Catalytic Enantioselective Synthesis of Aryl Substituted 3-hydroxy-2-oxindoles and 3,3-disubstituted-2-oxindoles 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 Catalytic Enantioselective Synthesis of Aryl Substituted 3-hydroxy-2-oxindoles and 3,3-disubstituted-2-oxindoles PDF full book. Access full book title Catalytic Enantioselective Synthesis of Aryl Substituted 3-hydroxy-2-oxindoles and 3,3-disubstituted-2-oxindoles by Aziza Hatice Sahin. Download full books in PDF and EPUB format.
Author: Aziza Hatice Sahin
Publisher:
ISBN: 9781124223438
Category :
Languages : en
Pages :
Get Book Here
Book Description
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.
Author: Aziza Hatice Sahin
Publisher:
ISBN: 9781124223438
Category :
Languages : en
Pages :
Get Book Here
Book Description
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.
Author: Albert Moyano
Publisher: Elsevier Inc. Chapters
ISBN: 0128084693
Category : Science
Languages : en
Pages : 83
Get Book Here
Book Description
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.
Author: Dalpozzo Renato
Publisher: World Scientific
ISBN: 1786347318
Category : Science
Languages : en
Pages : 320
Get Book Here
Book Description
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.
Author: Renato Dalpozzo
Publisher:
ISBN: 9781786347305
Category : Asymmetric synthesis
Languages : en
Pages : 320
Get Book Here
Book Description
"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."--
Author: Ivory Derrick Hills
Publisher:
ISBN:
Category :
Languages : en
Pages : 376
Get Book Here
Book Description
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 PDF](https://books.google.com/books/content/images/frontcover/-s_-nQEACAAJ?fife=w80-h100)
Author: Nadine Victor Hanhan
Publisher:
ISBN: 9781303153518
Category :
Languages : en
Pages :
Get Book Here
Book Description
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.
Author: Andy Wei Jen Yen
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
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.
Author: Joseph Jesse Badillo
Publisher:
ISBN: 9781321013184
Category :
Languages : en
Pages :
Get Book Here
Book Description
The development of regio- and stereoselective methods for the synthesis of oxindoles and spirocyclic oxindoles is important due to the prevalence of these structures in natural products and medicinal agents. This dissertation describes both Lewis acid and organocatalytic strategies for the regio-, diastereo-, and enantioselective synthesis of several classes of 3,3'-oxindoles and 3,3'-spirooxindoles. These strategies are applied to several synthetic transformations including allylsilane annulations, Friedel-Crafts alkylations, and Pictet-Spengler reactions. Chapter one describes an overview of recent methods for the enantioselective synthesis of oxindoles and spirooxindoles with a particular focus on scaffolds relevant to drug discovery. This overview is organized by type of catalyst and strategy in order to compare traditional organometallic and Lewis acid methods with recent organocatalytic methods. This chapter also features a section on multicomponent and cascade reaction strategies. Chapter two describes the development of synthetic methodology using titanium(IV)-catalysis for the selective synthesis of two new classes of spirocyclic oxindoles. In the first section, I present a highly regio- and diastereoselective method for the synthesis of spiro[3,3'oxindoleoxazolines] upon addition of 5-methoxy-2-oxazoles to isatins. In the second section, I present a method for the addition of 5-methoxy-2-aryloxazoles to [alpha],[beta]-unsaturated alkylidene oxindoles to provide access to spiro[3,3'oxindole-1-pyrrolines] with excellent yields and diastereoselectivities. This methodology is also effective for the diastereoselective synthesis of 1-pyrrolines derived from coumarins and simple malonates. Chapter three describes the condensation cyclization between isatins and 5-methoxytryptamine catalyzed by chiral phosphoric acids to provide spirooxindole tetrahydro-[beta]-carboline products in excellent yields and enantioselectivity. A comparison of catalysts provides insight for the reaction scope and factors responsible for efficient catalytic activity and selectivity in these Pictet-Spengler type spirocyclization reactions. In addition I show that chiral phosphoric acids with different 3,3'-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration. Chapter four describes a strategy for the efficient two-step synthesis of triazole derivatives of oxindoles and spirooxindoles. Using a common set of N-propargylated isatins, a series of mechanistically distinct stereoselective reactions with different combinations of nucleophiles and catalysts provides access to diverse hydroxy-oxindoles, spiroindolones, and spirocyclic oxazoline structures. The resulting N-propargylated oxindoles are then converted to triazoles using copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. This strategy is used for the synthesis of a 64-member pilot-scale library of diverse oxindoles and spirooxindoles. Chapter five describes the first catalytic asymmetric [3+2] allylsilane annulation for the synthesis of cyclopentanes containing an all-carbon quaternary spirocenter. The annulation reaction is catalyzed with a chiral scandium(III)-indapybox complex where a sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF) anion is essential for catalytic activity and stereoselectivity. Lactone formation affords evidence for an ester stabilized [beta]-silyl carbocation. Further transformations provide access to N-H spirooxindoles and allow transformation of the silyl group to a hydroxyl moiety. This catalyst complex is also effective for the asymmetric Friedel-Crafts conjugate addition of variety of additional pi-nucleophiles (i.e. indoles, pyrroles, anilines) to [alpha],[beta]-unsaturated alkylidene oxindoles. This methodology is also effective for the diastereoselective synthesis of coumarin and simple malonate derivatives.
Author: Stacey L. McDonald
Publisher: Springer
ISBN: 3319388789
Category : Science
Languages : en
Pages : 162
Get Book Here
Book Description
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.
Author: Nessa Carson
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
