Nickel Catalyzed Amide Carbon Nitrogen Bond Activation Methodologies And Progress Toward The Total Synthesis Of Dodecahedrane

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Nickel-Catalyzed Amide Carbon-Nitrogen Bond Activation Methodologies and Progress Toward the Total Synthesis of Dodecahedrane

Author : Jacob Edward Dander
Publisher :
ISBN 13 :
Total Pages : 419 pages
Book Rating : 4.:/5 (116 download)

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Book Synopsis Nickel-Catalyzed Amide Carbon-Nitrogen Bond Activation Methodologies and Progress Toward the Total Synthesis of Dodecahedrane by : Jacob Edward Dander

Download or read book Nickel-Catalyzed Amide Carbon-Nitrogen Bond Activation Methodologies and Progress Toward the Total Synthesis of Dodecahedrane written by Jacob Edward Dander and published by . This book was released on 2020 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes efforts in the field of nickel-catalyzed amide C-N bond activations and studies toward the total synthesis of dodecahedrane. Although amide C-N bonds are generally considered inert, recent progress in the activation of these bonds has allowed for their use as synthetic building blocks. Herein, several nickel-catalyzed transformations of amides and strategies to improve the practicality of these reactions are outlined. Each of these studies highlights the utility of nickel catalysis and amides in the context of organic synthesis. Furthermore, a synthetic strategy for and experimental progress toward the synthesis of dodecahedrane are reported. The realization of this total synthesis is expected to push our understanding of molecular reactivity and represent a milestone in the field of total synthesis. Chapters one, two, and three describe the development of transformations and experimental techniques that improve the scope and practicality of nickel-catalyzed activations of aryl amide C-N bonds. More specifically, chapter one describes a nickel-catalyzed alkylation of amides to access aryl-alkyl ketone products. This catalytic methodology represents a mild approach to synthesizing these products that is complementary to the Weinreb ketone synthesis. Chapter two details a strategy for the benchtop delivery of Ni(cod)2. The air- and moisture-sensitivity of this important nickel precatalyst limits its general utility. By utilizing paraffin-Ni(cod)2 capsules, a variety of nickel-catalyzed transformations, including aryl amide cross-couplings, can be performed outside of a glovebox. Chapter three outlines efforts to deploy paraffin-Ni(cod)2 capsules in an undergraduate organic chemistry laboratory. Through the use of these reagents in an esterification of an aryl amide, students gain meaningful insights into frontiers in cross-coupling research, nickel catalysis, and the use of amides in synthetic organic chemistry. Chapters four and five are concerned with the development of nickel-catalyzed transformations of aliphatic amides. Chapter four specifically details efforts to develop a nickel-catalyzed transamidation of aliphatic secondary amides. Through the use of a two-step activation-cross-coupling approach, we have achieved a mild and general solution to this long-standing problem in organic chemistry. Chapter five describes a method for performing arylations of aliphatic amides on the benchtop. By employing paraffin-Ni(cod)2/Benz-ICy[TM]HCl capsules, Suzuki-Miyaura cross-couplings of aliphatic amides to generate aryl-alkyl ketones can be achieved without the need for glovebox manipulations. Both of these studies expand the field of nickel-catalyzed amide C-N bond activations and promote amides as useful synthetic building blocks. Chapter six illustrates a chemoenzymatic approach to enantioselective transformations of amides. The development of a one-pot Suzuki-Miyaura cross-coupling and ketoreductase-mediated reduction allows for rapid, selective access to enantioenriched alcohol products from amides. This methodology represents the first enantioselective transformation of amides that relies on amide C-N bond activation and is expected to guide the development of other asymmetric transformations of amides. Finally, chapter seven details a strategy for the total synthesis of the complex hydrocarbon dodecahedrane. Our proposed symmetry-based approach to this fascinating icosahedral molecule relies on an ambitious [2+2+2+2+2] cyclization to assemble five key C-C bonds in a single synthetic operation. Current efforts to synthesize the necessary substrate for the [2+2+2+2+2] cyclization are detailed. If successful, these studies should provide efficient access to dodecahedrane and are expected to lead to insights into new modes of reactivity.

Total Synthesis of Welwitindolinones and Nickel-Catalyzed Reactions of Amide Derivatives

Author : Nicholas Anthony Weires
Publisher :
ISBN 13 :
Total Pages : 560 pages
Book Rating : 4.:/5 (17 download)

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Book Synopsis Total Synthesis of Welwitindolinones and Nickel-Catalyzed Reactions of Amide Derivatives by : Nicholas Anthony Weires

Download or read book Total Synthesis of Welwitindolinones and Nickel-Catalyzed Reactions of Amide Derivatives written by Nicholas Anthony Weires and published by . This book was released on 2017 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes our efforts toward the total synthesis of welwitindolinone natural products, as well as the development of reactions involving the nickel-catalyzed activation of amide C-N bonds. The welwitindolinones have been long-standing targets in total synthesis for over two decades, and this dissertation describes two completed total syntheses of these alkaloids. In addition, several nickel-catalyzed transformations of amides are outlined, each of which demonstrate the powerful reactivity of nickel and highlight the utility of amides as synthetic building blocks. Chapters one and two present our enantiospecific total syntheses of the welwitindolinone alkaloids N-methylwelwitindolinone D isonitrile and N-methylwelwitindolinone B isothiocyanate. Our approach to these natural products features an aryne cyclization to construct the bicyclo[4.3.1]decane core of the molecules, as well as a C-H nitrene insertion reaction to introduce the bridgehead nitrogen substituent. In chapter one, a dual C-H functionalization event installs the challenging ether linkage and allows for completion of (-)-N-methylwelwitindolinone D isonitrile. In chapter two, a regio- and diastereoselective chlorinative oxabicyclic opening is detailed, which enables the first total synthesis of N-methylwelwitindolinone B isothiocyanate. Chapters three, four, and five describe the development of nickel-catalyzed carbon-carbon bond-forming reactions of amides. More specifically, chapters three and four outline the Suzuki-Miyaura couplings of aromatic and aliphatic amides, respectively, whereas chapter five details the alkylation of amide derivatives. These methodologies represent mild and complementary tools to the Weinreb ketone synthesis, proceeding through the nickel-catalyzed activation of the amide C-N bond. It is shown that amides, which were traditionally thought of as inert functionalities, can be utilized as synthons in C-C bond-forming reactions. Chapter six describes a method for the benchtop delivery of Ni(cod)2 involving the encapsulation of Ni(cod)2 in paraffin wax. Due to air- and moisture-sensitivity, Ni(cod)2 is normally handled under an inert atmosphere. Using our method of wax encapsulation, several nickel-catalyzed transformations are performed without the use of a glove box, including various amide C-N bond cleavage reactions. These studies are aimed at promoting the widespread use of nickel in transition metal catalysis. Chapter seven illustrates the kinetic modeling of the nickel-catalyzed esterification of amides. By developing a kinetic model, an optimization is undertaken that allows for the employment of catalyst loadings as low as 0.4 mol% nickel. This demonstration is intended to foster the advancement of kinetic modeling as a powerful tool in methodology development.

Total Synthesis of Tubingensin B and Nickel-Catalyzed Methodologies Involving C-O Or C-N Bond Activation

Author : Junyong Kim
Publisher :
ISBN 13 :
Total Pages : 326 pages
Book Rating : 4.:/5 (17 download)

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Book Synopsis Total Synthesis of Tubingensin B and Nickel-Catalyzed Methodologies Involving C-O Or C-N Bond Activation by : Junyong Kim

Download or read book Total Synthesis of Tubingensin B and Nickel-Catalyzed Methodologies Involving C-O Or C-N Bond Activation written by Junyong Kim and published by . This book was released on 2018 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes the total synthesis of tubingensin B and the development of two nickel-catalyzed methods. The two methodologies include the amination of aryl electrophiles in the green solvent 2-methyl-THF and the Suzuki-Miyaura coupling of aliphatic amides via the activation of amide C-N bonds. Chapter One highlights indole terpenoid natural products as the inspiration for the development of new synthetic methodologies and innovative strategies. This review showcases recent total syntheses of the natural products, penitrem D, emindole SB, paspaline, dixiamycin B, and tubingensins A and B. Chapter Two pertains to the total synthesis of (-)-tubingensin B. Key steps of the synthesis involves a B-alkyl Suzuki-Miyaura reaction, a carbazolyne cyclization, and a radical cyclization to construct the core architecture of the molecule. Key to the synthesis of tubingensin B was the utilization of a heterocyclic aryne intermediate for the formation of a scaffold bearing vicinal quaternary centers. This synthesis illustrates the capability of aryne methodology in generating stereochemically complex structures. Chapter Three describes the development of a green variant of a nickel-catalyzed amination reaction. As solvents comprise 85% of pharmaceutical waste, the use of a green solvent provides a considerable benefit for the potential application of the methodology to industrial problems. We developed a method employing 2-Me-THF as a green solvent for the amination of aryl chlorides and sulfamates. Chapter Four demonstrates the nickel-catalyzed Suzuki-Miyaura coupling of aliphatic amide derivatives. The methodology can be used to activate typically unreactive amide C-N bonds and, in turn, access an array of heterocyclic ketones.

Nickel Catalysis in Organic Synthesis

Author : Sensuke Ogoshi
Publisher : John Wiley & Sons
ISBN 13 : 3527344071
Total Pages : 348 pages
Book Rating : 4.5/5 (273 download)

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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.

Nickel-Catalyzed Reactions of Amides and New Methods for the Synthesis of Nitrogen-Containing Heterocycles

Author : Bryan Joseph Simmons
Publisher :
ISBN 13 :
Total Pages : 558 pages
Book Rating : 4.:/5 (11 download)

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Book Synopsis Nickel-Catalyzed Reactions of Amides and New Methods for the Synthesis of Nitrogen-Containing Heterocycles by : Bryan Joseph Simmons

Download or read book Nickel-Catalyzed Reactions of Amides and New Methods for the Synthesis of Nitrogen-Containing Heterocycles written by Bryan Joseph Simmons and published by . This book was released on 2019 with total page 558 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation is divided into two main themes concerning transition metal-mediated methodologies and the synthesis of nitrogen-containing heterocycles. The first part of this dissertation focuses on the development of three new reaction pathways utilizing nickel and palladium. The impact of transition metals in the field of synthetic organic chemistry cannot be overstated, with the 2010 Nobel Prize being awarded for the use of palladium cross-coupling in organic synthesis. The second part of this dissertation aims to expand the synthetic toolbox towards the generation of nitrogen-containing heterocycles. With over 100 FDA-approved drugs containing a nitrogen atom, new methodologies toward these scaffolds remain highly sought after. Chapters One, Two, and Three focus on the development of new methodologies utilizing nickel and palladium catalysis. Chapters One and Two describe our efforts towards the functionalization of the amide moiety. Although amides were once thought to be unreactive due to their resonance stabilization, we sought to probe the utility of amides as a functional group handle. Chapter One focuses on the alkylation of amides using nickel and an organozinc source to generate sp2-sp3 C-C bonds. Chapter Two showcases a methodology to convert secondary and tertiary amides to their corresponding amines using a silane reducing agent and nickel catalysis. Chapter Three discusses an academic and industrial collaboration towards the synthesis of tetra-ortho-substituted biaryls using palladium catalysis. These studies culminated in an extensive computational analysis of the reaction mechanism and the synthesis of numerous atropisomeric biaryls. Chapters Four, Five, and Six detail new methodologies towards the generation of nitrogen-containing heterocycles. With the nitrogen atom being prevalent in numerous FDA-approved drugs, facile routes towards their incorporation remain highly valued. Chapter Four illustrates the elusive 3,4-piperidyne's use in a variety of cycloaddition reactions. This study led to the formation of numerous annulated piperidines and exemplifies the utility of our methodology. Chapters Five and Six utilize the interrupted Fischer indolization reaction to produce an assortment of furanoindoline and pyrrolidinoindoline products. Chapter Five centers on the synthesis of the aza-analogues of these products by employing pyridylhydrazines. A computational study was undertaken to determine the cause of success or failure in this transformation. Chapter Six describes a variation of interrupted Fischer indolization methodology performed in a microfluidic device, which should enable its use in medicinal chemistry.

Catalytic Methods for Carbon-carbon and Carbon-nitrogen Bond Formation

Author : Stephen David Ramgren
Publisher :
ISBN 13 :
Total Pages : 511 pages
Book Rating : 4.:/5 (911 download)

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Book Synopsis Catalytic Methods for Carbon-carbon and Carbon-nitrogen Bond Formation by : Stephen David Ramgren

Download or read book Catalytic Methods for Carbon-carbon and Carbon-nitrogen Bond Formation written by Stephen David Ramgren and published by . This book was released on 2014 with total page 511 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation describes the study of metal-catalyzed cross-coupling reactions to construct carbon-carbon and carbon-heteroatom bonds. The key feature of much of this work is the use of inexpensive Ni and Fe catalysts to enable the coupling of unconventional electrophilic substrates, specifically aryl O-sulfamates and O-carbamates. The ability to use O-sulfamates and O-carbamates in catalytic processes is notable, as these substrates are readily derived from phenols and can be used for directed arene functionalization. Chapter one provides a summary of the efforts towards using alcohol-based solvents for the Suzuki-Miyaura cross-coupling reaction. Emphasis is placed on the cross-coupling of heterocycles, which are commonly encountered in natural product synthesis and in the pharmaceutical sector. Chapters two, three, and four describe carbon-nitrogen bond forming reactions. Chapter two pertains to the nickel-catalyzed amination of sulfamates, which culminated in the synthesis of the antibacterial drug, linezolid. Chapter three covers the amination of aryl O-carbamates and their use in sequential functionalization/site-selective cross-couplings. Chapter four describes a more user-friendly variant of the amination reaction, which relies on a bench-stable Ni(II) precatalyst, rather than a more commonly used Ni(0) precatalyst. Chapters five, six, and seven focus on carbon-carbon bond formation via Fe-, Ni- and Pd-mediated processes. Chapter five pertains to iron-catalyzed couplings of sulfamates and carbamates to generate sp2-sp3 carbon-carbon bonds. This method can be used to assemble sterically-congested frameworks. Chapter six describes the nickel-catalyzed Suzuki-Miyaura reactions of halides and phenol derivatives in `green' solvents, which was applied to the preparative scale assembly of bis(heterocycles) using low nickel catalyst loadings. Chapter seven pertains to the acetylation of arenes using palladium catalysis, which provides a simple and efficient means for the construction of a variety of aryl methyl ketones.

The Development of New, Direct and Asymmetric Ni(II) Catalysed Carbon-carbon Bond Forming Reactions and Their Application to Total Synthesis

Download The Development of New, Direct and Asymmetric Ni(II) Catalysed Carbon-carbon Bond Forming Reactions and Their Application to Total Synthesis PDF Online Free

Author : Stuart Kennington
Publisher :
ISBN 13 :
Total Pages : 277 pages
Book Rating : 4.:/5 (125 download)

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Book Synopsis The Development of New, Direct and Asymmetric Ni(II) Catalysed Carbon-carbon Bond Forming Reactions and Their Application to Total Synthesis by : Stuart Kennington

Download or read book The Development of New, Direct and Asymmetric Ni(II) Catalysed Carbon-carbon Bond Forming Reactions and Their Application to Total Synthesis written by Stuart Kennington and published by . This book was released on 2021 with total page 277 pages. Available in PDF, EPUB and Kindle. Book excerpt: "This thesis focuses on the search for new methodologies for the direct, stereoselective and catalytic formation of carbon-carbon bonds through the formation of chiral nickel(II) enolate species and the application of such methods to the synthesis of natural products. The project starts with the stereocontrol coming from chiral auxiliaries, developed first by Evans and then later by Crimmins and Nagao, following the previous experience and expertise of the research group. These auxiliaries have proved to be a reliable and high yielding option to afford excellent levels of stereocontrol in various reactions. Furthermore, they can be removed after such processes to leave enantiopure synthons. However, they do have their drawbacks, one being the inability of synthesising all of the available stereoisomers from one starting material. To combat this issue, the second part of the thesis is centred around the development of a new methodology based on achiral starting materials (scaffolds) with chiral nickel(II) complexes, which both enable the reaction and control its stereochemical outcome.In the first Chapter, methods previously developed in the group were applied to the synthesis of a fragment of the marine sponge macrolide Peloruside A, which has shown to have anticancer activity, especially against leukaemia. Three key steps involve reactions based on the use of chiral auxiliaries that had been developed in the group: a nickel catalysed reaction with trimethyl orthoformate, a titanium-mediated acetate aldol reaction, and a titanium-mediated addition of an acetate enolate to an acetal. The overall yield of the synthesis of the target fragment C9-C19 was 24% over 14 steps.Chapter 2 presents a new reaction based on the addition of enolates, generated from chiral N-acyl thiazolidinethiones with an achiral nickel(II) complex, to stable carbocationic salts. This alkylation reaction was first thoroughgoingly optimised and later applied to a large range of substrates with wide success. Moreover, it was applied to a highly challenging electrophile successfully which lead to the discovery of a reversible alkylation process. The products were also transformed via the removal of the auxiliary to leave a variety of functional groups.In Chapter 3 the stereocontrol is passed from the starting material to the catalyst in an ambitious advancement of the group's chemistry. After an extensive study of potential achiral scaffolds to provide the platform for the reactions and chiral diphosphine ligands to provide the enantiocontrol, we observed the best scaffold was the 6-memberd thiazinanethione structure and the best ligand DTBM-SEGPHOS®. We were able to apply this methodology to the reaction of: trimethyl orthoformate (an oxocarbenium precursor), tropylium tetrafluoroborate (a cationic salt), a diaryl methyl ether (a carbenium precursor), and also a more complex diaryl ketal electrophile with high yields and exceptional control over the one stereocentre formed. Furthermore, using a dimethyl acetal we were able to exert some control over the relative configuration of two stereocentres whilst maintaining exceptional enantioselectivity. Calculations and elucidation of the configuration of the new stereocentre formed support our hypothesis for the mechanism for such a process. We also demonstrated the ease with which the scaffold can be removed and were able to synthesise a wide variety of synthons with differing functional groups. Finally, we were able to scale up and apply the methodology to the synthesis of Peperomin D, a five membered lactone containing two stereocentres.Finally, in the last Chapter we present a new methodology for the asymmetric aldol reaction of N-acyl thiazinanethiones with aromatic aldehydes catalysed by a chiral nickel (II) complex, which involves the simultaneous silyl protection of the adducts. This new reaction proceeds through an open transition state and leads to the anti-aldol products. We were able to optimise the reaction to achieve a high diastereoselectivity, exceptional enantioselectivity, and excellent yield. Furthermore, we were able to apply the conditions to various aromatic aldehydes and N-acyl thiazinanethiones. Finally, the scope of the reaction was expanded to three different electrophiles, opening new lines of investigation" -- TDX.

Reaction Discovery Using Nickel Catalysis and Total Syntheses of Indolactam Alkaloids

Author : Noah Frederick Fine Nathel
Publisher :
ISBN 13 :
Total Pages : 574 pages
Book Rating : 4.:/5 (927 download)

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Book Synopsis Reaction Discovery Using Nickel Catalysis and Total Syntheses of Indolactam Alkaloids by : Noah Frederick Fine Nathel

Download or read book Reaction Discovery Using Nickel Catalysis and Total Syntheses of Indolactam Alkaloids written by Noah Frederick Fine Nathel and published by . This book was released on 2015 with total page 574 pages. Available in PDF, EPUB and Kindle. Book excerpt: Transition metal-catalyzed cross-coupling reactions are useful tools to assemble carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. Traditionally, electrophilic halides and pseudohalides have been cross-coupled to their nucleophilic counterparts with palladium. Recently, however, the implementation of nickel as a catalyst for cross-coupling reactions has enabled the use of less reactive cross-coupling partners, such as carbamates, sulfamates, and amides. This dissertation describes the development of nickel-catalyzed cros-couplings of untraditional electrophiles to forge carbon-heteroatom (C-X) bonds. Additionally, the total syntheses of four indolactam alkaloids, indolactam V, pendolmycin, lyngbyatoxin A1 and teleocidin A-2, using both a key distortion-controlled indolyne reaction and palladium-catalyzed sp2-sp3 C-C bond construction, are described. Chapters one and two describe the development of nickel-catalyzed amination reactions of aryl electrophiles to form carbon-nitrogen (C-N) bonds. The amination reaction of aryl carbamates to form aryl amines is discussed. Subsequently, the development of green cross-couplings of aryl sulfamates and chlorides to similarly form aryl amines is reported. Chapter three introduces a means to accomplish a controlled cine substitution. This two-step process is comprised of a carbamate-directed ortho-lithiation/functionalization of an arene, followed by a nickel-catalyzed reductive deoxygenation of the directing group. This sequence provides a new strategy for synthesis and complements the more commonly employed ipso substitution in arene functionalization. Chapter four concerns 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 C-X and C-C bonds. Chapter five describes the total syntheses of ( - )-indolactam V and its C7-substituted natural product derivatives, ( - )-pendolmycin, ( - )-lyngbyatoxin A1 and ( - )-teleocidin A-2. The C4-N linkage is constructed with a distortion-controlled indolyne functionalization. The total synthesis of ( - )-indolactam V provides a platform for the divergent syntheses of the other three natural products via a palladium-catalyzed cross-coupling to functionalize C7 and introduce a quaternary center.

Development of Nickel-Catalyzed Cross-Coupling Reactions

Author : Liana Hie
Publisher :
ISBN 13 :
Total Pages : 620 pages
Book Rating : 4.:/5 (17 download)

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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.

Advances in Late-Metal Carbon-Nitrogen Bond Formation for the Synthesis of Substituted Heterocycles

Author : Nicolas Rotta-Loria
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (134 download)

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Book Synopsis Advances in Late-Metal Carbon-Nitrogen Bond Formation for the Synthesis of Substituted Heterocycles by : Nicolas Rotta-Loria

Download or read book Advances in Late-Metal Carbon-Nitrogen Bond Formation for the Synthesis of Substituted Heterocycles written by Nicolas Rotta-Loria and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Late-metal catalyzed cross-couplings have emerged as efficient and selective methodologies for the formation of C-C and C-N bonds. The ability to synthesize complex heterocycles from cheap and abundant starting materials is an invaluable asset to the pharmaceutical industry, given that many pharmaceuticals contain at least one heterocyclic component. This reactivity can be achieved by tuning the steric and electronic properties of ancillary ligands to support metal catalysts in the reaction steps leading to the target substrate. The Stradiotto group has developed several state-of-the-art methodologies involving ligands for palladium catalysis, for both C-C and C-N bond-forming reactions. These methodologies can be amalgamated into a multicomponent reaction platform to synthesize more complex products from simple materials. Chapter 1 outlines this concept with the application of a Mor-DalPhos/Pd catalyst in the one-pot synthesis of indoles from acetone and simple amines involving C-C and C-N bond formation. The robust nature of this method can be extended to include benchtop reaction conditions in a one-step, one-pot synthesis of indoles, thus representing a useful synthetic protocol. While palladium provides a powerful tool for C-C and C-N bond formation, the general trend in catalysis has shifted away from the precious metals toward first row metals as economic alternatives. Nickel complexes have recently emerged as excellent catalysts for a number of amination reactions. The ability to utilize ammonia also represents a sought after reaction, due to the widespread availability and synthetic utility of amino-functionalized products. In this regard, Chapter 2 will focus on the development and application of both commercially available and strategically designed ligand classes for the monoarylation of ammonia with substituted heterocycles. Hydrazine represents an important synthon in synthetic chemistry. It is synthesized on multi-ton scale every year and represents an important building block in many industrial processes. Many synthetic challenges arise from using free hydrazine as reactant, which has led to lethargic growth of its application in the field of late-metal catalyzed C-N bond-formation. However, gold-catalyzed methodologies have been developed utilizing NHC ligands to allow for the hydrohydrazination of alkynes with parent hydrazine. Chapter 4 examines the development and application of a series of (PR3)AuCl complexes for use in such transformations, leading to the identification of the first effective phosphine-bound gold complex for use in the hydrohydrazination of alkynes at room temperature.

Nickel-catalyzed Cross-couplings Via Activation of Alkyl Carbon-nitrogen Bonds

Author : Corey Howard Basch
Publisher :
ISBN 13 : 9780438241411
Total Pages : 405 pages
Book Rating : 4.2/5 (414 download)

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Book Synopsis Nickel-catalyzed Cross-couplings Via Activation of Alkyl Carbon-nitrogen Bonds by : Corey Howard Basch

Download or read book Nickel-catalyzed Cross-couplings Via Activation of Alkyl Carbon-nitrogen Bonds written by Corey Howard Basch and published by . This book was released on 2018 with total page 405 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Nickel-catalyzed Intramolecular [4+4] Cycloaddition Methodology

Author : Nathan Charles Ihle
Publisher :
ISBN 13 :
Total Pages : 632 pages
Book Rating : 4.F/5 ( download)

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Book Synopsis Nickel-catalyzed Intramolecular [4+4] Cycloaddition Methodology by : Nathan Charles Ihle

Download or read book Nickel-catalyzed Intramolecular [4+4] Cycloaddition Methodology written by Nathan Charles Ihle and published by . This book was released on 1988 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Catalyst Design for Asymmetric Organozinc Addition to Aldehydes and Progress Toward the Total Synthesis of the Marine Alkaloid, ( - )-Lepadiformine

Download Catalyst Design for Asymmetric Organozinc Addition to Aldehydes and Progress Toward the Total Synthesis of the Marine Alkaloid, ( - )-Lepadiformine PDF Online Free

Author :
Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (656 download)

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Book Synopsis Catalyst Design for Asymmetric Organozinc Addition to Aldehydes and Progress Toward the Total Synthesis of the Marine Alkaloid, ( - )-Lepadiformine by :

Download or read book Catalyst Design for Asymmetric Organozinc Addition to Aldehydes and Progress Toward the Total Synthesis of the Marine Alkaloid, ( - )-Lepadiformine written by and published by . This book was released on 2004 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: A novel dihydropyridone was synthesized in search for a chiral ligand for the asymmetric addition of an alkyl group to an aldehyde. The target amine was derived from an enamine through a hydrogenation reaction. A study directed toward the total synthesis of the marine alkaloid ( - )-lepadiformine was carried out. Two approaches were investigated toward the core perhydroquinoline system. The first approach utilized a Grignard addition to an N-acylpyridinium salt and a [2+2] photochemical addition as the key synthetic steps. The second approach was based upon quinoline chemistry. The model study was completed with a one-carbon alkene homologation to form a terminal butane. An asymmetric route was examined.

Biocatalytic Methods for Carbon-nitrogen Bond Formation Via Hemoprotein-catalyzed Group Transfer Reactions

Author : Viktoria Steck
Publisher :
ISBN 13 :
Total Pages : 254 pages
Book Rating : 4.:/5 (129 download)

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Book Synopsis Biocatalytic Methods for Carbon-nitrogen Bond Formation Via Hemoprotein-catalyzed Group Transfer Reactions by : Viktoria Steck

Download or read book Biocatalytic Methods for Carbon-nitrogen Bond Formation Via Hemoprotein-catalyzed Group Transfer Reactions written by Viktoria Steck and published by . This book was released on 2019 with total page 254 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Our group has recently established that heme-containing proteins, in particular myoglobin and cytochrome P450s, constitute promising biocatalysts for the formation of carbon-nitrogen and carbon-carbon bonds via nitrene and carbene transfer reactions, a class of synthetically valuable transformations not occurring in nature. Building upon this work, a first goal of this research was to improve the scope and efficiency of these nitrene transfer biocatalysts for C-H amination reactions. To this end, we identified a novel, unusual P450-type enzyme named XplA, which catalyzes the intramolecular C-H amination of arylsulfonyl azide substrates with a significant enhancement of activity and chemoselectivity in comparison to other P450s, which efficiency in this reaction is limited by the generation of reduced byproducts. Primary kinetic isotope effect studies revealed that the mechanism proceeds with C-H bond activation as the rate limiting step and provided insights into the competition between productive vs. non-productive nitrene transfer pathways. Furthermore, we discovered that non-heme Rieske dioxygenases are viable C- H amination biocatalysts and explored their potential value in nitrene transfer reactions by means of protein engineering, large scale reactions in a bioreactor, and analysis of their reaction and substrate scope. In a second part, we expanded and modulated the reactivity of myoglobin biocatalysts in carbene transfer reactions. A series of artificial myoglobin-based metalloenzymes containing manganese, iron, cobalt, ruthenium, rhodium and iridium were investigated for cyclopropanation and Y-H (Y = N, S) carbene insertion reactions. Engineered variants containing a ruthenium cofactor were found to be excellent S-Hinsertion catalysts, while variants harboring an iridium cofactor were capable of C-H insertion reactions not supported by the parent protein. Next, we demonstrated how cofactor variation in combination with mutations of the proximal ligand anchoring the metalloporphyrin in the active site pocket drastically influences catalyst chemoselectivity. Specifically, we developed a serine-ligated cobalt-porphyrin variant that favors the more challenging olefin cyclopropanation reaction in the presence of competing functional groups. In contrast, the native protein with a histidine-ligated heme cofactor selectively undergoes the complementary Y-H (Y = N, Si) insertion reaction in the presence of unsaturated bonds. In a further study, we successfully extended the substrate scope of engineered myoglobin 'carbene transferases' for realizing N-H insertion reactions between benzyl- and alkylamines and different diazo precursors, which was previously not reported for other hemoproteins, thereby enabling access to valuable functionalized benzyland alkylamines. Finally, we devised a biocatalytic strategy for the asymmetric synthesis of chiral amines via myoglobin-catalyzed N-H insertion. Achieving high enantioselectivity in carbene-mediated N-H insertion reactions has been notoriously challenging. To this end, reactions involving a combination of evolved myoglobin variants with engineered diazo compounds led to the first report and highest enantioselectivity achieved by a biocatalyst in this reaction to date. In addition, stereodivergent biocatalysts were developed to obtain both mirror-image forms of chiral anilines. Altogether, these studies highlight how protein engineering provides a powerful strategy for expanding the biocatalytic toolbox toward synthetically useful yet challenging abiological biotransformations under environmentally friendly and sustainable conditions"--Pages xi-xii.

Nickel-catalyzed Reductive Coupling of Alkyl, Allyl and Vinyl Electrophiles

Author : Michael R. Prinsell
Publisher :
ISBN 13 :
Total Pages : 187 pages
Book Rating : 4.:/5 (944 download)

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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.

A Computational Study of C-CN Bond Activation Through Nickel Catalysis Using the Random Phase Approximation

Author : Craig Waitt
Publisher :
ISBN 13 :
Total Pages : 112 pages
Book Rating : 4.:/5 (991 download)

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Book Synopsis A Computational Study of C-CN Bond Activation Through Nickel Catalysis Using the Random Phase Approximation by : Craig Waitt

Download or read book A Computational Study of C-CN Bond Activation Through Nickel Catalysis Using the Random Phase Approximation written by Craig Waitt and published by . This book was released on 2017 with total page 112 pages. Available in PDF, EPUB and Kindle. Book excerpt:

March's Advanced Organic Chemistry

Author : Michael B. Smith
Publisher : John Wiley & Sons
ISBN 13 : 0470084944
Total Pages : 2379 pages
Book Rating : 4.4/5 (7 download)

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Book Synopsis March's Advanced Organic Chemistry by : Michael B. Smith

Download or read book March's Advanced Organic Chemistry written by Michael B. Smith and published by John Wiley & Sons. This book was released on 2007-01-29 with total page 2379 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Sixth Edition of a classic in organic chemistry continues its tradition of excellence Now in its sixth edition, March's Advanced Organic Chemistry remains the gold standard in organic chemistry. Throughout its six editions, students and chemists from around the world have relied on it as an essential resource for planning and executing synthetic reactions. The Sixth Edition brings the text completely current with the most recent organic reactions. In addition, the references have been updated to enable readers to find the latest primary and review literature with ease. New features include: More than 25,000 references to the literature to facilitate further research Revised mechanisms, where required, that explain concepts in clear modern terms Revisions and updates to each chapter to bring them all fully up to date with the latest reactions and discoveries A revised Appendix B to facilitate correlating chapter sections with synthetic transformations