Dissertations / Theses on the topic 'C-N bond forming'

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.

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.

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.

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 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

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Vita. Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references.
Chapter 1: A highly active catalyst system based upon a biaryl monophosphine ligand, XPhos, for the palladium-catalyzed Stille reaction has been developed. This method allows for the coupling of aryl chlorides with a range of tributylarylstannanes to produce the corresponding biaryl compounds in good to excellent yields (61-98%) in short reaction times (4 h). Palladium(II) acetate [Pd(OAc)2] and XPhos in a 1:1.1 ratio were milled into a fine powder that was used as pre-catalyst for these reactions. Chapter 2: A catalyst system for the Stille cross-coupling reactions of aryl mesylates and tosylates is reported. Using the combination of Pd(OAc)2, XPhos, and CsF in t-BuOH an array of aryl and heteroaryl sulfonates were successfully employed in these reactions. Morever, heteroarylstannanes, such as furyl, thienyl, and N-methylpyrrolyl, which are often prone to decomposition, were efficiently coupled under these conditions. Ortho-substitution on the stannane coupling partner was well tolerated; however, the presence of ortho substituents on the aryl sulfonates greatly reduced the efficiency of these reactions. Chapter 3: A continuous-flow, multistep Heck synthesis was made possible by integrating microreactors, liquid-liquid extraction, and microfluidic distillation. The microfluidic distillation enabled solvent exchange from CH2Cl2 in the first reaction step to N,N-dimethylformamide (DMF) in the final reaction step. Chapter 4: A method to mitigate clogging of microsystems during Pd-catalyzed C-N bond-forming reactions under continuous flow conditions was developed. Bridging of particles across the channel and deposition of materials on the walls of the microreactor were both found to be causes that led to clogging and techniques to minimize their effects using sonication were developed. This system allows Pd-catalyzed amination reactions for the formation of a diaryl amines to proceed for extended periods of time without significant pressure increase in the reactor. Chapter 5: A highly efficient method for the Pd-catalyzed coupling of aryl chloride and anilines has been developed. Catalysts based on allyl palladium chloride dimer and BrettPhos, using biphasic reaction conditions of toluene and water with KOH as a base, provided excellent yields for these reactions. The use of a packed bed reactor allowed for these reactions to be run in a continuous flow manner.
by John R. Naber.
Ph.D.

El creixent interès per a l’obtenció de compostos enantiomèricament purs, ha conduït a un important desenvolupament de la catàlisi asimètrica. En aquest context, aquesta tesis és centra en la síntesis de vàries famílies de lligands quirals altament modulars a partir de compostos de fàcil disponibilitat. Concretament, s'ha treballat en la síntesis de lligands fosfit-tioèter, fosfit-piridina, fosfit-triazola i lligands hidroaximida i tioamida. Tots ells tenen en comú que són sòlids, estables i per tant de fàcil manipulació. Aquests lligands s'han aplicat en la hidrogenació d’olefines funcionalitzades i no funcionalitzades catalitzada per Rh i Ir, en la reducció de cetones mitjançant transferència d’hidrogen catalitzada per Rh i Ru, en reaccions de substitució alílica catalitzada per Pd i en l'addició d'organoaluminats a aldehids catalitzada per Ni. A més a més, en alguns casos s'han realitzat estudis DFT per tal d'agilitzar el procés d'optimització dels lligands. Així doncs, s'ha aconseguit l'obtenció de diferents compostos químics quirals d'alt interès sintètic (alcohols, alcans funcionalitzats i no funcionalitzats, al·lils substituits) en grans enantioselectivitats i en el millor dels casos s'han aconseguit els productes en la seva forma enantiomèricament pura (>99% ee).
El creciente interés para la obtención de compuestos enantioméricamente puros para la obtención de compuestos enantioméricamente puros, ha conducido a un importante desarrollo de la catálisis asimétrica. En este contexto, esta tesis se centra en la síntesis de varias familias de ligandos quirales altamente modulares a partir de compuestos de fácil disponibilidad. Concretamente, se ha trabajado en la síntesis de ligandos fosfito-tioéter, fosfito-piridina, fosfito-triazoles y ligandos hidroaximida y tioamida. Todos ellos tienen en común que son sólidos, estables y por lo tanto de fácil manipulación. Estos ligandos se han aplicado en la hidrogenación de olefinas funcionalizadas y no funcionalizadas catalizada por Rh e Ir, en la reducción de cetonas mediante transferencia de hidrógeno catalizada por Rh y Ru, en reacciones de sustitución alílica catalizada por Pd y en el adición de organoaluminiatos a aldehídos catalizada por Ni. Además, en algunos casos se han realizado estudios DFT para agilizar el proceso de optimización de los ligandos. Así pues, se ha logrado la obtención de diferentes compuestos químicos quirales de alto interés sintético (ej. alcoholes, alcanos funcionalizados y no funcionalizados, alilos sustituidos) en grandes enantioselectividades y en el mejor de los casos se han conseguido los productos en su forma enantioméricamente pura (> 99% ee).
The growing interest in obtaining enantiomerically pure compounds in obtaining enantiomerically pure compounds has led to a significant development in the field of asymmetric catalysis. In this context, this thesis is focused on the synthesis of several families of highly modular chiral ligands from readily available compounds. Specifically, we worked on the synthesis of thioether-phosphite ligands, phosphite-pyridine, phosphite-triazole and hidroaximide and thioamide ligands. They all have in common that are solid, stable and therefore easy to handle. These ligands have been applied in the Rh- and Ir-catalyzed hydrogenation of functionalized and unfunctionalized olefins, in the Ru- and Rh-catalyzed asymmetric transfer hydrogenation of ketones, in Pd-catalyzed allylic substitution reactions and in the Ni-catalyzed addition of organoalumininum to aldehydes. Moreover, in some cases DFT studies have been performed to speed up the optimization of ligands. Hence, a variety of chiral chemical compounds of high synthetic interest (i. e. alcohols, functionalized and non-functionalized alkanes, substituted allyl) lhigh enantioselectivities were achieved and in some cases the products were obtained in their enantiomerically pure form(> 99% ee).

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.

Chapters 1 and 2 describe the development of photoinduced, Cu-catalyzed coupling reactions of unactivated secondary alkyl halides with amide and cyanide nucleophiles. These reactions may be conducted at room temperature under operationally simple conditions. Mechanistic studies are consistent with the intermediacy of alkyl radicals in these processes.

Chapter 3 describes progress toward the development of the first enantioselective Ni-catalyzed cross coupling of racemic alkyl halides and heteroatom nucleophiles. Borylation of secondary benzylic chlorides with B₂(pin)₂ may be achieved in good yield and promising levels of enantioselectivity.

Chapter 4 describes enantioselective Ni-catalyzed couplings of α-substituted lactam enolates with benzonitrile derivatives resulting in formal intermolecular C- acylation via in situ hydrolysis of an imine intermediate.

The research has been originated from an attempt to explore direct and selective transformation of c-h bonds that are mediated either by metal coordination or by protonation of anilido substrate oxidative dimerization and polymerization reactions
The research guide was Prof. Sreebrata Goswami of Inorganic Chemistry division under SCS [School of Chemical Science]
Research was conducted under CSIR fellowship in IACS

Oxygen and Nitrogen containing compounds are of utmost importance due to their interesting and diverse biological activities. The construction of the C-O and C–N bonds is of significance as it opens avenues for the introduction of ether and amine linkages in organic molecules. Despite significant advancements in this field, the construction of C-O and C–N bonds is still a major challenge for organic chemists, due to the involvement of harsh reaction conditions or the use of expensive catalysts or ligands in many cases. Thus, it is a challenge to develop alternative, milder, cheaper and more reproducible methodologies for the construction of these types of bonds. Herein, we introduce a new efficient ligand free catalytic system for C-O and C-N bond formation reactions.

In the pursuit of increasingly efficient and/or new chemical transformations, homogeneous transition metal catalysts are proving to be invaluable components of the synthetic chemist’s toolbox. Notwithstanding the many important contributions made to the area of synthetic chemistry utilizing other transition metal catalysts, palladium-catalyzed cross-coupling techniques have been demonstrated to allow for a plethora of otherwise very difficult or even impossible bond forming reactions to be realized. In this context, appropriately designed ancillary ligands, which upon binding to a metal center can influence metal-centred reactivity, have played an essential role in the advancement of palladium-catalyzed cross-coupling reactions. This thesis describes a multi-faceted approach to the identification of effective ligands for the palladium-catalyzed construction of (sp2)carbon-nitrogen and -oxygen bonds. A new series of P,O-DalPhos ligands were developed and applied in the synthesis of of N-substituted indoles via tandem palladium-catalyzed cross-coupling/cyclizations of ortho-alkynylhalo(hetero)arenes with primary amines. Notably, one P,O-DalPhos variant, OTips-DalPhos, was demonstrated to offer the broadest known substrate scope in this important class of transformations, affording a variety of structurally diverse indoles and related heterocyclic derivatives in high yields. Also described herein is the identification of the previously reported ligand BippyPhos as an extremely robust and versatile ligand in both palladium-catalyzed carbon-nitrogen and -oxygen cross-coupling applications. Indeed, the use of a Pd/BippyPhos catalyst enabled the cross-coupling of a range of (hetero)aryl (pseudo)halides with primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, with representative examples being accommodated in air. The unprecedented scope of the Pd/BippyPhos catalyst in carbon-nitrogen cross-coupling allowed for the development of two novel one-pot, two-step syntheses of N¬-aryl heterocycles from ammonia, ortho-alkynylhalo(hetero)arenes and (hetero)aryl halides through tandem N-arylation/hydroamination reactions. A marked selectivity profile was also observed for the Pd/BippyPhos catalyst and successfully exploited in the chemoselective monoarylation of substrates featuring two distinct and potentially reactive NH-containing moieties. Finally, Pd/BippyPhos mixtures served as robust and efficient catalysts for the hydroxylation of a range of (hetero)aryl halides and ortho-alkynyl(halo)heteroarenes to form phenols and phenol-derived heterocycles.