Download or read book Nickel and Palladium Catalyzed Routes to Carbocycles and Heterocycles written by Ashish Thakur and published by . This book was released on 2015 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Palladium and Nickel Catalyzed Transformations Forming Functionalized Heterocycles written by Hyung Yoon and published by Springer Nature. This book was released on 2020-09-02 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents Pd- and Ni-catalyzed transformations generating functionalized heterocycles. Transition metal catalysis is at the forefront of synthetic organic chemistry since it offers new and powerful methods to forge carbon–carbon bonds in high atom- and step-economy. In Chapter 1, the author describes a Pd- and Ni-catalyzed cycloisomerization of aryl iodides to alkyl iodides, known as carboiodination. In the context of the Pd-catalyzed variant, the chapter explores the production of enantioenriched carboxamides through diastereoselective Pd-catalyzed carboiodination. It then discusses Ni-catalyzed reactions to generate oxindoles and an enantioselective variant employing a dual ligand system. Chapter 2 introduces readers to a Pd-catalyzed diastereoselective anion-capture cascade. It also examines diastereoselective Pd-catalyzed aryl cyanation to synthesize alkyl nitriles, a method that generates high yields of borylated chromans as a single diastereomer, and highlights its synthetic utility. Lastly, Chapter 3 presents a Pd-catalyzed domino process harnessing carbopalladation, C–H activation and π-system insertion (benzynes and alkynes) to generate spirocycles. It also describes the mechanistic studies performed on these reactions.
Download or read book Exploring Nickel and Iron Catalyzed Cycloaddition Routes to N Heterocycles written by Brendan Roberto D'Souza and published by . This book was released on 2012 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Palladium catalyzed and Electrophilic Cyclization Approaches to Carbocycles and Heterocycles written by Shilpa Arvind Worlikar and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book New Palladium catalyzed Approaches to Heterocycles and Carbocycles written by Qinhua Huang and published by . This book was released on 2004 with total page 629 pages. Available in PDF, EPUB and Kindle. Book excerpt: The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I2, ICl, PhSeCl, and p-O2NC6H4SCl to give the corresponding halogen-, selenium-, and sulfur containing disubstituted isoquinolines and naphthyridines, respectively. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The Pd(II)-catalyzed cyclization of 2-(1-alkynyl)arylaldimines in the presence of various alkenes provides an efficient way to synthesize a variety of 4-(1-alkenyl)-3-arylisoquinolines in moderate to excellent yields. The introduction of an ortho-methoxy group on the arylaldimine promotes the Pd-catalyzed cyclization and stabilizes the resulting Pd(II) intermediate, improving the yields of the isoquinoline products. Highly substituted naphthalenes have been synthesized by the palladium-catalyzed annulation of a variety of internal alkynes, in which two new carbon-carbon bonds are formed in a single step under relatively mild reaction conditions. This method has also been used to synthesize carbazoles, although a higher reaction temperature is necessary. This method accommodates a variety of functional groups and affords the anticipated highly substituted naphthalenes and carbazoles in good to excellent yields. Novel palladium migration/arylation methodology for the synthesis of complex fused polycycles has been developed, in which one or more sequential Pd-catalyzed intramolecular migration processes involving C-H activation are employed. The chemistry works best with electron-rich aromatics, which is in agreement with the idea that these palladium-catalyzed C-H activation reactions parallel electrophilic aromatic substitution. A relatively efficient synthesis of cyclopropanes has been developed using palladium-catalyzed C-H activation chemistry, in which two new carbon-carbon bonds are formed in a single step. This method involves the palladium-catalyzed activation of relatively unreactive C-H bonds, and provides a very efficient way to synthesize cyclopropapyrrolo[1,2-a]indoles, analogues of the mitomycin antibiotics.
Download or read book Palladium catalyzed and Electrophilic Cyclization Approaches to Important Heterocycles and Carbocycles written by Saurabh Mehta and published by . This book was released on 2009 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book New Palladium catalyzed Approaches to Heterocycles and Carbocycles written by Guangxiu Dai and published by . This book was released on 2003 with total page 714 pages. Available in PDF, EPUB and Kindle. Book excerpt: A wide variety of 3,4-disubstituted isoquinolines containing an aryl, allylic, benzylic, alkynyl and vinylic group at the 4 position have been prepared via cross-coupling of 2-(1-alkynyl)benzaldimines with organic halides in the presence of a palladium catalyst. The best results are obtained by employing 5 mol % Pd(PPh3)4, 5 equiv of K2CO3 in DMF at 100°C. The electronic effect of the imine substrates and organic halides on the yields has been discussed. 3-Substituted 4-aroylisoquinolines have been prepared in high yields via carbonylative cross-coupling of 2-(1-alkynyl)benzaldimines with aromatic iodides or aroyl chlorides in the presence of a palladium catalyst under 1 atm of CO pressure. Imine substrates having an aryl, vinylic or alkyl substituent on the distal end of the triple bond all undergo this palladium-catalyzed carbonylative cross-coupling cyclization in high yields. The palladium(II)-catalyzed oxidative carbonylation of 2-(1-alkynyl)benzaldimines for synthesis of the corresponding isoquinoline-4-carboxylates has been studied and the optimal reaction conditions have been investigated. Although this methodology study has not provided an efficient route to synthesize methyl 3-substituted isoquinoline-4-carboxylates in synthetically useful yields, it provides an insight into the nature of the palladium-catalyzed cyclization reactions promoted by organopalladium intermediates. A novel intramolecular alkyl-to-aryl palladium rearrangement has been observed by trapping the arylpalladium intermediate with an olefin by a Heck reaction. The reaction conditions have been optimized and the reaction scope has been extensively studied. In all of the successful examples, migration products were isolated exclusively. In addition, this alkyl-to-aryl palladium migration can be controlled by simply modifying the reaction conditions.
Download or read book N Heterocyclic Carbenes in Transition Metal Catalysis written by Frank Glorius and published by Springer. This book was released on 2010-11-19 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In this book leading experts have surveyed major areas of application of NHC metal complexes in catalysis. The authors have placed a special focus on nickel- and palladium-catalyzed reactions, on applications in metathesis reactions, on oxidation reactions and on the use of chiral NHC-based catalysts. This compilation is rounded out by an introductory chapter and a chapter dealing with synthetic routes to NHC metal complexes.
Download or read book Nickel Catalyzed Reactions of Amides and New Methods for the Synthesis of Nitrogen Containing Heterocycles written by Bryan Joseph Simmons and published by . This book was released on 2019 with total page 558 pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation is divided into two main themes concerning transition metal-mediated methodologies and the synthesis of nitrogen-containing heterocycles. The first part of this dissertation focuses on the development of three new reaction pathways utilizing nickel and palladium. The impact of transition metals in the field of synthetic organic chemistry cannot be overstated, with the 2010 Nobel Prize being awarded for the use of palladium cross-coupling in organic synthesis. The second part of this dissertation aims to expand the synthetic toolbox towards the generation of nitrogen-containing heterocycles. With over 100 FDA-approved drugs containing a nitrogen atom, new methodologies toward these scaffolds remain highly sought after. Chapters One, Two, and Three focus on the development of new methodologies utilizing nickel and palladium catalysis. Chapters One and Two describe our efforts towards the functionalization of the amide moiety. Although amides were once thought to be unreactive due to their resonance stabilization, we sought to probe the utility of amides as a functional group handle. Chapter One focuses on the alkylation of amides using nickel and an organozinc source to generate sp2-sp3 C-C bonds. Chapter Two showcases a methodology to convert secondary and tertiary amides to their corresponding amines using a silane reducing agent and nickel catalysis. Chapter Three discusses an academic and industrial collaboration towards the synthesis of tetra-ortho-substituted biaryls using palladium catalysis. These studies culminated in an extensive computational analysis of the reaction mechanism and the synthesis of numerous atropisomeric biaryls. Chapters Four, Five, and Six detail new methodologies towards the generation of nitrogen-containing heterocycles. With the nitrogen atom being prevalent in numerous FDA-approved drugs, facile routes towards their incorporation remain highly valued. Chapter Four illustrates the elusive 3,4-piperidyne's use in a variety of cycloaddition reactions. This study led to the formation of numerous annulated piperidines and exemplifies the utility of our methodology. Chapters Five and Six utilize the interrupted Fischer indolization reaction to produce an assortment of furanoindoline and pyrrolidinoindoline products. Chapter Five centers on the synthesis of the aza-analogues of these products by employing pyridylhydrazines. A computational study was undertaken to determine the cause of success or failure in this transformation. Chapter Six describes a variation of interrupted Fischer indolization methodology performed in a microfluidic device, which should enable its use in medicinal chemistry.
Download or read book Synthesis of Aromatic Heterocycles and Carbocycles Through Tandem Palladium Catalyzed Cross Coupling Reactions of Gem dihaloolefins written by Christopher Scott Bryan and published by . This book was released on 2010 with total page 798 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our group has developed a strategy for the synthesis of benzofused carbocycles and heterocycles through tandem palladium-catalyzed reactions of gem-dibromoolefins. In these syntheses, one bromide undergoes a Pd-catalyzed cyclization reaction, and the other participates in an orthogonal inter- or intramolecular Pd-catalyzed reaction to functionalize or annulate that ring, respectively.Chapter 2 describes the synthesis of benzothiophenes through the combination of a Pd-catalyzed C--S coupling with an orthogonal Suzuki, Heck, or Sonogashira reaction. This represents the first example of the incorporation of Pd-catalyzed C--S coupling into a tandem reaction.Chapter 1 describes the pairing of an intramolecular C--N bond forming reaction (the Buchwald- Hartwig coupling) with an intramolecular direct arylation for the synthesis of fused indole derivatives. A range of previously unknown heterocycles were synthesized through this method.In Chapter 3, a tandem intramolecular Heck / intermolecular Suzuki reaction is described for the synthesis of methyleneindenes. Studies on this reaction have provided advanced understanding of the mechanism, including how variation of the ligand controls the regioselectivity of the reaction.
Download or read book The Palladium Catalyzed Multicomponent Synthesis of M nchnones written by Rajiv Dhawan and published by . This book was released on 2004 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Chapter 6 describes some preliminary studies on the mechanism of Munchnone synthesis. Based upon kinetic data and catalyst resting state analyses, the rate determining step was suggested to possibly be N-acyliminium salt oxidative addition to Pd(0). In addition, crystal structures of {[P( o-Tol)3]Pd(eta2-CH(Tol)N(PMB)COPh)} and its dimeric precursor {Pd(eta2-CH(Tol)N(PMB)COPh)}2 were obtained." --
Download or read book Palladium catalyzed Asymmetric Trimethylenemethane Cycloaddition written by Steven Mark Silverman and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of new methods for chemical synthesis is motivated by the desire to add efficient chemo-, regio-, diastereo-, and enantioselective reactions to the repository of transformations available to researchers. In addition to reaction development, a primary goal of methodology research is to fundamentally understand chemical reactivity. This understanding provides the impetus for further discovery, inevitably allowing for the rapid synthesis of complex molecules as well as the development of industrially feasible processes. The research described herein discusses method development and seeks to place it within this context. Cycloaddition reactions have been widely used in organic synthesis since initial accounts of the Diels-Alder reaction were reported over 80 years ago. These reactions can proceed by either stepwise or concerted processes, can be thermally or photochemically initiated, metal catalyzed or non-metal catalyzed, but one unifying feature of this reaction class is the ability to quickly assemble a complex molecular architecture. A method for the synthesis of cyclopentane rings was disclosed by the Trost group in 1979 through the controlled generation of trimethylenemethane (TMM), a three-carbon dipole capable of participating in a palladium-catalyzed stepwise cycloaddition. Over the ensuing 20 years, this procedure was expanded to other five-membered rings, including pyrrolidines and tetrahydrofurans. It was generalized to include [4+3] and [6+3] cycloadditions in addition to the initial [3+2] reaction. However, only minimal advances were made in the establishment of a catalytic, asymmetric variant of the reaction, which would have enormous value in that chiral variants of the above molecules could be prepared. A protocol for the enantioselective TMM reaction was developed and is described herein. The synthesis of novel phosphoramidite ligands was critical in this effort, and the preparation and reactivity of these ligands is detailed. The evolution of the ligand design, commencing with acyclic amine-derived phosphoramidites and leading to cyclic azetidine and pyrrolidine structures is discussed. The initial conditions used to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of alkene acceptors, providing the desired cyclopentanes with high levels of enantioselectivity. The donor scope was also explored and various substituted systems were tolerated, including one bearing a nitrile moiety and a one bearing a propiolate function. These were reactive with unsaturated acylpyrroles, giving the product cyclopentane rings bearing three stereocenters in high enantioselectivity and complete diastereoselectivity. The nitrile donor was reactive with methyleneoxindoles, providing products containing up to three adjacent stereocenters, two being all-carbon quaternary. Furthermore, ligand controlled diastereoselection was seen. The methodology was further applied to the synthesis of heterocycles. The parent donor successfully reacted with N-aryl and N-Boc imines. A nitrile donor was found to react with a series of N-Tosyl imines, giving the pyrrolidines in high yield. Multiple regioisomers were formed and reaction conditions were developed to favor each product. In the case of N-Tosyl ketimines, the desired cycloadducts containing tetrasubstituted centers were prepared with nearly complete enantio- and diastereoselectivity. The protecting group could be removed to afford a synthetically versatile compound with several handles for further elaboration. Conditions were also developed to perform an enantioselective TMM reaction with aldehydes, giving the desired tetrahydrofurans in moderate to good enantioselectivity. Finally, an asymmetric [4+3] cycloaddition utilizing ortho-quinone methides was successfully performed in an effort to prepare oxepanes. Taken collectively, these results demonstrate that the palladium-phosphoramidite catalyst system represents a versatile method for the rapid assembly of complex molecular architectures from simple starting materials via cycloaddition.
Download or read book Norbornene mediated Palladium catalyzed Synthesis of Fused Aromatic Carbocycles and Heterocycles by Dino Alberico written by Dino Alberico and published by . This book was released on 2006 with total page 748 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapter 2 examines a sequence in which two alkyl-aryl bonds and one alkenyl/aryl bond are formed in one pot. The reaction conditions were optimized and the scope was examined. A variety of symmetrical and unsymmetrical tricyclic heterocycles were synthesized in good yields from a Heck acceptor and an aryl iodide containing two tethered alkyl bromides. This methodology was applied to the synthesis of a tricyclic mescaline analogue. We have developed a norbornene-mediated palladium-catalyzed tandem reaction for the preparation of fused aromatic carbocycles and heterocycles. Chapter 1 describes an alkylation/alkenylation sequence using aryl iodides and bromoenoates. The effect of substitution on the bromoenoate was evaluated. A wide variety of carbon-, oxygen-, and nitrogen-containing functional groups are tolerated allowing for rapid access to highly functionalized aromatic carbocycles. Chapter 3 describes an alkylation/C-H functionalization sequence. In this highly efficient approach, an alkyl-aryl bond and an aryl-heteroaryl bond are created from two C-H bonds in a one-pot process. A wide range of functionalized annulated indoles were synthesized in a convergent manner in high yields.
Download or read book Palladium catalyzed Synthesis of Functionalized Aromatic Carbocycles and Heterocycles written by Alena Rudolph and published by . This book was released on 2009 with total page 802 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our group has expanded the synthetic utility of a palladium-catalyzed norbornene-mediated domino process first described by Catellani, to access a variety of fused aromatic heterocycles and medicinally relevant scaffolds.Chapter 1 describes a domino aromatic alkylation/Heck reaction sequence to generate tricyclic heterocycles. We significantly expanded the scope of this reaction to include a variety of heteroatoms including sulphur, nitrogen, benzylic oxygens and silicon. In particular, tricyclic analogues of mescaline, implicated in the treatment of disorders such as schizophrenia and depression, are easily accessed by this method.Chapter 2 examines the application of unactivated secondary alkyl halides as the aromatic alkylating reagent in this process. We have successfully demonstrated that secondary alkyl halides react intramolecularly and intermolecularly, and stereospecifically to afford a variety of polycyclic heterocycles. A number of termination steps have also proved to be compatible with this process, such as the Heck reaction, the direct arylation of heterocycles and a Buchwald-Hartwig amination. Notably, we used the structural features of these secondary alkyl halides to gain key stereochemical and mechanistic information for the overall palladium-catalyzed reaction.Chapter 3 describes a second area of research within our group that investigates the development of desymmetrizing ring-opening reactions via the addition of nucleophiles to strained meso bicyclic alkenes to afford tetrahydronaphthalene cores. Specifically the palladium-catalyzed, asymmetric ring opening of azabenzonorbornadiene with organoborons is investigated, which proceeds with moderate to good enantioselectivities depending on the nature of the boronic acid employed. Others in our group have recently demonstrated the utility of this methodology in the first asymmetric syntheses of a family of naturally occurring alkaloids, displaying a wide variety of pharmacological activities.
Download or read book Synthesis of Aromatic Heterocycles and Carbocycles Through Tandem Palladium catalyzed Cross couplings of Gem dihaloolefins written by Christopher Bryan and published by . This book was released on 2010 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nickel and Palladium Catalyzed Cross Coupling Reactions written by Rebecca Green and published by . This book was released on 2016 with total page 183 pages. Available in PDF, EPUB and Kindle. Book excerpt: The following dissertation discusses the development of a nickel catalyst for the synthesis of Csp2-Csp bonds in addition to the development and mechanistic studies of nickel and palladium catalysts for the synthesis of Csp2-N bonds. The first chapter is a review of the cross-coupling reactions discussed in this dissertation. Nickel and palladium will be compared with respect to physical properties and reactivity differences. The challenges associated with nickel-catalyzed cross coupling will be illustrated, while drawing analogies to analogous palladium-catalyzed reactions. The literature background for the synthesis of Csp2-Csp bonds, catalyzed by palladium and palladium/copper catalytic systems, will be reviewed, while highlighting the challenges and limitations of the field. The field of Csp2-N bond-forming reactions will be examined, as the differences in reactivity between nickel and palladium will be emphasized. Chapter 2 discusses our efforts towards the development of a nickel catalyst for the development of a Csp2-Csp bond forming reaction, performed in the absence of a copper co-catalyst. Chapter 3 describes the development of a single-component nickel complex that catalyzes the coupling of aryl chlorides with primary alkylamines. A series of mechanistic experiments, including synthesis of catalytic intermediates and kinetic experiments, were performed to elucidate the mechanism of the reaction. Chapter 4 discusses our report the palladium-catalyzed coupling of aryl halides withammonia and gaseous amines as their ammonium salts. A difference in selectivity between reactions of aryl chlorides and aryl bromides was discovered and investigated. Chapter 5 describes the development of a single-component nickel catalyst for the coupling of aryl chlorides with ammonia and ammonium sulfate to form the corresponding primary arylamines. The application of ammonium salts was extended to the coupling of gaseous amines, such as methylamine and ethylamine, which were subjected to the reaction conditions as their hydrochloride salt.
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). " --
