Total Synthesis of Tubingensin B and Nickel-Catalyzed Methodologies Involving C-O Or C-N Bond Activation PDF Download
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Author: Junyong Kim Publisher: ISBN: Category : Languages : en Pages : 326
Book Description
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.
Author: Junyong Kim Publisher: ISBN: Category : Languages : en Pages : 326
Book Description
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.
Author: Jacob Edward Dander Publisher: ISBN: Category : Languages : en Pages : 419
Book Description
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.
Author: Sensuke Ogoshi Publisher: John Wiley & Sons ISBN: 3527344071 Category : Science Languages : en Pages : 348
Book Description
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.
Author: Stuart Kennington Publisher: ISBN: Category : Languages : en Pages : 277
Book Description
"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.
Author: Jie Jack Li Publisher: Springer Science & Business Media ISBN: 3642340652 Category : Science Languages : en Pages : 292
Book Description
'Total Synthesis of Natural Products' is written and edited by some of today's leaders in organic chemistry. Eleven chapters cover a range of natural products, from steroids to alkaloids. Each chapter contains an introduction to the natural product in question, descriptions of its biological and pharmacological properties and outlines of total synthesis procedures already carried out. Particular emphasis is placed on novel methodologies developed by the respective authors and their research groups. This text is ideal for graduate and advanced undergraduate students, as well as organic chemists in academia and industry.
Author: Neil Garg Publisher: ISBN: 9780692860540 Category : Languages : en Pages : 30
Book Description
This coloring book brings to life the magic and impact of organic chemistry for children and adults alike. With more than 25 pages to color, kids will have fun and even learn some science too! The molecules featured in this book include sucrose, aspirin, caffeine, cellulose, proteins, and many more. This educational coloring book was created by two children, with the help of their father, a UCLA Chemistry Professor. "This coloring book brings the unbridled curiosity of a young mind together with the wonders of our molecular world in ways that will surely inspire discovery, fun, and perhaps a lifelong appreciation of the ubiquity and impact of chemistry" -Professor Paul Wender (Stanford University)
Author: Guangbin Dong Publisher: Springer ISBN: 364255055X Category : Science Languages : en Pages : 265
Book Description
The series Topics in Current Chemistry presents critical reviews of the present and future trends in modern chemical research. 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. Review articles for the individual volumes are invited by the volume editors. Readership: research chemists at universities or in industry, graduate students
Author: Olivier Piva Publisher: John Wiley & Sons ISBN: 1786303493 Category : Science Languages : en Pages : 314
Book Description
For chemists, attempting to mimic nature by synthesizing complex natural products from raw material is a challenge that is fraught with pitfalls. To tackle this unique but potentially rewarding task, researchers can rely on well-established reactions and methods of practice, or apply their own synthesis methods to verify their potential. Whatever the goal and its complexity, there are multiple ways of achieving it. We must now establish a strategic and effective plan that requires the minimum number of steps, but lends itself to widespread use. This book is structured around the study of a dozen target products (butyrolactone, macrolide, indole compound, cyclobutanic terpene, spiro- and polycyclic derivatives, etc.). For each product, the different disconnections are presented and the associated syntheses are analyzed step by step. The key reactions are described explicitly, followed by diagrams showing the range of impact of certain transformations. This set of data alone is conducive to understanding syntheses and indulging in this difficult, but worthwhile activity.
Author: Junyong Kim
Author: Junyong Kim
Author: Jacob Edward Dander
Author: Sensuke Ogoshi
Author: Craig Waitt
Author: Stuart Kennington
Author: Jie Jack Li
Author: Neil Garg
Author: Guangbin Dong
Author: Douglass F. Taber
Author: Olivier Piva