Palladium-catalyzed Direct Arylation Via Sp2 and Sp3 C-H Activation of Hetero(aromatics) and Hydrocarbons for C-C Bond Formation PDF Download
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Author: Liqin Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 184
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Book Description
During this thesis, we were interested in the sp2 and sp3 C-H bond activation catalyzed by palladium catalysts for the preparation of (hetero)aryl-aryls and biaryls. This method is considered as cost effective and environmentally attractive compared to the classical couplings such as Suzuki, Heck, or Negishi. First we described the palladium-catalyzed direct C2-arylation of benzothiophene in the absence of phosphine ligand with high selectivity. We also demonstrated that it is possible to active both C2 and C5 C-H bonds for access to 2,5-diarylated compounds in one step, and also to non-symmetrically substituted 2,5-diarylpyrroles via sequential C2 arylation followed by C5 arylation. We also studied the reactivity of polychlorobenzenes via palladium-catalyzed C-H activation. We finally examined the palladium-catalysed selective sp2 and sp3 C-H bond activation of guaiazulene. The selectivity depends on the solvent and base: sp2 C2-arylation (KOAc in ethylbenzene), sp2 C3-arylation (KOAc in DMAc) and sp3 C4-Me arylation (CsOAc/K2CO3 in DMAc). Through this method, a challenging sp3 C-H bond was activated.
Author: Liqin Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 184
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Book Description
During this thesis, we were interested in the sp2 and sp3 C-H bond activation catalyzed by palladium catalysts for the preparation of (hetero)aryl-aryls and biaryls. This method is considered as cost effective and environmentally attractive compared to the classical couplings such as Suzuki, Heck, or Negishi. First we described the palladium-catalyzed direct C2-arylation of benzothiophene in the absence of phosphine ligand with high selectivity. We also demonstrated that it is possible to active both C2 and C5 C-H bonds for access to 2,5-diarylated compounds in one step, and also to non-symmetrically substituted 2,5-diarylpyrroles via sequential C2 arylation followed by C5 arylation. We also studied the reactivity of polychlorobenzenes via palladium-catalyzed C-H activation. We finally examined the palladium-catalysed selective sp2 and sp3 C-H bond activation of guaiazulene. The selectivity depends on the solvent and base: sp2 C2-arylation (KOAc in ethylbenzene), sp2 C3-arylation (KOAc in DMAc) and sp3 C4-Me arylation (CsOAc/K2CO3 in DMAc). Through this method, a challenging sp3 C-H bond was activated.
Author: Sophie Rousseaux
Publisher:
ISBN:
Category : Arylation
Languages : en
Pages :
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Book Description
Palladium-catalyzed reactions for carbon-carbon bond formation have had a significant impact on the field of organic chemistry in recent decades. Illustrative is the 2010 Nobel Prize, awarded for "palladium-catalyzed cross couplings in organic synthesis", and the numerous applications of these transformations in industrial settings. This thesis describes recent developments in C(sp2)-C(sp3) bond formation, focusing on alkane arylation reactions and arylative dearomatization transformations. In the first part, our contributions to the development of intramolecular C(sp3)-H arylation reactions from aryl chlorides are described (Chapter 2). The use of catalytic quantities of pivalic acid was found to be crucial to observe the desired reactivity. The reactions are highly chemoselective for arylation at primary aliphatic C-H bonds. Theoretical calculations revealed that C-H bond cleavage is facilitated by the formation of an agostic interaction between the palladium centre and a geminal C-H bond. In the following section, the development of an alkane arylation reaction adjacent to amides and sulfonamides is presented (Chapter 3). The mechanism of C(sp3)-H bond cleavage in alkane arylation reactions is also addressed through an in-depth experimental and theoretical mechanistic study. The isolation and characterization of an intermediate in the catalytic cycle, the evaluation of the roles of both carbonate and pivalate bases in reaction mechanism as well as kinetic studies are reported. Our serendipitous discovery of an arylation reaction at cyclopropane methylene C-H bonds is discussed in Chapter 4. Reaction conditions for the conversion of cyclopropylanilines to quinolines/tetrahydroquinolines via one-pot palladium(0)-catalyzed C(sp3)-H arylation with subsequent oxidation/reduction are described. Initial studies are also presented, which suggest that this transformation is mechanistically unique from other Pd catalyzed cyclopropane ring-opening reactions. Preliminary investigations towards the development of an asymmetric alkane arylation reaction are highlighted in Chapter 5. Both chiral carboxylic acid additives and phosphine ligands have been examined in this context. While high yields and enantiomeric excesses were never observed, encouraging results have been obtained and are supported by recent reports from other research groups. Finally, in part two, the use of Pd(0)-catalysis for the intramolecular arylative dearomatization of phenols is presented (Chapter 7). These reactions generate spirocyclohexadienones bearing all-carbon quaternary centres in good to excellent yields. The nature of the base, although not well understood, appears to be crucial for this transformation. Preliminary results in the development of an enantioselective variant of this transformation demonstrate the influence of catalyst activation on levels of enantiomeric excess.
Author: Kassem Beydoun
Publisher:
ISBN:
Category :
Languages : en
Pages : 212
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During this thesis, we were interested in the C-H bonds activation catalyzed by palladium catalysts such PdCl(C3H5)(dppb) and ligand-free or ligand associated Pd(OAc)2 for the préparation of biaryls. This method is considered as cost effective and environmentally attractive compared to other types of couplings such as Suzuki, Stille, or Negishi. First we demonstrated that it is possible to apply C-H bond activation method for the direct arylation of formyl or acetyl halothiophene derivatives. The corresponding products could be further functionalized due to the presence of the halo and carbonyl groups. We have also demonstrated that the use of cyclopentyl methyl ether (CPME) as solvent, which is considered as a greener solvent compared to more toxic traditional solvents generally employed for the coupling reactions, lead to a variety of arylated heteroaromatic derivatives. We then established palladium-catalyzed systems for the selective O- or C2- arylation of non-protected phenol derivatives. We found that a simple change of the nature of the base used in this reaction would lead to different selectivities. We also studied the direct arylation of dithienylperfluorocyclopentene derivatives via palladium-catalyzed C-H activation. This method provides a simpler access for substituted photochromic molecules. In addition we showed that it is possible, using sequential addition of reagents, to prepare thieno- or furo-quinoline derivatives starting from thieno- or furo-carboxaldehyde and 2-haloaniline derivatives in a one pot reaction. We also demonstrated that palladium catalyzed direct arylation method could be applied for the arylation of ligands already coordinated to iridium complexes. With this method, a variety of complexes with different physical properties were obtained.
Author: Louis-Charles Campeau
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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The biaryl core has been identified by medicinal chemists as a privileged structure in pharmaceutical compounds as it is found in 4.3% of all drugs. For over a century, synthetic chemists have sought new methods for their preparation. Breakthroughs in synthetic catalytic methodology over the past thirty years gave rise to now routine reactions such as the Suzuki and Stille couplings. Unfortunately, the need for pre-activation of both coupling partners makes for wasteful installation and subsequent removal of activating agents. Direct arylation reactions are attractive alternatives to traditional cross-coupling methods, as one of the pre-activated partners is replaced with a simple arene. The organometallic coupling partner is typically replaced as it is the most difficult to prepare. Although the advantages of this approach have made it a popular research topic for more than twenty-five years, no general catalysts exist for this transformation, and in a lot of cases reactivity remains a challenge. This thesis will outline our work in this area of research. First, our efforts toward the development of a general catalyst for the intramolecular direct arylation of aryl halides with simple arenes will be presented. These studies led to the development of three new catalysts for this transformation, affording a process general for aryl chlorides, bromides and iodides. Additionally, mechanistic studies performed on this system have brought to the forefront the concerted metallation-deprotonation mechanistic model for direct arylation. Ultimately, these studies led to the first non-directed intermolecular direct arylation of a simple arene. In a second section, efforts toward the inclusion of pi-deficient heteocycles as a substrate class in direct arylation will be outlined. These studies led to the development of a novel cross-coupling reaction of azine N-oxides with aryl halides. Greater mechanistic understanding, made possible through the use of computational tools, was crucial in extending this methodology to azole N-oxides. Finally, the development of novel direct functionalization reactions with picoline derivatives is described. These substrates are among the first to be suitable for catalyst controlled site-selective functionalization of a sp2 or sp3 C-H bond.
Author: Lu Chen
Publisher:
ISBN:
Category :
Languages : en
Pages : 156
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During my thesis, I focused on condition for the activation / functionalisation of C-H bonds for the construction of biaryl derivatives tolerant to the reactive functional groups such as silyl, alkenes, esters or amides. Compared to classic cross-coupling protocols (Suzuki, Stille or Negishi), C-H bond functionalisation provides a costly effective and environmentally attractive procedures. At first, we observed that the silyl-substituted thiophenes can be directly arylated with aryl bromides without desilylation, using the simple Pd(OAc)2/dppb precatalyst for both conversion and desilylation inhibition. Then, we have demonstrated that the Pd(OAc)2/KOAc catalyst system without phosphine ligand, even using as few as 0.1 mol% of Pd catalyst, promotes the direct arylation of heteroaromatics and inhibits the Heck type reaction with 1,2-disubstituted alkenes. In addition, we demonstrated that easily accessible esters on heteroaromatics can be advantageously employed as blocking groups in the course of the direct arylation of several heteroaromatic derivatives. Finally, the palladium-catalyzed direct heteroarylation of 2- or 4-bromobenzamide with heteroarenes was studied. In the presence of KOAc as the base, no formation of C-N or C-C bonds by coupling of two bromobenzamide was observed.
Author: Olivier René
Publisher:
ISBN:
Category : University of Ottawa theses
Languages : en
Pages : 212
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Author: Anant R. Kapdi
Publisher: Elsevier
ISBN: 0128052554
Category : Science
Languages : en
Pages : 502
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Strategies for Palladium-Catalyzed Non-directed and Directed C-H Bond Functionalization portrays the complete scope of these two aspects of C-H bond functionalization in a single volume for the first time. Featured topics include the influence of palladacyclic systems in C-H bond functionalization (need for newer catalytic systems for better efficiency), mechanistic aspect of the functionalization strategies leading to better systems, and applications of these methodologies to natural product synthesis and material synthesis. Addresses the involvement of catalytic systems (palladacycles) for better functionalization of (hetero)arenes to emphasize the need for developing better, more selective systems Covers the use of powerful mechanistic tools for understanding and assisting the development of better functionalization strategies Discusses the finer aspects of C-H bond functionalization, such as control of regioselectivity with or without directing groups Includes a chapter detailing the synthesis of naturally occurring molecules or functional molecules via both pathways for assessing the applicability of the functionalization strategies
Author: Ramesh Giri
Publisher:
ISBN:
Category : Catalysis
Languages : en
Pages : 1280
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Carbon-hydrogen (C-H) bonds are ubiquitous in organic molecules. Utilization of such abundant chemical moieties as functional group equivalents could shorten route to synthetic targets and provide chemists with new disconnections in retrosynthesis. As such regio- and stereoselective functionalization of unactivated C-H bonds has remained one of the major challenges in organic chemistry. The majority of the transition metals have been rigorously examined for their efficacy in transforming unactivated C-H bonds (pKa >35) into useful functional groups or into C-C bonds. Among those metals, palladium is particularly effective in activating both aromatic (sp2) and aliphatic (sp3) C-H bonds. This thesis explores the reactivity of palladium catalysts in both of these areas. The research herein was conducted using directing groups for C-H cleavage with special focus on utilizing simple functionality such as carboxylic acids. Chapter one details different types of directing groups and their utility in a variety of reactions. Chapters two and three contain details of research on C-heteroatom (C-I and C-O) and C-C bond formation, respectively, with palladium acetate as a catalyst. The iodination and acetoxylation reactions proceed under mild conditions and moderate to excellent levels of diastereoselectivity (up to 99.9%) have been observed with both sp2 and sp3 C-H bonds using oxazoline as the directing group. Mechanistic investigations have been carried out in order to understand the high level of stereoselection and, in this process, a number of palladacycle intermediates have been characterized by X-ray crystallography which led us to assign the absolute stereochemistry of C-H activation. Moreover, the iodination protocol could also be extended to prepare diiodides as intermediates for cyclopropanation which provides a new disconnection approach to construct cyclopropanes. Chapter two discusses C-C bond formation via cross-coupling reactions with organoboron reagents and carbon monoxide using the carboxylic acids as the directing group. Detailed mechanistic investigation along with characterization of intermediate palladacycle formed from sodium toluate have revealed an unprecendented directing ability of carboxylate groups in which the carbonyl oxygen, rather than the O-anion, directs palladium for C-H cleavage.
Author: Enrico Tapire Nadres
Publisher:
ISBN:
Category : Organic
Languages : en
Pages :
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Book Description
Palladium-catalyzed functionalization of C-H bonds is becoming an important synthetic tool that allows the preparation of desired substances in fewer steps and higher yields compared to traditional synthetic routes. The C-H bonds can be directly converted to C-C or C-heteroatom bonds. However, the ubiquity of C-H bonds in organic compounds can lead to problems in chemo- and regioselectivity. In heterocycles, the control of regioselectivity of the reaction is governed by the difference in acidity of the heterocyclic ring C-H bonds. An economical method for the arylation of C-H bonds of pyrroles and furans by aryl chlorides was developed. The method employs a palladium acetate catalyst, 2-(dicyclohexylphosphino)biphenyl ligand, and an inorganic base. Electron-rich, electron-poor, and heterocyclic aryl chloride coupling partners can be used and arylated heterocycles are obtained in moderate to good yields. The functionalization of sp2 and sp3 C-H bonds can be promoted by the use of directing groups that coordinate the Pd catalyst and activate the desired C-H functionalities. Use of Pd(OAc)2 in conjunction with cesium acetate or potassium carbonate bases allows functionalization of sp2 and sp3 C-H bonds in amides possessing picolinic acid directing group. Stoichiometric silver additive is not required in contrast with previously published procedure. Arylations are effective for sp2 as well as primary and secondary sp3 C-H bonds. Alkylations of sp2 C-H bonds are successful in most cases. Both primary and secondary alkyl iodides are reactive but secondary alkyl iodides afford low yields. Alkylation of sp2 C-H bonds is low yielding and the reaction requires further optimization. Alkyl and aryl iodides as well as benzyl bromides are reactive. Aryl and alkyl bromides afford no product. Direct conversion of C-H bonds to C-N bonds was also developed. Pd-catalyzed method for pyrrolidine, indoline, and isoindoline formation by cyclization via C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)2 oxidant, and toluene solvent at 80-120 °C. Cyclization is effective for sp2 as well as aliphatic and benzylic sp3 C-H bonds.
Author: Steven P. Breazzano
Publisher:
ISBN:
Category : Activation (Chemistry)
Languages : en
Pages : 72
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