for facile deoxygenation of 2-pyridylcarbinols in a one-pot reaction with straightforward incorporation of a deuterium label from deuteromethanol. An intramolecular conjugate addition of a secondary benzylzinc reagent with an alpha,beta-unsaturated ester is also demonstrated.

Download or read book Palladium and Nickel catalyzed C N Cross coupling Reactions Featuring Soluble Organic Bases written by Joseph Michael Dennis (Jr.) and published by . This book was released on 2020 with total page 549 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapter 1: Breaking the Base Barrier: An Electron-Deficient Palladium Catalyst Enables the Use of a Common Soluble Base in C-N Coupling Due to the low intrinsic acidity of amines, palladium-catalyzed C-N cross-coupling plagued continuously by the necessity to employ strong, inorganic, or insoluble bases. To surmount the many Due to the low intrinsic acidity of amines, palladium-catalyzed C-N crosscoupling has been practical obstacles associated with these reagents, we utilized a commercially available dialkyl triarylmonophosphine-supported palladium catalyst that facilitates a broad range of C-N coupling reactions in the presence of weak, soluble bases. The mild and general reaction conditions show extraordinary tolerance for even highly base-sensitive functional groups. Additionally, insightful heteronuclear NMR studies using −15N-labeled amine complexes provide evidence for the key acidifying effect of the cationic palladium center. Chapter 2: Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines The ability to use soluble organic amine bases in Pd-catalyzed C-N cross-coupling reactions has provided a long-awaited solution to the many issues associated with employing traditional, heterogeneous reaction conditions. However, little is known about the precise function of these bases in the catalytic cycle or about the effect of variations in base structure on catalyst reactivity. We used 19F NMR to analyze the kinetic behavior of C-N coupling reactions facilitated by different organic bases. In the case of aniline coupling reactions employing DBU, the resting state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction was found to be inhibited by base. Generally, however, depending on the binding properties of the chosen organic base, increasing the concentration of the base can have a positive or negative influence on the reaction rate. Furthermore, the electronic nature of the aryl triflate employed in the reaction directly affects the reaction rate. The fastest reaction rates were observed with electronically neutral aryl triflates, while the slowest were observed with highly electron-rich and electrondeficient substrates. We propose a model in which the turnover-limiting step of the catalytic cycle is dependent on the relative nucleophilicity of the base, compared to that of the amine. This hypothesis guided the discovery of new reaction conditions for the coupling of weakly binding amines, including secondary aryl amines, which were unreactive nucleophiles in our original protocol. Chapter 3: Use of a Droplet Platform to Optimize Pd-Catalyzed C-N Coupling Reactions Promoted by Organic Bases Recent advances in Pd-catalyzed carbon-nitrogen cross-coupling have enabled the use of soluble organic bases instead of insoluble or strong inorganic bases that are traditionally employed. The single-phase nature of these reaction conditions facilitates their implementation in continuous flow systems, high-throughput optimization platforms, and large-scale applications. In this work, we utilized an automated microfluidic optimization platform to determine optimal reaction conditions for the couplings of an aryl triflate with four types of commonly employed amine nucleophiles: anilines, amides, primary aliphatic amines, and secondary aliphatic amines. By analyzing trends in catalyst reactivity across different reaction temperatures, base strengths, and base concentrations, we have developed a set of general recommendations for Pd-catalyzed crosscoupling reactions involving organic bases. The optimization algorithm determined that the catalyst supported by the dialkyltriarylmonophosphine ligand AlPhos was the most active in the coupling of each amine nucleophile. Furthermore, our automated optimization revealed that the phosphazene base BTTP can be used to facilitate the coupling of secondary alkylamines and aryl triflates. Chapter 4: The Quest for the Ideal Base: Rational Design of a Nickel Precatalyst Enables Mild, Homogeneous C-N Cross-Coupling Palladium-catalyzed amination reactions using soluble organic bases have provided a solution to the many issues associated with heterogeneous reaction conditions. Still, homogeneous C-N crosscoupling approaches cannot yet employ bases as weak and economical as trialkylamines. Furthermore, organic base-mediated methods have not been developed for Ni(0/II) catalysis, despite some advantages of such systems over analogous Pd-based catalysts. We designed a new air-stable and easily prepared Ni(II) precatalyst bearing an electron-deficient bidentate phosphine ligand that enables the cross-coupling of aryl triflates with aryl amines using triethylamine (TEA) as base. The method is tolerant of sterically-congested coupling partners, as well as those bearing base- and nucleophile-sensitive functional groups. With the aid of density functional theory (DFT) calculations, we determined that the electron-deficient auxiliary ligands decrease both the pK[subscript a] of the Ni-bound amine and the barrier to reductive elimination from the resultant Ni(II)-amido complex. Moreover, we determined that precluding Lewis acid-base complexation between the Ni catalyst and the base, due to steric factors, is important for avoiding catalyst inhibition.