Catalytic Enantioselective Synthesis of Aryl Substituted 3-hydroxy-2-oxindoles and 3,3-disubstituted-2-oxindoles
Catalytic Enantioselective Synthesis of Aryl Substituted 3-hydroxy-2-oxindoles and 3,3-disubstituted-2-oxindoles

Author: Aziza Hatice Sahin

Publisher:

Published: 2010

Total Pages:

ISBN-13: 9781124223438

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In Chapter One, a catalytic enantioselective method for the synthesis of 3- hydroxy-2-oxindoles is described. 3-Hydroxy-2-oxindoles were synthesized by a nucleophilic addition of electron-rich arenes and aromatic heterocycles to substituted indole-2,3-diones (isatins) catalyzed by scandium(III) and indium(III)-inda-pybox complexes. The use of a bulky chiral ligand hindered the formation of the achiral 3,3-diaryl-2-oxindole side product. Substituted 3-hydroxy-2-oxindoles were formed in high yield and high enantioselectivity (up to 99% ee). In Chapter Two, a method for the synthesis of chiral 3,3-disubstituted-2-oxindoles from a nucleophilic substitution at the stereocenter of a substituted 3-hydroxy-2-oxindole is described. This SN̳1-like process is catalyzed by a Lewis or a Brønsted acid, which eliminates water to form an indolenium ion intermediate. Chiral BINOL-derived phosphoric acids and phosphoramides are promising catalysts for an asymmetric process, as the conjugate base can act as a counteranion that coordinates to the carbocation intermediate to direct an asymmetric nucleophilic addition. Catalyst and solvent effects have been investigated with yields ranging from 68-97%. Preliminary enantioselectivity has been observed and further optimization is underway.

Studies in Natural Products Chemistry
Studies in Natural Products Chemistry

Author: Albert Moyano

Publisher: Elsevier Inc. Chapters

Published: 2013-06-25

Total Pages: 83

ISBN-13: 0128084693

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Functional diversity and molecular architecture in biologically active oxindoles. Transition metal-catalyzed intramolecular Heck reactions and amide alpha-arylations. Asymmetric rearrangements of O-carbonylated oxindoles and related processes. Amination, hydroxylation, and halogenation reactions of 3-substituted oxindoles. Conjugate addition and alkylation reactions of 3-substituted oxindoles. Asymmetric aldol and Mannich reactions of isatins. Michael additions to isatin-derived electron-deficient alkynes. Nucleophilic substitution reactions of functionalized 3-substituted oxindoles. Enantioselective construction of spirooxindoles by cycloaddition, annulation, and cascade cyclization reactions of methyleneindolinone derivatives. The 3,3-disubstituted-2-oxindole moiety is present in many chiral alkaloids that exhibit interesting biological activities. The enantioselective synthesis of chiral oxindole derivatives has been mainly achieved by asymmetric catalytic methods. In this review we highlight the most important catalytic methods relevant to the synthesis of chiral, non-spirocyclic 3,3-disubstituted oxindoles.

Asymmetric Synthesis Of 3, 3-disubstituted Oxindoles
Asymmetric Synthesis Of 3, 3-disubstituted Oxindoles

Author: Dalpozzo Renato

Publisher: World Scientific

Published: 2019-09-11

Total Pages: 320

ISBN-13: 1786347318

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Indole derivatives are the most common heterocycle compounds present in nature, for this reason, they have been referred to as 'privileged structures'. In fact, many approved drugs — and natural products — belong to this family. Among indole derivatives, oxindoles have a structural complexity, which have stimulated generations of synthetic chemists to design strategies for assembling these structures, and their enantioselective synthesis is still growing.This book proposes to describe the known enantioselective syntheses of oxindole derivatives. It is divided in six chapters each referring to a specific class of asymmetric oxindole derivatives. After the introduction, Chapter 2 describes all-carbon spirooxindoles; Chapter 3, open chain 3,3-dialkyloxindoles; Chapter 4, 3-substituted-3-aminooxindoles; Chapter 5, 3-substituted-3-hydroxyoxindoles; Chapter 6, 3-hetero-3-substituted oxindoles. It will be a useful tool for synthetic chemists, who assemble total synthesis of natural products, as well as for drug discovery chemists either in academic or in industry R&S laboratories.

Asymmetric Synthesis of 3, 3-disubstituted Oxindoles
Asymmetric Synthesis of 3, 3-disubstituted Oxindoles

Author: Renato Dalpozzo

Publisher:

Published: 2019

Total Pages: 320

ISBN-13: 9781786347305

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"Indole derivatives are the most common heterocycle compounds present in nature, for this reason, they have been referred to as "privileged structures". In fact, many approved drugs - and natural products - belong to this family. Among indole derivatives, oxindoles have a structural complexity, which have stimulated generations of synthetic chemists to design strategies for assembling these structures, and their enantioselective synthesis is still growing. This book proposes to describe the known enantioselective syntheses of oxindole derivatives. It is divided in six chapters each referring to a specific class of asymmetric oxindole derivatives. After the introduction, Chapter 2 describes all-carbon spirooxindoles; Chapter 3, open chain 3,3-dialkyloxindoles; Chapter 4, 3-substituted-3-aminooxindoles; Chapter 5, 3-substituted-3-hydroxyoxindoles; Chapter 6, 3-hetero-3-substituted oxindoles. It will be a useful tool for synthetic chemists, who assemble total synthesis of natural products, as well as for drug discovery chemists either in academic or in industry R&S laboratories."--

Catalytic Enantioselective Synthesis of Oxindoles and Benzofuranones Bearing a Quaternary Stereocenter and Reactions of Palladium Bisphosphine Complexes Relevant to Catalytic C-C Bond Formation
Catalytic Enantioselective Synthesis of Oxindoles and Benzofuranones Bearing a Quaternary Stereocenter and Reactions of Palladium Bisphosphine Complexes Relevant to Catalytic C-C Bond Formation

Author: Ivory Derrick Hills

Publisher:

Published: 2004

Total Pages: 376

ISBN-13:

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In Part I the development of a new method for the construction of oxindoles and benzofuranones bearing quaternary stereocenters is discussed. A planar-chiral PPY derivative catalyzes the O-to-C acyl group migration (Black rearrangement) in a highly efficient and enantioselective manner. The utility of this method is further demonstrated by the formal total synthesis of the natural product aplysin. In Part II reactivity of bisphosphine palladium-complexes is discussed. It is shown that the oxidative addition of bisphosphine palladium-complexes bearing P(t-Bu2)Me occurs through an SN2-type mechanism. This discovery allows us rationalize the difference in catalytic activity between Pd(P(t-Bu2)Me)2 and Pd(P(t-Bu2)Et)2 for the cross-coupling of alkyl electrophiles. The reductive elimination of H-X from bisphosphine palladium-hydride complexes is also discussed. The discovery that (P(t-Bu)3)2PdHCl undergoes facile reductive elimination in the presence of Cy2NMe, while (PCy3)2PdHCl does not, is explained using X-ray crystal structures. These reactivity patterns may help to explain why Pd(P(t-Bu)3)2 is a much better catalyst than Pd(PCy3)2 for the Heck coupling of aryl chlorides. Finally, Part III describes preliminary work on a palladium-hydride catalyzed isomerization of allylic alcohols as well as initial attempts to study the mechanism of nickel-catalyzed cross-couplings of secondary alkyl-electrophiles.

Scandium(III)- and Indium(III)-catalyzed Enantioselective Additions to Isatin for the Synthesis of 3-hydroxy-2-oxindoles and [(3'-trialkylsilyl)-tetrahydrofuranyl]spirooxindoles
Scandium(III)- and Indium(III)-catalyzed Enantioselective Additions to Isatin for the Synthesis of 3-hydroxy-2-oxindoles and [(3'-trialkylsilyl)-tetrahydrofuranyl]spirooxindoles

Author: Nadine Victor Hanhan

Publisher:

Published: 2013

Total Pages:

ISBN-13: 9781303153518

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The enantioselective synthesis of oxindole products is desirable, for they comprise an important structural motif of various natural products, complex bioactive molecules, andpharmaceutical lead compounds. This dissertation presents the development of efficient andhighly enantioselective methods for the synthesis of 3-substituted-3-hydroxy-2-oxindoles and 3-spirocyclic-2-oxindoles. These efficient and operationally simple methods generate oxindoleproducts from direct additions of π-nucleophiles to isatins. Chapter one provides a summary of literature that highlights strategies for the catalyticasymmetric synthesis of 3-hydroxy-2-oxindoles, spirocyclic oxindoles, and other spirocycliccompounds. The notable spirocyclization examples presented are focused on strategies thatcreate a spirocenter within the key step of a catalytic asymmetric process. Chapter two describes my strategy for the development of the first catalytic asymmetricand direct addition of π-nucleophiles to isatin electrophiles for the synthesis of biologically relevant substituted 3-hydroxy-2-oxindoles. This chapter demonstrates the first example of anenantioselective scandium(III)- and indium(III)-pybox catalyzed addition of indoles, otherelectron rich arenes, silyl enol ethers, and allylstannanes to both N-alkylated and NH isatins.The chapter provides a comparison of reactivity and enantioselectivity of metal complexes in the nucleophilic addition to isatin. It specifically describes the ability of these catalysts to suppress the formation of the 3,3-diaryloxindole product while facilitating the enantioselective synthesis of 3-indolyl-3-hydroxy-2-oxindoles. Chapter three presents the development of a scandium(III)-catalyzed enantioselective Hosomi-Sakurai allylation of isatins with various substituted allylic silanes. Catalyst loading as low as 0.05 mol % can be utilized at room temperature to afford the 3-allyl-3-hydroxy-2-oxindoles in excellent yields and enantioselectivity up to 99% ee, including a demonstration of a gram-scale reaction. The effects of additives and varying silyl groups were explored to demonstrate the scope and application of this reaction. Chapter four describes the discovery and development of the first catalytic asymmetric [3+2] allylsilane annulation reaction, allowing for the enantioselective synthesis of silyl and hydroxy spirooxindoles. The method for this annulation reaction utilizes a chiral ScCl2(SbF6)-indapybox complex with TMSCl as a promoter to afford spirooxindoles in excellent enantioselectivity (99% ee) at room temperature.

Catalytic Arylation Methods
Catalytic Arylation Methods

Author: Anthony J. Burke

Publisher: John Wiley & Sons

Published: 2015-02-09

Total Pages: 530

ISBN-13: 3527335188

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This "hands-on" approach to the topic of arylation consolidates the body of key research over the last ten years (and up to around 2014) on various catalytic methods which involve an arylation process. Clearly structured, the chapters in this one-stop resource are arranged according to the reaction type, and focus on novel, efficient and sustainable processes, rather than the well-known and established cross-coupling methods. The entire contents are written by two authors with academic and industrial expertise to ensure consistent coverage of the latest developments in the field, as well as industrial applications, such as C-H activation, iron and gold-catalyzed coupling reactions, cycloadditions or novel methodologies using arylboron reagents. A cross-section of relevant tried-and-tested experimental protocols is included at the end of each chapter for putting into immediate practice, along with patent literature. Due to its emphasis on efficient, "green" methods and industrial applications of the products concerned, this interdisciplinary text will be essential reading for synthetic chemists in both academia and industry, especially in medicinal and process chemistry.

Artificial Metalloenzymes and MetalloDNAzymes in Catalysis
Artificial Metalloenzymes and MetalloDNAzymes in Catalysis

Author: Montserrat Diéguez

Publisher: John Wiley & Sons

Published: 2018-02-21

Total Pages: 431

ISBN-13: 3527804072

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An important reference for researchers in the field of metal-enzyme hybrid catalysis Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a comprehensive review of the most current strategies, developed over recent decades, for the design, synthesis, and optimization of these hybrid catalysts as well as material about their application. The contributors—noted experts in the field—present information on the preparation, characterization, and optimization of artificial metalloenzymes in a timely and authoritative manner. The authors present a thorough examination of this interesting new platform for catalysis that combines the excellent selective recognition/binding properties of enzymes with transition metal catalysts. The text includes information on the various applications of metal-enzyme hybrid catalysts for novel reactions, offers insights into the latest advances in the field, and contains an informative perspective on the future: Explores the development of artificial metalloenzymes, the modern and strongly evolving research field on the verge of industrial application Contains a comprehensive reference to the research area of metal-enzyme hybrid catalysis that has experienced tremendous growth in recent years Includes contributions from leading researchers in the field Shows how this new catalysis combines the selective recognition/binding properties of enzymes with transition metal catalysts Written for catalytic chemists, bioinorganic chemists, biochemists, and organic chemists, Artificial Metalloenzymes and MetalloDNAzymes in Catalysis offers a unique reference to the fundamentals, concepts, applications, and the most recent developments for more efficient and sustainable synthesis.

Copper-Catalyzed Electrophilic Amination of sp2 and sp3 C−H Bonds
Copper-Catalyzed Electrophilic Amination of sp2 and sp3 C−H Bonds

Author: Stacey L. McDonald

Publisher: Springer

Published: 2016-08-18

Total Pages: 162

ISBN-13: 3319388789

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This thesis reports the latest developments in the direct amination of various C−H bonds using an H−Zn exchange/electrophilic amination strategy. McDonald and co-workers reveal this approach to be a rapid and powerful method for accessing a variety of functionalized amines. The material outlined in this book shows how McDonald achieved C−H zincation using strong, non-nucleophilic zinc bases and subsequent electrophilic amination of the corresponding zinc carbanions with copper as a catalyst and O-benzoylhydroxylamines as the electrophilic nitrogen source. McDonald’s findings are of relevance to medicinal chemistry, drug discovery and materials science. Her thesis is a source of inspiration for scientists entering the field and students beginning their PhD in a related area.

Rhodium-Catalyzed Enantioselective Desymmetrizations of Oxabicyclic Alkenes and Alkene Difunctionalization Via Nickel-Catalyzed Arylcyanation
Rhodium-Catalyzed Enantioselective Desymmetrizations of Oxabicyclic Alkenes and Alkene Difunctionalization Via Nickel-Catalyzed Arylcyanation

Author: Andy Wei Jen Yen

Publisher:

Published: 2020

Total Pages: 0

ISBN-13:

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The synthesis of heterocycles using transition metal catalysis is a topic of broad interest in the field of organic chemistry. Transition metal catalysts allow many diverse bond disconnections to be realized, allowing for many ways to assemble heterocycles. Many of the transformations developed in the Lautens group are aimed at atom economical bond construction processes that streamline synthesis and minimize waste. The arylcyanation reaction and the asymmetric ring opening (ARO) reaction are two examples of methods developed in our group that embody this design principle. Chapter 1 of this thesis describes the development of a nickel-catalyzed arylcyanation reaction for the synthesis of 3,3-disubstituted oxindoles. This method was inspired by our work on the palladium-catalyzed arylcyanation reaction, originally developed to address challenges in the formal synthesis of (+)-corynoline. This nickel-catalyzed reaction uses an air-stable catalyst precursor to achieve a highly practical synthesis of a nitrile-containing oxindole via a domino Heck-cyanide capture cascade. Derivatizations of the nitrile group affords a series of novel heterocyclic scaffolds. Chapter 2 details the discovery and development of a novel enantioselective cycloisomerization reaction of oxabicyclic alkenes. Our work on developing the intramolecular asymmetric ring opening reaction led to the discovery of a novel epoxide synthesis. Specifically, when bridgehead substituted oxabicyclic alkenes with non-nucleophilic side chains are reacted with the [Rh(cod)2]OTf/PPF-PtBu2 catalyst in the absence of an external nucleophile, chiral epoxides are obtained. The synthesis of epoxides through cycloisomerization reactions possesses 100% atom economy and avoids the use of external oxidant. Chapter 3 describes an asymmetric ring opening reaction, specifically to address gaps in the methodology concerning amine nucleophiles. We were inspired by our group's previous attempts to use amino acid derived nucleophiles in the ARO reaction. We developed a way to incorporate amino acids into the ARO reaction by employing their 2-nitrobenzenesulfonamide (nosyl) derivatives as pronucleophiles. Intriguingly, we observed a divergence in reactivity between the diastereomeric hydroxyester products, in that one diastereomer was capable of lactonization and the other was not. This led to the enantioselective synthesis of chiral oxazinones, which are similar to the naphthoxazine class of compounds which possess dopaminergic activity.