Download or read book Palladium mediated Carbon carbon Bond Formation Methodology and Mechanism Part I Palladium catalyzed arylation of Aryl Nitromethanes Phosphonoacetates and Phosphine Oxides Part II Mechanistic Study of the Palladium mediated Chemoselective Activation of C sp3 H Bonds written by Kelsey Faith VanGelder and published by . This book was released on 2016 with total page 606 pages. Available in PDF, EPUB and Kindle. Book excerpt: Part II: A unique C(sp3)–H bond activation of toluene by Pd(OAc)2 was recently discovered. The mechanism of this reaction was studied. The initially proposed mechanism was ruled out, and another mechanism, more consistent with experimental evidence, is proposed. Evidence for a rate-limiting C–H activation event is presented, as is as evidence for radical character in both the oxazolone starting material and toluene coupling partner. Kinetics studies were undertaken, which revealed a completely zero-order reaction, perhaps implicating an intramolecular rate-determining step.
Download or read book Palladium Catalyzed C sp2 C sp3 Bond Formation written by Sophie Rousseaux and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Palladium Catalyzed Carbon carbon Bond Formation at Carbon hydrogen Bonds written by Louis-Charles Campeau and published by . This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Advances in Palladium catalyzed Carbon carbon Bond Formation Via Functionaliszaton of Carbon hydrogen Bonds written by Olivier René and published by . This book was released on 2010 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Strategies for Palladium Catalyzed Non directed and Directed C bond H Bond Functionalization written by Anant R. Kapdi and published by Elsevier. This book was released on 2017-05-23 with total page 502 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Palladium catalyzed Direct Arylation Via Sp2 and Sp3 C H Activation of Hetero aromatics and Hydrocarbons for C C Bond Formation written by Liqin Zhao and published by . This book was released on 2014 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Development and Application of Palladium catalyzed Carbon nitrogen Bond Forming Reactions written by Seble-Hiwot Teshome Wagaw and published by . This book was released on 1999 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Chelation assisted Palladium catalyzed Activation of C H Bonds written by Ramesh Giri and published by . This book was released on 2009 with total page 1280 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Developments and Applications of Methods for Palladium and Copper catalyzed Carbon nitrogen Bond Formation written by Jeffrey Chih-Yeh Yang and published by . This book was released on 2018 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: The studies presented in this dissertation are aimed at the development and application of methodologies that enable carbon-nitrogen (C-N) bond formation catalyzed by late transition metals such as palladium and copper. The first part of this thesis focuses on the use of palladium catalysis for the construction of a carbon(sp2)-nitrogen bond in the context of a biphasic continuous-flow system (Chapter 1). The second part of this thesis describes the recent developments of copper-hydride (CuH) catalyzed asymmetric hydroamination for the formation of a-chiral carbon(sp3)-nitrogen bonds from olefins. This work includes the application of CuH catalysis to the synthesis of chiral N-alkyl aziridines (Chapter 2), and the discovery and development of novel electrophilic amines to enable CuH-catalyzed asymmetric hydroamination to directly access primary amines (Chapter 3). Part I. Chapter 1. Use of a "Catalytic" Cosolvent, N,N-Dimethyl Octanamide, Allows the Flow Synthesis of Imatinib with no Solvent Switch A general, efficient method for C-N cross-coupling has been developed using N,N-dimethyloctanamide as a cosolvent for biphasic continuous-flow applications. In addition to utilizing a proper co-solvent, the described method harnesses the superior mixing abilities of a stainless-steel powder packed tube reactor to efficiently couple a wide range of aryl/heteroaryl halides and aryl/heteroaryl/alkyl amines in a short period of time (
Download or read book Application of a Palladium tri tert butylphosphine Catalyst System Towards Mild and General Methods for Carbon carbon Bond Formation written by Adam Francis Littke and published by . This book was released on 2002 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: (Cont.) A wide variety of olefins could be employed in these couplings, including disubstituted olefins. In addition, these Heck reactions could be performed on multigram scale with minimal purification of starting materials, emphasizing the practicality and robustness of this method. Prior to 1999 there were no reports of palladium-catalyzed Stille couplings of unactivated aryl chlorides; utilizing Pd/P(t-Bu)3 in tandem with a fluoride activation strategy, we were able to develop the first general method for Stille couplings of aryl chlorides. More recently, we have considerably increased the scope of this reaction, including the synthesis of tetra-ortho-substituted biaryls, selective couplings of chlorides over triflates, and couplings of some aryl chlorides at room temperature. We have also undertaken mechanistic, kinetic, and reactivity studies using 1H NMR, P NMR, and GC. As a result of these studies, we believe that a monophosphine palladium species is the active catalyst in many of these couplings. The bisphosphine palladium complex Pd(P(t-Bu)3)2 is the resting state; yet by itself it is an ineffective catalyst for room-temperature couplings of aryl chlorides. The addition of phosphine-free Pd2(dba)3 to Pd(P(t-Bu)3)2 generates an efficient catalyst for room-temperature couplings and inspired us to try to utilize crystalline and now commercially available Pd(P(t-Bu)3)2 as a catalyst to eliminate the need to handle air-sensitive P(t-Bu)3. For the most part we have been quite successful in this regard; mixtures of Pd(P(t-Bu)3)2 and Pd2(dba)3 are efficient catalysts for many room-temperature couplings of aryl chlorides. ...
Download or read book Palladium in Organic Synthesis written by Jiro Tsuji and published by Springer Science & Business Media. This book was released on 2005-07-06 with total page 348 pages. Available in PDF, EPUB and Kindle. Book excerpt: with contributions by numerous experts
Download or read book Mechanistic Studies of Palladium II mediated Carbon carbon Bond Formation written by Francis Charles Rix and published by . This book was released on 1994 with total page 368 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Higher Oxidation State Organopalladium and Platinum Chemistry written by Allan J. Canty and published by Springer. This book was released on 2011-02-25 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: Kyle A. Grice, Margaret L. Scheuermann and Karen I. Goldberg: Five-Coordinate Platinum(IV) Complexes.- Jay A. Labinger and John E. Bercaw: The Role of Higher Oxidation State Species in Platinum-Mediated C-H Bond Activation and Functionalization.- Joy M. Racowski and Melanie S. Sanford: Carbon-Heteroatom Bond-Forming Reductive Elimination from Palladium(IV) Complexes.- Helena C. Malinakova: Palladium(IV) Complexes as Intermediates in Catalytic and Stoichiometric Cascade Sequences Providing Complex Carbocycles and Heterocycles.- Allan J. Canty and Manab Sharma: h1-Alkynyl Chemistry for the Higher Oxidation States of Palladium and Platinum.- David C. Powers and Tobias Ritter: Palladium(III) in Synthesis and Catalysis.- Marc-Etienne Moret: Organometallic Platinum(II) and Palladium(II) Complexes as Donor Ligands for Lewis-Acidic d10 and s2 Centers.
Download or read book Development of New Classes of Palladium and Nickel Catalyzed Carbonylation Reactions written by Jevgenijs Tjutrins and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "This thesis describes the development of new palladium and nickel catalyzed carbonylation reactions to efficiently and rapidly generate products with minimal waste. These reactions can be carried out using commercially and/or readily available starting materials, including imines, acid chlorides, aryl iodides, alkynes, alkenes and carbon monoxide. In chapter 2, we describe a palladium catalyzed carbonylative synthesis of polysubstituted imidazoles. This transformation involves a tandem catalytic process, where a single palladium catalyst mediates both the carbonylation of aryl halides to form acid chlorides, as well as cyclocarbonylation of a-chloroamides, to generate 1,3-dipoles. Finally, a regioselective 1,3-dipolar cycloaddition with electron poor imines furnishes tetra-substituted imidazoles. Overall this provides a route to prepare imidazoles from five readily available building blocks: two electronically distinct imines, aryl halides and two molecules of CO. In chapter 3, we describe a nickel catalyzed approach to synthesize of isoindolinones via the carbonylation of aryl iodides in the presence of imines. In this, the nickel catalyzed in situ generation of acid chlorides via aryl halide carbonylation allows the formation of a chloroamides, which in turn undergo an intramolecular cyclization to form isoindolinones. This reaction offers an efficient alternative to traditional syntheses of isoindolinones, which often require the initial assembly of the appropriate aryl-tethered precursors for cyclization. In chapter 4, we describe the development of a palladium catalyzed, electrophilic approach to the carbonylative C-H bond functionalization of a range of heterocycles. Mechanistic studies show that the Pd/PtBu3 catalyst can mediate the in situ formation of highly electrophilic aroyl iodide intermediates, which react with heterocycles forming aryl-(hetero)aryl ketones. This provides a general methodology to construct ketones from aryl iodides and electron rich heterocycles without the need to prefunctionalize the heterocycle, install directing groups, or exploit high energy starting materials (e.g. acid chlorides). Chapter 5 describes mechanistic studies on the palladium catalyzed multicomponent synthesis of 1,3-oxazolium-5-olates (Münchnones). Previous work in our laboratory has shown that Münchnones can be generated via the palladium catalyzed multicomponent coupling of acid chlorides, imines and CO. In order to better understand this reaction, we synthesized and characterized key reactive intermediates, studied stoichiometric model reactions, and performed kinetic studies on catalytic reaction. These allowed the elucidation of the role of the catalyst structure, rate determining steps, as well as the importance of off cycle steps in this transformation. In chapter 6, we show how the mechanistic insights laid out in the previous chapter can be applied to create a highly active catalytic system for synthesis of 1,3-oxazolium-5-olates. By employing a sterically encumbered pyrrole-based phosphine ligand, which can be more easily displaced by carbon monoxide for carbonylation, we have created a catalyst that is more than ten times more active that previous systems for this reaction. When coupled with alkyne cycloaddition, this offers a broadly generalizable route to form polysubstituted pyrroles from simple imines, acid chlorides and alkynes. This approach has been applied to the multicomponent synthesis of Atorvastatin (i.e., Lipitor). " --
Download or read book Palladium Assisted Synthesis of Heterocycles written by Navjeet Kaur and published by CRC Press. This book was released on 2019-05-01 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a compilation of the recent applications of palladium catalysts in organic synthesis. The book demonstrates that it is a highly dynamic research field. This methodology has emerged as a powerful tool for the efficient and chemoselective synthesis of heterocyclic molecules. In the past few years, several strategies have been pointed out to pursue more efficient, sustainable, and environment friendly chemical processes. Among those strategies, catalysis and the design of new processes that avoid the use of toxic reagents have been the focus of intense research.
Download or read book Palladium Catalyzed Carbon nitrogen Bond Formation written by Alejandra Domínguez Huerta and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "This thesis describes the design and development of reductive amination methodologies of unactivated carbon-oxygen bonds using palladium on charcoal as a heterogeneous catalyst. The underlying premise is the transformation of starting materials that can be obtained from bio-renewable resources into commodity chemicals. Specifically, 2-cyclohexen-1-one and phenol were used as lignin building-block surrogates for C-N bond formation. The first chapter places the work developed in this thesis both in a global and a scientific context. Its objective is to provide an overview of our societal needs while describing the latest scientific developments related to this thesis topic. Thus, it begins by exploring the United Nation's Sustainable Goals, followed by an overview of petroleum and lignin chemistry, and finishes with a review on amino acid N-modification. In chapter two, the development of a novel methodology for the N-arylation of [alpha]-amino acids using 2-cyclohexen-1-one is described. Palladium on carbon was chosen as the catalyst, and several reaction conditions were explored to obtain optimal yields. This methodology's attractiveness lies in the absence of an aryl halide or protecting group on the 2-cyclohexen-1-one for the N-arylation to proceed. The reaction requires substoichiometric amounts of base and oxygen as the terminal oxidant. Aliphatic amino acids were ideal substrates for the reaction, and cyclohexanone provided the N-biarylated amino acids in good yields (up to 74%). Chapter three describes efforts to improve the harsh conditions required for the N-arylation of [alpha]-amino acids, resulting in the development of a novel methodology for their N-cyclohexylation in water, at room temperature, using phenol as a coupling partner. The reaction successfully achieves N-cyclohexylation for 17 out of the 20 naturally occurring amino acids without racemization with up to quantitative yields. Furthermore, small peptides were also successful substrates for the reaction. The fourth chapter explores the possibility of applying the latter methodology for the formation of one- and two-component peptide staples using tyrosine as a handle. The one component staple was investigated using acetyl-lysine and acetyl-tyrosine, while the two-component staple was investigated using acetylated-tyrosine 2,2'-(ethylenedioxy)bis(ethylamine). While model substrates proved to couple successfully under previously optimized conditions, concentration and characterization proved to be challenging for working with larger peptides. Additional experiments exploring the possibility of using tyrosine amination as a pH responding hydrogel are also described in this chapter. Finally, chapter five explores the possibility of synthesizing diphenylamines from phenol and ammonia formate as a convenient ammonia surrogate. Seventeen different diarylamines were synthesized with palladium on charcoal as the catalyst, with yields ranging from good to excellent. Notably, water and CO2 were the only byproducts generated from this transformation. Triphenylamine was also obtained in combination with the methodology described in Chapter 1"--
Download or read book Advances in Palladium catalyzed Carbon carbon Bond Formation Via Functionaliszaton of Carbon hydrogen Bonds written by Olivier René and published by . This book was released on 2010 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
