The regioselectivity in Pd(0)-catalyzed direct arylation of pyrrole, thiophene, and indole can be improved by blocking some of the reactive sites with a chloride group, leading to increased yields of the desired regioisomers. Competition experiments and computational studies show that the blocking group also activates the substrates toward arylation. Due to the activated nature of chlorinated heteroaromatics, rare and sought after regioisomers, such as 3-arylthiophenes, can be obtained under mild conditions in good yields. Chlorine-bearing thiophenes arylated at C3 and C4 have the potential to undergo controlled regioregular polymerization under conditions developed in the field of polythiophene chemistry. Mechanistic studies support the hypothesis that the arylation of the substrates under investigation likely proceeds via the CMD transition state.

The regioselectivity in Pd(0)-catalyzed direct arylation of pyrrole, thiophene, and indole can be improved by blocking some of the reactive sites with a chloride group, leading to increased yields of the desired regioisomers. Competition experiments and computational studies show that the blocking group also activates the substrates toward arylation. Due to the activated nature of chlorinated heteroaromatics, rare and sought after regioisomers, such as 3-arylthiophenes, can be obtained under mild conditions in good yields. Chlorine-bearing thiophenes arylated at C3 and C4 have the potential to undergo controlled regioregular polymerization under conditions developed in the field of polythiophene chemistry. Mechanistic studies support the hypothesis that the arylation of the substrates under investigation likely proceeds via the CMD transition state.

Design and Synthesis of New Polyaromatic Scaffolds for Nano-Scale ApplicationsResumen: En la última década, el diseño y la síntesis de nuevos sistemas poliaromáticos han resultado de gran interés gracias a sus propiedades únicas y sus aplicaciones potenciales para la obtención de dispositivos electrónicos, y como precursores de fullerenos. Hemos estudiado el mecanismo que procede a través de la activación del enlace C-H en la reacción intramolecular de arilación directa catalizada por paladio, para la formación de sistemas biarílicos, demostrando que la reacción procede a través de la abstracción del protón asistido por la base. Aplicando condiciones optimizadas hemos preparado la molécula C60H24 que al ser irradiada da lugar a la formación del fullereno C60, mediante la reacción de arilación directa formando seis nuevos enlaces C-C en una única etapa. Además, en una colaboración interdisciplinar con físicos teóricos y experimentales, en el proyecto PicoInside, hemos participado en el diseño y la síntesis de moléculas poliaromáticas para su posterior aplicación como dispositivos electrónicos moleculares.Abstract:In the last decade, the design and synthesis of new polyaromatic scaffolds have attracted a broad interest due to their exceptional properties and their potential applications in material science like molecular electronic devices and as precursors of fullerene.Based in the intramolecular palladium-catalyzed direct arylation reaction we developed new procedures as reliable tools for the biaryl coupling through C-H activation. Insight mechanistic studies showed a proton abstraction mechanism assisted by the base rather than activation of aromatic systems towards electrophilic attack. Applying optimized reaction conditions, formation up to six C-C bonds, and in situ dehydrogenation, allows for the synthesis of C60H24, crushed fullerene in one single step that upon laser irradiation leads to C60 fullerene. Moreover, in an interdisciplinary collaboration with theoretical and experimental physicist, PicoInside project, we have participated in the design and synthesis of Y-shaped polyaromatic molecules required for single molecule electronic devices.

The regioselectivity in Pd(0)-catalyzed direct arylation of pyrrole, thiophene, and indole can be improved by blocking some of the reactive sites with a chloride group, leading to increased yields of the desired regioisomers. Competition experiments and computational studies show that the blocking group also activates the substrates toward arylation. Due to the activated nature of chlorinated heteroaromatics, rare and sought after regioisomers, such as 3-arylthiophenes, can be obtained under mild conditions in good yields. Chlorine-bearing thiophenes arylated at C3 and C4 have the potential to undergo controlled regioregular polymerization under conditions developed in the field of polythiophene chemistry. Mechanistic studies support the hypothesis that the arylation of the substrates under investigation likely proceeds via the CMD transition state.

The regioselectivity in Pd(0)-catalyzed direct arylation of pyrrole, thiophene, and indole can be improved by blocking some of the reactive sites with a chloride group, leading to increased yields of the desired regioisomers. Competition experiments and computational studies show that the blocking group also activates the substrates toward arylation. Due to the activated nature of chlorinated heteroaromatics, rare and sought after regioisomers, such as 3-arylthiophenes, can be obtained under mild conditions in good yields. Chlorine-bearing thiophenes arylated at C3 and C4 have the potential to undergo controlled regioregular polymerization under conditions developed in the field of polythiophene chemistry. Mechanistic studies support the hypothesis that the arylation of the substrates under investigation likely proceeds via the CMD transition state.

This thesis is divided into two parts. In the first part there is reported palladium- catalysed regioselective direct arylation of benzofurans with arylsulfonyl chlorides as the coupling partner to C2 carbon. The best reaction conditions of this reaction were investigated, then the influence of various arylsulfonyl chloride substituents to the reaction and finally it is reported direct arylation of C2-arylated benzofuran to C3 carbon to give diarylated benzofuran with different aryl substituents. In the second part, there is reported the synthesis of 2-(hydroxymethyl)-5,7-bis{5- [(2,2':6',2''-terpyridine)-4'-yl]thiophen-2-yl}-2,3-dihydrothieno[3,4-b][1,4]dioxin and modification of its sidechain. As a starting material of the synthesis it was used commercially available 4'-bromo-(2,2':6',2''-terpyridine). The synthetic sub-steps included Suzuki cross- coupling, bromination and C-H bond activation. Then it was also reported the complexation of synthesized oligomer with zinc and iron cations.

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C-H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metallation-deprotonation (CMD) pathway. Competition experiments were conducted using N-oxides of varying electronic characters, and results revealed an enhancement of rate when using a more electron-deficient species which is in support of a CMD transition state. The effect of base on reaction rate was also examined and it was found that a carboxylate base was required for the reaction to proceed. This led to the conclusion that Pd(OAc)2 plays a pivotal role in the reaction mechanism as more than merely a pre-catalyst, but as a source of acetate base required for the C-H bond cleavage step.

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C-H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metallation-deprotonation (CMD) pathway. Competition experiments were conducted using N-oxides of varying electronic characters, and results revealed an enhancement of rate when using a more electron-deficient species which is in support of a CMD transition state. The effect of base on reaction rate was also examined and it was found that a carboxylate base was required for the reaction to proceed. This led to the conclusion that Pd(OAc)2 plays a pivotal role in the reaction mechanism as more than merely a pre-catalyst, but as a source of acetate base required for the C-H bond cleavage step.

Trichloroethylene, a simple and very inexpensive material, has been identified as a tri- and tetrafunctionalizable building block. A combination of selective palladium-catalyzed cross-coupling reactions with standard lithiation and electrophilic quenching yields a wide variety of unsaturated linear or cyclic compounds in excellent yields in few synthetic steps. Dichlorovinyl ethers, obtained from a nucleophilic displacement reaction with trichloroethylene, are the basic starting materials. Two sets of conditions have been developed to achieve the reaction of either electron-rich or –deficient phenols with trichloroethylene to give the resultant dichlorovinyl ethers in high yields. Site selective palladium-catalyzed cross-coupling for the specific functionalization of a single C-Cl bond was developed, and could install alkyl, alkenyl, alkynyl and (hetero)aryl moieties. The resulting electrophiles could be reacted with a second organometallic nucleophile forming trisubstituted, electron-rich alkenes, dienes, trienes or enynes in only two or three steps. Alternatively, the product from the first cross-coupling reaction could be isolated, deprotonated and quenched with an electrophile, then cross-coupled with a second organometallic nucleophile to give tetrasubstituted, electron-rich alkenes and dienes. In the course of studying the site selective cross-coupling, it was found that prolonged exposure of the C1-functionalized materials to palladium promoted an intramolecular C-H activation, forming 2-substituted benzofurans. This reaction proved to be very general, and a wide variety of benzofurans were synthesized, containing both electron-withdrawing and electron-donating group groups in the donor arenes, as well as alkyl, alkenyl, alkynyl and aryl functionalities at the 2-position. This method was also extended to the synthesis of 2-substituted indoles from anilines, trichloroethylene and boronic acids.

Detailed mechanistic studies on the palladium-catalyzed direct arylation of pyridine N-oxides are presented. The order of each reaction component is determined to provide a general mechanistic picture. The C-H bond cleaving step is examined in further detail through computational studies, and the calculated results are in support of an inner-sphere concerted metallation-deprotonation (CMD) pathway. Competition experiments were conducted using N-oxides of varying electronic characters, and results revealed an enhancement of rate when using a more electron-deficient species which is in support of a CMD transition state. The effect of base on reaction rate was also examined and it was found that a carboxylate base was required for the reaction to proceed. This led to the conclusion that Pd(OAc)2 plays a pivotal role in the reaction mechanism as more than merely a pre-catalyst, but as a source of acetate base required for the C-H bond cleavage step.