Dissertationen zum Thema „C-c bond forming processes“

The effects of substituting (pseudo)halide for imidate ligands in Au(I) and Au(III) ([AuBr(NHC)] and [AuBr3(NHC)]), Ru(II) ([RuCl2(CHR)(L2)]) and Pd(II) ([Pd(OAc)2]) complexes has been investigated. The activity of these complexes as (pre)catalysts in enyne cycloisomerisation and propargylic nucleophilic substitution, diene ring-closing metathesis and ring-opening metathesis polymerisation and direct arylation reactions, respectively, has been determined. [Au(N-imidate)(NHC)] and [AuBr2(N-imidate)(NHC)] complexes were prepared and the structure and bonding of the complexes examined spectroscopically and crystallographically. The [AuBr2(N-imidate)(NHC)] complexes, in combination with co-catalytic silver salts, were tested for activity in the cycloisomerisation of 1,5- and 1,6- enynes and found to be more effective than tribromide analogues. Kinetic analysis of the reactions showed subtle changes to the imidate structure had a pronounced effect on the activity of the complexes and the use of the silver salt Ag[Al(OC(CF3)3)4] as a co-catalyst greatly increased catalytic activity. The complexes were also found to catalyse a unique tandem nucleophilic substitution-cycloisomerisation of propargyl alcohols and allylsilanes. [AuBr2(N-tfs)(ItPe)] was found to be an effective precatalyst for this reaction whilst Au(III) tribromide and Au(I) complexes were ineffective. 1,3-Diarylbicyclo[3.1.0]hexenes products were found to undergo a post-reaction ambient temperature 1,3-carbon shift isomerisation. The complex [Ru(N-tfs)2(o-iPrO-CHPh)(IMesH2)] was prepared and characterised spectroscopically and crystallographically. The complex was found to be inactive in the ring-closing metathesis and ring-opening metathesis polymerisation of alkenes. Attempts to selectively substitute chloride for imidate ligands derived from imides with higher pKa’s of 8.3-9.7 (in water) resulted in decomposition of the alkylidene or benzylidene ligand. [Pd(imidate)2(MeCN)] and [Pd(imidate)2(THT)] complexes were prepared and analysed by NMR and infra-red spectroscopy. The complexes were tested for activity in the direct arylation of imidazole with iodoarenes without added base or neutral ligands. The activity of the complexes was to some degree dependant on the structure of the imidate ligand, possessing moderate activity in comparison with [Pd(OAc)2]. The activity of other palladium sources and conditions for this reaction were investigated and it was found that the formation of Pd nanoparticles may be key to reaction progression.

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.
Cataloged from PDF version of thesis. Volume 1 (page 1 to page 510) ; Volume 2 (page 511 to 881). Duplicated pages for pages 195 to 240 are bound after page 881.
Includes bibliographical references.
Part I. Palladium-Catalyzed Carbon-Carbon Bond Forming Cross-Couplings Chapter 1. Ligand-Controlled Palladium-Catalyzed Regiodivergent Suzuki-Miyaura Cross-Coupling of Allylboronates and Aryl Halides An orthogonal set of catalyst systems based on the use of two biarylphosphine ligands has been developed for the Suzuki-Miyaura coupling of 3,3-disubstituted and 3-monosubstituted allylboronates with (hetero)aryl halides. These methods allow for the regiodivergent preparation of either the ct- or the [gamma]-isomeric coupling product with high levels of site selectivity using a common allylboron building block. Preliminary investigations have demonstrated the feasibility of an enantioselective variant for the [gamma]-selective cross-coupling using chiral monodentate biarylphosphine ligands. Chapter 2. Palladium-Catalyzed Completely Linear-Selective Negishi Coupling of 3,3-Disubstituted Organozinc Reagents with Aryl and Vinyl Electrophiles A palladium-catalyzed general and completely linear-selective Negishi coupling of 3,3- disubstituted allyl organozinc reagents with (hetero)aryl and vinyl electrophiles has been developed. This method provided an effective means for accessing highly functionalized aromatic and heteroaromatic compounds bearing prenyl-type side chains. The utility of the current protocol was further illustrated in the concise synthesis of the anti-HIV natural product siamenol. Chapter 3. Palladium-Catalyzed Highly Selective Negishi Cross-Coupling of Secondary Alkylzinc Reagents with Aryl and Heteroaryl Halides The palladium-catalyzed Negishi cross-coupling of secondary alkylzinc reagents and heteroaryl halides with high levels of regioisomeric retention has been described. The development of a series of biarylphosphine ligands has led to the identification of an improved catalyst for the coupling of electron-deficient heterocyclic substrates. Preparation and characterization of oxidative addition complex (L)Pd(Ar)(Br) provided insight into the unique reactivity of palladium catalysts based on CPhos-type biarylphosphine ligands in facilitating challenging reductive elimination processes. Chapter 4. Mechanistic Studies on the Aryl-Trifluoromethyl Reductive Elimination from Pd(II) Complexes Based on Biarylphosphine Ligands A series of monoligated (L)Pd(Ar)(CF₃) (L = dialkyl biarylphosphine) have been prepared and studied in an effort to shed light on the mechanism of the aryl-trifluoromethyl reductive elimination from these systems. Combined experimental and computational investigations revealed unique reactivity and binding modes of (L)Pd(Ar)(CF₃) complexes derived from BrettPhos-type biarylphosphines. In contrast to a variety of C-C and C-heteroatom bond forming reductive eliminations, kinetic measurements showed this Ar-CF₃ reductive elimination is largely insensitive to the electronic nature of the to-be-eliminated aryl substituent. Furthermore, the aryl group serves as the nucleophilic coupling partner in this reductive elimination process. The structure-reactivity relationship of biarylphosphine ligands was also investigated, uncovering distinct roles of the ipso-arene and alkoxy interactions in affecting these reductive elimination reactions. Part II. Copper-Catalyzed Carbon-Carbon and Carbon-Nitrogen Bond Formation via Olefin Functionalization Chapter 5. Copper-Catalyzed ortho C-H Cyanation of Vinylarenes A copper-catalyzed regioselective ortho C-H cyanation of vinylarenes has been developed. This method provides an effective means for the selective functionalization of vinylarene derivatives. A copper-catalyzed cyanative dearomatization mechanism is proposed to account for the regiochemical course of this reaction. This mechanism has been validated through density functional theory calculations. Computational studies revealed that the high level of ortho selectivity in the electrophilic cyanation event originates from a unique six-membered transition state that minimizes unfavorable steric repulsions. Chapter 6. Regio- and Stereospecific 1,3-Allyl Group Transfer Triggered by a Copper-Catalyzed Borylation/ortho-Cyanation Cascade A copper-catalyzed borylation/cyanation/allyl group transfer cascade has been developed. This process features an unconventional copper-catalyzed electrophilic dearomatization followed by the subsequent regio- and stereospecific 1,3-transposition of the allyl fragment enabled by the aromatization-driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with high levels of stereochemical purity. Chapter 7. Copper-Catalyzed Asymmetric Hydroamination of Unactivated Internal Olefins: an Effective Means to Access Highly Enantioenriched Aliphatic Amines Catalytic assembly of enantiopure aliphatic amines from abundant and readily available precursors has long been recognized as a paramount challenge in synthetic chemistry. We describe a mild and general copper-catalyzed hydroamination that effectively converts unactivated internal olefins-an important yet unexploited class of abundant feedstock chemicals-into highly enantioenriched [alpha]-branched amines (>/= 96% ee) featuring two minimally differentiated aliphatic substituents. This method provides a powerful means to access a broad range of advanced, highly functionalized enantioenriched amines of interest in pharmaceutical research and other areas.
by Yang Yang.
Ph. D. in Organic Chemistry

Thesis: S.B., Massachusetts Institute of Technology, Department of Chemistry, 2017.
Cataloged from PDF version of thesis. "June 2017."
Includes bibliographical references.
Chapter 1. Copper-Catalyzed Asymmetric Addition of Olefin-Derived Nucleophiles to Ketones A copper (I) catalyzed coupling olefins and ketones has been developed for the diastereo- and enantioselective generation of homopropargyl alcohols bearing vicinal stereocenters. This method allows for the generation of enantioenriched tertiary alcohols with a high degree of functional group compatibility. The utility of the process is further illustrated by a large scale synthesis with extremely low catalyst loading as well as the late stage modification of several pharmaceuticals. Chapter 2. Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines We describe the catalytic generation of amines bearing vicinal stereocenters with a moderate degree of diastereoselectivity. The stereoselective hydrocupration of an unactivated olefinic component is followed by nucleophilic addition of the organocuprate to an N-phosphinoyl protected imine. The mild and general process tolerates a broad-range of functionality, and the process was shown to be successful at a gram-scale synthesis. Chapter 3. Palladium-facilitated Regioselective Nucleophilic Fluorination of Aryl and Heteroaryl Halides. The preliminary findings regarding an aryl and heteroaryl halide fluorination process facilitated by palladium as a reagent is described. Stoichiometric studies illustrate the utility of the method in producing aryl fluorides with unprecedented regioselectivity, and preliminary studies into the fluorination of five- and six-membered heteroaryl bromides are described. Halogen atom substitution as a route to irreversible oxidative addition of aryl and heteroaryl halides is discussed. This strategy may serve to facilitate the fluorination of particularly problematic heteroaryl bromide and chloride substrates.
by Ian B. Perry.
S.B.

Els complexos organometàl·lics de coure, plata i or juguen un paper fonamental com espècies reactives en diverses transformacions químiques. Aquesta tesi aporta coneixement sobre el comportament d’aquests complexos en la formació d’enllaços C-C i/o C-N. En concret, estudiem: i) el mecanisme de reacció a través del qual els complexos de coure co-catalitzen un acoblament oxidant en el context de sistemes bimetàl·lics de rodi i coure; ii) el potencial de nucleòfils de plata com a agents transmetal·lants en reaccions de trifluorometilació catalitzades per pal·ladi; iii) el mecanisme de reacció de sistemes bimetàl·lics de Pd/Ag emprant un sistema model; i iv) el comportament de complexos bis(trifluorometil) cuprat, argentat i aurat com a nucleòfils. En aquesta tesi, on s´han combinat estudis experimentals i computacionals, s’ha adquirit nou coneixement sobre els processos estudiats, i s’ha contribuït al camp de la recerca química basada en el coneixement.
Los complejos organometálicos de cobre, plata y oro juegan un papel fundamental como especies reactivas en diversas transformaciones químicas. Esta tesis aporta conocimiento sobre el comportamiento de estos complejos en la formación de enlaces C-C y/o C-N. En concreto, estudiamos: i) el mecanismo de reacción por el cual complejos de cobre co-catalizan un acoplamiento oxidante en el contexto de sistemas bimetálicos de rodio y cobre; ii) el potencial de nucleófilos de plata como agentes transmetalantes en reacciones de trifluorometilación catalizadas por paladio; iii) el mecanismo de reacción de sistemas bimetálicos de Pd/Ag usando un sistema modelo; y iv) el comportamiento de complejos bis(trifluorometil) cuprato, argentato y aurato como nucleófilos. En esta tesis, donde se han combinado estudios experimentales y computacionales, se ha adquirido nuevo conocimiento sobre los procesos estudiados, y se ha contribuido al campo de la investigación química basada en el conocimiento.
Organometallic coinage metal complexes are be key reactive species for promoting a wide variety of chemical transformations. This thesis improves the understanding the behavior of these complexes in relevant C-C and/or C-N bond-forming reactions. Specifically, we have explored: i) the mechanistic intricacies of copper species as co-catalyst in the context of rhodium/copper-catalyzed oxidative coupling reactions; ii) the capability of silver nucleophiles as transmetalating agents in palladium-catalyzed trifluoromethylation reactions; iii) the reaction mechanism of Pd/Ag bimetallic reactions using a model system as probe; and, iv) the study of bis(trifluoromethyl) coinage metallates as nucleophiles. The fundamental insights gathered in this Thesis, encompassing both experimental and computational approaches, improve our understanding of the processes under study and make a contribution to the general field of knowledge-driven research in Chemistry.

This thesis is concerned with the use of palladacyclic complexes as catalysts for C-C and C-heteroatom bond-forming reactions in which an oxidation state change of the metal centre is not part of the catalytic cycle. To this end, the investigation of a range of known K²-C,L-based palladacycles in the allylation of aldehyde and imine substrates using stannanes, as well as the 1,4-conjugate arylation of enones and imines using arylboronic acids under mild conditions is described. In each case the commercially available phosphite-based dimeric palladacycle is found to be the most active complex capable of achieving excellent conversions (>90%) at the 0.5 - 2.5mol% loading range. Three previously unknown phosphinite and amidophosphinite palladium pincer complexes are also synthesised, characterised (including crystallographically) and tested in the 1,4-conjugate addition of phenylboronic acid to chalcone and found to be inactive.

After spending so many years in the shadow of magnesium chemistry the chemical abilities of the heavier alkaline earth metals, calcium, strontium and barium are beginning to emerge. This thesis is concerned with the development of a catalytic reactivity for the heavier alkaline earth metals. By taking inspiration from lanthanide metal catalysis, this thesis will begin by describing the hydroamination and hydrophosphination of unsaturated molecules catalysed by lanthanide and group 2 metals before extending this work to the group 2 catalysed hydroacetylation of terminal acetylenes (chapter 2), and the insertion of unsaturated bonds of carbodiimides (chapter 4), and organic isocyanates (chapter 5) into the polarised M-C bonds of group 2 acetylides. The third chapter of this thesis will describe the observation of the first acetylide coupling with a group 2 metal complex and extension of this reactivity to a catalytic process.

Toutes les formes de vie assemblent et désassemblent continuellement des composés chimiques via un processus de consommation d'énergie appelé métabolisme. Le métabolisme est généralement modélisé en chimie et biologie par un cycle. Ce modèle dynamique traduit la transformation de composés de base en une cascade de produits appelés métabolites. Celui-ci est comparable à un ouragan à l’échelle moléculaire. De manière analogique et imagée un cyclone est constitué de deux éléments, l'air et l'eau, et transforme l’environnement qui l’entoure par un processus endothermique (consommateur d’énergie). Traditionnellement, la recherche chimique sur les origines de la vie est concentrée principalement sur la synthèse de composés chimiques sans suffisamment apprécier leur place dans la plus grande organisation biochimique de la vie. La vie construit toutes ses molécules à partir du dioxyde de carbone, pourtant elle manque étonnamment d'innovation à cet égard. Malgré presque 4 milliards d'années d'évolution, les organismes autotrophes utilisent seulement six voies différentes pour construire leurs molécules à partir du CO2. Parmi elles, deux voies – la voie de l’acétyle CoA (aussi appelée voie Wood-Ljungdahl) et le cycle du rTCA (également appelé le cycle de Krebs inverse) - sont considérées comme primitives, et contiennent les cinq molécules servant de précurseurs chimiques universels pour toute la biochimie. Comment et pourquoi les voies de l’acétyle CoA et du rTCA sont-elles apparues? Pour répondre à cette question, une recherche systématique a été effectuée afin de trouver des catalyseurs chimiques non-enzymatiques ou des minéraux simples, ainsi que des réactifs pouvant promouvoir les réactions d'anabolisme principal, particulièrement la voie de l’Acétyle CoA et le cycle de rTCA. A l’origine, pour créer les molécules organiques complexes comme les enzymes il a fallu que des molécules plus simples avec un moins grand nombre de carbone se forme sur terre et cela à partir du CO2. On peut donc supposer que les premiers produits à plusieurs carbones sont issus de synthèse totalement inorganique comme celles développer dans notre laboratoire, plutôt que d’une évolution chimique et organométallique simultanée, c’est-à-dire une interaction efficace entre une molécule carbonée et un ou plusieurs métaux à l’instar de certains enzymes. Après avoir trouvé autant de façons possible de promouvoir individuellement chaque étapes des cycles catalytiques étudiés, seules les conditions réactionnelles mutuellement compatibles (à savoir des conditions permettant de produire l’ensemble des métabolites dans le bon ordre) ont été retenu
All life forms continuously build up and break down its constituent chemical building blocks, through an energy consuming process called metabolism. Just like a hurricane’s dynamic patterns and its building blocks (air and water) as being equally fundamental to its nature, so too should metabolism’s dynamic chemical patterns and chemical building blocks be viewed as equally characteristic. Traditionally, much chemical research on the origins of life is overly focused on the synthesis of chemical building blocks without sufficiently appreciating their place in life’s larger biochemical self-organization. Life ultimately builds all of its molecules from carbon dioxide, yet it is surprisingly lacking in innovation in this respect. Despite nearly 4 billion years of evolution, autotrophic organisms use only six pathways to build their molecules from CO2. Two of these pathways – the acetyl CoA pathway (also known as the Wood-Ljungdahl pathway) and rTCA cycle (also known as the reverse Krebs cycle) - are thought to be ancestral, with just five molecules within them serving as the universal chemical precursors for all of biochemistry. How and why did these pathways get their start? To answer this question, a systematic search was designed to find simple, non-enzymatic chemical or mineral catalysts and reagents, that can promote the reactions of core anabolism, particularly the acetyl CoA pathway and the rTCA cycle. After finding as many ways as possible to promote each reaction, they could be narrowed down to mutually compatible conditions where many reactions can occur in sequence. The more of core anabolism that can be achieved under a single set of purely chemical conditions, the more likely it is to have constituted early prebiotic chemistry rather than a later product of chemical and biological evolution

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1999.
Includes bibliographical references.
New methods for the palladium-catalyzed amination of aryl halides are described. Key to these is the development of new catalysts and reaction conditions for these transformations. Initially, P(o-tol)3 ligated palladium catalysts were investigated but gave way to systems that used chelating phosphine ligands which substantially expanded the scope of the catalytic amination methodology. Palladium catalyst systems based on BINAP ((2,2'-diphenylphosphino)-1, 1 '-binaphthyl) allowed for the transformation of a much wider range of amines and aryl halide substrates, as well as aryl triflates. Of practical significance was that the use of cesium carbonate as a base at 100 °C substantially increased the functional group tolerance of the method. Palladium catalysts supported by novel, bulky, electron-rich phosphine ligands are exceptionally effective in the C-N, C-0, and C-C coupling procedures. For some substrate combinations, these palladium catalysts are effective for the room-temperature catalytic amination of aryl chlorides. These palladium catalysts are also highly effective for Suzuki coupling reactions of aryl bromides and chlorides at room temperature. Suzuki coupling reactions of aryl bromides and aryl chlorides are effective at very low catalyst loadings (0.000001-0.005 mol % Pd for ArBr, 0.02-0.05 mol % for ArCI) at 100 °C, and reactions of hindered aryl halides or boronic acids are effected at moderate catalyst loadings (1 mol % Pd). The high reactivity of these catalysts towards aryl chlorides challenges the conventional dogma that chloride substrates cannot be transformed under mild conditions with palladium catalysts, and significantly expands the pool of substrates available for cross-coupling chemistry.
by John P. Wolfe.
Ph.D.

In questo lavoro di tesi è riportato l'impiego di alcuni strumenti della Green Chemistry (come la CO2, i liquidi ionici e i dialchilcarbonati) per la messa a punto di metodologie innovative a ridotto impatto ambientale per la formazione di legami C-C, C-N e C-O. Sono state investigate le seguenti reazioni: la metatesi dell'1-ottene catalizzata da sistemi a base di Re ossido, in presenza di CO2 densa come solvente; l'addizione di Michael di nitroalcani e beta-dichetoni a chetoni alfa,beta-insaturi catalizzata da liquidi ionici; la selettiva mono-idrossialchilazione di aniline con la glicerina carbonato, catalizzata da faujasiti; la selettiva bis-N-alchilazione di aniline da parte del dimetilcarbonato prodotto in situ via transesterificazione di carbonati ciclici con metanolo, catalizzata da faujasiti; l'alchilazione di aniline con carbonati ciclici catalizzata da liquidi ionici; la reazione di decarbossilazione dei dialchilcarbonati in presenza di diversi catalizzatori eterogenei; la reazione tra fenolo e glicerina carbonato catalizzata da faujasiti.
In this PhD thesis it is presented the use of some Green Chemistry Tools (supercritical carbon dioxide, ionic liquids and dialkylcarbonates) for the set up of new green methodologies for C-C, C-N and C-O bond forming reactions. The following reactions have been investigated: the self-metathesis of 1-octene catalysed by supported Re oxide systems, carried out using dense CO2 as solvent; the Michael addition of nitroalkanes and beta-diketones to alpha,beta-unsaturated ketons catalyzed by task specific phosphonium based ionic liquids; the selective mono-hydroxyalkylation of anilines with glycerol carbonate catalysed by alkali metal exchanged faujasites; the selective bis-N-methylation of anilines carried by dimethylcarbonate prepared in situ via the transesterification of alkylene carbonate with methanol catalysed by alkali metal exchanged faujasites; the alkylation of primary aromatic amines with alkylene carbonates, catalysed by phosphonium based ionic liquids; the decarboxylation reaction of dialkyl carbonates catalyzed by different heterogeneous systems; the reaction of glycerol carbonate with phenol, in the presence of faujasites as catalysts.

Bifunctional catalysis is a well understood phenomenon in nature, with enzymes frequently using two (or more) functional groups to accomplish selective transformations on a suitable substrate. It is becoming clear however, that bifunctional catalysis is not merely of interest to explain or mimic biological efficiency and rate enhancement, but is a viable design principle for the development of new molecular catalysts. In this thesis we have prepared achiral amino-boronic acid compounds with different scaffold structures based on general structures 1 and 2.(^5). although these compounds did not show any reactivity towards the MBH and aza-MBH reaction, they were very successful as catalysts for the aldol reaction. For this reaction it was possible to select the wanted product (aldol or chalcone product) using the same bifunctional catalyst only by changing the solvent. Also with hydroxyacetone some excellent results were gained with yields between 49 to 97% for both aromatic and aliphatic aldehydes in very high regioselectivity.

Thesis advisor: James P. Morken
This dissertation will describe the development of three transition metal-catalyzed syntheses of nonracemic organoboronates. The first chapter explains the development of a palladium-catalyzed enantiotopic-group-selective cross-coupling of geminal bis(boronates) with alkenyl electrophiles. This process enables the synthesis of highly valuable nonracemic disubstituted allylic boronates. Chapter two describes a palladium-induced 1,2-metallate rearrangement of vinylboron “ate” complexes. The newly developed process incorporates an alternative route for the transmetallation step of Suzuki-Miyaura cross-couplings. Lastly, an enantioselective platinum-catalyzed hydrosilylation of alkenyl boronates is disclosed. This reaction enables the synthesis of nonracemic geminal silylboronates for the divergent synthesis of functionalized
Thesis (PhD) — Boston College, 2018
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

El principal objectiu científic dels meus estudis de doctorat va ser demostrar que la reactivitat en estat excitat dels intermedis organocatalítics són capaços de proporcionar noves oportunitats per desenvolupar noves reaccions catalítiques mitjançant radicals per a la formació d'enllaços C-C i C-B. La fotoexcitació d'intermedis organocatalítics van proporcionar radicals mitjançant transferència d'un sol electró o homòlisis. En el capítol II, analitzo el desenvolupament d'una funcionalització asimètrica organocatalítica fotoquímica de C-H del toluè i derivats. El nostre sistema aprofita les propietats oxidatives millorades dels ions d’imini quirals excitats amb llum visible i el caràcter bàsic dels seus contraanions per activar, a través d'una transferència d'electrons acoblada a protons multilloc, derivats de toluè. El radical resultant és atrapat més tard per l'intermedi organocatalític quiral amb alt estereocontrol. A la segona part dels meus estudis de doctorat, em vaig concentrar en la generació catalítica de compostos fotó làbils basats en tiocarbonil per promoure la formació d'enllaços C-B i C-C. Com es detalla en el capítol III, utilitzem un organocatalitzador nucleofílic d'anió ditiocarbonil per activar electròfils d’alquil a través d'una via SN2. El producte intermedi resultant que absorbeix fotons, després de l'absorció de llum visible, genera radicals a través de l'escissió homolític de l'enllaç C-S feble. El radical generat és llavors interceptat per bis(catecolat)diboro per proporcionar productes d'èster alquilborònic. El capítol IV destaca com aquest enfocament fotolític es va expandir a l'activació dels clorurs d'acil i carbamoil a través d'una via de substitució d'acil nucleofílica. Els radicals acil i carbamoil generats fotoquímicament s'han utilitzat en reaccions de tipus Giese amb olefines pobres en electrons per formar nous enllaços C-C. Una investigació mecanística detallada, basada en anàlisis espectroscòpics i electroquímics juntament amb la caracterització d'intermedis clau, va identificar una varietat d'equilibris fora del cicle que cooperen per controlar les concentracions generals dels radicals, contribuint a l'eficiència del procés.
El principal objetivo científico de mis estudios de doctorado fue demostrar que la reactividad en estado excitado de los intermedios organocatalíticos son capaces de proporcionar nuevas oportunidades para desarrollar nuevas reacciones catalíticas mediante radicales para la formación de enlaces C-C y C-B. La fotoexcitación de intermedios organocatalíticos proporcionaron radicales mediante transferencia de un solo electrón u homólisis. En el Capítulo II, analizo el desarrollo de una funcionalización asimétrica organocatalítica fotoquímica de C-H del tolueno y derivados. Nuestro sistema aprovecha las propiedades oxidativas mejoradas de los iones de iminio quirales excitados con luz visible y el carácter básico de sus contraaniones para activar, a través de una transferencia de electrones acoplada a protones multisitio, derivados de tolueno. El radical resultante es atrapado más tarde por el intermedio organocatalítico quiral con alto estereocontrol. En la segunda parte de mis estudios de doctorado, me concentré en la generación catalítica de compuestos fotolábiles basados en tiocarbonilo para promover la formación de enlaces C-B y C-C. Como se detalla en el Capítulo III, empleamos un organocatalizador nucleofílico de anión ditiocarbonilo para activar electrófilos de alquilo a través de una vía SN2. El producto intermedio resultante que absorbe fotones, tras la absorción de luz visible, genera radicales a través de la escisión homolítica del enlace C-S débil. El radical generado es entonces interceptado por bis(catecolato)diboro para proporcionar productos de éster alquilborónico. El Capítulo IV destaca cómo este enfoque fotolítico se expandió a la activación de los cloruros de acilo y carbamoilo a través de una vía de sustitución de acilo nucleofílica. Los radicales acilo y carbamoilo generados fotoquímicamente se han utilizado en reacciones de tipo Giese con olefinas pobres en electrones para formar nuevos enlaces C-C. Una investigación mecanística detallada, basada en análisis espectroscópicos y electroquímicos junto con la caracterización de intermedios clave, identificó una variedad de equilibrios fuera del ciclo que cooperan para controlar las concentraciones generales de los radicales, contribuyendo a la eficiencia del proceso.
The main scientific objective of my doctoral studies was to demonstrate that the excited-state reactivity of organocatalytic intermediates could provide new opportunities to develop novel catalytic radical C-C and C-B forming reactions. The photoexcitation of organocatalytic intermediates afforded radicals through either single-electron transfer or homolysis. In Chapter II, I discuss the development of an asymmetric organocatalytic photochemical C-H functionalization of toluene and derivatives. Our system harnesses the enhanced oxidative properties of visible-light excited chiral iminium ions and the basic character of their counteranions to activate, through a multisite proton coupled electron transfer, toluene derivatives. The ensuing radical is later trapped by the chiral organocatalytic intermediate with high stereocontrol. In the second part of my doctoral studies, I focused on the catalytic generation of photolabile thiocarbonyl-based compounds to promote the formation of C-B and C-C bonds. As detailed in Chapter III, we employed a nucleophilic dithiocarbonyl anion organocatalyst to activate alkyl electrophiles through an SN2 pathway. The ensuing photon-absorbing intermediate, upon visible light absorption, generates radicals through homolytic cleavage of the weak C-S bond. The generated radical is then intercepted by bis(catecholato)diboron to afford alkyl boronic ester products. Chapter IV highlights how this photolytic approach was expanded to the activation of acyl and carbamoyl chlorides through a nucleophilic acyl substitution pathway. The photochemically generated acyl and carbamoyl radicals have been used in Giese-type reactions with electron-poor olefins to form new C-C bonds. A detailed mechanistic investigation, based on spectroscopic and electrochemical analyses along with the characterization of key intermediates, identified a variety of off-the-cycle equilibriums that cooperate to control the overall concentrations of the radicals, contributing to the efficiency of the process.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2006.
Vita.
Includes bibliographical references.
Chapter 1. The first detailed study of the palladium-catalyzed amination of aryl nonaflates is reported. Use of bulky electron-rich monophosphinobiaryl ligands or BINAP allow for the catalytic amination of electron-rich and -neutral aryl nonaflates with both primary and secondary amines. Using XantPhos, the catalytic amination of a variety of functionalized aryl nonaflates resulted in excellent yields of anilines; even 2-carboxymethyl aryl nonaflate is effectively coupled with a primary alkyl amine. Moderate yields were obtained when coupling halo-aryl nonaflates with a variety of amines, where in most cases the aryl nonaflate reacted in preference to the aryl halide. Overall, aryl nonaflates are an effective alternative to aryl triflates in palladium-catalyzed C-N bond-forming processes due to their increased stability under the reaction conditions. Chapter 2. A catalyst comprised of a Pd precatalyst and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl is explored in C-N bond-forming processes. This catalyst displayed unprecedented stability and scope allowing, for the first time, the coupling of substrates bearing a carboxylic acid or a primary amide.
(cont.) Also, the more bulky catalyst system Pd/2-tert-butylphosphino-2',4',6'-triisopropylbiphenyl was found to be effective for the Narylation of 2-aminoheterocycles and weakly basic HN-heterocycles: pyrazole and indazole. The chemoselectivity for amination using these catalysts was explored where the rough order of reactivity for amines is: aryl amines >> primary and secondary alkyl amines > 2-aminoheterocycles > primary amides - HN-heterocycles. Chapter 3. The palladium-catalyzed Suzuki-Miyaura coupling of haloaminoheterocycles and functionalized organoboronic acids using a highly active and stable monophosphinobiaryl ligand, 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl, efficiently produced aminoheterocyclic biaryl derivatives. This same catalyst was effective in coupling 2-haloaminoaryl compounds with 2-formyl or 2-acetylphenyl boronic acids, providing the fused heterocyclic compounds phenanthridine, benzo[c][1 ,8]naphthridine and benzo[c][1,5]naphthridine in excellent yields. Chapter 4. A water-soluble monophosphinobiaryl ligand, sodium -dicyclohexylphosphino-2',6'-dimethoxybiphenyl-3'-sulfonate, was synthesized by electrophilic sulfonation of the lower-aromatic ring of 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl.
(cont.) This ligand was utilized in the palladium-catalyzed Suzuki-Miyaura reaction of water-soluble aryl/heteroaryl halides and organoboronic acids. The catalyst displays unprecedented reactivity and stability for Suzuki-Miyaura reactions conducted in water. Chapter 5. A water-soluble monophosphinobiaryl ligand, sodium 2'-(dicyclohexyl-osphanyl)-2,6-diisopropyl-biphenyl-4-sulfonate, was synthesized by a proposed electrophilic ipso-substitution/reverse Friedel-Crafts alkylation of the lower-aromatic ring on 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl. This ligand was utilized in the palladium-catalyzed Heck alkynylation (copper-free Sonogashira coupling) of hydrophobic and hydrophilic aryl halides and terminal alkynes conducted in an aqueous acetonitrile solvent system. For the first time, an electron-deficient terminal alkyne, propiolic acid, was successfully coupled with aryl bromides. We also demonstrated that this catalyst is useful in the reaction of benzyl chlorides and terminal alkynes to provide benzyl alkynes in good yields. We show that by using an excess amount of base (> 1.0 equiv.) and higher reaction temperatures ( 80 °C), base-catalyzed isomerization to the corresponding aryl allenes can be achieved in a one-pot process.
by Kevin W. Anderson.
Ph.D.

Un dels principals mètodes per a sintetitzar productes enantiomericament purs és la catàlisi asimètrica utilitzant compostos organometàl•lics quirals. En aquesta estrategia, el disseny i preparació de lligands quirals és molt important. En aquest context, nosaltres hem desenvolupat nous lligands quirals per diverses reaccions de catàlisi asimètrica. Concretament ens hem centrat en: (a) L’aplicació d’una llibreria de lligands fosfit-fosforoamidit i difosforoamidit derivats de carbohidrats en la hidrogenació de olefines proquirals. Aquests lligands han donat excel•lents enantioselectivitats (up to >99% ee). (b) L’aplicació de les llibreries de lligands tioèter-fosfit, tioèter-fosfinit i tioèter-fosforoamidit derivats de carbohydrats en la hidrogenació catalitzada per iridi de olefins no funcionalitzades i en reaccions de substitució al•lílica catalitzada per paladi. Els resultats obtinguts en hidrogenació competeixen favorablement amb els millors resultats publicats prèviament. (c) L’aplicació de llibreries de lligands pseudo-dipèptids i tioamides derivats de carbohidrats en transferència d’hidrogen de cetones. Els resultats obtinguts, novament competeixen favorablement amb els publicats anteriorment obtenint excel•lents enantioselectivitats (up to 99%) per un ampli rang de substrats.
One of the main methods for producing enantiomerically pure compounds is metal asymmetric catalysis. An important step in this strategy is the design and preparation of chiral ligands. In this context, we have developed new chiral ligands for several important asymmetric catalytic reactions. Specifically we have focused on: (a) The application of a furanoside phosphite-phosphoroamidite and diphosphoroamidite ligand library in the hydrogenation of prochiral olefins. These ligands have provided excellent enantioselectivities (up to >99% ee). (b) The application of furanoside thioether-phosphite, thioether-phosphinite and thioether-phosphoroamidite ligand libraries in the challenging Ir-catalyzed hydrogenation of unfunctionalized olefins and in Pd-allylic substitution reactions. The results in hydrogenation compete favourable with the best ones previously reported. (c) The application of carbohydrate-based pseudo-dipeptide and thioamide ligand libraries in transfer hydrogenation of ketones. The results again compete favourable with the best one previously reported. Unprecedent enzyme-like behaviour has been obtained, providing ee’s up to 99% for a wide range of substrates.

La primera parte de la tesis se dedica al estudio del mecanismo de una reacción de activación C-H por un complejo de niobio. Se racionalizó el mecanismo de activación de enlaces C-H del benceno por el complejo TpMe2NbCH3(c-C3H5)(MeCCMe). El intermedio clave es un complejo inusual de 2-ciclopropeno. Conseguimos también racionalizar las selectividades obtenidas para la activación de varios alquilaromáticos por el complejo de niobio 2-ciclopropeno. También se investigó el papel del ligando alquino en estos complejos y su posible papel en procesos de migración de ligandos. En la segunda parte de la tesis, se investigaron las reacciones de acoplamiento cruzado con reactivos basados en silicio. Los resultados sugieren que la transmetalación es más fácil después de la disociación de la fosfina, o cuando un ligando bromuro está coordinado al paladio. El efecto beneficioso de la dibencilidenoacetona en el acoplamiento también fue aclarado.
The first part of the thesis is mainly devoted to the mechanism of a C-H activation reaction by a niobium complex. The mechanism of C-H bond activation of benzene by the TpMe2NbCH3-(c-C3H5)-(MeCCMe) complex was rationalized. The key intermediate is an unusual 2-cyclopropene complex. We rationalized the selectivities obtained for the activation of several alkylaromatics by the 2-cyclopropene niobium complex. The intriguing role of the alkyne ligand of the same complex, and its possible role in the migration processes, was investigated. In the second part of the thesis, we focused on the silicon based cross-coupling. The results suggest than the transmetalation is easier after phosphine dissociation, and in presence of the bromide ligand on the palladium. The beneficial effect of dibenzylideneacetone on the coupling was clarified.

Esta tesis doctoral se centró en la síntesis y la caracterización de nanopartículas metálicas (Pd, Ni, Pt) estabilizadas por varios tipos de ligandos y el uso de estas nanopartículas en reacciones de formación de nuevos C-C o C-heteroatomo: a) Reacción de substitución alílica catalizadas por Pd; b) Reacción de acoplamiento asimétrico de Suzuki-Miyaura; c) Reacción de acoplamiento de Suzuki-Miyaura; d) reacción de adición 1,4 de ácidos borónicos a cetonas. En cada una de estas reacciones se llevó a cabo la síntesis y caracterización de nanoparticulas metálica y complejos moleculares usando muchos tipos de ligandos en los sistemas moleculares y los sistemas análogos cataliazados por nanopartículas. Excelentes actividades y enatioselectividades fueron obtenidas en la reacción de alquilación y aminación alílica. Además, estos sistemas fueron reciclados usando líquidos iónicos. También, nuevos y selectivas nanoparticulas fueron sintetizadas y caracterizadas. Estas nanopartículas fueron usadas exitosamente en varias reacciones de formación de nuevos enlaces C-C.
This doctoral thesis focuses on the synthesis and characterization of metal nanoparticles (Pd, Ni, Pt) stabilized by several types of ligands and the used of these nanoparticles in new C-C or C-heteroatom bond formation reactions: a) Pd-catalysed asymmetric allylic substitution reactions; b) Pd-catalysed asymmetric Suzuki-Miyaura coupling reactions; c) Ni-catalysed Suzuki-Miyaura coupling reactions; d) Pt-catalysed 1,4-addition of phenylboronic acid to 2-cyclohexen-1-one reaction. For each reaction, the synthesis and characterization of metal nanoparticles and molecular complexes using several types of ligands were performed and both types of catalytic systems were tested in the appropriate reactions. Remarkably, excellent enantioselectivities using Pd/phosphite ligand were obtained in allylic substitution reaction. An efficient recovery of the catalytic system was carried out using ionic liquids as reaction medium. New active and selective nanoparticles were synthesized and characterized. These nanoparticles were applied successfully in various C-C bond formation reactions.

El objetivo principal de esta tesis doctoral ha sido la activación de enlaces inertes C-H de forma catalítica para la construcción de enlaces C-O. El primer proyecto desarrollado ha consistido en la funcionalización de enlaces C(sp3)-H para la síntesis directa de phthalides catalizado por Pd, utilizando simples ácidos benzoicos como materiales de partida. Continuando con la misma línea de investigación, el segundo proyecto realizado se ha basado en la utilización de catalizadores simples y de bajo coste de Cu para la funcionalización de enlaces C(sp2)-H/formación de enlaces C-O para la síntesis de benzolactonas. Finalmente, se ha desarrollado una metodología libre de metales para la síntesis de benzolactonas generando reactivos hipervalentes de I(III) de forma catalítica.
The main objective of this Thesis has been the activation of inert C-H bonds catalytically for the construction of C-O bonds. The fist project developed consisted on the activation of C(sp3)-H bonds for the direct synthesis of phthalides catalyzed by Pd, employing simple benzoic acids as starting materials. Continuing in the same research line, the second project described deals with the utilization of cheaper and easy to handle Cu salts as catalyst for the functionalization of C(sp2)-H bonds towards the formation of C-O bonds for the synthesis of benzolactones. Finally, the last project discovered handles a metal-free C-H functionalization approach for the synthesis of benzolactones by using simple iodoarenes as catalyst, thus

Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.
Title from electronic title page (viewed Apr. 25, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.

Redox-active ligands deliver redox equivalents to impart multi-electron functionality at 3d metals that typically undergo to one electron redox events. It was proposed that 3d metals with redox-active ligands could form unusually well-defined catalysts for C-C bond forming reactions to mimic palladium-type reactivity. Therefore, several new complexes containing an iron or cobalt with redox-active ligands were synthesized and tested for their ability to form new C-C bonds. A bis(iminosemiquinone) iron (III) complex was able to homocouple aryl Grignards using dioxygen as the terminal oxidant. However, ligand redistribution prevented detailed mechanistic study of the C-C bond forming reaction and led to catalyst degradation. To address the challenges seen in the iron catalyst a new cobalt electron transfer (ET) series containing a pincer-type bis(phenolate) N-heterocyclic carbene ligand (CoNHC) was synthesized. Studies indicate the CoNHC ET series spans multiple-electrons by corporative metal and ligand redox. These complexes were evaluated for cross-coupling of alkyl halides and aryl Grignards. Mechanistic studies imply that the low cross-coupling yields were due to ligand degradation. However, CoNHC catalytically activate cross-couples ether nitriles and aryl Grignards via a novel C-O bond activation leading to a new C-C bond. Findings concerning redox-active ligands on iron and cobalt for C-C bond forming reactions and implications for future research are discussed.

This thesis is centred around sequential C-C bond forming processes using oxygenated electrophiles. A major part of this research focuses on the constructive deoxygenation of 2-methoxyphenol (guaiacol), a major breakdown product of the renewable feedstock, lignin. 1,2-dielectrophiles are known to be challenging substrates for catalysis if both leaving groups are of similar reactivity, however high selectivity was observed in the palladium- catalysed Grignard cross-coupling of 2-methoxyphenyl-1H-imidazole-1-sulfonate. The previously untested Grignard cross-coupling catalyst, [PdCl₂(Xylyl-Phanephos)], was found to be highly active. A 2-benzoxazolyl functionality was shown to be an excellent directing group for the chelation-controlled nucleophilic aromatic substitution of aryl methyl ethers. However, this modified Meyers reaction is limited to aryl ethers containing an ortho-chelating group. To expand the ether scope, nickel-catalysed Grignard cross-coupling was studied. [NiCl₂(PⁿBu₃)2] showed increased activity in the Grignard cross-coupling of challenging ortho-substituted anisoles compared to the well-renowned [NiCl₂(PCy₃)2] and several Ni0 -NHC systems, with a ligand steric effect demonstrated. The success of [NiCl₂(PⁿBu₃)2] was extended to more activated methoxynaphthalene substrates, in which the lowest reported catalyst loadings (0.1-0.25 mol%) were reported. Induction periods at 0.1 mol% suggested the requirement of inorganic Lewis-acidic magnesium salts to be formed in situ before any considerable activity was observed. Further work is required to increase reaction and ether scope, but this work provides a basis for exploiting lignin- derived phenols as a framework in the synthesis of functionalised chemicals of higher value. The final results chapter concerns an alternative sequential C-C bond forming process using another oxygenated electrophile. [PdCl₂((S)-Xylyl-Phanephos)] was used to accomplish a Grignard cross-coupling of vinyl tosylate, with the product then subjected to a highly enantioselective methoxycarbonylation using the same catalyst. This lead to a concise synthesis of (S)-Flurbiprofen.

Abstract: This thesis demonstrates our accomplishments in the field of N-heterocyclic carbene catalysis and aryne chemistry to construct novel organic scaffolds. Chapter 1 is divided into three sections. Section 1 provides information on NHC catalyzed reactions, in particular, the Stetter reaction with selected examples from literature, whereas section 2 and 3 deals with our work on N-heterocyclic carbene catalyzed Stetter reactions of aromatic aldehydes with maleimides and N-substituted itaconimides, respectively. The developed Stetter reactions worked well under operationally simple reaction conditions to afford value added succinimide derivatives. Chapter 2 describes our novel work on the application of NHC catalysis in the total synthesis of cruciferane natural product. Herein, we have developed an intramolecular 3+2 cyloaddtion of homoenolate with imine as a key step to construct the cruciferane scaffold. Chapter 3 is divided into three sections. Section 1 provides information on various modes of aryne reactions and illustrates the reactivity and selectivity of aryne insertion reaction in elementalelemental bond with the help of representative examples from the literature. Section 2 and 3 describes our studies on aryne insertion reaction in C-C and C-S bond, respectively. Section 2 shows the preparation of valuable ortho-methyl trifluoromethyl sulfide substituted benzophenones through aryne insertion in C-C bond. Due to fluorine’s intrinsic property of modifying the pharmacological properties of drug molecules, its installation in the organic molecule through aryne chemistry was our prime motive, which was achieved successfully. Section 3 involves utilization of sulfur ylide for difunctionalization of aryne via C-S bond insertion. This section demonstrates novel reactivity for sulfur ylides.
AcSIR

Durant els últims anys, els compostos fosfit han demostrat ser lligands eficients en diverses reaccions catalitzades por metalls de transició. En aquest context, hem desemvolupat diverses lligandoteques fosfit per la seva aplicació en reaccions per obtenit productes enantiomericament purs. Més concretament hem estudiat: (a) La síntesis i aplicació de 9 lligandoteques fosfit-nitrogen en l’hidrogenació d’olefines mínimament funcionalizades catalitzada per iridi i les reaccions de substitució al•lílica i Heck catalitzades per pal•ladi. Aquests lligands s’han dissenyat mitjançant variacions sistemàtiques de diversos paràmetres del lligand. En tots els casos s’han obtingut activitats i selectivitats excel•lents (ee’s superiors als 99%) per un ampli rang de substrats. Els resultats competeixen favorablement amb els publicats prèviament en la bibliografia. (b) L’aplicació de diversos tipus de lligandoteques fosfit en la hidrofomilació de vinilarens, olefines heterocícliques i enol esters terminals catalitzada per rodi obtenint resultats prometedors (ee’ de fins el 76%).
During the last years, phosphite-containing compounds have proved to be efficient ligands for several metal-catalyzed transformations. In this context, we have developed several phosphite-containing ligand libraries for their application in reactions leading to enantiomerically pure products. More concretely we have studied: (a) the synthesis and screening of 9 phosphite-nitrogen ligand libraries in the Ir-catalyzed hydrogenation of minimally functionalized olefins, Pd-catalyzed allylic substitution and Heck reactions. These ligand libraries have been designed by systematic modification of several ligand parameters. In all cases excellent activities, regio- and enantioselectivities (ee’s up to >99%) have been obtained for a broad range of substrates. These results compete favorably with those reported previously in the literature. (b) the screening of several types of phosphite containing ligand libraries in the Rh-catalyzed hydroformylation of vinylarenes, heterocyclic olefins and 1,1’-terminal enol esters obtaining promising results (ee’s up to 76%).

Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2015.
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
The work presented in this dissertation addresses the development of new methodologies and processes to form carbon-nitrogen (C-N) and carbon-fluorine (C-F) bonds. The development of methods for the formation of C-N and C-F bonds are highly important to chemistry in general and find broad application in many different areas of research. With regard to C-N bond formation, the development of new nickel and palladium catalyst for C-N cross-coupling is presented. Finally, the development of a new process to enable the rapid preparation of aryl fluorides via the Balz-Schiemann reaction is explored. Chapter 1. Development of an Air-Stable Nickel Precatalyst for the Amination of Aryl Chlorides, Sulfamates, Mesylates, and Triflates. A new air-stable nickel precatalyst for C-N cross-coupling is reported. The developed catalyst system displays a greatly improved substrate scope for C-N bond formation to include both a wide range of aryl and heteroaryl electrophiles and aryl, heteroaryl, and alkyl amines. The catalyst system is also compatible with weak base, allowing for the amination of substrates containing base-sensitive functional groups. Chapter 2. Design of New Ligands for the Palladium-Catalyzed Arylation of a- Branched Secondary Amines. In Pd-catalyzed C-N cross-coupling reactions, a-branched secondary amines are difficult coupling partners and often produce low yields of the desired product. To provide a robust method for accessing N-aryl a-branched tertiary amines, new catalysts have been designed to suppress undesired side reactions often encountered when these amine nucleophiles are used. These advances enabled the arylation of a wide array of sterically encumbered amines, highlighting the importance of rational ligand design in facilitating challenging Pd-catalyzed cross-coupling reactions. Chapter 3. Rapid Synthesis of Aryl Fluorides in Continuous Flow via the Balz- Schiemann Reaction. The synthesis of aryl fluorides (ArF) is of critical importance for the development of new and potent pharmaceuticals and agrochemicals. While there have been numerous and intense research efforts focused on developing new fluorination methods, the Balz-Schiemann reaction remains a valuable and efficient means of aryl C-F bond construction from a vast pool of available aryl amines. However, the harsh reaction conditions, modest yields, and often prohibitive safety concerns have limited the general application of this methodology. Here, we have developed a semi-flow process that enables safe handling of the potentially explosive aryl diazonium salt intermediates as well as improved yields of the desired aryl fluoride products. This process has been demonstrated on an array of different aryl and heteroaryl amine substrates containing a variety of different functional groups.
by Nathaniel H. Park.
Ph. D. in Organic Chemistry

This thesis focusses on synthetic studies and mechanistic investigations into reactions involving hydrogen-transfer processes. In the first part, the development of an efficient method for the synthesis of β-hydroxy ketones (aldols) and β-amino ketones (Mannich products) from allylic alcohols and aldehydes is described. These reactions use  Ru(η5-C5Ph5)(CO)2Cl as the catalyst. The reaction parameters were optimised in order to suppress the formation of undesired by-products. Neutral and mild reaction conditions enabled the synthesis of a variety of aldol products in up to 99% yield, with a good syn/anti ratio. The influence of the stereoelectronic properties of the catalyst on the reaction outcome was also studied. Based on the results obtained, a plausible reaction mechanism has been proposed, involving as the key steps the 1,4-addition of hydride to α,β-unsaturated ketones and the formation of ruthenium (Z)-enolates. In the second part of this thesis, a ruthenium-catalysed tandem isomerisation/C-H activation reaction is presented. A number of ruthenium complexes, phosphine ligands, and additives were evaluated in order to establish the optimal reaction conditions. It was found that the use of a stable ruthenium catalyst, Ru(PPh3)3Cl2, together with PtBu3 and HCO2Na resulted in an efficient tandem transformation. Using this procedure, a variety of ortho-alkylated ketones were obtained in excellent yields. Moreover, homoallylic alcohols could also be used as starting materials for the reaction, which further expands the substrate scope. Mechanistic investigations into the isomerisation part of the process were carried out. The last project described in the thesis deals with the design and preparation of novel bifunctional iridium complexes containing an N-(2-hydroxy-isobutyl)-N-Heterocyclic carbene ligand. These complexes were used as catalysts to alkylate amines using alcohols as latent electrophiles. The catalytic system developed here was found to be one of the most active systems reported to date, allowing the reaction to be performed at temperatures as low as 50 °C for the first time. A broad substrate scope was examined. Combined experimental and theoretical studies into the reaction mechanism are consistent with a metal-ligand bifunctional activity of the new catalyst.

El uso de compuestos de paladio(II) para catalizar reacciones de copolimerización de monóxido de carbono y olefinas así como otros tipos de reacciones de formación de enlaces C-C muestra un creciente interés, prueba de ello es el importante numero de publicaciones realizadas en estos últimos años.
En catálisis una de las mayores causas de baja productividad es la degradación del catalizador a especies menos activas. Por este motivo se dedican constantemente esfuerzos al diseño de ligandos capaces de estabilizar al catalizador evitando así su degradación. Así por ejemplo, en la reacción de copolimerización de monóxido de carbono y etileno se ha demostrado que modificando los ligandos difosfina 1,2-di(fenilfosfino)etano (dppe) y 1,3-di(fenilfosfino)propano (dppp) mediante la introducción de grupos o-metoxi en los anillos fenilo se observa un aumento importante en la productividad del catalizador. El estudio del efecto causado por la introducción de grupos ometoxi ha sido y es objeto de numerosas publicaciones científicas. En gran parte de ellas se sugiere que el aumento de la productividad es debido a factores tanto estéricos como electrónicos, si bien resulta difícil establecer cual de ellos contribuye en mayor medida.
En la primera parte de la tesis se estudia el efecto positivo, en términos de productividad y peso molecular promedio del copolímero obtenido, debido a la introducción de los grupos o-metoxi en los grupos fenilo de los ligandos difosfina dppe y dppp en la reacción de copolimerización de monóxido de carbono y etileno desde un punto de vista catalítico y mecanístico.
La segunda parte de la tesis se centra en la exploración de rutas sintéticas sostenibles para la obtención de nuevos ligandos fosfina sulfonato, en la síntesis de nuevos complejos catiónicos, aniónicos y neutros de paladio(II) y de su aplicación en la reacción de copolimerización no alternada de monóxido de carbono y etileno además de en la reacción de formación de enlaces C-C Suzuki-Miyaura.
Con la finalidad de conseguir estos objetivos: 1) se han sintetizado nuevos ligandos y nuevos complejos neutros, cationicos y aniónicos de paladio; 2) se han desarrollaron rutas sintéticas alternativas para: 2.1) introducir los grupos ometoxi en los ligandos difosfina dppe y dppp; 2.2) sintetizar nuevos ligandos fosfina sulfonato; 3) se han realizado experimentos catalíticos en diferentes medios de reacción; 4) se han llevado a cabo experimentos de RMN de alta presión.
En el capitulo 1 se recoge la literatura básica además de los avances más recientes en la reacciones de copolimerización alternada y no alternada de monóxido de carbono y etileno y en la reacción de formación de enlaces C-C de Suzuki-Miyarura.
En el capitulo 2 se discute el efecto de los grupos o-metoxi introducidos en los ligandos difosfina dppe y dppp aplicados en la reacción de copolimerización alternada de monóxido de carbono y etileno. Para ello, se ha usado una ruta sintética alternativa para la obtención de los ligandos difosfina, 1,2-bis(di(2-metoxifenil)fosfino)etano (o-MeO-dppe) y 1,3-bis(di(2-metoxifenil)fosfino)propano (o-MeO-dppp). Estos dos ligandos y sus correspondientes ligandos difosfina (no sustituidos) dppe y dppp se han utilizado en la síntesis de complejos neutros y catiónicos de paladio(II). Estos complejos de paladio se han aplicado para estudiar su comportamiento como precursores catalíticos en la reacción de copolimerización de monóxido de carbono y etileno. Los complejos de paladio sintetizados se ha usado también en la realización de experimentos de RMN de alta presión tanto in situ como operando, estos experimentos nos han facilitado importante información sobre la productividad, la longitud de la cadena polimérica, los intermedios y los "resting states" de la reacción objeto de estudio. Se ha demostrado que los precursores catalíticos de paladio estabilizados con los ligandos difosfina o-MeO-dppe y o-MeO-dppp son más activos y dan lugar a copolímeros de mayor peso molecular que los precatalizadores estabilizados por los ligandos dppe y dppp. Se ha publicado que el uso de 2,2,2-trifluoetanol (TFE) como medio de reacción tiene como consecuencia un aumento de la productividad y de la longitud de la cadena polimérica, en nuestro caso este aumento se ha observado solamente en los precursores catalíticos estabilizados con los ligandos dppe y dppp, mientras que el los precursores catalíticos estabilizados con los ligandos modificados sufrían una disminución en su actividad. Este hecho se ha atribuido a la formación de una red de enlaces de hidrógeno con las moléculas del disolvente (TFE), produciéndose así la congestión del centro metálico y por consiguiente una disminución de la velocidad de propagación.
Los estudios mecanísticos han revelado que la cinética de la reacción estudiada se ve afectada por la presencia de lo grupos o-metoxi, se ha visto que la inserción migratoria de las especies paladio(alquil)(CO) limitan la etapa de carbonilación de los beta-quelatos haciendo que el proceso global de copolimerización sea independiente de la presión de monóxido de carbono en el rango de presiones estudiadas (5-30 bar). Las especies paladio(alquil)(CO) responsables de la limitación de la etapa de carbonilación han sido interceptadas y caracterizadas in situ por primera vez.
En el capitulo 3, se ha comparado el efecto que el aumento de la rigidez del ligando tiene en la reacción de copolimerización de monóxido de carbono y etileno. Las difosfinas objeto de estudio han sido la rac-2,4-bis(di(2-metoxifenil)fosfino)pentano (o-MeO-bdpp) y la 6,7-bis(di(2-metoxfenil)fosfinil-2,2,4,4-tetra(di-2-metoxifenil)-2l4,4l4-difosfoniumbiciclo[3.1.1]heptano-bis(PF6)(o-MeO-PCP)(PF6)2). Para ello se ha llevado a cabo la síntesis de la nueva difosfina o-MeO-bdpp a través de la ruta sintética descrita en el capitulo 2. Este nuevo ligando se ha utilizado en la síntesis de los complejos neutros [PdCl2(PxP)] y [Pd(OAc)2(P-P)]. Estos complejos de neutros de paladio(II) estabilizados por ambos ligandos difosfina se aplicaron como precursores catalíticos en la reacción de copolimerización de monóxido de carbono y etileno usando como medios de reacción, metanol en el caso de los precursores [Pd(OAc)2(P-P)] o una mezcla de acido acético y agua en el caso de los complejos [PdCl2(P-P)].
Los datos obtenidos han revelado que los precursores catalíticos estabilizados por el ligando menos rígido o-MeO-bdpp daban lugar a la producción de copolímeros de mayor peso molecular. Esto resultados se han interpretado en términos de "chain transfer" concluyéndose que esta mayor velocidad de "chain transfer" es debido a las propiedades estéricas y electrónicas del ligando más rígido (o-MeO-PCP)(PF6)2.
El capitulo 4 se discuten la síntesis de nuevos ligandos fosfina sulfonato, de nuevos complejos aniónicos y neutros de paladio(II) y su aplicación en la reacción de copolimerización no alternada de monóxido de carbono y etileno además de en al reacción de Suzuki-Miyaura. Los ligandos fosfina sulfonato 2-{bis(o-metoxifenil)fosfino}etanosulfonato (a) y 3-{bis(ometoxifenil)fosfino}propanosulfonato (b) se han preparado a través de una
nueva ruta sintética.
En al sección 4.1 se han comparado el ligando a y el ligando más rígido 2-{bis(o-metoxifenil)fosfino}bencenosulfonato (c) desde un punto de vista mecanístico y catalítico, para ello se han sintetizado complejos de paladio(II) con ambos ligandos (a y c) y se han aplicado en la reacción de copolimerización no alternada de monóxido de carbono y etileno. Además, con el objetivo de obtener información del poco conoció mecanismo de esta reacción se han llevado a cabo experimentos de RMN de alta presión.
De las reacciones catalíticas se ha concluido que el efecto de la rigidez del ligando es importante en este tipo de reacción catalítica, los resultados muestran que con el ligando menos rígido a se obtienen copolímeros de bajo peso molecular debido a una mayor velocidad de "chain transfer", en cuanto a la productividad los precursores catalíticos estabilizados con el ligando más rígido c se mostraron mucho más activos que los estabilizados con a.
Los experimentos de RMN de alta presión han evidenciado en ambos casos que las especies beta-quelato son el "resting state" de esta reacción de copolimerización no alternada de monóxido de carbono y etileno catalizada por complejos neutros de Pd(P-O).
En la sección 4.2, se han usado con éxito los nuevos ligandos sintetizados a y b en la reacción de Suzuki-Miyaura utilizando como medio de reacción agua y usando tecnología de microondas. Los resultados obtenidos muestran que estos ligandos en combinación con una fuente de paladio son activos en el "cross-coupling" de arilcloruros y arilbromuros con ácidos borónicos.
The interest in the palladium(II)-catalysed copolymerisation reaction of carbon monoxide and ethene as well as other reactions involving the formation of the C-C bond is increasing because of the possibilities of application in synthesis of new products and materials. This interest is reflected in the large number of reports published in recent years.
Since catalyst degradation to inactive species, is the major cause of the low productivity, considerable research effort is being made to design diphosphine ligands that can prevent them from degrading. Many papers have shown that the introduction of an o-methoxy substituent on the P-aryl rings of the diphosphine enhances the productivity in comparison with the unsubstituted ligands. It has been suggested that both steric and electronic factors are responsible for the positive effect of the o-methoxy groups on catalyst activity.
This thesis focuses on elucidating the effect of the o-methoxy group introduced on the P-aryl rings of the diphosphine ligands in the copolymerization reaction of carbon monoxide and ethene from a catalytic and a mechanistic point of view.
In the second part, the thesis focuses on the synthesis of new phosphine sulfonated ligands for the less well known reaction of non-alternating copolymerisation of CO and ethene and the applications of the later ligands in the Suzuki-Miyaura cross-coupling reaction in aqueous media.
To achieve these objectives, new ligands and neutral, cationic as well as anionic palladium complexes have been synthesised. New alternative synthetic protocols have been developed to: 1) introduce the -OMe group on the P-aryl rings of known and new diphosphine ligands, 2) synthesise new phosphine sulfonated ligands.
Catalytic reactions are carried out in different media as well as high pressure NMR experiments in an attempt to better understand the beneficial effect of omethoxy groups and the less well known mechanism of the non-alternating copolymerisation of CO and ethene.
Chapter 1 covers the basic literature and most recent development in the alternating copolymerisation of carbon monoxide and ethene, non-alternating copolymerisation of carbon monoxide and ethene and Suzuki-Miyaura crosscoupling >reaction.
Chapter 2 discusses the effect of the o-methoxy group on the alternating copolymerisation reaction of carbon monoxide and ethene. Diphosphine ligands 1,2-bis(di(2-methoxyphenyl)phosphino)ethane,1,3-bis(di(2-methoxyphenyl)phosphino)propane are synthesised by an alternative synthetic protocol. Both ligands and their phenyl counterparts for comparative purpose, are used to synthesise neutral and cationic palladium(II) complexes. The complexes are used to catalyse the CO-ethene copolymerisation reaction in either protic or aprotic solvents. In situ and operando high-pressure NMR experiments provide valuable information on catalysis resting states and intermediates. In addition, important steps in the CO/ethene copolymerisation reaction are studied by in situ high-pressure NMR spectroscopy, which helps rationalise the effect of the o-methoxy group.
In Chapter 3, the new diphosphine (o-MeO-bdpp) rac-2,4-bis(di(2-methoxyphenyl)phosphino)pentane is synthesised. This ligand is used to synthesise new neutral palladium(II) complexes. The ligand and complexes are fully characterised in solution by multinuclear NMR spectroscopy. This C2-bridged ligand is compared with the C3-bridged ligand and the more rigid ligand bis-cationic diphosphonium-diphosphine 6,7-di(di-2-methoxyphenyl)phosphinyl-2,2,4,4-tetra(di-2-methoxyphenyl)-2l4,4l4-diphosphoniumbicyclo[3.1.1]heptanebis(PF6) (o-MeO-PCP)(PF6)2) in the copolymerisation of CO with ethene in different reaction media in order to compare the effect of backbone rigidity.
Chaper 4 deals with the synthesis of new phosphine sulfonated ligands. The ligands are prepared through a new and sustainable synthetic route and used to synthesise new palladium(II) anionic complexes. The later anionic complexes are used in the less well known non-alternating copolymerisation reaction of carbon monoxide and ethene and compared with other phosphine sulfonate ligands that have been applied in this kind of catalysis. In addition, high pressure NMR experiments are carried out in order to go further into the mechanism of this polymerisation reaction.
Furthermore, taking advantage of the fact that the new phosphine sulfonated ligands are both water-soluble and air stable, they are successfully applied in palladium-catalysed Suzuki-Miyaura cross-coupling reactions in neat water in conjunction with microwave heating.

L’obtenció de compostos enantiomèricament purs ha esdevingut una necessitat que ha conduit a un important progrés en la catàlisi asimètrica, principalment usant compostos organometàl•lics quirals. Entre les diferents estratègies en l’optimització dels catal•litzadors per aconseguir elevades selectivitats i activitats, el disseny i correcta selecció de lligands quirals, modificant-ne les seves propietats és fonamental i la més utilitzada. Que un lligand sigui fàcil de sintetitzar a partir de compostos de partida accessibles i que aquests lligands siguin estables i fàcils de manipular, tenen un elevat interès en la industria. En aquest context, el principal objectiu d’aquesta tesi és la síntesi de diferents famílies de lligands quirals, acomplint els requisits prèviament esmentats, i la seva posterior aplicació a diverses reaccions asimètriques d’elevat interès industrial: hidrogenació d’olefines funcionalitzades i no funcionalitzades catalitzada per Rh i Ir, hidrogenació de cetones catalitzada per Ir, reaccions de substitució al•lílica catalitzades per Pd i reaccions de substitució propargílica catalitzada per Cu. S’han sintetitzat diverses famílies fosfit/fosfinit-tioèter/selenoèter, carbè-tioèter, amino-fosfit/fosfinit/fosfina, i varies famílies de lligands tridentats.
La obtención de compuestos enantioméricamente puros se ha convertido una necesidad que ha conducido a un importante progreso en la catálisis asimétrica, principalmente usando compuestos organometalicos quirales. Entre las diferentes estrategias en la optimización de los catalizadores para conseguir elevadas selectividades y actividades, el diseño y la correcta selección de ligandos quirales, modificando sus propiedades es fundamental y la más utilizada. Que un ligando sea fácil de sintetizar a partir de compuestos de partida accesibles y que estos ligandos sean estables y fáciles de manipular, tienen un elevado interés en la industria. En este contexto, el principal objetivo de esta tesis es la síntesis de distintas familias de ligandos quirales, cumpliendo con los requisitos previamente mencionados, y su posterior aplicación en distintas reacciones asimétricas de alto interés industrial: hidrogenación de alquenos funcionalizados y no funcionalizados catalizados por Rh y Ir, hidrogenación de cetonas catalizada por Ir, reacciones de substitución alílica catalizada por Pd y reacciones de substitución propargílica catalizada por Cu. Se han sintetizado diferentes familias de ligandos Fosfito/fosfinito-tioéter/selenoéter, carbeno-tioéter, amino-fosfito/fosfinito/fosfina, y varias familias de ligandos tridentados.
The obtaining of enantiomerically pure compounds has become a need that led to an important progress in asymmetric catalysis, mainly using organometallic chiral compounds. Among different strategies to optimize catalysts in order to obtain high selectivities and activities, the design and the correct selection of chiral ligands, modifying their properties, is fundamental and the most used strategy. Ligands easy to synthesize from readily accessible starting material and stable and easy to manipulate ligands, have a high interest in the industry. In this context, the main objective of this thesis is the synthesis of different chiral ligand families, according to the previously mentioned requirements, and their application in different asymmetric reactions with high industrial interest: Rh- and Ir-catalyzed hydrogenation of functionalized and minimally functionalized olefins; Ir-catalyzed hydrogenation of simple ketones; Pd-catalyzed asymmetric substitution of allylic acetates and Cu-catalyzed propargylic substitution. There have been synthesized different phosphite/phosphinite-thioether/selenoether, carbene-thioether, amino-phosphite/phosphinite/phosphine and various tridentated ligand families.

The major part of this thesis concerns the development of catalytic methodologies based on palladium nanoparticles immobilized on aminopropyl-functionalized siliceous mesocellular foam (Pd0-AmP-MCF). The catalytic activity of the precursor to the nanocatalyst, PdII-AmP-MCF is also covered by this work. In the first part the application of Pd0-AmP-MCF in Suzuki-Miyaura cross-coupling reactions and transfer hydrogenation of alkenes under microwave irradiation is described. Excellent reactivity was observed and a broad range of substrates were tolerated for both transformations. The Pd0-AmP-MCF exhibited high recyclability as well as low metal leaching in both cases. The aim of the second part was to evaluate the catalytic efficiency of the closely related PdII-AmP-MCF for cycloisomerization of various acetylenic acids. The catalyst was able to promote formation of lactones under mild conditions using catalyst loadings of 0.3 - 0.5 mol% at temperatures of up to 50 oC in the presence of Et3N. By adding 1,4-benzoquinone to the reaction, the catalyst could be recycled four times without any observable decrease in the activity. The selective arylation of indoles at the C-2 position using Pd-AmP-MCF and symmetric diaryliodonium salts is presented in the third part. These studies revealed that Pd0-AmP-MCF was more effective than PdII-AmP-MCF for this transformation. Variously substituted indoles as well as diaryliodonium salts were tolerated, giving arylated indoles in high yields within 15 h at 20 - 50 oC in H2O. Only very small amounts of Pd leaching were observed and in this case the catalyst exhibited moderate recyclability. The final part of the thesis describes the selective hydrogenation of the C=C in different α,β-unsaturated systems. The double bond was efficiently hydrogenated in high yields both under batch and continuous-flow conditions. High recyclability and low metal leaching were observed in both cases.

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Submitted.

 

Thesis advisor: Amir H. Hoveyda
Chapter 1. In this chapter, the ability of chiral bidentate N-heterocyclic carbenes (NHCs) to activate alkylmetal reagents directly in order to promote C‒C bond forming reactions in the absence of a Cu salt is presented. Highly regio- and enantioselective Cu-free allylic alkylation reactions of di- and trisubstituted allylic substrates with organomagnesium, organozinc, and organoaluminum reagents are demonstrated. Chiral bidentate sulfonate-bearing NHC-Zn and NHC-Al complexes are isolated and fully characterized. Based on crystal structures of these catalytic complexes, mechanistic details regarding Cu-free allylic alkylations with alkylmetal reagents are proposed. Chapter 2. New methods for efficient and highly enantioselective Cu-catalyzed allylic alkylation reactions of a variety of trisubstituted allylic substrates with alkylmagnesium and alkyl-, aryl-, 2-furyl-, and 2-thiophenylaluminum reagents are presented. Transformations are promoted by a chiral NHC complex in the presence of commercially available, inexpensive and air stable CuCl2*H2O. Enantiomerically enriched compounds containing difficult-to-access all-carbon quaternary stereogenic centers are obtained. Chapter 3. New methods for highly site- and enantioselective Cu-catalyzed allylic alkylation reactions of allylic phosphates with vinylaluminum reagents are presented. The requisite vinylaluminums are prepared by reaction of readily accessible terminal alkynes with DIBAL-H and used directly without further purification. Vinyl additions are promoted in the presence of a chiral bidentate sulfonate-based NHC complex and a Cu salt. The desired SN2' products are obtained in >98% E selectivities, >98% SN2' selectivities, >98% group selectivities (<2% i-Bu addition) and high enantioselectivities. The enantioselective total synthesis of the natural product bakuchiol highlights the versatility of the one-pot hydroalumination/Cu-catalyzed enantioselective allylic vinylation process. Chapter 4. Efficient and highly site-selective Cu-catalyzed hydroboration reactions of 1,2-disubstituted aryl olefins with bis(pinacolato)diboron (B2(pin)2) are presented. Transformations are promoted by an NHC-Cu complex in the presence of MeOH, affording only secondary β-boronate isomers. A Cu-catalyzed method for the synthesis of enantiomerically enriched secondary alkylboronates promoted by chiral NHC complexes is disclosed. Chapter 5. A new method for efficient and site-selective tandem Cu-catalyzed copper-boron additions to terminal alkynes with B2(pin)2 in the presence of an NHC-Cu complex is demonstrated. In a one-pot process, Cu-catalyzed hydroboration of alkynes provides vinylboronates in situ, which undergo a second site-selective hydroboration to afford vicinal diboronates. Highly Enantiomerically enriched diboronates obtained through Cu-catalyzed enantioselective dihydroboration in the presence of chiral bidentate sulfonate-based NHC-Cu complex are obtained. The control of site selectivity in the first-stage hydroboration of alkynes is critical for efficient and highly enantioselective reactions in the tandem dihydroboration. Functionalizations of the vicinal diboronates described herein underline the significance of the current method
Thesis (PhD) — Boston College, 2010
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

In the following thesis, new methodologies towards harnessing C-S activation processes are documented. These methods utilise rhodium catalysis and are focused on the activation of aryl methyl sulfides. Chapter 1 provides an overview of the development of metal-catalysed C-S activation chemistry, with a focus on the catalytic systems, reagents and starting materials used to facilitate various C-C bond forming transformations. Chapter 2 describes a novel rhodium-catalysed cross-coupling reaction of aryl and alkyl terminal alkynes with simple aryl sulfides. This resulted in a Sonogashira-type transformation which exhibited orthogonality with traditional palladium catalysed Sonogashira chemistry. Chapter 3 documents a new catalytic system which allowed for the practical and efficient alkyne carbothiolation reactions of ketone-baring methyl sulfides. The carbothiolation products can be conveniently utilised in a one-pot three-component reaction to form highly substituted isoquinolines. Chapter 4 discusses the potential for future work. Chapter 5 presents the experimental data.

Thesis (Ph.D.)--Indiana University, Dept. of Chemistry, 2004.
Title from PDF t.p. (viewed Nov. 10, 2008). Source: Dissertation Abstracts International, Volume: 67-02, Section: B, page: 0900. Adviser: Jeffrey N. Johnston.

Chiral molecules play a central role in our daily life and in nature, for instance the different enantiomers or diastereomers of a chiral molecule may show completely different biological activity. For this reason, it is a vital goal for synthetic chemists to design selective and efficient methodologies that allow the synthesis of the desired enantiomer. In this context, it is highly important that the concept of green chemistry is considered while designing new approaches that eventually will provide more environmental and sustainable chemical synthesis.The aim of this thesis is to develop the concept of combining transition metal catalysis and aminocatalysis in one process (dual catalysis). This strategy would give access to powerful tools to promote reactions that were not successful with either transition metal catalyst or the organocatalyst alone. The protocols presented in this thesis based on organocatalytic transformations via enamine or iminium intermediates or both, in combination with transition metal catalysis, describes new enantioselective organocatalytic procedures that afford valuable compounds with high chemo- and enantioselectivity from inexpensive commercial available starting materials. In paper I, we present a successful example of dual catalysis: the combination of transition metal activation of an electrophile and aminocatalyst activation of a nucleophile via enamine intermediate. In paper II, the opposite scenario is presented, here the transition metal activates the nucleophile and the aminocatalyst activates the electrophile via an iminium intermediate. In paper III,we present a domino Michael/carbocyclisation reaction that is catalysed by a chiral amine (via iminium/enamine activation) in combination with a transition metal catalysts activation of an electrophile. In paper IV, the concept of dual catalysis was further extended and applied for the highly enantioselective synthesis of valuable structural scaffolds, namely poly-substituted spirocyclic oxindoles. Finally, in paper V the concept of dual catalysis was expanded, by investigating more challenging and environmentally benign processes, such as the successful combination of a heterogeneous palladium and amine catalysts for the highly enantioselective synthesis of functionalised cyclopentenes, containing an all carbonquaternary stereocenter, dihydrofurans and dihydropyrrolidines.

During the last decade, our group of research has developed new synthetic strategies for the preparation of NHC-based homogeneous catalysts with novel stereoelectronic properties. Within this context, this work is focused on the synthesis and characterization of new metallic complexes containing different N-heterocyclic carbene ligands, the study of their reactivity and the exploration of their catalytic properties. A set of simple `Ru(¿6-arene)(NHC)¿ and `IrCp*(NHC) complexes with different NHC ligands (imidazolylidene, pyrazolylidene and triazolylidene) have been prepared. The new Ru(II) and Ir(III) complexes have been tested in several catalytic C-H bond activation processes, especially regarding reactions through a borrowing-hydrogen mechanism and functionalization of arenes. The main goal is to perform the catalytic reactions under the `greenest¿ possible conditions, thus using non-toxic solvents under the highest atom-economic conditions and minimum waste of energy. Two different classes of bis-NHC ligands coordinated to Ir(I) and Rh(I) metal centers have been described in this chapter. The first methodology used provides an alternative to the use of the traditional azolium salts. The double C(sp3)-H2 dehydrogenation of a saturated heterocycle is a novel and interesting way to obtain complexes containing different architectures.

La creixent demanda de compostos enantiomèricament purs, ha incrementat l’interès pel desenvolupament de metodologies per l’obtenció d'aquests compostos. Entre elles, la catàlisi asimètrica és la tècnica més emprada. En aquesta metodologia, l'elecció lligand quiral és clau per l'obtenció de elevades activitats i enantioselectivitats. En aquest context, aquesta tesis és centra en la síntesis de diferents famílies de lligands quirals altament modulars a partir de productes de partida d'elevada disponibilitat. Més concretament, s’han sintetitzat diverses famílies de lligands heterodadors P-oxazolina (P= fosfina, fosfinit, fosfit, fosforamidit), P-altres grups N-dadors (P= fosfit, fosforamidit, fosfonit i N= tiazol, sulfoximina, hidrazona, amina, piridina), P-tioèter (P= fosfina, fosfinit, fosfit) i una família de lligands fosfina quiral-fosfit. Aquests lligands s'han aplicat en la reacció d’hidrogenació d’olefines funcionalitzades i mínimament funcionalitzades catalitzada per Rh i Ir, la reacció de substitució al·lílica i la reacció de protonació descarboxilativa d’oxindoles ambdues catalitzades per Pd. A més a més, en alguns casos, s'han dut a terme estudis computacionals en combinació amb assajos experimentals per estudiar l'origen de les enantioselectivitats obtingudes o bé per guiar l'optimització dels lligand.
La creciente demanda de compuestos enantioméricamente puros, ha incrementado el interés por el desarrollo de metodologías para la obtención de dichos compuestos. Entre ellas, la catálisis asimétrica es la técnica mas utilizada. En dicha metodología, la elección del ligando quiral es clave para la obtención de elevada actividades i enantioselectividades. En este contexto, esta tesis se centra en la síntesis de diferentes familias de ligandos quirales altamente modulares a partir de productos de partida de elevada disponibilidad. Más concretamente, se ha trabajado en la síntesis de ligandos heterodadores P-oxazoline (P= fosfina, fosfinito, fosfito, fosforamidito), P-otros grupos N-dadores (P= fosfito, fosforamidito, fosfonito y N= tiazol, sulfoximina, hidrazona, amina, piridina), P-tioéter (P= fosfina, fosfinito, fosfito) i una familia de ligandos fosfina quiral-fosfito. Estos ligandos se han aplicado en la reacción de hidrogenación de olefinas funcionalitzadas i mínimamente funcionalitzadas catalizada por Rh i Ir, la reacción de substitución alílica y la reacción de protonación descarboxilativa de oxindolas ambas catalizadas por Pd. Además, en algunos casos, se han realizado cálculos computacionales en combinación con ensayos experimentales para estudiar el origen de las enantioselectividades obtenidas o bien para guiar la optimización de los ligandos.
The growing demand on enantiomerically pure compounds has stimulated the interest for the development of methodologies to obtain these compounds. Among them, asymmetric catalysis is one of the most employed tools. In this technic, the choice of the chiral ligand is fundamental to obtain high levels of activity and enantioselectivity. In this context, this thesis is focused on the synthesis of several families of highly modular chiral ligands from readily available starting materials. Particularly, we worked on the synthesis of P-oxazoline (P= phosphine, phosphinite, phosphite, phosphoroamidite), P-other N-donor groups (P= phosphite, phosphoroamidite, phosphonite and N= thiazole, sulfoximine, hydrazone, amine, pyridine), P-thioether (P= phosphine, phosphinite, phosphite) and a family of P*-stereogenic phosphine-phosphite ligands. These ligands have been applied in the Rh- and Ir-catalyzed hydrogenation of functionalized and minimally functionalized olefins, Pd-catalyzed allylic substitution reaction and Pd-catalyzed decarboxylative protonation. Furthermore, in some cases, DFT studies in combination with experimental ones have been performed to better understand the origin of the obtained enantioselectivities or in order to guide the ligand optimization.