Strategies Towards the Synthesis of Welwitindolinone C PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Strategies Towards the Synthesis of Welwitindolinone C PDF full book. Access full book title Strategies Towards the Synthesis of Welwitindolinone C by Jennifer Pitzen. Download full books in PDF and EPUB format.
Author: Jennifer Pitzen
Publisher:
ISBN: 9781339528717
Category :
Languages : en
Pages : 207
Get Book Here
Book Description
Progress towards the total synthesis of N-methylwelwitindolinone C isothiocyanate is reported. The tetracyclic core is established by a key alkylation--type 2 intramolecular Diels--Alder cascade reaction, forming three new carbon-carbon bonds and five stereocenters in one step. Mechanistic studies suggest that alkylation proceeds via a zinc enolate intermediate instead of a silyl ketene aminal, shortening the synthesis by one step. Elaboration of the welwitindolinone core was accomplished with novel use of chlorinating agent MoCl5 to selectively convert a ketone to the vinyl chloride found in the natural product. To circumvent the problematic differentiation of two esters and install a bridgehead amine at an early stage in the synthesis, a series of new dienophiles were prepared. Ultimately selective protection of a diol intermediate allowed for differentiation, but methylation to install the final quaternary center proved to be challenging and remains one of the last hurdles in completing the synthesis.
Author: Jennifer Pitzen
Publisher:
ISBN: 9781339528717
Category :
Languages : en
Pages : 207
Get Book Here
Book Description
Progress towards the total synthesis of N-methylwelwitindolinone C isothiocyanate is reported. The tetracyclic core is established by a key alkylation--type 2 intramolecular Diels--Alder cascade reaction, forming three new carbon-carbon bonds and five stereocenters in one step. Mechanistic studies suggest that alkylation proceeds via a zinc enolate intermediate instead of a silyl ketene aminal, shortening the synthesis by one step. Elaboration of the welwitindolinone core was accomplished with novel use of chlorinating agent MoCl5 to selectively convert a ketone to the vinyl chloride found in the natural product. To circumvent the problematic differentiation of two esters and install a bridgehead amine at an early stage in the synthesis, a series of new dienophiles were prepared. Ultimately selective protection of a diol intermediate allowed for differentiation, but methylation to install the final quaternary center proved to be challenging and remains one of the last hurdles in completing the synthesis.
Author: Alexander David Huters
Publisher:
ISBN:
Category :
Languages : en
Pages : 254
Get Book Here
Book Description
Chapter one provides a summary of efforts towards the syntheses of the welwitindolinones with bicyclo[4.3.1]decane cores. Emphasis is given to more recent approaches that have successfully assembled the bicyclic core of the natural products. Chapters two and three are a discussion of our studies relating to a model system of the welwitindolinone natural products. Chapter two focuses on the use of an aryne cyclization to assemble the bicyclo[4.3.1]decane framework of the welwitindolinones. Chapter three covers initial attempts to install the bridgehead nitrogen substituent present in the natural products in addition to the synthesis of a functionalized aryne cyclization substrate. Chapters four and five present our total syntheses of the welwitindolinone natural products. The enantiospecific total syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone C isonitrile, 3-hydroxy-N-methylwelwitindolinone C isothiocyanate and 3-hydroxy-N-methylwelwitindolinone C isonitrile are detailed. The 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 late-stage nitrene insertion reaction to install the bridgehead nitrogen substituent. The use of a deuterium kinetic isotope effect to improve the yield of the nitrene insertion is also presented. In addition, a computational method to predict the stereochemistry of a previously unconfirmed stereocenter in the hydroxylated natural products as well as experimental validation of the computational findings is discussed.
Author: Miguel A. Sierra
Publisher: John Wiley & Sons
ISBN: 352765464X
Category : Science
Languages : en
Pages : 297
Get Book Here
Book Description
Success comes in many forms and in synthesis it can be a failure that results in their ultimate successful solutions. This long-awaited sequel to "Dead Ends and Detours" retains the proven concept while featuring over 20 new case studies of failed strategies and their (successful) solutions in natural product total synthesis. Additionally, computational models are used to discuss the problem in much more detail and to provide readers with additional information not found in the primary literature. The topics range from classic synthetic reactions (e.g. Diels Alder reaction), metal-mediated coupling reactions, metathesis, and asymmetric catalysis to the importance of protecting and activating groups. This book will benefit not only graduate students in organic chemistry but also advanced researchers as they gain knowledge derived from the step-by-step analysis of mistakes made in the past and, thus be able to improve their own chemical reaction planning. With its coverage of the most commonly applied reaction types, the book perfectly complements its predecessor, which focuses on general aspects, such as reactivity and selectivity.
Author: Krishna C. Majumdar
Publisher: John Wiley & Sons
ISBN: 3527634894
Category : Science
Languages : en
Pages : 648
Get Book Here
Book Description
Filling a gap on the market, this handbook and ready reference is unique in its discussion of the usefulness of various heterocyclic systems in the synthesis of natural products. Clearly structured for easy access to the information, each chapter is devoted to a certain class of heterocycle, providing a tabular presentation of the natural products to be covered containing the particular heterocyclic ring system along with their biological profile, occurrence and most important physical properties, backed by the appropriate references. In addition, the application of the heterocyclic system to the synthesis of natural products ic covered in detail. Of great interest to organic, natural products, medicinal and biochemists, as well as those working in the pharmaceutical and agrochemical industry.
Author: Kiran Guthikonda
Publisher:
ISBN:
Category :
Languages : en
Pages : 322
Get Book Here
Book Description
Author:
Publisher: Elsevier
ISBN: 0124115691
Category : Science
Languages : en
Pages : 358
Get Book Here
Book Description
This series is world-renowned as the leading compilation of current reviews of this vast field. Internationally acclaimed for more than 40 years, The Alkaloids, founded by the late Professor R.H.F. Manske, continues to provide outstanding coverage of this rapidly expanding field. Each volume provides, through its distinguished authors, up-to-date and detailed coverage of particular classes or sources of alkaloids. - Up-to-date reviews on a large and very important group of natural products from both a chemical and biological perspective - Comprehensive, dynamic reviews written by leading authors in the respective fields - Broad coverage on the biological aspects
Author: Kyle Wayne Quasdorf
Publisher:
ISBN:
Category :
Languages : en
Pages : 369
Get Book Here
Book Description
Chapter one provides a survey of the wide variety of unconventional phenol derivatives that are now available for use in traditional cross-coupling reactions. Emphasis is given to carbon-carbon (C-C) bond forming reactions with a brief discussion of other transformations. Chapters two and three are a discussion of our work in the field of nickel-catalyzed cross-coupling reactions of phenol derivatives. The use of aryl pivalates, sulfamates, carbamates, and carbonates in the nickel-catalyzed Suzuki-Miyaura coupling is described, along with synthetic applications utilizing these phenol derivatives. A computational and experimental mechanistic study for the cross-coupling of aryl sulfamates and carbamates is also reported. Chapters four and five detail our efforts in the total synthesis of the welwitindolinone natural products. The enantiospecific total syntheses of ( - )-N-methylwelwitindolinone C isothiocyanate and ( - )-N-methylwelwitindolinone C isonitrile, as well as their respective C3-hydroxylated analogs are reported. The synthetic routes feature an aryne cyclization to rapidly construct the [4.3.1]-bicyclic core of these molecules, as well as a late-stage intramolecular nitrene insertion to functionalize a bridgehead carbon. The strategic use of a deuterium kinetic isotope effect to improve the efficiency of the nitrene insertion is also discussed. A computational prediction for the stereochemical configuration at C3 of the hydroxylated welwitindolinones is presented, which was subsequently confirmed by experimental studies.
Author: K. C. Nicolaou
Publisher: John Wiley & Sons
ISBN: 3527329579
Category : Science
Languages : en
Pages : 788
Get Book Here
Book Description
K.C. Nicolaou - Winner of the Nemitsas Prize 2014 in Chemistry Adopting his didactically skillful approach, K.C. Nicolaou compiles in this textbook the important synthetic methods that lead to a complex molecule with valuable properties. He explains all the key steps of the synthetic pathway, highlighting the major developments in blue-boxed sections and contrasting these to other synthetic methods. A wonderful tool for learning and teaching and a must-have for all future and present organic and biochemists.
Author: Julio Alvarez-Builla
Publisher: John Wiley & Sons
ISBN: 3527332014
Category : Science
Languages : en
Pages : 2531
Get Book Here
Book Description
Eine Fülle von Information zum attraktiven Preis bietet Ihnen dieses vierbändige Handbuch der Heterocyclenchemie.
Author: Nicholas Anthony Weires
Publisher:
ISBN:
Category :
Languages : en
Pages : 560
Get Book Here
Book Description
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.
