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Progress In Nucleophilic Catalysis And Development Of Nickel Catalyzed Cross Couplings Of Propargylic Halides
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Book Synopsis Progress in Nucleophilic Catalysis and Development of Nickel-catalyzed Cross-couplings of Propargylic Halides by : Sean Wesley Smith
Download or read book Progress in Nucleophilic Catalysis and Development of Nickel-catalyzed Cross-couplings of Propargylic Halides written by Sean Wesley Smith and published by . This book was released on 2009 with total page 353 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapter 1 describes the development of two organocatalytic processes. The first is a 13-alkylation reaction of Michael acceptors, and represents a novel umpolung process catalyzed by N-heterocyclic carbenes. The second section discusses the first successful phosphine-catalyzed, y-alkylation reaction of isomerizable allenoates. A highly enantioselective variant of this reaction is described. Chapter 2 discusses nickel-catalyzed cross-coupling reactions of secondary propargylic halides with a variety of organozinc nucleophiles. Section 2.2 describes progress toward an asymmetric alkylation reaction. In Section 2.3, the development of the first alkyl-alkyl secondary-secondary cross-coupling is described; Section 2.4 describes the application of this coupling reaction to the formal synthesis of a-cembra-2,7,1 1-triene-4,6-diol. The last section of this thesis (Section 2.5) discusses the development of the first asymmetric Negishi reaction of arylzinc reagents with secondary electrophiles.
Book Synopsis Nickel Catalysis in Organic Synthesis by : Sensuke Ogoshi
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.
Book Synopsis Nickel-catalyzed Reductive Coupling of Alkyl, Allyl and Vinyl Electrophiles by : Michael R. Prinsell
Download or read book Nickel-catalyzed Reductive Coupling of Alkyl, Allyl and Vinyl Electrophiles written by Michael R. Prinsell and published by . This book was released on 2013 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The nickel-catalyzed reductive coupling of two organic electrophiles to form new carbon-carbon bonds is a fast emerging field of chemistry, with applications to the synthesis of medicinally interesting compounds. This method is an alternative to traditional transition metal-catalyzed cross-coupling reactions of organic electrophiles with organometallic nucleophiles. This thesis details the author's work towards the development of several reactions to reductively couple organic molecules to form Csp3-Csp3 bonds, including alkyl, allyl and vinyl halides. Chapter 1 delves into the background of traditional metal-catalyzed crosscoupling reactions as well as the advantages and challenges associated with using a reductive method to construct C-C bonds. In particular this chapter presents the specific challenges associated with the formation of a carbon-carbon bond between two Csp3 hybridized carbons. Chapter 2 outlines the development of a mild, general dimerization reaction of alkyl halides. This chapter also focuses on the use of sodium iodide to extend the coupling to molecules that are unreactive to the standard reaction conditions. Chapter 3 details work towards the cross-coupling of two alkyl halides. While cross-selectivity remains a challenge, some potential solutions are discussed. Chapter 4 presents the optimization and reaction scope of the coupling of allyl acetates with secondary alkyl halides, as well as progress towards couplings with primary alkyl halides. In addition, the first report of the catalytic coupling of vinyl bromides with allyl acetates is reported. Chapter 5 focuses on work towards the reductive cyclization of alkyl halides and allyl acetates. Initial results show promising diastereomeric ratios. Chapter 6 details work on the dehydrogenative synthesis of bipyridine and terpyridine ligands. These ligands are useful and are used for many reductive coupling reactions in the Weix group"--Pages vi.
Book Synopsis Nickel-catalyzed Electrophile Cross-coupling of Aryl Halides with Alkyl Halides by : Daniel A. Everson
Download or read book Nickel-catalyzed Electrophile Cross-coupling of Aryl Halides with Alkyl Halides written by Daniel A. Everson and published by . This book was released on 2013 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: "This thesis details the author's contributions to the emerging field of electrophile cross-couplings. This new field is related to the well-established field of conventional cross-coupling that uses transition metal-catalysts to facilitate coupling reactions between electrophile-nucleophile pairs. Electrophile cross-coupling uses a conceptually different approach because it seeks to selectively join two different electrophiles with a transition metal-catalyst. The issue of developing cross-selective reactions is the central challenge addressed. Chapter 1 details recent advances and the state-of-the-art in conventional cross-coupling only for the purpose of conceptual comparison to electrophile cross-coupling. Additionally, a review of similar coupling reactions and their mechanisms are presented with the earliest examples of the unique reactivity that guided development of the reactions in this thesis. Chapter 2 details the first cross-selective nickel-catalyzed electrophile cross-coupling of iodoarenes with iodoalkanes. The new method displays exceptional functional group compatibility (-C(O)Me, -NHBoc, 1° and 2° alkyls, -OH) and the catalyst shows chemoselective reaction at C-I bonds over C-B bonds on bifunctional substrates. Mechanistic studies reveal that the reaction likely proceeds without the intermediacy of a carbon nucleophile, and that dimeric by-products arise from disproportionation of nickel intermediates. Chapter 2 also summarizes a detailed mechanistic study conducted in our lab that indicates the cross-coupled product is formed by a radical chain mechanism. Chapter 3 expands on the results of Chapter 2 by increasing the scope of the method to include bromo- and chloroarenes for the first time. Additional competition experiments reveal that the new catalysts and reaction conditions are chemoselective for the cross-coupling of two electrophilic C-Br bonds over conventional cross coupling of C-Br bonds with C-B, C-Sn, or C-Si bonds. Further mechanistic work reveals that [upsilon] [is proportional to] [bromoalkane][^x][catalyst][^y]/[bromoarene][^z] (x, y, and z are positive numbers and could be non-integers). Chapter 4 presents the first electrophile cross-couplings of halogenated pyridines with alkyl bromides. Scope and limitations are discussed in the context of improving the method. Chapter 5 details the effect of additives on other related electrophile coupling reactions"--Pages vii-viii.
Book Synopsis Modern Organonickel Chemistry by : Yoshinao Tamaru
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.
Book Synopsis Ni- and Fe-Based Cross-Coupling Reactions by : Arkaitz Correa
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.
Book Synopsis Nickel-catalyzed Asymmetric Cross-couplings of Secondary Alkyl Electrophiles and Photoinduced, Copper-catalyzed C-N Couplings by : Junwon Choi (Ph. D.)
Download or read book Nickel-catalyzed Asymmetric Cross-couplings of Secondary Alkyl Electrophiles and Photoinduced, Copper-catalyzed C-N Couplings written by Junwon Choi (Ph. D.) and published by . This book was released on 2014 with total page 361 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapter 1 describes the development of three nickel-catalyzed asymmetric Negishi cross-couplings of secondary alkyl electrophiles via a stereoconvergent process. In Section 1.1, asymmetric Negishi arylations and alkenylations of [alpha]-bromonitriles with arylzinc and alkenylzinc reagents are achieved using a nickel/bis(oxazoline) catalyst. Section 1.2 describes stereoconvergent cross-couplings of secondary unactivated alkyl electrophiles, specifically, Negishi arylations and alkenylations of [alpha]-bromosulfonamides and abromosulfones with arylzinc reagents and alkenylzirconium reagents, respectively. Section 1.3 details progress toward asymmetric cross-couplings between [alpha]-haloboronate esters and alkylzinc reagents using a nickel/diamine catalyst. Chapter 2 describes the development of photoinduced, copper-catalyzed C-N couplings between N-heterocycles and aryl halides. In particular, a variety of N-heterocycles, such as indoles, benzimidazoles, imidazoles, and carbazoles, undergo Ullmann couplings under mild conditions (room temperature) with an inexpensive catalyst (Cul, without an added ligand).
Book Synopsis Exploring Ligand-Enabled Nickel-Catalyzed Cross-Coupling of Sulfur-Based Nucleophiles by : Connor Simon
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.
Book Synopsis Development of Nickel-Catalyzed Cross-Coupling Reactions by : Liana Hie
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.
Book Synopsis Development of Nickel-catalyzed Cross-electrophile Coupling of Aryl Chlorides and Triflates with Alkyl Halides by : Seoyoung Kim
Download or read book Development of Nickel-catalyzed Cross-electrophile Coupling of Aryl Chlorides and Triflates with Alkyl Halides written by Seoyoung Kim 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.
Book Synopsis Advances in Nickel-Catalyzed C-N Cross-Coupling Enabled by Tailored Ancillary Ligand Design by : Christopher Lavoie
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.
Book Synopsis Nickel-Catalyzed Cross-Coupling Reactions by : Luke Edward Hanna
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.
Book Synopsis Challenging Nickel-Catalyzed Cross-Couplings Enabled by Ligand Design by : Ryan McGuire
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.
Book Synopsis Development of Nickel-Catalyzed Coupling Reactions by : Mikhail Olegovich Konev
Download or read book Development of Nickel-Catalyzed Coupling Reactions written by Mikhail Olegovich Konev and published by . This book was released on 2017 with total page 503 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition metal catalyzed reactions are ubiquitous in the realm of synthetic chemistry, allowing for the strategic construction of complex molecular frameworks of pharmaceuticals, natural products, and synthetic materials. Palladium-catalyzed cross-coupling reactions are part of the foundation of these transformations, insofar as they were recognized with the 2010 Nobel Prize in chemistry. Traditionally, these reactions have relied on aryl and vinyl electrophiles, whereas the alkyl counterparts have only recently begun to emerge in the literature. Nickel has been on the forefront of enantioconvergent alkyl cross--coupling reactions due to its propensity to undergo single electron chemistry. However, under special conditions, it has a unique ability to break strong carbon--oxygen bonds in a stereospecific manner, making research into its reactivity a valuable endeavor to the field of organometallic chemistry.Chapter 1 describes the development of a stereospecific intramolecular alkyl-Heck cyclization of benzylic ethers. The reaction proceeds with inversion at the electrophilic carbon, for the synthesis of methylenecyclopentanes of both extended pi-electron and simple aromatic systems. The enantioenriched products can be effectively derivatized to cyclic alpha-aryl ketones in good yields with good transfer of chirality. Avenues to expand the utility of this reaction have been identified and further studies are ongoing.Chapter 2 discusses the development of nickel-catalyzed cross-electrophile coupling reactions of benzylic esters and aryl halides. An intermolecular reaction proceeds in high yields for primary benzylic esters for the synthesis of pharmacologically relevant diarylmethanes. The corresponding intramolecular cyclization proceeds under mild conditions, demonstrating the first example of a stereospecific cross-electrophile coupling of secondary benzylic esters. A variety of heterocyclic and functionalized substrates are tolerated under the reaction conditions.Chapter 3 examines the development a regio- and stereoselective nickel-catalyzed hydroarylation of alkynes with arylboronic acids. The reaction is facilitated by propargyl carbamates as directing groups. The reaction is tolerant of a range of functional groups and heterocycles. Mechanistic studies reveal that the acidic protons of the arylboronic acid coupling partner serve as the origin of hydrogen. Furthermore, the synthesis of tamoxifen can be completed in two steps from a simple hydroarylation product.
Book Synopsis Development of Nickel-catalyzed Stereospecific Cross-coupling Reactions by : Buck L. H. Taylor
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.
Book Synopsis Nickel-catalyzed Reductive Coupling of Aryl Halides with Alkyl Electrophiles by : Lukiana L. Anka-Lufford
Download or read book Nickel-catalyzed Reductive Coupling of Aryl Halides with Alkyl Electrophiles written by Lukiana L. Anka-Lufford and published by . This book was released on 2015 with total page 208 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The direct transition-metal catalyzed cross-coupling of two different electrophiles is a fast emerging synthetic method, as it avoids the use of carbon nucleophiles. Despite being a synthetically valuable strategy, a central challenge of cross-electrophile coupling is achieving selectivity for cross-coupled product over dimerization products. This thesis details the author's work towards the development of cross-selective methods for the formation of Csp2-Csp3 bonds. Chapter 1 introduces the conventional cross-coupling method of forming C-C bonds and highlights the advantages of using the reductive cross-electrophile coupling approach instead. The selectivity challenges associated with reductive cross-coupling and the origins of selectivity in the cross-coupling reactions of aryl halides with allylic acetates and benzyl mesylates are discussed. Motivations towards the adaptation of our cross-electrophile coupling methods to more environmentally responsible solvents and reductants are also described. Chapter 2 details a general protocol for the coupling of aryl halides with allylic acetates and shows that high cross-selectivity can be achieved with the use of a terpyridine nickel catalyst. Strength's of the method are presented such tolerance for electrophilic (ketone (71%), aldehyde (70%)) and acidic (sulfonamide (73%), trifluoroacetamide (64%)) substrates and the ability to couple with a variety of substituted allylic acetates. The reductive method addresses the regioselectivity and substrate availability limitations observed in past approaches to allylated arenes. Chapter 3 presents the first synthesis of diarylmethanes from benzyl mesylates and aryl halides using cobalt phthalocyanine (Co(Pc)), a new co-catalyst for radical generation that is compatible with nickel-catalysis. Studies are shown demonstrating the orthogonal reactivity of (dtbbpy)Ni and Co(Pc) and the application of this selectivity to the coupling of functionalized benzyl mesylates with aryl halides. The adaptation of the method to the less reactive benzyl phosphate ester and an enantioconvergent reaction are also presented. Chapter 4 shows studies towards the adaptation of cross-electrophile coupling to more environmentally friendly solvents and reductants. Here, a homogeneous, two electronic organic reductant, 1,2,2-tetrakis(dimethylamino)ethylene (TDAE), is shown to be effective for nickel-catalyzed cross-electrophile coupling in various green solvents such as propylene carbonate and acetonitrile. These reactions are close in yield to our best-reported results in amide or urea solvents using zinc or manganese as the reductant. Chapter 5 describes initial studies towards nickel-catalyzed decarbonylative coupling reactions of acid chloride derivatives with aryl and alkyl halides and nickel-catalyzed coupling reactions of aryl halides with small cyclic alkyl bromides and oxetane tosylate. Further optimization strategies are presented."--Pages viii-ix.
Book Synopsis Development of Stereospecific Nickel-Catalyzed Cross-Coupling and Reductive Cross-Electrophile Coupling Reactions by : Lucas William Erickson
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.
