Dissertationen zum Thema „C heteroatom“

Tot i que el camp de l'acoblament creuat ha desenvolupat increïbles avenços, la gran majoria de processos encara es basen en l'ús d'halurs d'aril. No obstant, aquest tipus d’electròfils presenten una toxicitat intrínseca i, al mateix temps, la seva síntesis resulta tediosa, especialment quan es tracta d'halurs d'aril altament funcionalitzats. A causa d'això, la comunitat sintètica s'ha bolcat en la recerca d'alternatives a l'ús d'halurs d'aril en química d'acoblament creuat. Grans esforços s'han desenvolupat en la última dècada per implementar els derivats del fenol en aquest tipus de transformacions a causa de l'abundància natural i comercial d'aquests compostos i a la seva baixa toxicitat en comparació amb els organohalurs. No obstant, l'alta energia d'activació necessària per trencar els enllaços C-O ha limitat considerablement l'ús de derivats de fenol en reaccions d’acoblament creuat, sobretot si es tracta d'éters de metil. Actualment la gran majoria de mètodes basats en aquesta família d’electròfils s'utilitzen en la formació d'enllaços C-C. Altrament, gairebé no existeixen tècniques per obtenir enllaços Cheteroàtom probablement a causa de la baixa reactivitat dels nucleòfils, on la densitat de càrrega negativa resideix en un heteroàtom. La present tesi doctoral s'ha centrat en el desenvolupament de noves metodologies per a la creació d'enllaços de tipus C-heteroàtom mitjançant l’activació catalítica d'enllaços C-O amb complexes de Ni. S'han descrit nous mètodes de sililació i borilació d'ésters i metil éters d’aril i benzil. Aquests mètodes suposen una via alternativa per a la síntesis de silans i boronats, els quals són intermedis de gran utilitat en síntesis orgànica. A més, el descobriment d'unes condicions totalment inusuals per activar enllaços de tipus C-OMe ha obert noves perspectives sobre la reactivitat d'aquest tipus d'enllaços i, alhora, ha suggerit l'existència de nous mecanismes d'activació.
A pesar de que el campo del acoplamiento cruzado ha desarrollado increíbles avances, la gran mayoría de procesos todavía se basa en el uso de halogenuros de arilo. Sin embargo, este tipo de electrófilos presentan una toxicidad intrínseca y, a su vez, su síntesis resulta tediosa, especialmente cuando se trata de halogenuros de arilo altamente funcionalizados. Debido a ello, la comunidad sintética se ha volcado en la búsqueda de alternativas al uso de halogenuros de arilo en química de acoplamiento cruzado. Un gran esfuerzo se ha desarrollado en la última década para implementar los derivados del fenol en este tipo de transformacions debido a la abundancia natural y comercial de dichos compuestos y a su baja toxicidad en comparación con los organohalogenuros. Sin embargo, la alta energía de activación necesaría para romper los enlaces C-O ha limitado considerablemenete el uso de derivados del fenol en reacciones de acomplamineto cruzado, sobre todo si se trata de éteres de metilo. Actualmente la gran mayoría de métodos basados en esta familia de electrófilos se utilizan en la formación de enlaces C-C. De lo contrario, apenas existen técnicas para obtener enlaces C-heteroátomo probablemente debido a la baja reactividad de los nucleófilos donde la densidad de carga negativa reside en un heteroátomo. La presente tesis docotoral se ha centrado en el desarrollo de nuevas metodologías para la creación de enlaces de tipo C-heteroatomo mediante la activción catalítica de enlaces C-O con complejos de Ni. Se han descrito novedosos métodos de sililación y borilación de ésteres y metil éteres de arilo y bencilo. Dichos métodos suponen una via alternativa para la síntesis de silanos y boronatos, los cuales son intermedios de gran utilidad en síntesis orgánica. Además, el descubrimiento de unas condiciones totalmente inusuales para activar enlaces de tipo C-OMe ha abierto nuevas perspectivas sobre la reactividad de este tipo de enlaces y, a la vez, ha sugerido la existencia de nuevos mecanismos de activación.
While the field of cross-coupling has reached remarkable levels of sophistication, the vast majority of processes are still being conducted with organic halide counterparts. Drawbacks associated to their toxicity and the limited accessibility of densely functionalized aryl halides have prompted chemists to develop powerful, yet practical, alternatives. Among these, the utilization of phenol derivatives as coupling partners via C-O bond cleavage would be particularly rewarding due to their readily availability and benign nature. However, the high activation energy required for effecting C–O bond cleavage has become a daunting challenge when devising catalytic techniques using phenol derivatives, specially always-elusive aryl methyl ethers. At present, the vast majority of cross-coupling reactions using phenol derivatives remains confined to C–C bond formation, whereas the formation of C-heteroatom bonds has been poorly studied, likely due to the less reactivity of heteroatom-based nucleophiles. This doctoral thesis has focused on the development of new methodologies for forging C-heteroatom bonds via Ni-catalyzed C-O bond cleavage. It has been described new protocols for the silylation and borylation of aryl and benzyl esters and methyl ethers. These methodologies can be used as useful alternatives towards the synthesis of aryl and benzyl silanes and boronates, incredible important intermediates in organic synthesis. Furthermore, the discovery of unusual, yet surprising, conditions for the cleavage of C-OMe bonds have opened up new vistas towards the reactivity of aryl and benzyl methyls ethers while suggesting new activation pathways.

La química sintètica és gairebé inimaginable sense tres elements principals del grup, a saber, boro, silici i estany. Quan s'uneixen a un àtom de carboni de qualsevol hibridació, aquests grups funcionals serveixen de linchpins excepcionalment versàtils en síntesi, transformant-se selectivament en una enorme amplitud d'enllaços C-C i C-X, per tant, descobrir nous mètodes per forjar el valor afegit C-Si, Els enllaços C-B i C-Sn sempre tenen una gran demanda. D'acord amb l'interès de la investigació en el grup de Martín per activar enllaços o molècules inerts, aquesta tesi doctoral se centra en el desenvolupament de noves tècniques per fer ús de l'enllaç d'interrelació de silici-heteroatoma per funcionalitzar l'enllaç C-O i C-H inerts mitjançant una catàlisi de níquel o sistema lliure de transició de metalls. Hem desenvolupat tres nous mètodes per a la funcionalització d’enllaços C-O i C-H inerts mitjançant l’ús d’enllaços d’interrelació basats en silici. Totes les transformacions anteriors presenten un excel·lent perfil de quimioselectivitat en condicions suaus. Es duen a terme estudis i debats sobre mecanismes previs per entendre com i per què van continuar aquestes reaccions. Les transformacions realitzades contribueixen a la comprensió de l’ús més prolífic d’enllaços químics inerts en els compostos de valor afegit de síntesi. Creiem que aquests protocols contribuirien
La química sintética es casi inimaginable sin tres elementos principales del grupo, a saber, boro, silicio y estaño. Cuando se unen a un átomo de carbono de cualquier hibridación, estos grupos funcionales sirven como linchpins excepcionalmente versátiles en síntesis, transformándose selectivamente en una enorme variedad de enlaces C-C y C-X, por lo tanto, descubren nuevos métodos para forjar el valor agregado C-Si, Los bonos C-B y C-Sn siempre tienen una gran demanda. En línea con el interés de la investigación en el grupo de Martín de la activación de enlaces o moléculas inertes, esta tesis doctoral se centra en el desarrollo de nuevas técnicas para hacer uso del enlace de interelemento de silicio-heteroátomo para funcionalizar el enlace inerte C-O & C-H a través de catálisis de níquel o sistema sin transición de metal. Hemos desarrollado tres nuevos métodos para la funcionalización de enlaces inertes C-O y C-H mediante el uso de enlaces de interelemento basados ​​en silicio. Todas las transformaciones anteriores muestran un excelente perfil de quimioselectividad en condiciones suaves. Se realizan estudios y debates mecanicistas preliminares para comprender cómo y por qué se produjeron estas reacciones. Las transformaciones realizadas contribuyen a la comprensión del uso más prolífico de enlaces químicos inertes a los compuestos de valor agregado de síntesis.
Synthetic chemistry is almost unimaginable without three main group elements, namely, boron, silicon, and tin. When attached to a carbon atom of any hybridization, these functional groups serve as exceptionally versatile linchpins in synthesis, selectively transforming into an enormous breadth of C-C and C-X bonds, thus, discover new methods to forge value added C-Si, C-B and C-Sn bonds are always in highly demand. In line with the research interest in Martín’s group of activating inert bonds or molecules, this doctoral thesis focuses on the development of novel techniques to make use of silicon-heteroatom interelement linkage to functionalize inert C-O & C-H bond via either nickel catalysis or transition metal free system. We have developed three new methods towards the functionalization of inert C-O & C-H bonds by using silicon-based interelement linkages. All the above transformations display excellent chemoselectivity profile under mild conditions. Preliminary mechanistic studies and discusses are carried out to understand how and why these reactions proceeded. The transformations realized contribute to the understanding of more prolific use of inert chemical bonds to the synthesis value added compounds. We believe these protocols would definitely contribute to a systematic utilization of silicon-heteroatom reagent in the arena of inert chemical bond functionalization.

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

Thesis (Ph.D.)--University of Mississippi, 2008.
Typescript. Vita. Major professor: Dr. John M. Rimoldi "November 2008." Includes bibliographical references (leaves 114-136). Also available online via ProQuest to authorized users.

Les travaux rapportés dans ce mémoire concernent le développement de nouvelles réactions métallo-catalysées pour la création de liaison carbone-hétéroatome et carbone-carbone ainsi que leurs applications à la synthèse de produits biologiquement actifs. La première partie de ce manuscrit est consacrée à l'étude de la réactivité des sucres dans les couplages organométalliques. Des conditions ont été développées pour la création de la liaison C-S entre glycosyl thiols et partenaires arylés. De plus, la création de la liaison carbone azote de glycosyl amines avec des acides boroniques a été étudiée. Les produits synthétisés dans cette première partie ont été évalués pour leur potentiel d'inhibition de la Lectine A chez Pseudomonas aeruginosa, impliquée dans de sévères infections pulmonaires.La seconde partie de ce travail est dédiée à la création d'une série inédite d'analogues du 6BrCaQ, inhibiteurs de la Hsp90 ainsi que leur évaluation biologique. Cette nouvelle série est obtenue grâce à une nouvelle méthodologie de synthèse basée sur l'activation C-H entre un hétérocycle halogéné et son partenaire C-H activable. L'activité antiproliférative et l'inhibition de la Hsp90 ont été évaluées et seront présentées dans ce manuscrit
The work reported in this dissertation concerns the development of new metal-catalyzed reactions for the creation of carbon-heteroatom and carbon-carbon bonds as well as their applications to the synthesis of biologically active products.The first part of this manuscript is devoted to the study of the reactivity of sugars as nucleophiles in organometallic couplings. Conditions were developed for the creation of the C-S bond between glycosyl thiols and aryl partners. Moreover, the creation of the nitrogen carbon bond of glycosyl amine with boronic acids was studied. The products synthesized in this first part have been evaluated for their potential to inhibit the lectin A, in Pseudomonas aeruginosa related lung infections.The second part of this work is dedicated to the creation of a new series of 6BrCaQ analogues as Hsp90 inhibitors and their biological evaluation. This new series was synthetized through a new CH activation methodology. The antitumoral potential was evaluated and will be presented in this manuscript

Les ligands multidentes montrent généralement de très bonnes activités dans la catalyse organométallique au palladium à faibles charges. Parmi ces ligands, l'utilisation des ligands polyphosphines ferrocéniques mènent à des résultats intéressants. Des systèmes catalytiques palladium/triphosphine ferrocénique robustes ont permis d'obtenir d'une part des diarylamines et d'autre part des éthers d'aryle et d'hétéroaryle avec de faibles charges catalytiques. Des calculs théoriques de DFT sur le cycle catalytique lors de la formation d'éthers d'aryle et d'hétéroaryle ont été réalisés. La présence d'un troisième groupement phosphino permettrait de stabiliser les états de transition et accélèrerait l'élimination réductrice. Les triarylamines ont pu être obtenues à l'aide d'une diphosphine ferrocénique avec une charge de 2 mol% de palladium. Des résultats modérés à excellents ont été obtenus. Enfin, les thioéthers d'aryle et d'hétéroaryle ont été obtenus avec d'excellents résultats à l'aide d'une tétraphosphine ferrocénique en présence de 0,2 mol% de palladium

Les nanoparticules métalliques (MNPs) ont un grand succès dans les dernières décennies dû à la variété d'applications dans différents domaines (microélectronique, matériaux, catalyse). Mis à part les solvants organiques, les liquides ioniques, l'eau, le CO2 supercritique et les polyols, en particulier le glycérol, ont démontré leur capacité à stabiliser et immobiliser les nanoparticules métalliques. Ces milieux évitent l'agglomération des MNPs et facilitent leur recyclage. Des nanoparticules de Pd(0) et Ni(0) dans le glycérol, sphériques, petites en taille et bien dispersées, ont été synthétisées avec succès à partir d'une méthodologie simple sous pression d'hydrogène, en présence de différents stabilisants (alkaloïdes, phosphine, polymer). La caractérisation complète de ces matériaux en solution et à l'état solide, ainsi que la possibilité de faire des synthèses à grande échelle et de stocker les solutions catalytiques longtemps, montrent la grande stabilité de ces solutions colloïdales. Les nanoparticules dans le glycérol ont été impliquées dans une large variété de transformations : hydrogénations, hydrodéhalogénations, couplages de Hiyama, additions conjuguées et hydrosilylations. De plus, nous avons étudié l'effet du stabilisant sur la réactivité catalytique, nous permettant de contrôler l'état de surface des nanoparticules et moduler ainsi leur réactivité. Nous avons montré, de même, la capacité du glycérol pour immobiliser les catalyseurs, ce qui s'est traduit par la possibilité de recycler la phase catalytique entre 4 et 10 fois sans perte de metal. En parallèle, nous avons évalué le comportement du Ni(OAc)2 libre de ligands dans le glycérol, en tant que catalyseur alternatif pour des couplages C-C et C-hétéroélément. Nous présentons aussi une étude en flux continu, en collaboration avec la Maison Européenne des Procédés Innovants (MEPI), pour l'hydrogénation de différents groupes fonctionnels, en utilisant les PdNPs dans le glycérol synthétisées préalablement
Metal nanoparticles (MNPs) have been largely studied in the last decades due to their interesting properties which found applications in several fields (microelectronics, materials and catalysis, among others). In contrast to common organic solvents, ionic liquids, water, supercritical CO2, polyols such as glycerol, represent innovative solvents for the immobilization of MNPs, avoiding their agglomeration and facilitating their recycling. Small, spherical, and well-dispersed Pd(0) and Ni(0) nanoparticles were synthesized under hydrogen pressure in glycerol, in the presence of different kinds of stabilizers (cinchona-based alkaloids, phosphine, polymer). The high stability of these colloidal solutions permitted the full characterization both in solution and at solid state, large-scale synthesis, and stocking the solutions for months. These colloidal catalysts were applied in a large variety of transformations including hydrogenations, hydrodehalogenations, Hiyama C-C couplings, hydrosilylation reactions, and Michael conjugate additions. Furthermore, we conducted a comparative study exhibiting the differences in catalytic reactivity by effect of the stabilizer, allowing us tuning the surface-state of the nanoparticles. Moreover, we showed the ability of glycerol to immobilize metal nanoparticles permitting the recycle of the catalytic phase between 4 and 10 times, without metal leaching. Additionally, we studied the behavior of ligand-free Ni(OAc)2 in glycerol as an alternative catalyst for C-C and C-heteroatom couplings. Also, we developped a continuous flow study, in collaboration with the Maison Européenne des Procédés Innovants (MEPI), for the hydrogenation of different functional groups, using PdNPs in glycerol

Transition metals catalysis represents an important and versatile tool for the organic synthesis. Indeed its use is associated with several advantages in terms of reaction selectivity, and “atom economy”. In the last decade the growing utilization of transition metals catalysis has deeply influenced and modified the design of heterocyclic synthesis as testified by the wide amount of studies on the palladium-catalyzed cross-coupling reaction that in 2010 led Prof. Richard F. Heck (University of Delaware, USA), Prof. Ei-ichi Negishi (Purdue University, USA) and Prof. Akira Suzuki (Hokkaido University, Japan) to achieve the Nobel Prize for Chemistry. In this context, during my doctorate activity, we investigated the construction of heterocyclic rings and the production of derivatives of heterocyclic compounds of biological interest through palladium, copper and gold catalyzed reactions. As part of our studies on the palladium catalysis we developed several synthetic strategy for the construction of different classes of compounds such us functionalized 2,3-dihydrofurans, substituted 2,3-substituted quinolin-4-(1H)-ones, dibenzo[a,c]carbazoles, 2-amino ketones and aryl sulfones. Then, the economic attractiveness of copper-based methods and the growing interest in copper-catalyzed syntheses stimulated us to investigate some copper-catalyzed protocol. In this area we studied the oxidation reaction of the 1,2-diarylethanones and the cyclization reaction of the N-(2-bromoaryl)enaminones to obtain 2,4-diarylbenzo[b][1,4]oxazepines. Finally, using gold complexes we developed a new sinthetical approach to 2,4-diaryl-2,3- dihydro-1H-benzo[b][1,4]diazepines.

The thesis presents photocatalytic methods for synthesizing small organic molecules at room temperature. The thesis is divided into four sections. Section A presents the general introduction to the thesis. Section B is presented as a single chapter, which describes an intramolecular ipso-arylative cyclization of aryl alkynoate with tricarbonyl compounds under photocatalytic conditions via radical addition cascade cyclization (RACC). The methodology could be extended to the arylpropiolamides and arylthioates as well. Section C is presented in two Chapters, Chapters 3 and 4. Chapter 3 describes a visible light-mediated difunctionalization of activated alkynes to form coumarin and spirolactones. The coumarins and spirolactones could be formed selectively by tuning the substituent present in the aryl alkynoate. The spirolactones synthesized in this method can be transformed into complex spirocyclic structures under a separate visible light-mediated reaction. Chapter 4 describes a visible light-mediated radical addition cascade cyclization (RACC) between maleimides and phenethylboronic acids to access fused tetrahydro-1H-benzo[e]isoindole-1,3(2H)-diones. The last section is presented as Chapter 5, which deals with a photocatalytic approach to the direct acylation of electron-deficient heteroarenes. The methodology could be used to synthesize biologically active small molecules.

The thesis entitled “Copper-Catalyzed Novel Oxidative Transformations: Construction of Carbon-Hetero Bonds” is divided into two main sections. Section A deals with the utility of azide as a nitrogen source for C-N bond formation, which is further divided into 4 chapters, and section B presents decarboxylative radical coupling reaction for C-heteroatom bond formation which is further divided in to two chapters. Section A Chapter 1 describes an approach for the direct synthesis of nitrile from the corresponding alcohols using azide as a nitrogen source. Nitrile functionality is a versatile and ubiquitous which occurs in a variety of natural products. Nitrile functionality can be easily transformed into a variety of functional groups and products such as aldehydes, ketones, acids, amines, amides and nitrogen-containing heterocycles, such as tetrazoles and oxazoles. In this chapter a successful attempt for developing a novel methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been described. This strategy uses DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H2O. A few representative examples are highlighted in Scheme 1.1 Scheme 1. Oxidative conversion of alcohols to nitriles Second chapter represents a protocol for the synthesis of 1,5-disubstituted tetrazoles from the corresponding secondary alcohols. Among heterocyles, tetrazole and its derivatives are important class of nitrogen containing molecules. Due to their well-known biological activities as well as vast applications in pharmaceuticals and material science, they are potential targets for synthetic organic chemists. Therefore, a simple and user-friendly method for the synthesis of tetrazole is desirable. In this chapter, a mild and convenient method to synthesize 1,5-disubstituted tetrazoles using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 2).2 Scheme 2. Oxidative conversion of secondary alcohols to tetrazoles Third chapter presents a method for synthesizing amides from their corresponding secondary alcohols. Amide functionality is a crucial backbone in peptide chemistry, it also serve as an important precursor or intermediate for variety of organic transformations. In this contention, a mild and convenient method to synthesize amides using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 3).3 Scheme 3. Oxidative conversion of secondary alcohols to amides Additionally, the application of this methodology has also been revealed for the synthesis azides directly from their alcohols. Some of the representative examples are shown in the Scheme 4.3 Scheme 4. Direct conversion of alcohols to their azides. Fourth chapter describes highly chemoselective Schmidt reaction. The classical Schmidt reaction involves the formation of new carbon-nitrogen bonds in a reaction of a carbon-centred electrophile with hydrazoic acid followed by loss of nitrogen, which usually occurs via a rearrangement. It is well known that under the Schmidt reaction conditions, ketones and carboxylic acids are converted into their corresponding amides and amines respectively, whereas aldehydes furnish a mixture of formanilides and nitriles. In this chapter, Schmidt reaction of aldehydes to obtain their nitriles without formation of the corresponding formanilide is presented (Scheme 5).4 It was also observed that aromatic ketones and acids functionalities were intact under the reaction condition, unlike the conventional Schmidt reaction. Scheme 5. Highly chemoselective Schmidt reaction Section B It is divided into two chapters, describes a copper catalyzed decarboxylative radical coupling for the synthesis of vinyl sulfones and nitroolefins (Scheme 6). Scheme 6. General strategy for the second part First chapter narrates a strategy for synthesizing nitroolefins from the α,β-unsaturated carboxylic acids. Nitroolefins represent a unique class of nitro compounds, which have multifaceted utility in organic synthesis. They possess antibacterial, rodent-repelling, and antitumor activities. They serve as important intermediates in organic synthesis. Nitroolefins also react with a variety of nucleophiles, and their electron-deficient character renders them as a powerful dienophiles in Diels-Alder reactions. In our attempt to use the decarboxylative strategy, this chapter describes a method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their corresponding nitroolefins. This nitrodecarboxylation reaction is performed using catalytic amount of CuCl in the presence of air using TBN as a nitrating source (Scheme 7).5 Besides, the reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives which are generally difficult to access from other conventional methods. Scheme 7. Decarboxylative nitration Second chapter presents a new protocol for the synthesis of vinyl sulfones from the α,β-unsaturated carboxylic acid. Vinyl sulfones are versatile building blocks, which find their utility as Michael acceptors and used in cycloaddition reactions. This functional group has also been shown to potently inhibit a variety of enzymatic processes, and thus provides unique properties for drug design and medicinal chemistry. Vinyl sulfones are prominent in medicinal chemistry owing to their wide presence in pharmaceutically active molecules, such as enzyme inhibitors and biological activity. In this chapter, we report a method for the construction of C-S bonds via ligand promoted decarboxylative radical sulfonylation of ,-unsaturated carboxylic acids to synthesize vinyl sulfones using Cu catalysis (Scheme 8).6 This is the first report for this particular conversion. Scheme 8. Decarboxylative sulfonation

The thesis entitled “Copper-Catalyzed Novel Oxidative Transformations: Construction of Carbon-Hetero Bonds” is divided into two main sections. Section A deals with the utility of azide as a nitrogen source for C-N bond formation, which is further divided into 4 chapters, and section B presents decarboxylative radical coupling reaction for C-heteroatom bond formation which is further divided in to two chapters. Section A Chapter 1 describes an approach for the direct synthesis of nitrile from the corresponding alcohols using azide as a nitrogen source. Nitrile functionality is a versatile and ubiquitous which occurs in a variety of natural products. Nitrile functionality can be easily transformed into a variety of functional groups and products such as aldehydes, ketones, acids, amines, amides and nitrogen-containing heterocycles, such as tetrazoles and oxazoles. In this chapter a successful attempt for developing a novel methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been described. This strategy uses DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H2O. A few representative examples are highlighted in Scheme 1.1 Scheme 1. Oxidative conversion of alcohols to nitriles Second chapter represents a protocol for the synthesis of 1,5-disubstituted tetrazoles from the corresponding secondary alcohols. Among heterocyles, tetrazole and its derivatives are important class of nitrogen containing molecules. Due to their well-known biological activities as well as vast applications in pharmaceuticals and material science, they are potential targets for synthetic organic chemists. Therefore, a simple and user-friendly method for the synthesis of tetrazole is desirable. In this chapter, a mild and convenient method to synthesize 1,5-disubstituted tetrazoles using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 2).2 Scheme 2. Oxidative conversion of secondary alcohols to tetrazoles Third chapter presents a method for synthesizing amides from their corresponding secondary alcohols. Amide functionality is a crucial backbone in peptide chemistry, it also serve as an important precursor or intermediate for variety of organic transformations. In this contention, a mild and convenient method to synthesize amides using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 3).3 Scheme 3. Oxidative conversion of secondary alcohols to amides Additionally, the application of this methodology has also been revealed for the synthesis azides directly from their alcohols. Some of the representative examples are shown in the Scheme 4.3 Scheme 4. Direct conversion of alcohols to their azides. Fourth chapter describes highly chemoselective Schmidt reaction. The classical Schmidt reaction involves the formation of new carbon-nitrogen bonds in a reaction of a carbon-centred electrophile with hydrazoic acid followed by loss of nitrogen, which usually occurs via a rearrangement. It is well known that under the Schmidt reaction conditions, ketones and carboxylic acids are converted into their corresponding amides and amines respectively, whereas aldehydes furnish a mixture of formanilides and nitriles. In this chapter, Schmidt reaction of aldehydes to obtain their nitriles without formation of the corresponding formanilide is presented (Scheme 5).4 It was also observed that aromatic ketones and acids functionalities were intact under the reaction condition, unlike the conventional Schmidt reaction. Scheme 5. Highly chemoselective Schmidt reaction Section B It is divided into two chapters, describes a copper catalyzed decarboxylative radical coupling for the synthesis of vinyl sulfones and nitroolefins (Scheme 6). Scheme 6. General strategy for the second part First chapter narrates a strategy for synthesizing nitroolefins from the α,β-unsaturated carboxylic acids. Nitroolefins represent a unique class of nitro compounds, which have multifaceted utility in organic synthesis. They possess antibacterial, rodent-repelling, and antitumor activities. They serve as important intermediates in organic synthesis. Nitroolefins also react with a variety of nucleophiles, and their electron-deficient character renders them as a powerful dienophiles in Diels-Alder reactions. In our attempt to use the decarboxylative strategy, this chapter describes a method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their corresponding nitroolefins. This nitrodecarboxylation reaction is performed using catalytic amount of CuCl in the presence of air using TBN as a nitrating source (Scheme 7).5 Besides, the reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives which are generally difficult to access from other conventional methods. Scheme 7. Decarboxylative nitration Second chapter presents a new protocol for the synthesis of vinyl sulfones from the α,β-unsaturated carboxylic acid. Vinyl sulfones are versatile building blocks, which find their utility as Michael acceptors and used in cycloaddition reactions. This functional group has also been shown to potently inhibit a variety of enzymatic processes, and thus provides unique properties for drug design and medicinal chemistry. Vinyl sulfones are prominent in medicinal chemistry owing to their wide presence in pharmaceutically active molecules, such as enzyme inhibitors and biological activity. In this chapter, we report a method for the construction of C-S bonds via ligand promoted decarboxylative radical sulfonylation of ,-unsaturated carboxylic acids to synthesize vinyl sulfones using Cu catalysis (Scheme 8).6 This is the first report for this particular conversion. Scheme 8. Decarboxylative sulfonation