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1
Arismendi, Romero Graciela. "Paladium catalized cross-coupling reactions." Revista de Química, 2012. http://repositorio.pucp.edu.pe/index/handle/123456789/101014.
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El premio Nobel en Química de este año ha sido otorgado a los investigadores Richard Heck (EE.UU.), Ei-ichi Negishi (EE.UU.) y Akira Suzuki (Japón), por sus valiosos aportesen el desarrollo de un tipo específico de reacciones para la formación de enlaces C-C: “Reacciones de acoplamientocruzado catalizadas por paladio”. La creciente demanda de nuevas sustancias para el desarrollo de medicamentos, materiales y/o compuestos biológicamente activos ha hecho de este descubrimiento una importante herramienta para los químicos, dándoles la capacidad de atender estas necesidades con la creación de moléculas complejas de utilidad industrial.This year´s Nobel Prize in Chemistry has been awarded to the researchers Richard Heck (USA), Ei-Ichi Negishi(USA) and Akira Suzuki (Japan), for their valuable contributions to the development of a specific type of reaction for the formation of carbon-carbon bonds: “Palladium-catalyzed cross couplings”. The growing demand for new substances for drug development, materials and/or biologically active compounds has made this discovery an important tool for chemists, giving them the ability to meet these needs through the creation of complex molecules of industrial utility.
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Black, Daniel. "Imines in copper-catalyzed cross-coupling reactions." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102960.
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The purpose of this study was to develop new catalytic methods to mediate carbon-carbon bond forming reactions with imines under mild conditions and in a general manner. We found that copper catalysts were compatible in cross-coupling of a range of mild organometallic reagents, providing simple, efficient routes to alpha-substituted amides and amines.Chapter 2 of this thesis describes a new copper-catalyzed multicomponent synthesis of alpha-substituted amides. This reaction was developed based upon previous work in this laboratory, which showed that palladium catalysts were competent in Stille-type cross-coupling of imines, acid chlorides, and organostannanes. While providing a mild method of generating the amide products, a more general procedure able to incorporate a wider range of organostannanes was sought. This chapter details the development of a copper-catalyzed protocol, which, as well as performing the cross-coupling under mild reaction conditions, proceeds with a diverse range of aryl-, heteroaryl-, and vinyl-substituted organostannanes and employs an inexpensive and readily available catalyst. Through this system, control over regioselectivity of addition to alpha,beta-unsaturated imines is also possible.
Chapter 3 demonstrates that, in addition to organostannanes, other substrates are viable in copper-catalyzed cross-coupling with imines and acid chlorides. Herein, the coupling of terminal alkynes with imines and acid chlorides is described, leading to an efficient synthesis of tertiary propargylamides directly from simple starting materials. This synthesis incorporates a wide variety of substituted imines, acid chlorides/chloroformates, and terminal alkynes, providing a rapid synthesis of these useful building blocks (reaction completion in only 15 minutes). In addition, the process is shown to work with aza-aromatic heterocycles, such as pyridine, where the alkynylation occurs exclusively at the 2-position.
Chapter 4 describes the utility of these rapid multicomponent reactions, where the products are directly converted into oxazole heterocycles. Copper-catalyzed- and zinc-catalyzed protocols are developed for the synthesis of secondary propargylamides from silyl-imines, acid chlorides, and terminal alkynes. The secondary propargylamide products are then, in a one pot sequence, transformed into trisubstituted oxazoles.
Chapter 5 describes the development of an atom-economical, non-toxic alternative to the organotin coupling described in Chapter 2. This involves the use of tri- and tetraorgano-indium reagents, which can transfer all of their organic groups in a copper-catalyzed coupling with imines and acid chlorides. This reaction shows good functional group compatibility and further expands the scope of alpha-substituted amides and N-protected amines that can be synthesized through mild copper catalysis.
Chapter 6 explores the enantioselective alkynylation of nitrogen-containing heterocycles. As described in Chapter 3, heterocycles such as pyridine can undergo copper-catalyzed 1,2-addition with terminal alkynes upon activation by chloroformates. As this process generates a stereocenter, it is possible to introduce enantio-control into the reactions by using a chiral copper catalyst. With ligands from the PINAP series, enantioselectivities of up to 84% can be induced in the coupling of nitrogen-containing heterocycles (e.g., quinoline), chloroformates, and terminal alkynes. This provides a mild and simple synthesis of chiral 2-alkynyl-1,2-dihydroquinolines directly from simple starting materials.
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Hall, Mark Andrew. "Iron-catalysed cross-coupling and reduction reactions." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.551314.
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Iron nanoparticles of size 6-16 nm have been successfully prepared by the reduction of FeCb with 3-pentylmagnesium bromide in the presence of polyethylene glycol. These nanoparticles show excellent activity in the catalytic dehalogenation of a range of alkyl and aryl halides when used at 5 mol% loadings, if an excess of the Grignard is present to ensure the regeneration of the catalyst. Alkyl halides react to give mixtures of alkane, alkene and homocoupled products, with good selectivity of the alkane product being observed. Aryl halides undergo hydrodehalogenation cleanly and do not undergo homocoupling. A general methodology, previously developed within the group for the cross-coupling of benzyl halides with diarylzinc reagents has been applied to other substrates. This includes 2-halopyridines and N-(bromomethyl)phthalimide, with the former exhibiting slower reaction rates so higher temperatures were required. Surprisingly, in the case of N-(bromomethyl)phthalimide, the coupling reaction was found to proceed without the need for a catalyst. This has been demonstrated for a number of diarylzinc reagents, which resulted in the cross-coupled product being formed in good to excellent yields. Furthermore,. this substrate undergoes cross- coupling with a range of boronic acids via transmetallation to diethylzinc.
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Zhou, Jianrong (Jianrong Steve). "Cross-coupling reactions of unactivated alkyl halides." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/33655.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005.Vita.
Includes bibliographical references.
My graduate research at MIT has been focused on the development of palladium- or nickel-catalyzed cross-coupling reactions using unactivated alkyl electrophiles (e.g., halides and sulfonates). Although aryl and alkenyl electrophiles have been commonly used in such processes, the utility of alkyl substrates has been underdeveloped, and merits further exploration. We have developed the first palladium-based catalyst that is effective for Negishi couplings of primary alkyl electrophiles. A single protocol (2%Pd₂(dba)₃/8%P(Cyp)₃/NMI in THF/NMP at 80⁰C) can be applied to a broad spectrum of electrophiles, including chlorides, bromides, iodides, and tosylates. Concerning the scope of the nucleophilic components, an array of alkyl-, alkenyl-, and arylzinc halides can be coupled. The process is tolerant of a variety of functional groups, including esters, amides, imides, nitriles, and heterocycles. Furthermore, geometrically- defined alkenylzinc species, generated from titanium-mediated hydrozincation of internal alkynes, can be directly used in the process. Despite the progress in nickel- and palladium-catalyzed C(sp³)-C(sp³) bond formation, the methods had been limited to primary alkyl electrophiles.
(cont.) No doubt, the ability to use more challenging, secondary ones will further augment the usefulness of these metal- catalyzed processes. To this end, we have determined that Ni(cod)₂/s-Bu-Pybox can catalyze room-temperature Negishi couplings of an array of functionalized alkyl bromides and iodides. To the best of our knowledge, this is the first nickel- or palladium- catalyzed cross-coupling procedure for unactivated, [beta]-hydrogen-containing secondary alkyl halides. In addition, preliminary studies using substrate-based probes suggest that the oxidative addition proceeds through a radical pathway. This may explain the unparalleled reactivity of the nickel catalyst. As an extension of the nickel catalysis, we have established that the combination of Ni(cod)₂ and bathophenanthroline can effect Suzuki reactions of secondary halides and organoboronic acids. These organoboron reagents are particularly widely used in the cross-coupling chemistry, owing to their chemical stability, biological non-toxicity, and commercial availability. Again, mechanistic evidence has been collected to support the involvement of organic radicals during the oxidative addition step.
by Jianrong (Steve) Zhou.
Ph.D.
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Moriwaki, Yuya. "Cross-Coupling Reactions in Flow Microreactor Systems." 京都大学 (Kyoto University), 2015. http://hdl.handle.net/2433/200446.
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Adams, Kirsty. "Metal catalysed cross-coupling reactions of heterocycles." Thesis, University of Huddersfield, 2013. http://eprints.hud.ac.uk/id/eprint/20889/.
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This report describes two methodology studies dedicated towards development of metal catalysed crosscoupling reactions in the synthesis of novel heterocyclic compounds. Firstly, a Heck-Mizoroki arylation reaction is reported for the direct functionalisation of tetrahydropyridines, towards the synthesis of kainoid analogues. Kainoids are a group of non-proteinogenic pyrrolidine dicarboxylic acids, which have attracted considerable interest because of their potent biological activity, including insecticidal, anthelmintic and neuroexcitatory properties. The ideal synthesis of kainoids would allow the ability to introduce various side chains at the C-4 position to access diverse pharmacologically active kainoid analogues. Tandem asymmetric Heck-Mizoroki arylation reaction and [2,3]-sigmatropic rearrangement provides a quick and efficient way to access these molecules. The Heck-Mizoroki arylation of 1-methyl-1,2,5,6-tetrahydropyridine and its hydrochloride salt is reported, with the arylation in the 3- position of the tetrahydropyridine as the major product. The reaction has been applied to a variety of substituted aryliodides, with promising results, demonstrating functional group tolerance of the method, however isolation and purification of the resulting compounds has remained challengeing. Diarylation of tetrahydropyridines has also been achieved. Secondly, a new catalytic method for arylative spirocyclisation is reported, using stoichiometric Grignard reagents and iron(III) catalysts, to induce cyclisation of 2-iodo benzyl ethers of furan in a highly stereoselective manner to produce novel functionalised spirocyclic compounds. Method optimisation and application of a variety of Grignard reagents is reported with aryl cross-coupling achieved in high yields. Alkyl- cross coupling has also been achieved with ethylmagnesium bromide Grignard reagent.
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García, Melchor Maximiliano. "Theoretical Study on Pd-catalyzed Cross-Coupling Reactions." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/96827.
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D’ençà el seu descobriment, fa ja prop de tres dècades, les reaccions d’acoblament creuat C-C catalitzades per Pd han esdevingut una de les transformacions més poderoses dins la química organometàl·lica. De fet, tres dels desenvolupadors de les reaccions d’acoblament més emprades (reaccions de Heck, Suzuki i Negishi) van ésser guardonats l'any 2010 amb el premi Nobel de Química. El mecanisme general de les reaccions d'acoblament creuat C-C consisteix en tres etapes: addició oxidant, transmetal·lació, i eliminació reductiva. La millora d’una reacció comporta el coneixement profund del seu mecanisme de reacció, o el que és el mateix, la comprenssió del seu funcionament a nivell molecular. Així doncs, aquesta tesi doctoral s'ha centrat en l’estudi del mecanisme de reacció de diferents reaccions d’acoblament creuat C-C catalitzades per Pd: la reacció de Negishi, la reacció de Sonogashira en la seva variant sense coure, i una versió enantioselectiva de la reacció de Suzuki-Miyaura. Tots aquests estudis s'han dut a terme mitjançant càlculs mecano-quàntics i en estreta col·laboració amb grups experimentals de prestigi mundial.
En el cas de la reacció de Negishi, s'ha investigat el procés de transmetal·lació amb ZnMeCl i ZnMe2 amb l'objectiu de proporcionar una visió detallada dels respectius mecanismes de reacció. Concretament, per a la transmetal·lació amb ZnMeCl, els càlculs teòrics han mostrat les elevades probabilitats que existeixen de generar-se nous intermedis que donarien lloc a productes d'homo-acoblament no desitjats. Per altra banda, per a la transmetal·lació amb ZnMe2, els resultats teòrics han demostrat l'existència d'intermedis catiònics a priori inesperats. A més, s'han identificat altres mecanismes de transmetal·lació competitius que fins ara no s'havien proposat mai. En resum, en aquest estudi s'ha obtingut una visió detallada dels mecanismes de reacció involucrats en aquestes reaccions.
Per a la reacció de Sonogashira sense coure, s'han investigat els dos mecanismes de reacció proposats en la literatura. Els resultats teòrics han permès descartar un d'aquests mecanismes (carbopal·ladació) i han demostrat que l'altre (desprotonació) és factible. A més, l'anàlisi dels mecanístic ha portat a la proposta d'un nou mecanisme de reacció (iònic). Aquest mecanisme consisteix en la desprotonació de l'alquí i la posterior reacció d'aquesta espècie amb el catalitzador de Pd. L'efecte dels substituents en l'alquí en aquests mecanismes de reacció també s'ha analitzat. En termes generals, aquest estudi mecanistic ha revelat que, de la mateixa manera que en altres reaccions d'acoblament, hi ha varis mecanismes competitius i que el canvi de les condicions de reacció (solvent, lligands, substrat, base) pot afavorir un o altre.
Finalment, s'ha investigat el mecanisme de reacció per un acoblament assimètric de Suzuki-Miyaura catalitzat per un complex de Pd bis-hidrazona. Els resultats derivats d'aquest estudi han revelat que el mecanisme de transmetal·lació difereix del camí general proposat a la literatura: en aquest cas dos etapes addicionals són necessàries. Aquesta modificació es pot atribuir a la capacitat del lligand bis-hidrazona de dissociar un dels àtoms de N directament coordinat al catalitzador de Pd (comportament hemilàbil). Pel que fa referència a l'estereoquímica de la reacció, els càlculs realitzats fins ara no han pogut donar una explicació clara de les enantioselectivitats observades experimentalment.
En resum, els resultsats teòrics obtinguts en aquesta tesi han demostrat que els càculs teòrics són una eina de gran ajut per a l’elucidació i/o proposta de mecanismes de reacció d'aquest tipus de processos.Since its discovery, nearly three decades ago, the Pd-catalyzed cross-coupling reactions have become one of the most powerful transformations in organometallic chemistry. In fact, three of the developers of the most widely used cross-coupling reactions were awarded in 2010 with the Nobel Prize in Chemistry. The general reaction mechanism for C-C cross-coupling consists in three main steps: oxidative addition, transmetalation, and reductive elimination. The reaction improvement entails a deep knowledge of their complete mechanism, or what is the same thing, how they work at the molecular level. Thus, this thesis has been focused on studying the reaction mechanism for different Pd-catalyzed cross-coupling reactions: the Negishi reaction, the copper-free Sonogashira reaction, and an enantioselective version of the Suzuki-Miyaura reaction. All these studies have been carried out by means of quantum-mechanics calculations and in close collaboration with top experimental groups worldwide. In the case of the Negishi reaction, the transmetalation process with ZnMeCl and ZnMe2 reagents has been investigated in order to provide a detailed picture of their reaction mechanisms. In particular, for the transmetalation with ZnMeCl, calculations have pointed out the many chances for the generation of new intermediates that would eventually give rise to homocoupling side products. On the other hand, for the transmetalation with ZnMe2, the theoretical results have proved the existence of previously unexpected cationic intermediates. Moreover, additional competitive transmetalation pathways for this reaction, some of which had not been invoked before, have been also identified. Overall, in this study a general picture of the reaction mechanisms involved in these reactions has been obtained. For the copper-free Sonogashira reaction, the two reaction mechanisms proposed in the literature have been evaluated. Theoretical results, have been able to discard one of those mechanisms (carbopalladation), whereas the other one (deprotonation) has been found to be feasible. Furthermore, the mechanistic analysis have conducted to the proposal of a new reaction mechanism (ionic). This mechanism involves the deprotonation of the alkyne and the subsequent reaction of this species with the Pd catalyst. The effect of the alkyne's substituents on these reaction mechanisms has been also analyzed. Overall, the mechanistic study reported in this thesis has revealed that, just like in other cross-coupling reaction, there are several competing reaction pathways and a change on the reaction conditions (e.g. solvent, ligands, substrate, base) might favor one over the other ones. Finally, the theoretical investigation on the reaction mechanism for an asymmetric Suzuki-Miyaura coupling catalyzed by a bis-hydrazone Pd catalyst has been carried out. The results derived from this study have revealed that the transmetalation mechanism differs from the common reaction pathway proposed in the literature: the transmetalation process requires two additional steps. This modification can be attributed to the relative ability of the bis-hydrazone ligand, which can easily dissociate one of the N atoms directly coordinated to Pd catalyst (hemilabile behavior). As far as the stereochemistry of the reaction is concerned, calculations so far do not provide a clear explanation for the high enantioselectivities observed in the experiments. In summary, the theoretical results derived from this thesis have demonstrated that theoretical calculations are a very useful tool for elucidating and/or proposing reaction mechanisms for these type of processes.
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Munday, Rachel Hannah. "Vinyldimethylphenylsilanes as latent partners in cross-coupling reactions." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430546.
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Zhang, Liang. "Catalytic Conjunctive Cross-Coupling and Catalytic Diboration Reactions." Thesis, Boston College, 2017. http://hdl.handle.net/2345/bc-ir:107561.
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Thesis advisor: James P. MorkenThis dissertation will present four main projects focused on stereoselective construction of borylated compounds as well as their applications in asymmetric syntheses. The first two projects describe the development of a catalytic conjunctive cross-coupling reaction. By merging three simple starting materials, an organolithium reagent, an organoboronate, and an organic electrophile, a synthetically valuable secondary boronate is furnished by the conjunctive cross-coupling in an efficient and enantioselective fashion. Next, this strategy is expanded to synthesize severely hindered tertiary boronates, a synthetic challenging but powerful building block to access a variety of quaternary stereocenters. The third project presents a platinum-catalyzed enantioselective diboration of alkenyl boronates to furnish a broad range of 1,1,2-tris(boronates) products. A deborylative alkylation of the 1,1,2-tris(boronates) leads to a variety of internal vicinal bis(boronates) with high diastereoselectivity. In the final chapter, a general and practical synthesis of alkenyl boronates via the boron-Wittig reaction is disclosed. Utilizing readily accessible geminal bis(boronates) and aldehydes, a broad range of disubstituted and trisubstituted alkenyl boronates are afforded with good yield and stereoselectivity
Thesis (PhD) — Boston College, 2017
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Parry, Paul Richard. "New pyridylboronic acids and their cross-coupling reactions." Thesis, Durham University, 2003. http://etheses.dur.ac.uk/3705/.
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The novel substituted pyridylboronic acids 2-bromo-5-pyridylboronic acid 92, 3-hromo-5- pyridylboronic acid 97, 2-chloro-5-pyridylboronic acid 103, 2-fluoro-5- pyridylboronic acid 108, 2-methoxy-5-pyridylboronic acid 123, 2-ethoxy-5- pyridylboronic acid 125, 2-medioxy-3-pyridylboronic acid 131, 3-bromo-6-methoxy-4- pyridylboronic acid 134, 3-chloro-6-methoxy-4-pyridylboronic acid 137 and 3-hromo-6- ethoxy-4-pyridylboronic acid 138 have been synthesised and shown to undergo palladium-catalysed Suzuki cross-coupling reactions with a vast variety of heteroaryl bromides to yield novel heteroarylpyridine derivatives.5-Formylfnran-2-boronic acid 170 has been synthesised and isolated and has been shown to undergo palladium-catalysed Suzuki cross-coupling reactions with a variety of heteroaryl bromides to yield novel heteroaryl substituted furyl derivatives. These derivatives have been shown to undergo efficient functionalisation by Wittig chemistry.
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Pye, Dominic Richard. "Improved and new iron-catalysed cross-coupling reactions." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687060.
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Iron-catalysed cross-coupling chemistry is undergoing a renaissance due advantages in cost, toxicity and abundance compared to traditional cross-coupling catalysts. In Chapter 2 it is shown that expensive, synthetically challenging bis-phosphines used in the iron-catalysed cross-coupling of alkyl halides and arylboronic acid pinacol esters can be replaced in many cases with simple iron salts in phosphine-free procedures. More challenging substrates require the use of cheap, widely available bis-phosphines such as dppe (l,2-bis(diphenylphosphino)ethane) or dppp (1,3- bis(diphenylphosphino)propane). An EPR spectrum of the reaction mixture shows the presence of previously reported iron(l) complex [FeBr(dppehL which is the likely resting state in the catalytic cycle. Kinetic studies indicate oxidative addition of the alkyl halide via single-electron transfer to a three-coordinate iron species to be the rate-determining step. Having demonstrated that the key feature for facilitating iron-catalysed Suzuki coupling is the activation of a boronic acid pinacol ester with an organometallic nucleophile, in Chapter 3 it was shown that this form of activation could be applied to bis(pinacolato)diboron, allowing the iron catalysed borylation of alkyl, allyl, benzyl and, to a lesser extent, aryl halides. A unique, low-valent, phosphine-supported iron-boryl complex, [Fe(Bpin)(dpbzhL (pin = pinacolato) was isolated from the reaction of [FeCI₂(dpbz)₂] (l,2-bis(diphenylphosphino)benzene) and Li[B₂pin₂(¹Bu)], however this complex failed to react in stoichiometric reactions with 1- bromobutane, reflecting the finding that excess phosphine greatly retards the rate of ironcatalysed borylation. The uniqueness of these low-valent iron-boryl intermediates provided an opportunity to investigate new forms of catalysis based on these complexes. Chapter 4 describes attempts to catalyse the boryl/electrophile difunctionalisation of styrene using Li[B₂pin₂(¹Bu)) and iron precatalysts. It was found that stoichiometric iron is capable of mediating the boryl protonation of styrene; however attempts to trap the organometallic intermediate proved fruitless, and deuterium labelling studies were unable to determine the origin of the a-hydrogen in the resultant product. In order to expand the utility of iron-catalysed cross-coupling, in Chapter 5 attempts to couple electrophiles ·derived from enantiomerically pure l,2-amino alcohols are described. A range of electrophiles including l,2-amino halides, cyclic sulfamidates, oxazolidinones, and oxazolinethiones were screened for activity in iron- and nickel-catalysed cross-coupling; however none of these furnished the desired products.
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Siddle, James Spencer. "Metal-catalysed cross-coupling reactions of nitrogen heterocycles." Thesis, Durham University, 2010. http://etheses.dur.ac.uk/617/.
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Described herein are copper-catalysed N-C heteroarylations of benzimidazole, 1-methylbenzimidazolone, imidazole and pyrrole. The products of these reactions then undergo palladium-catalysed C-C cross-couplings with aryl or heteroarylboronic acids under Suzuki-Miyaura conditions to provide a rapid entry to tris(hetero)aryl scaffolds comprising two or three N-heterocyclic rings. The sequential N-C and C-C couplings can be performed in a one-pot process. 1,5-Di(hetero)arylated-pyridin-2(1H)-one derivatives have been synthesised in good yields starting from (2-fluoro-5-pyridyl)boronic acid. The sequence comprises three steps: (i) palladium-catalysed Suzuki-Miyaura reaction; (ii) basic hydrolysis; (iii) copper-catalysed C-N coupling. X-ray crystal structures are reported for selected pyridin-2(1H)-one derivatives. These compounds are of interest as new scaffolds for drug discovery. A one-pot synthesis of 2-chloro-3,4-diiodopyridine from 2-chloropyridine is described via a Directed ortho Metallation (DoM)/Halogen Dance (HD) mechanism in 26-28% yields. By performing sequential iterative Suzuki-Miyaura cross-couplings using a variety of functionalised heteroaryl and arylboronic acids, a series of novel 2,3,4-triheteroarylpyridine scaffolds have been accessed in synthetically viable yields, including sterically hindered derivatives. An iterative two-fold Sonogashira/Suzuki-Miyaura reaction sequence gave access to 5-[3,4-bis(2-phenylethynyl)pyridine-2-yl]-2-fluoropyridine in 48% overall yield. Disclosed is a novel route towards benzimidazolo[1,2-f]phenanthridines starting from 4-tert-butyl-N-(2-iodophenyl)benzamide via a intermolecular palladium-catalysed N-C bond formation and dehydration to form 2-(4-tert-butylphenyl)-1-(2-bromophenyl)-1H-benzo[d]imidazole. Performing an intramolecular C-H activation reaction on this provided 6-tert-butylbenzimidazolo[1,2-f]phenanthridine. This compound could be of interest to materials science or as a new scaffold for drug discovery. Synthesis of novel soluble, shielding auxiliary ligand 4-(4-(2-ethylhexyloxy)-2,6-dimethylphenyl)pyridine-2-carboxylic acid (G1pic) has been achieved via a five step synthesis from commercially available starting materials utilising the Suzuki-Miyaura reaction on demanding substrates. A route towards a more shielded auxiliary ligand have been explored eventually providing 3-(4-pyridyl)-1,5-bis(4-(2-ethylhexyloxy)phenyl)-2,4-dimethylbenzene as an intermediate for future work. Ir(III) complexes have been synthesised with G1pic and picolinic acid.
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Dunet, Guillaume. "Preparation and Reactions of Allylic Zinc Reagents and Transition Metal-Catalyzed Cross-Coupling Reactions." Diss., lmu, 2007. http://nbn-resolving.de/urn:nbn:de:bvb:19-78249.
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Masson-Makdissi, Jeanne. "Controlling Selectivity in Cross-Coupling Reactions with Ester Electrophiles." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38398.
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First popularized in the 1970s, transition metal-catalyzed cross-couplings now constitute staple reactions for the formation of carbon-carbon and carbon-heteroatom bonds. Recent endeavours in the field have been invested towards expanding the range of compatible coupling partners, with the aim of accessing complex molecules from simple, widely available starting materials. Notably, esters represent an attractive class of alternative coupling partners compared to traditional aryl halides, due to their ubiquity and robustness. Moreover, different cleavage modes can be accessed with esters. Which bond cleavage occurs is highly dependent on which catalyst is used, providing an opportunity to quickly access diverse products from a common precursor. Chapter 1 of this thesis provides a literature overview of cross-couplings with carboxylic acid derivatives to contextualize our contributions described in Chapter 2 and 3.
Chapter 2 describes the Pd-catalyzed cross-coupling of phenyl esters with alkyl boranes. Two reaction modes are enabled, namely C(acyl)–O bond activation with carbonyl-retention and C(acyl)–O bond activation with decarbonylation. As such, both alkyl ketones and alkylated arenes are accessed selectively by simple changes in the catalytic system. The disclosed reaction is applied to the diversification of bioactive molecules and discussed in light of recent mechanistic studies of related transformations.
In Chapter 3, the first additive-free Ni-catalyzed amidation and transesterification of methyl esters are disclosed. In both transformations, a simple Ni catalyst enables widely available methyl or ethyl esters to be converted into value-added products, producing methanol as the only stoichiometric waste by-product. The Ni-catalyzed amidation protocol strongly contrasts wasteful yet common methods used to convert methyl esters into amides, involving wasteful hydrolysis and coupling with stoichiometric activating agents.
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Woods, Tom MacDonald. "Phosphinates as new electrophilic reagents for cross-coupling reactions." Thesis, Durham University, 2008. http://etheses.dur.ac.uk/2130/.
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Activated esters, e.g. triflates, sulfonates, nonaflates and phosphates are excellent electrophiles for a variety of cross-coupling reactions. However, other phosphorus-based esters have received little attention in these protocols. This thesis discusses the synthesis and cross-coupling chemistry of vinyl phosphinates, a new class of electrophilic species. A simple model vinyl phosphinate, N-(tert-butyloxycarbonyl)-4,5,6,7-tetrahydro-1H-azepin-2-yl-diphenylphosphinate, was prepared in excellent yield from commercially available caprolactam. A screening study identified Suzuki cross-coupling conditions under which this phosphinate smoothly coupled with a variety of electron-rich, electron-poor and sterically-hindered boronic acids. The scope and limitations of this chemistry were investigated and a variety of electron-withdrawing nitrogen protecting groups, e.g. Boc, CO(_2)Ph, C0(_2)Bn and Ts could be used without problem. However, electron-donating protecting groups, e.g. Me and Bn proved unsuccessful. Additionally, where seven and eight-membered ring lactam phosphinates coupled efficiently, five and six-membered ring derivatives proved largely unsuccessful. Relative reactivity studies were carried out with N-phenyloxycarbonyl-2- (diphenylphosphinoyloxy)-3,4-dihydro-6-bromoquinolone and indicated that the reactivity of vinyl phosphinates lies between that of aryl chlorides and aryl bromides in the Suzuki reaction. Attempts to improve the efficiency of the cross-coupling of this substrate using DoE and PCA modelling was attempted, but was largely unsuccessful. Studies towards the total synthesis of Lennoxamine via a cross-coupling reaction between a benzazepine-derived vinyl phosphinate and 2,3-dimethoxy-N-(2'-phenylpropan-2-yl)-6-(tributylstannyl) benzamide were commenced. Synthesis of the stannane was achieved in high yield via a directed metallation strategy. Unfortunately, preliminary attempts to cross-couple this stannane with N-(benzyloxycarbonyl)-4,5,6,7- tetrahydro-1 H-azepin-2-yl diphenylphosphinate in a model reaction were unsuccessful. Synthesis of the desired benzazepine phosphinate fragment proved more difficult and although progress has been made, this work remains unfinished. Additionally, treatment of N-([4'-methylphenyl]sulfonyl)-2-oxo-azepane with LDA/TMEDA in the presence of diphenylphosphoryl chloride afforded the sultam 1,2,3,4-tetrahydro-7-methylazepino[1,2-b][1,2]benzothiazole-10,10-dioxide in moderate yield. A range of aryl sulfonamides could be used affording the corresponding sultams in moderate yields.
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Ellis, Peter J. "Mechanistic studies of cross-coupling reactions using Pd nanoparticles." Thesis, University of York, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516508.
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Nunn, Joshua. "Insights into cross-coupling reactions using cheaper metal catalysts." Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687059.
Full textAbstract:
The mechanisms of a range of cross-coupling reactions catalysed by cheaper metal catalysts have been investigated in detail using a combination of spectroscopic techniques and computational modelling. For iron-catalysed Negishi cross-coupling reactions supported by phosphine ligands, it is shown that the iron(II) pre-catalysts are reduced in situ to iron(I), which is found to be the only kinetically relevant oxidation state. The characterisation of a range of relevant low-spin iron(l) phosphine complexes has allowed the study of the mechanism in significantly greater detail than before via direct detection of in situ formed iron(I) intermediates using EPR and UV-Vis spectroscopy. Through the study of reaction kinetics, an Eyring analysis and detailed computational modelling, it has been possible to determine the most likely mechanism for the oxidative addition of the electrophile during cross-coupling. The importance of spin-state changes has been demonstrated through computational modelling; only the involvement of high-spin intermediates, arising from the lowspin ground state, can permit the observed rates. iron-catalysed cross-coupling reactions using amine ligands or ligand-free conditions have been shown to behave in a very different manner to those employing phosphine ligands, with a further clear distinction between systems using aryl- and alkyl-based nucleophiles. The use of alkyl nucleophiles containing β-hydrogen atoms leads to immediate decomposition of iron intermediates, whilst the use of β-hydrogen-free alkyl nucleophiles give thermally stable homoleptic 'ate' complexes including [FeBn₃] and [FeBn₄]. Two classes of intermediates are formed simultaneously from aryl based nucleophiles; a thermally stable iron(I) complex proposed as [Fe(ɳ⁶-(4,4'-bitoly)4-tolyl)₂], and thermally labile homoleptic iron(II) 'ate' complexes including [Fe(4-tolyl)₃] and [Fe(4-tolyl)₄]². Crucially, the identity of the metal in the nucleophile is central to the observed reactivity. Computational modelling has been used to investigate the mechanism of transmetallation and aryl transfer in mixtures of boronic acids, diethylzinc and benzyl halides to form diarylmethanes. It is proposed that transmetallation between boron and zinc occurs by direct alkyl and aryl transfer via boron-zinc zwitterionic-like intermediates. The calculated distribution of organoboron and zinc intermediates based on this mechanism in a range of solvents is in good agreement with existing experimental results. A number of potential mechanisms have been considered, using computational modelling, in the coupling of benzyl bromide with mixtures of diethylzinc and aryl boronic acids.
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Blanc, Guilaine F. "New strategies for pinacol cross-couplings and alkenation reactions." Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/2227/.
Full textAbstract:
The research described herein involves the study of new approaches to alkenation and pinacol cross-coupling. The competition between modified Julia alkenation and Peterson alkenation was studied. Heterocyclic sulfides were oxidised to sulfones by dimethyldioxirane. Reactions between sulfones and aldehydes gave vinyl sulfones in good yields, rather than vinyl silanes, confirming that the Peterson alkenation is preferred in this system. Pinacol cross-coupling between an aldehyde or ketone in solution and a more easily reduced aldehyde immobilised on resin was attempted, but proved unsuccessful. However, aldehydes bearing the salts of tertiary amines were found to be good substrates for pinacol homo-coupling giving diols. The formation of salt avoided unwanted reduction of the aldehyde to a primary alcohol. A wide range of approaches to anisomycin using titanium reagents were investigated. These were based on the formation of the bond between C-3 and C-4 by alkylidenation of esters and ring-closing metathesis (RCM) or intramolecular alkylidenation or radical cyclization. The presence and position of the nitrogen atom proved an insurmountable obstacle to this strategy. The solid-phase synthesis of 4-amino-ketones was achieved. Resin-bound esters were alkylidenated using a novel titanium reagent generated in situ by reduction of a thioacetal with a low valent titanium reagent. Treating the resulting enol ethers with acid gave ketones in good yield and high purity because of the switch in the nature of the linker from acid-stable to acid-sensitive (a chameleon catch strategy). Amino-ketones are potential precursors of pyrrolidines.
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Hua, Xi Ye. "Expanding the Scope of Coupling Partners in Catalytic Cross-Coupling Reactions." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35521.
Full textAbstract:
Carbon-carbon (C-C) bond formation is among the most important processes in organic chemistry. Transition metal catalyzed C-C bond formation is an active research area that shows great potential due to high selectivity and relatively mild conditions.
In Chapter 1, a new reaction for direct acylation of aryl halides is discussed. Specifically, the catalytic reaction between aryl halides/pseudohalides and aldehydes is explored. The choice of ligand, base, solvent, temperature, catalyst and substrates are important factors for optimizing this catalytic reaction. The various combinations of all these factors have, therefore, been examined by high-throughput screening (HTS) in order to develop the new C-C coupling reaction.
In Chapter 2, a new methodology is reported in order to expand the scope of the Kumada-Corriu cross-coupling reaction. The strategy to achieve this goal is mechanistically based, matching oxidative addition rates with the rate of syringe pump addition of the Grignard to minimize the exposure of sensitive groups to the aggressive nucleophile. Aryl chlorides containing esters, amides, nitriles, pyrazines, carbamates, ketones, and other sensitive functionalities are all demonstrated to undergo chemoselective cross-coupling with this technique. The mechanistic reason for the effectiveness of this strategy is uncovered by continuous-infusion ESI-MS studies.
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Blaisdell, Thomas Powers. "New Strategies for Hydroxyl-Directed Organic Reactions." Thesis, Boston College, 2015. http://hdl.handle.net/2345/bc-ir:104626.
Full textAbstract:
Thesis advisor: Kian L. TanThesis advisor: James P. Morken
Described herein are four different research projects spanning over two different research groups. The first two projects describe the development and application of scaffolding catalysts for the (1) site-selective silylation of ribonucleosides and (2) the distal and diastereoselective hydroformylation of homoallylic alcohols. These projects emphasize the effectiveness of scaffolding catalysts to bind a hydroxyl-containing substrate and control the site- or regioselectivity of a reaction using said substrate. The third project describes a hydroxyl-directed diboration of homoallylic and bis-homoallylic alcohols. The hydroxyl-containing 1,2-bis(boronates) are valuable intermediates for further synthetic manipulations. One such manipulation, a hydroxyl-directed Suzuki cross-coupling reaction, is the focus of the final project. This directed cross-coupling reaction forges carbon-carbon bonds in a stereoselective manner, highlighted in the total synthesis of the naturally occurring compound, debromohamigeran E
Thesis (PhD) — Boston College, 2015
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
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Jensen, Anne Eeg. "Transition metal-catalyzed cross-coupling reactions of functionalized organometallic reagents." Diss., lmu, 2001. http://nbn-resolving.de/urn:nbn:de:bvb:19-2331.
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Hammann, Jeffrey [Verfasser], and Paul [Akademischer Betreuer] Knochel. "Cobalt-catalyzed cross-coupling reactions / Jeffrey Hammann ; Betreuer: Paul Knochel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2017. http://d-nb.info/1130587401/34.
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Sun, Shangzheng. "Building up molecular complexity by Ni-catalyzed cross-coupling reactions." Doctoral thesis, Universitat Rovira i Virgili, 2020. http://hdl.handle.net/10803/670603.
Full textAbstract:
En línia amb la investigació desenvolupada al nostre grup basada en l’elaboració de noves reaccions d’acoblament
creuat, hem decidit centrar la tesis doctoral en l’estudi de la formació de nous enllaços Csp3–Csp3, utilitzant reaccions
d’acoblament creuat reductores catalitzades per níquel.
Al primer capítol, els nostres esforços es centren en la preparació d’una nova metodologia basada en l’alquilació
reductiva de a-haloboronats, utilitzant com a matèria prima olefines no activades. Aquest nou protocol, quimio- i
regioselectiu, permet l’incorporació d’un fragment alquílic-boronat a olefines no activades, mitjançant condicions de
reacció suaus. Per altra banda, l’ús d’olefines internes permet la formació d’enllaços carboni-carboni en posicions C–H
sp3 llunyanes, a través del procés anomenat “chain-walking” catalitzat per níquel. Al segon capítol, continuant amb el
nostre interès en reaccions catalitzades per níquel, hem estudiat un mètode catalític d’alquilació desaminativa
d’olefines no activades. Aquesta nova metodologia opera sota condicions de reacció suaus i es caracteritza per l’ampli
espectre de compostos que poden acoblar-se selectivament. Aquesta tècnica pot tenir aplicació en el context de la
derivatització de l’etilè i per la funcionalització de molècules d’alt valor afegit.En línea con la investigación desarrollada en nuestro grupo basada en la elaboración de reacciones de acoplamiento cruzado, hemos decidido centrar la tesis doctoral en el estudio de la formación de enlaces Csp3–Csp3, usando reacciones de acoplamiento cruzado reductoras catalizadas por níquel. En el primer capitulo, nuestros esfuerzos se centran en la preparación de una nueva metodología basada en la alquilación reductiva de a-haloboronatos usando como materia prima olefinas no activadas. Este protocolo, quimio- y regioselectivo, permite la incorporación de un fragmento alquílico-boronato en olefinas no activadas, y presenta unas condiciones de reacción suaves. Por otro lado, el uso de olefinas internas permite la formación de enlaces carbonocarbono en posiciones C-H sp3 lejanas, a través del proceso llamado “chain-walking”, catalizado por níquel. En el segundo capitulo, siguiendo nuestro interés en reacciones catalizadas por níquel, hemos estudiado un método catalítico de alquilación desaminativa de olefinas no activadas. Esta nueva metodología opera bajo condiciones de reacción suaves y se caracteriza por el amplio espectro de compuestos que pueden acoplarse selectivamente. Esta técnica también puede ser aplicada en el contexto de la derivatización del etileno y para la funcionalización de moléculas de alto valor añadido.
In line with our group research interests on cross-coupling-reactions, we decided to focus this doctoral studies on the development of sp3 C–C bond formation by means of nickel catalyzed reductive-cross-coupling. Our first effort was focused on the development of a reductive alkylation of a-haloboronates with unactivated olefin feedstocks. We have developed a mild, chemo- and site-selective catalytic protocol that allows the incorporation of an alkylboron fragment into unactivated olefins. Moreover, the use of internal olefins enables C C bond-formation at remote sp3 C-H sites via nickel catalyzed chain-walking process. Following up our interest on nickel catalyzed chainwalking events, we reported a site-selective catalytic deaminative alkylation of unactivated olefins. This method operates under mild conditions and is characterized by a wide substrate scope and exquisite site-selectivity profile. Particularly noteworthy is that this technique could be employed in the context of ethylene derivatization and for the late-stage functionalization of complex molecules. Our final efforts for the sp3 C–C bond formation was focused on the development of a regio-selective cross-coupling of three electrophiles by means of nickel/photoredox dual catalysis. We developed a modular, chemo- and regio-selective 1,2-difunctionalization of simple vinyl boronates with readily available organic halides.
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Andrews, Philip Ian. "New organometallic strategies for conjugate addition and cross-coupling reactions." Thesis, University of Nottingham, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.606337.
Full textAbstract:
Enamine N-oxides have been reported only a very few times in the literature. Investigation into their reactivity has revealed that treatment with catecholborane can generate amines via an electrophilic iminium species, which provides evidence for a proposed reverse polarity reactivity, with respect to existing l,4-additions to nitro alkenes. Deprotonation at the a-carbon of enamine N-oxide double bonds has also been accomplished by 'BuLi, with deprotonation occurring fully after 5 min. Using methodology developed within the group, a novel enamine N-oxide has been synthesised in good yield, although attempts to form a cyclic enamine N-oxide were unsuccessful. The copper-catalysed asymmetric conjugate addition of trimethylaluminium to nitroalkenes was found to give moderate enantioselectivity (46 % ee) using Cu(OAc)2 and a phosphoramidite ligand in diethyl ether. Conjugate addition of dimethyl(alkynyl)aluminium reagents to cyclic and acyclic enones has been achieved in a racemic sense in good to excellent yields employing MTBE as the solvent with three equivalents of alkynylaluminium, although regioselectivity remains an issue depending on the enone substrate. Cross-coupling of dimethyl(alkynyl)aluminiums with aryl bromides, iodides and triflates catalysed by Pd2(dba)J'CHCh or Pd(dba)2 and DavePhos gave acetylene derivatives in good to excellent yields. These results are comparable with previously reported systems and in some cases gave improvements in yield. Using XPhos as ligand and adding DABCO, chlorobenzene was also coupled in moderate yield. Application to tetracene synthesis was not successful. Development of a novel method of alkyne hydroalumination usmg dichloroalane bis(tetrahydrofuran) adduct and catalytic Ti or Zr metallocene complexes gave high yields of vinyl aluminium reagents. Use of these reagents in Pd-catalysed cross-coupling with aryl halides gave good to excellent yields of (E)-alkenes, and is applicable to both aryl and alkyl terminal acetylenes. 1
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O'Brien, Harry. "Advances in iron-catalysed cross-coupling reactions : methodology and mechanism." Thesis, University of Bristol, 2018. http://hdl.handle.net/1983/84e24322-d526-4169-9ed4-e7a2fb2d710a.
Full textAbstract:
The replacement of noble metals with cheap, sustainable and non-toxic iron as catalysts for cross coupling reactions continues unabated. The significant advancement in methodology has been accompanied by elegant mechanistic studies; vital for further reaction development. Amongst this success, the development of reactions which work with milder coupling partners is paramount. Organoboron reagents are particularly useful, and accordingly there has been great progress in the development of iron-catalysed Suzuki cross-coupling reactions. However, the cross-coupling between an aryl halide and aryl boron reagent, a Suzuki biaryl cross-coupling, has not yet been achieved with iron-catalysis under mild conditions. Here, it is shown that the barrier to success has been in the activation of the aryl halide bond. This has been overcome by installation of an ortho N-pyrrole amide directing group. Notably, mechanistic studies reveal that the N-pyrrole amide works by tethering the iron-catalyst to the electrophile via π-coordination, and a single electron transfer process to afford an amino ketyl radical appears to be responsible for activation of the aryl halide bond. Asymmetric iron-catalysed cross-couplings are extremely rare, and the seminal example suffers from a restrictive electrophile scope. The enantioconvergent iron-catalysed cross-coupling of an unactivated alkyl halide substrate has also been investigated to broaden the scope of this methodology. Finally, a combined synthetic and mechanistic study was conducted to compare the activity of an N-heterocyclic carbene ligand with its N-heterocyclic germylene analogue in iron-catalysed cross couplings; affording insights into the role of carbene ligands in iron-catalysis.
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Ruiz-Castillo, Paula. "Palladium-catalyzed C-N and C-O cross-coupling reactions." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/105048.
Full textAbstract:
Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 375-410).
Chapter 1: This chapter describes a general method for the of the Pd-catalyzed N-arylation of hindered [alpha],[alpha],[alpha]-trisubstituted primary amines. The reaction utilized catalysts based on two biaryl phosphine ligands, which were developed via kinetics-based mechanistic analysis and rational design. These studies led to the first example of catalyst based on a hybrid (alkyl)aryl biaryl phosphine ligand that provides better results that its dialkyl- or diarylbiaryl analogues. The C-N coupling was efficient for a wide range of (hetero)aryl chlorides and bromides under mild conditions. Chapter 2: This chapter relates the development of the Pd-catalyzed C-O coupling of primary alkyl alcohols. The reaction of primary aliphatic alcohols bearing [beta]-hydrogen atoms can lead to undesired [beta]-hydride elimination pathways instead of the target reductive elimination from the [LPd(Ar)OAlk] intermediate, especially when using electron-rich aryl halides. Additionally, aryl chlorides have been shown to be more challenging coupling partners than the corresponding aryl bromides. The use of catalysts based on commercially available ligand t-BuBrettPhos and a novel hybrid ligand, AdCyBrettPhos, have allowed the C-O coupling reaction to proceed effectively at room temperature, minimizing the side reaction. A variety of functionalized primary alcohols have been successfully coupled with (hetero)aryl bromides and chlorides giving rise to medicinally interesting products. Chapter 3: This chapter is a compilation of the applications of Pd-catalyzed C-N coupling in various fields of chemical research since 2008. This work includes the reactions of nine classes of nitrogen-based coupling partners in the 1) synthesis of heterocycles, 2) medicinal chemistry, 3) process chemistry, 4) synthesis of natural products, 5) organic materials and chemical biology, and 6) synthesis of ligands. The large number of applications highlights the versatility and utility of this transformation both in academic and industrial settings.
by Paula Ruiz-Castillo.
Ph. D. in Organic Chemistry
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Chae, Junghyun 1973. "Development and application of transition metal-catalyzed cross-coupling reactions." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/17735.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004.Includes bibliographical references.
Chapter 1. PALLADIUM-CATALYZED REGIOSELECTIVE HYDRODEBROMINATION OF DIBROMOINDOLES A novel approach to the selective preparation of 4-bromoindoles has been developed via a Pd-catalyzed reaction. A variety of 4,6-dibromoindoles, which are prepared via Cu-catalyzed chemoselective C-N bond-forming reaction and subsequent Fischer indole cyclization, are transformed to 4-bromoindoles with high regioselectivity using a catalytic Pd(OAc)2/rac-BINAP system. This new method allowes for the preparation of a variety of 2,3,4,5-polysubstituted indoles from aryl halides. Chapter 2. ENANTIOSELECTIVE SYNTHESIS OF INDOLODIOXANE (S)- U86192A The enantioselective synthesis of the antihypertensive agent indolodioxane (S)-U86192A is described. The 4-bromo-5-alkoxy indole, a key intermediate of the synthesis, is prepared according to the new approach developed in chapter 1. The other noteworthy metal-catalyzed transformations, which play a crucial role in the synthesis, include a palladium-catalyzed intramolecular C-O bond-forming reaction to construct the 1,4-benzodioxane structure. The optical purity of U86192A arises from the use of cobalt-catalyzed enantioselective epoxide ring-opening reaction.
(cont.) Chapter 3. ONE-POT SEQUENTIAL COPPER-CATALYZED CONJUGATE REDUCTION AND PALLADIUM-CATALYZED SILYL ENOL ETHER ARYLATION Enantiomerically enriched 3-substituted diphenylsilyl enol ethers of cyclopentanones, which can be prepared from Cu-catalyzed asymmetric conjugate reduction, are utilized in the Pd-catalyzed arylation of various aryl bromides in the presence of CsF. This new method provides a simple means to access [alpha] aryl-[beta]-alkylcycloalkanones with two new tertiary stereogenic centers in excellent levels of enantiomeric and diastereomeric excess, which are difficult to prepare via other methods. The isolation of the intermediate diphenylsilyl enol ethers is not necessary. The procedure can be carried out in one-pot by choosing the proper solvents and catalyst loadings. This new protocol obviates the need to block the [alpha]'-carbon necessary in our previous method.
by Junghyun Chae.
Ph.D.
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Sherborne, Grant John. "Catalyst deactivation in copper-catalysed C-N cross-coupling reactions." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/17595/.
Full textAbstract:
This thesis details research into the mechanism of the copper-catalysed cross-coupling reaction, with a focus on the N-arylation of secondary amines and amides (Ullmann-Goldberg reaction). Issues limiting the application of the Ullmann-Goldberg reaction on industrial scale are uncovered and understood from a mechanistic point of view, to provide a platform for more efficient copper catalysts. In situ kinetic monitoring using 1H NMR spectroscopy is used to understand the role of each key component in the N-arylation of piperidine using a copper catalyst in a fully homogeneous system. Key roles of the amine and catalyst are observed, whilst product inhibition was found to significantly inhibit the reaction. Solvent effects are evaluated by repeating the in situ kinetic investigation in d7-DMF and d3-MeCN. The kinetic findings indicate deviation of the mechanism from the accepted literature mechanism, with a rate-limiting amine coordination proposed. Kinetic studies are also used to show the key role that the solubility of inorganic bases such as Cs2CO3 and K3PO4 play in rate-determining equilibria between copper species. Slow catalyst turnover was observed for up to 14 hours at lowered catalyst loadings, before a dramatic increase in the rate of reaction. A link between particle size, solubility and the deprotonation of the cyclic amide substrate are made, with the results having important implications on the use of inorganic bases in cross-coupling reactions. Inhibition of the reaction from inorganic side products and precipitation of copper from solution is combined with findings of a novel interaction between copper and cesium cation to give evidence for a non-innocent role of the cesium cation in copper-catalysed N-arylation. Heterogeneous catalysis is explored, where it is shown that copper precipitated from the reaction is capable of catalysis, introducing a question of a pseudo-heterogeneous mechanism and phase equilibria. A multi-edge XAFS (X-ray absorption fine structure) study is combined with laboratory experiments to uncover the activation, deactivation and reactivation pathways of an immobilised iridium transfer hydrogenation catalyst. The key role of an Ir-Cl bond is shown, where initial ligand exchange activates the catalyst, followed by further, slow ligand exchange, leading to deactivation of the catalyst.
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Sharma, Mahima. "Design of artificial metalloenzymes for C-C cross-coupling reactions." Thesis, University of Oxford, 2014. https://ora.ox.ac.uk/objects/uuid:8756ddda-60b7-45a6-9590-56eabf11f260.
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Artificial metalloenzymes enable several non-natural chemical transformations by hosting a metal catalyst and providing activating microenvironments to the metal. New strategies to combine the complementary features of enzyme and transition metal catalysis are crucial for exploiting the pre-evolved selectivities of enzymes in chemical synthesis. In order to exploit the inherent selectivity of a serine protease Subtilisin (SBL) for C-C crosscoupling reactions, the interplay of natural substrate binding pockets and the nucleophilic machinery of the enzyme with the metal catalyst was central to our approach. A catalytically potent metal catalyst (palladium) was appropriately positioned to carry out oxidative Heck reaction between an alkene and arylboronic acid substrates in the active site of SBL. Further characterization of SBL-based artificial metalloenzymes and step-wise elucidation of the biotransformation pathway was accomplished through X-ray crystallography and mass-spectrometry studies. Such interlacing of the metal and the enzyme steps for cross-coupling reactions presents an attractive route for performing important organic reactions enzymatically.
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Lima, Fabio. "Photoredox C-C cross-coupling reactions using boronic acid derivatives." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274928.
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In recent years, photoredox catalysis emerged as a privileged tool for small molecules activation via single-electron transfer mechanisms. Despite their ubiquity as reagents in organic synthesis, the use of boronic acid derivatives to generate carbon-centred radicals remains elusive. This dissertation explores the utilisation of photoredox catalysis to generate carbon radicals from boronic acid derivatives and subsequently engage them in C–C cross-coupling reactions. In the first chapter, an introduction to photoredox catalysis and organoboron reagents is provided, as well as a discussion on the key mechanistic aspects of photoredox catalysed C–C cross-coupling reactions. The second chapter presents our initial coupling strategy and how it evolved in understanding that pinacol boronic ester species can be used as a source of carbon radicals via single-electron oxidation from a photoredox catalyst. Coordination of the boronic esters with Lewis basic species was identified as a fundamental activating interaction. The synthetic utility of this discovery was highlighted by performing a wide range of photoredox catalysed arylations of pinacol boronic esters. The third chapter builds on our mechanistic understanding to identify a set of Lewis base catalysts that conveniently activates boronic esters and acids towards single-electron oxidation. The usefulness of this improved set of conditions was demonstrated by alkylating a wide range of boronic acid derivatives. The fourth chapter describes the application of this methodology in synthesising four active pharmaceutical ingredients from the GABA family. An emphasis was made on developing an efficient flow process and “transition metal free” conditions to survey the attractiveness of the method for the pharmaceutical industry. Finally, the fifth chapter describes the experimental procedures relevant to the results described in chapters 2 to 4.
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Brinkley, Kendra W. "The Synthesis of Solid Supported Palladium Nanoparticles: Effective Catalysts for Batch and Continuous Cross Coupling Reactions." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3959.
Full textAbstract:
Catalysis is one of the pillars of the chemical industry. While the use of catalyst is typically recognized in the automobile industry, their impact is more widespread as; catalysts are used in the synthesis of 80% of the US commercial chemicals. Despite the improved selectivity provided by catalyst, process inefficiencies still threaten the sustainability of a number of synthesis methods, especially in the pharmaceutical industry. Recyclable solid supported catalysts offer a unique opportunity to address these inefficiencies. Such systems coupled with continuous synthesis techniques, have the potential to significantly reduce the waste to desired product ratio (E-factor) of the production techniques. This research focuses developing sustainable processes to synthesize organic molecules by using continuous synthesis methods. In doing so, solid supported metal catalyst systems were identified, developed, and implemented to assist in the formation of carbon-carbon bonds. Newly developed systems, which utilized metal nanoparticles, showed reactivity and recyclability, comparable to commercially available catalyst.
Nanoparticles are emerging as useful materials in a wide variety of applications including catalysis. These applications include pharmaceutical processes by which complex and useful organic molecules can be prepared. As such, an effective and scalable synthesis method is required for the preparation of nanoparticle catalysts with significant control of the particle size, uniform dispersion, and even distribution of nanoparticles when deposited on the surface of a solid support. This project describes the production of palladium nanoparticles on a variety of solid supports and the evaluation of these nanoparticles for cross coupling reactions.
This report highlights novel synthesis techniques used in the formation of palladium nanoparticles using traditional batch reactions. The procedures developed for the batch formation of palladium nanoparticles on different solid supports, such as graphene and carbon nanotubes, are initially described. The major drawbacks of these methods are discussed, including limited scalability, variation of nanoparticle characteristics from batch to batch, and technical challenges associated with efficient heating of samples.
Furthermore, the necessary conditions and critical parameters to convert the batch synthesis of solid supported palladium nanoparticles to a continuous flow process are presented. This strategy not only alleviates the challenges associated with the robust preparation of the material and the limitations of scalability, but also showcases a new continuous reactor capable of efficient and direct heating of the reaction mixture under microwave irradiation. This strategy was further used in the synthesis of zinc oxide nanoparticles. Particles synthesized using this strategy as well as traditional synthesis methods, were evaluated in the context industrially relevant applications.
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Krahé, Barbara. "Similar perceptions, similar reactions : an idiographic approach to cross-situational coherence." Universität Potsdam, 1986. http://opus.kobv.de/ubp/volltexte/2009/3443/.
Full textAbstract:
The study provides a test of the interactionist concept of behavioral coherence
across situations. Following an approach suggested by D. Magnusson and B. Ekehammer (1978, Journal of Research in Personality, 12, 41-48), individual correlations between self-reported behavior patterns and perceived similarity ratings across anxiety-provoking situations are obtained as measures of coherence. Unlike the Magnusson and Ekehammar study, the present measures of situation cognition and behavior are based on an idiographic sampling of anxiety-provoking situations. As a step toward concept-based measurement of situation cognition, further measures of perceived situational similarity are derived from the script, prototype, and social episodes models in social psychology and correlated with cross-situational similarity of behavioral profiles. It is demonstrated, in comparison with the findings of Magnusson and Ekehammar, that correlations between similarity ratings and behavior patterns increase substantially as a result of an idiographic sampling of situations. Moreover, it is shown that "script," "prototype," and "social episode" measures can be utilized to investigate the covariation between situation cognition and behavior, thus contributing to the clarification of the principles of cognitive representation of situational experience.
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Marziale, Alexander [Verfasser]. "Palladium complexes for cross-coupling reactions in aqueous media / Alexander Marziale." München : Verlag Dr. Hut, 2011. http://d-nb.info/1013526619/34.
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Muñoz, Torres David [Verfasser]. "Molecular Rods and Stars through Cross-Coupling Reactions / David Muñoz Torres." München : Verlag Dr. Hut, 2013. http://d-nb.info/1037287061/34.
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Dahadha, Adnan [Verfasser], Wolfgang [Akademischer Betreuer] Imhof, and Matthias [Akademischer Betreuer] Westerhausen. "Catalytic cross coupling reactions / Adnan Dahadha. Gutachter: Wolfgang Imhof ; Matthias Westerhausen." Jena : Thüringer Universitäts- und Landesbibliothek Jena, 2012. http://d-nb.info/1024080420/34.
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Serra, Parareda Jordi. "Gold complexes for homogeneous cross-coupling catalysis and migratory insertion reactions." Doctoral thesis, Universitat de Girona, 2018. http://hdl.handle.net/10803/664428.
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Most of the different homogeneous reactions catalyzed by gold have been developed in the past fifteen years and stem from the ability of both Au(I) and Au(III) complexes to coordinate and activate multiple carbon-carbon bonds. However, the high ionization potential of gold has long hindered Au(I)/Au(III) catalytic cycles under homogeneous conditions, an underdeveloped field compared to classical cross-coupling methodologies. Although direct evidence for the main elementary steps of organometallic chemistry has been obtained very recently, their scope is still limited and much remains to be done before our knowledge on gold reaches that of other transition metals, especially of groups 9 and 10. Therefore, the unifying motivation behind the different research topics presented in this doctoral dissertation is to enhance our expertise concerning the factors governing the reactivity of gold complexes, with oxidative addition and migratory insertion particularly under the spotlightLa majoria de reaccions homogènies catalitzades per or han estat desenvolupades els darrers quinze anys, i aprofiten la capacitat dels complexes d’Au(I) i Au(III) per coordinar i activar enllaços múltiples carboni-carboni. No obstant l'elevat potencial de ionització de l’or ha privat l’accés a cicles catalítics del tipus Au(I)/Au(III) en condicions homogènies, un camp subdesenvolupat en comparació amb d’altres metodologies d’acoblament creuat clàssiques. Malgrat que recentment els processos fonamentals en química organometàl·lica han estat evidenciats, el seu abast és encara limitat i queda molt per recórrer abans que el nostre coneixement en or assoleixi el d’altres metalls de transició. Així doncs, la motivació principal rere els projectes de recerca presentats en aquesta tesi doctoral és incrementar la nostra expertesa pel que fa als factors que governen les reactivitat dels complexes d’or, amb especial incidència en l’addició oxidant i la inserció migratòria
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Yin, Lunxiang. "Synthesis of new calcineurin inhibitors via Pd-catalyzed cross coupling reactions." Doctoral thesis, [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975817868.
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Smith, Paul James. "Palladium catalysed Suzuki cross-coupling reactions in ambient temperature ionic liquids." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405785.
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Fleeman, Wendi L. "Self-quenching and cross-quenching reactions of platinum(II) dimine complexes." Cincinnati, Ohio : University of Cincinnati, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=ucin1070634712.
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Gallop, Christopher W. D. "N-heterocyclic carbene-palladium and -copper complexes in cross-coupling reactions." Thesis, University of Sussex, 2015. http://sro.sussex.ac.uk/id/eprint/54338/.
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Chapter 1 gives the reader a background on cross-coupling reactions, in particular palladium mediated couplings. Furthermore the importance of ligands, including phosphines and N-heterocyclic carbenes (NHC), in such cross-coupling reactions is explored. Chapter 2 provides a background to the reductive lithiation of phosphines, followed by an account of our investigation of BINAP functionalisation by means of reductive elimination.1 The reaction was examined by experimental means and through the use of density functional theory to predict 31P NMR chemical shifts. Chapter 3 provides background on the Heck reaction and selected developments over the years, with particular reference to the use of aryl chlorides in the reaction. A brief discussion of NHC based palladium complex sets the scene for our investigation of a new class of (NHC)-Pd catalysts developed by the Navarro group. Complexes of type (NHC)PdCl2(TEA) (TEA = triethylamine) have been tested for their activity in the Heck reaction, focusing on the scope of the reaction with electron-deficient aryl chlorides and electron-rich aryl bromides.2 Chapter 4 gives an account of the discovery and developments of the Sonogashira reaction. Particular attention is paid to non-classical systems such as palladium-only and copper-only protocols. Herein our investigation into the use of collaborative (NHC)-Pd and (NHC)-Cu in Sonogashira reactions is presented.3 Notable features of this system are the low catalyst loadings and the synthetically convenient conditions in which the reaction can be carried namely non-anhydrous solvents and in air. Publications: (1) Gallop, C. W. D.; Bobin, M.; Hourani, P.; Dwyer, J.; Roe, S. M.; Viseux, E. M. E. J. Org. Chem. 2013, 6522–6528. (2) Gallop, C. W. D.; Zinser, C.; Guest, D.; Navarro, O. Synlett 2014, 2225–2228. (3) Gallop, C. W. D.; Chen, M.-T.; Navarro, O. Org. Lett 2014, 3724–3727.
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Marset, Xavier. "Deep Eutectic Solvents: À la Carte Solvents for Cross-Coupling Reactions." Doctoral thesis, Universidad de Alicante, 2019. http://hdl.handle.net/10045/95790.
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En la presente memoria se describe el uso de líquidos eutécticos sostenibles (DESs en inglés) como medios de reacción, empleando diferentes catalizadores metálicos para llevar a cabo la síntesis de compuestos orgánicos de interés en química orgánica. En el Primer Capítulo se detalla el uso de un catalizador heterogéneo de cobre soportado sobre magnetita en el acoplamiento cruzado deshidrogenante de tetrahidroisoquinolinas en mezclas eutécticas. En el Segundo Capítulo se pormenoriza sobre la síntesis de un complejo tipo pinza de paladio y su empleo en la reacción de acoplamiento cruzado de Hiyama, tanto en mezclas eutécticas como en glicerol, como medios sostenibles de reacción. Asimismo, y con el fin de mejorar la compatibilidad de los catalizadores de paladio en estos líquidos eutécticos, se detalla el diseño y la síntesis de fosfinas catiónicas, las cuales han probado su efectividad como ligandos de paladio en reacciones típicas de acoplamiento cruzado (Suzuki, Heck y Sonogashira) en diferentes mezclas eutécticas. Finalmente, en el Tercer Capítulo se describen reacciones multicomponente de acoplamiento cruzado para la formación de enlaces C-S. Por un lado, se ha desarrollado una metodología para la inserción de SO2 catalizada por paladio a partir de ácidos borónicos y metabisulfito de sodio. Por otro lado, una variante de la metodología anterior permitió la síntesis de sulfonamidas sustituyendo los ácidos borónicos por compuestos de triarilbismuto y nitrocompuestos bajo catálsis de cobre. En este último caso, una nueva mezcla eutéctica ha sido descrita y caracterizada, tanto físco-química como biológicamente.
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Bae, Jin-Young. "Aryl mesylates in nickel (0) catalyzed homo- and cross coupling reactions." Case Western Reserve University School of Graduate Studies / OhioLINK, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=case1058375395.
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FLEEMAN, WENDI LEIGH. "SELF-QUENCHING AND CROSS-QUENCHING REACTIONS OF PLATINUM(II) DIIMINE COMPLEXES." University of Cincinnati / OhioLINK, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1070634712.
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Melzig, Laurin. "Sulfoxide-Controlled Functionalization of Arenes and Heterocycles Transition Metal-Catalyzed Cross-Coupling Reactions of Thioethers Chlorine-Zinc Exchange Reactions." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-129202.
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Swift, Elizabeth Claire. "Development of Palladium-Catalyzed Allylation Reactions of Alkylidene Malononitriles and Stereospecific Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Electrophiles." Thesis, University of California, Irvine, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3592019.
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Transition-metal catalysis has enabled the development of an unprecedented number of mild and selective C-C bond-forming reactions. We sought to access the reactivity of palladium and nickel catalysts for two types of transformations: conjugate allylations and sp3-sp 3 cross-coupling reactions.
Conjugate allylation of malononitriles was evaluated with N-heterocyclic carbene-ligated palladium complexes. The allylation was found to yield a variety of mono-allylated products. These results are in contrast to the bis-allylation of malononitriles using other palladium-based catalysts. Additionally, conjugate addition of α,β-unsaturated N-acylpyrroles was found to be accelerated in the presence of sulfoxide substitution on the pyrrole ring. These substrates are lead compounds for the development of an enantioselective allylation reaction.
Transition metal-catalyzed cross-coupling reactions have become standard practice in organic synthesis. Recent advances in alkyl-alkyl couplings have been transformative in the way organic chemists approach the construction of target molecules. This dissertation focuses on the development of stereospecific sp3-sp3 cross-coupling reactions. We discovered that in the presence of nickel catalysts, secondary benzylic ethers were found to undergo stereospecific substitution reactions with Grignard reagents. Reactions proceeded with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.
Subsequently, this reaction was expanded to dialkylzinc reagents and the first stereospecific Negishi cross-coupling reaction of secondary benzylic esters was developed. A series of traceless directing groups were evaluated for their ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially-available 2-(methylthio)acetic acid were found to be the most effective. The products were formed in high yield and with excellent stereospecificity. A variety of functional groups were tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation was highlighted in the enantioselective synthesis of a retinoic acid receptor (RAR) agonist.
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Chamoin, Sylvie. "Aryl-aryl Stille and Suzuzi-Miyaura cross-coupling reactions on solid support." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0022/NQ51184.pdf.
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Teverovskiy, Georgiy. "Development of novel transition metal-catalyzed cross-coupling reactions and applications thereof." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/82322.
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Thesis (Ph. D. in Organic Chemistry)--Massachusetts Institute of Technology, Dept. of Chemistry, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references.
Chapter 1 The first example of Pd(0)/(II) catalyzed fluorination of aryl bromides is reported herein. Based on these data, an analogous method was developed for the fluorination of aryl triflates. The reaction proceeds under mild conditions and represents the first report of reductive elimination from a Pd(II) center of a C-F bond. Chapter 2 Herein we report the first example of a Pd-catalyzed synthesis of aryl trifluoromethyl sulfides. A wide range of aryl bromides are converted to their corresponding trifluoromethyl sulfides in good to excellent yields. Furthermore, we were successful in synthesizing an intermediate in the synthesis of Toltrazuril in two steps from commercially available starting materials. Chapter 3 The development of a novel precatalyst for Ni-catalyzed C-N bond formation is described herein. Furthermore, the substrate scope of the reaction has been expanded to include a wide range of nucleophiles and electrophiles. Finally, we report the first use of weak base in the Nicatalyzed arylation of anilines. Chapter 4 The development of a novel triptycene-based hole-transport material is reported. Computational as well as preliminary photophysical and voltammetric data suggests that this class of compounds could serve as an excellent host material for blue triplet emitters.
by Georgiy Teverovskiy.
Ph.D.in Organic Chemistry
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Fors, Brett P. "Development and Applications of Pd Catalysts for C-N Cross-Coupling Reactions." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/65265.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
Chapter 1 A procedure for forming a highly active Pd(0) catalyst from Pd(OAc) 2, water, and biarylphosphine ligands has been developed. This protocol generates a catalyst system, which exhibits excellent reactivity and efficiency in the coupling of a variety of amides and anilines with aryl chlorides. Chapter 2 A new class of one-component Pd precatalysts bearing biarylphosphine ligands is described. These precatalysts are air- and thermally-stable, are easily-activated under normal reaction conditions at or below room temperature, and ensure the formation of the highly-active mono-ligated Pd(0) complex necessary for oxidative addition. The use of these precatalysts as a convenient source of LPd(0) in C-N cross-coupling reactions is explored. The reactivity that is demonstrated in this study is unprecedented in palladium chemistry. Chapter 3 A catalyst system based on a new biarylphosphine ligand that shows excellent reactivity for C-N cross-coupling reactions is reported. This catalyst system enables the use of aryl mesylates as a coupling partner in C-N bond-forming reactions. Additionally, the use of this ligand permits the highly selective monoarylation of an array of primary aliphatic amines and anilines at low catalyst loadings and with fast reaction times, including the first monoarylation of methylamine. Lastly, oxidative addition complexes based on the new ligand are included, which provide insight into the origin of reactivity for this system. Chapter 4 An investigation into the Pd-catalyzed C-N cross-coupling reactions of aryl iodides is described. Neal is shown to have a significant inhibitory effect on these processes. By switching to a solvent system in which the iodide byproduct was insoluble, reactions of aryl iodides were accomplished with the same efficiencies as aryl chlorides and bromides. Using catalyst systems based on certain biarylphosphine ligands, aryl iodides were successfully reacted with an array of primary and secondary amines in high yields. Lastly, reactions of heteroarylamines and heteroaryliodides were also conducted in high yields. Chapter 5 A catalyst based on a new biarylphosphine ligand for the Pd-catalyzed cross-coupling reactions of amides and aryl chlorides is described. This system shows the highest turnover frequencies reported to date for these reactions, especially for aryl chloride substrates bearing an ortho substituent. An array of amides and aryl chlorides were successfully reacted in good to excellent yields. Chapter 6. An efficient Pd-catalyst for the transformation of aryl chlorides, triflates and nonaflates to nitroaromatics has been developed. This reaction proceeds under weekly basic conditions and displays a broad scope and excellent functional group compatibility. Moreover, this method allows for the synthesis of aromatic nitro compounds that cannot be accessed efficiently via other nitration protocols. Mechanistic insight into the trasmetallation step of the catalytic process is also reported. Chapter 7. An alternative approach to catalyst development, which led to a Pd catalyst based on two biarylphosphine ligands for C-N cross-coupling reactions, is reported. By effectively being able to take the form of multiple catalysts this system manifests the best properties that catalysts based on either of the two ligands exhibit separately and displays the highest reactivity and substrate scope of any system that has been reported to date for these reactions.
by Brett P. Fors.
Ph.D.
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Yang, Yuan. "Graphene as a Solid-state Ligand for Palladium Catalyzed Cross-coupling Reactions." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5488.
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Palladium-catalyzed carbon-carbon cross-coupling reactions have emerged a broadly useful, selective and widely applicable method to synthesize pharmaceutical active ingredients. As currently practiced in the pharmaceutical industry, homogeneous Pd catalysts are typically used in cross-coupling reactions. The rational development of heterogeneous catalysts for cross-coupling reactions is critical for overcoming the major drawbacks of homogeneous catalysis including difficulties in the separation, purification, and quality control process in drug production. In order to apply heterogeneous catalysis to flow reactors that may overcome this limitation, the catalyst must be strongly bound to a support, highly stable with respect to leaching, and highly active. While the primary role of supports in catalysis has been to anchor metal particles to prevent sintering and leaching, supports can also activate catalytic processes. In this study, by using a xi combined theoretical and experimental method, we probed the effect of graphene as support in the complex reaction cycle of Suzuki reactions. The density functional theory study provides a fundamental understanding of how a graphene support strongly binds the Pd nanoparticles and act as both an efficient charge donor and acceptor in oxidation and reduction reaction steps. Theoretical investigations prove that the Pd-graphene interaction promotes electron flow between the metal cluster and the defected graphene to reduce reaction barrier. The ability for graphene to both accept and donate charge makes graphene an unusually suitable support for multi-step catalytic processes that involve both oxidation and reduction steps. The computer-aided catalyst design with the atomic precise accuracy demonstrates the Pd/graphene catalyst can be further optimized and the first-row transition metal nanoparticles have great potential to replace Pd to catalyze the Suzuki reaction. The corresponding experimental study shows that the method to immobilize the Pd nanoparticles on the graphene is crucial to increasing the reactivity and stability of the resulted catalyst. A comparison of the activation energy and turn over frequency for a series of supported and homogeneous catalysts indicates that exposing palladium-graphene to defect inducing microwave radiation results in dramatically lower activation energies and higher turnover frequencies. Furthermore, the heterogeneity tests demonstrate the Suzuki reactions are carried out on the surface of the immobilized Pd nanoparticle agreeing with the theoretical results. A method to engineer the 2-D graphene support to a 3-D structure to minimize the re-stacking and agglomeration of the graphene lattice will also be introduced in this study.
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Agata, Ryosuke. "Development of Iron-Catalyzed Selective Cross-Coupling Reactions toward Natural Product Synthesis." Kyoto University, 2019. http://hdl.handle.net/2433/242522.
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