This thesis details the attempt to design and synthesis a range of ligands and organocatalysts based on a common backbone design. Initial results were promising with a number of ligands being generated from our common C2-symmetric backbone. Unfortunately none of the molecules synthesises gave promising results in test reactions. Variations on the initial design also failed to give any encouraging results. More positively, work on phosphorus-nitrogen (P,N) ligands was successful, with a number of different ligands being synthesised and metal complexes prepared. Pleasingly we were able to obtain X-ray crystallography of one of these complexes indicating that the ligand was complexed to the metal via the phosphorus moiety. Work using the Buchwald-Hartwig reaction for coupling aryl bromides to both 1,2,3,4-tetrahydroisoquinoline and 1,2,3,4-tetrahydroquinoline was successful, with methodology being developed which we believe can be applied to the synthesis of Ancistrocladinium A. In particular the coupling between 1,2,3,4-tetrahydroisoquinoline and 1-bromonaphthalene afforded us the full carbon skeleton of the ring system of the natural product in one step, from which we were able to generate the iminium salt. We also investigated an alternative route for the synthesis of Ancistrocladinium A achieving atropoisomerism. Experimental data is provided in chapter three, and all X-ray crystallography structures reported in chapter two are provided in the appendix.

For the preparation of semiconducting polymers often ‘standard’ catalytic systems are used without further optimisation. New ligands, such as N-heterocyclic carbenes have shown excellent activity in cross-coupling reactions (e.g. Suzuki-Miyaura reaction, or Hartwig-Buchwald amination). These systems show excellent conversions under mild conditions and even allow the use of aryl chlorides as reagents. Nevertheless, previously no system has been reported for the synthesis of conjugated polymers, e.g. the Suzuki polycondensation or Buchwald-Hartwig type polycondensation using these catalysts. A NHC-Pd based catalytic system was optimised for a polyamination reaction and the catalyst [(IPr)Pd(allyl)Cl] was found to be the most active. Polytriarylamines were synthesised using the optimised catalytic system and tested in organic field-effect transistors. Mobilities found were low which was found to be attributed to the presence of high molecular weight fractions. Molecular weights were controlled using an in situ end-capping approach and polymers tested in the semiconducting layer of OFETs gave similar mobilities tothose reported earlier. Several polytriarylamines, which have not been reported previously, were synthesised using NHC-chemistry and the in situ end-cappingapproach, as well as polytriarylamines that have been reported previously using Pd/phosphine catalysts. One library containing polymers based on biphenyles andbridged biphenyles and another library containing polymers with bridged oligoarenes were synthesised. Suzuki polycondensation was also studied besides the polyamination protocol and low catalyst loadings and reaction temperatures could be realised using a NHC-Pd catalyst. Sulfur containing monomers that could not be polymerised using the polyamination were polymerised successfully. All polymers were fully characterised and studied as the active layer in organic field-effect transistors. The highest mobilities determined for these polymers (~10-2 cm2/Vs) is close to the highest reported for this class of polymer reported to date.

Un intérêt grandissant pour le système thiéno[2,3-b] pyridine est apparu ces trois dernières décennies. De nombreux chercheurs ont présentés des composés basés sur ce système comme traitement possible de l'anxiété et de la dépression, comme bactéricide, contre l'inflammation et la leishmania, la malaria et les maladies auto-immunes. Les ortho-amino acyl thiophènes sont des produits de départ possible pour synthétiser ces motifs. L'accès à ce type de composés sera la première étape de ce travail. Nous décrivons ici la première synthèse de 3-acétyl-2-aminothiophènes en utilisant la réaction à 3 composants de Gewald. Ces composés montrent différents modes de cyclisation dans le cas de traitement avec le réactif de Vilsmeier-Haack. comparé au ortho aminoacétophénones, leurs analogues benzéniques. Ceci semble être du à la présence du noyau thiophénique. Cette réaction a permis l'accès à de nouveaux dérivés 4-chlorothiéno[2,3-b]pyridines. Ces derniers ont été couplés via la réaction de Buchwald-Hartwig catalysée par le palladium.à des anilines avec des rendements moyens à bons. D'autre part, les 4-chloro-3-formylthiéno[2,3-b]pyridines ont été préparés par réaction du réactif de Vilsmeier-Haack sur les acétamido thiophènes correspondants dans les conditions classiques. Ces dérivés ne sont pas accessibles sans la protection de l'amine et non plus à partir des dérivés chlorés en 4. La synthèse de 4-méthylthiéno[2,3-b]pyridines a pu être réalisée par réaction des 3-acétyl-2-aminothiophènes avec des cétones dans les conditions de Friedländer / Significant interest in the thieno[2,3-b]pyridine nucleus has arisen during the last three decades. Many researchers have reported the use of compounds based on this scaffold as a possible treatment of anxiety and depression, bacterial infection, inflammation, leishmaniasis, malaria and autoimmune diseases. Ortho-amino acyl thiophenes are possible starting material allowing to reach the thienopyridine structure. Access to these compounds was our first task for this thesis. We report here the first synthesis of 3-acetyl-2-aminothiophene by using the three-component Gewald reaction. These compounds exhibit a different mode of cyclisation in the reaction with Vilsmeier–Haack reagent than that reported for the reaction with o-aminoacetophenone, which could be ascribed to the influence of the thiophene nucleus. This simple, two-step reaction allows the construction of some novel 4-chlorothieno[2,3-b]pyridine derivatives from very simple building unit while which reacted further with aniline by palladium-catalysed C–N cross-coupling to give the coupled product in moderate to high yield. On other hand, 4-chloro-3-formylthieno[2,3-b]pyridine derivatives were synthesized by reaction between protected 3-acetyl-2-aminothiophenes and vilsmeier-Haack reagent under normal conditions. These products were not accessible neither without N-protection of the starting materials nor by reaction between the reagent and 4-chlorothieno [2,3-b]pyridine under any condition. Some derivatives of 4-methylthieno[2,3-b]pyridine were prepared by reaction between 3-acetyl-2-aminothiophene and some ketones under Friedländer condition

Les travaux rapportés dans ce mémoire concernent le développement de nouvelles réactions métallo-catalysées pour la création de liaison carbone-hétéroatomes ainsi que leurs applications à la synthèse d’inhibiteurs de la protéine de choc thermique 90.Au cours de ce travail, l’étude de la réactivité d’hétérocycles de type quinoxalinones et N-aminoazoles vis-à-vis du couplage de Buchwald-Hartwig a été réalisée. Des conditions ont ainsi pu être développées pour créer la liaison carbone-azote entre des 3-chloroquinoxalinones et des partenaires nucléophiles azotés (amides, azoles…) afin de construire une bibliothèque d’analogues du 6BrCaQ en série quinoxalinone. Par ailleurs, la création de la liaison carbone-azote de motifs N-aminoazoles avec des partenaires hétérocycliques halogénés (coumarines, quinoléines…) ou aromatiques halogénés a été étudiée. Celle-ci a permis l’accès à une chimiothèque d’analogues du 6BrCaQ ainsi que le développement du couplage permettant la mono- ou di-substitutions des motifs N-aminoazoles.Dans le dernier chapitre de ce manuscrit, la création de la liaison carbone-soufre en série glycosidique métallo-catalysés (Pd et Ni) entre des thioglycosides et divers aglycones électrophiles (halogénures (hétéro)aromatiques, vinyliques et acétyleniques) a été examiné. Tous les composés obtenus lors de ce travail sont en cours d’évaluation biologique. / The development of new metal-catalyzed reactions to form carbon-heteroatom bonds have been studied in order to access to hsp90 inhibitors. For this purpose, reactivity of various 3-chloroquinoxalinone have been explored towards Pd-catalyzed Buchwald-Hartwig reaction with nitrogen nucleophiles (amides, azoles…) which allow access to a serie of 6BrCaQ analogues. In the same objective, the reactivity of N-aminoazole moieties in a Buchwald-Hartwig cross-coupling reaction has been also performed. This methodology led to the synthesis of new 6BrCaQ analogues. Moreover, conditions have been defined to access mono- or di-arylated N-aminoazoles structures starting from aryl chlorides. Finally, reactivity studies on metal-catalyzed carbon-sulfur bond forming reaction between thioglycosides as new nucleophiles partners with various aglycon halides ((hetero)aromatics, alkenyls and alkynyls halides) have been performed. Thanks to a nickel- or a palladium-catalysis, we have been able to introduce these thiosugars on various electrophiles partners and complex molecules. Thioglycosylated 6BrCaQ has been thus obtained.Biological evaluations of new synthesized compounds are currently in progress.

Nesta tese são apresentados, em dois capítulos, os resultados da reatividade química de quinoxalinas e os estudos visando à síntese de quinona natural, a vegfrecina. Modificações específicas em estruturas privilegiadas, padrões estruturais relevantes para bioatividade, representam uma alternativa viável na busca de novos ligantes para alvos macromoleculares. Neste cenário, as quinoxalinas apresentam destacada importância no âmbito da química medicinal, sendo assim é de grande importância o desenvolvimento de metodologias de funcionalização que conduzam a diversidade molecular deste núcleo. Neste contexto, foram realizadas reações de ativação C - H, como uma estratégia para a síntese de derivados vinil quinoxalinicos, com base na abordagem de Fujiwara-Moritani. Os resultados obtidos com este estudo indicaram que a densidade eletrônica das olefinas utilizadas neste estudo foi determinante para o rendimento reacional. Assim, as reações envolvendo olefinas ricas em elétrons, resultaram em maior rendimento do produto alquenilado, alcançando 89%. A deoxidação ocorreu em rendimentos de 43 - 54%, levando a ampliação da coleção de compostos desenvolvidos neste projeto. Os compostos aqui desenvolvidos foram testados quanto à atividade antimicobacteriana, entretanto, nenhum deles apresentou resultados promissores. O segundo capítulo desta tese abordou a síntese da Vegfrecina, que possui seletividade de inibição dos receptores do fator de crescimento endotelial vascular (VEGFR), bloqueando a ativação de VEGFR-1 e VEGFR-2 e, consequentemente, interferindo na vascularização, proliferação e metástase tumoral. Nossa estratégia utilizou o intermediário chave 6-Bromo-5,8-dimetoxi-2,2-dimetil-2,3-dihidroquinazolin-4(1H)-ona em reações de aminação de Buchwald Hartwig com três anilinas diferentes. Embora tenhamos obtido três intermediários sintéticos inéditos, em bons rendimentos, a etapa de oxidação não foi promissora, impossibilitando a obtenção da Vegfrecina e de seus análogos. / The study of chemistry reactivity of quinoxalines and the study aiming total syntheses of natural quinone, vegfrecine, are shown in this thesis in two chapters. The specific modifications privileged scaffold represents a promising way following for new macromolecular ligands targets. Considering the great importance of quinoxaline core in medicinal chemistry, the development of efficient methodologies in orther to obtain molecular diversity have attracted large attention. In this context, using Fujiwara-Moritani approach the C-H activation reactions were performed as good strategy in synthesis of vinyl- quinoxaline derivatives. Our results indicated the importance of olefin electron density in the reaction yields. In this way, reactions involving high electron density olefines, results in the high alkenilated products, achieving 89% of yield. The deoxygenation process occurred in yields of 43 until 54. The compounds obtained were tested against Mycobacterium tuberculosis, however no primissing results were observed. The second chapter in this thesis show our attempt to total synthesis of Vegfrecine, that have inhibitory activity of vascular endothelial growth factor receptor (VEGFR), Our strategy used the 6-bromo-5,8-dimethoxy-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-one in Buchwald Hartwig reaction with three different olefins. Although these new synthetic intermediates were obtained with good yield, the last step of oxidation didn\'t work. Therefore, it was not possible to obtain the Vegfrecine and its analogous.

Compostos heterociclos estão muito presentes em nossas vidas, desde processos biológicos até em fármacos. Dentre esses compostos, os carbazóis, vem ultimamente se mostrando promissores como alternativa terapêutica para diversas doenças, principalmente para o câncer. Muitos carbazóis são produtos naturais, como é o caso das Claurailas A-D. Baseando-se na estrutura da Clauraila A, esse trabalho propôs o desenvolvimento de uma biblioteca de análogos desse alcaloide a fim de prospecção biológica. Para a síntese da Clauraila A foram estudadas condições ideais da ciclodeidrogenação da diarilamina precursora desse alcaloide, através da reação de Åkermark-Knölker. Para a obtenção dessa diarilamina, foi realizado uma otimização da reação de aminação de Buchwald-Hartwig. Com o processo otimizado, foram obtidos diversos carbazóis, com diferentes padrões de substituição, em rendimentos bons à moderados, entre eles estão os produtos naturais 6-metoximurraianine e Clausenal. O rendimento global obtido na síntese desses produtos naturais e da Clauraila A são semelhantes aos previamente descritos na literatura, no entanto, em nosso trabalho foi realizada a síntese deste alcaloide em número reduzido de etapas. Durante o processo de otimização da reação de Åkermark-Knölker foi demonstrado, pela primeira vez, o uso de acetilacetonato de paládio como fonte de paládio II alternativa ao acetato de paládio. Além disso, com esses resultados foi possível inferir o possível mecanismo dessa reação. Adicionalmente, após tentativas por diversas alternativas sintéticas, foram obtidos compostos dimetilcromenos a partir de aminofenóis utilizando prenal e ácido fenilborônico, que podem ser úteis na síntese de outros carbazóis, como a Clauraila B. / Heterocyclic molecules are very important class of compounds in biological processes and drugs designing. Among all of them, carbazoles show great applicability for treatment of several diseases, especially against cancer. Many carbazoles are natural products, and one of our interests is Clauraila A. This work is based on the Clauraila A structure to development of a library of carbazoles for biological applications. The optimal conditions of the Åkermark-Knölker cyclodehydrogenation of diarylamine was studied to obtaind the carbazole core. The diarylamines were obtained by the optimized Buchwald-Hartwig amination reaction. This synthetic strategy was used to obtain the range of carbazoles, with different substituents in good and moderate yields, including natural products 6-methoxymurrayanine and Clausenal. The overall yield obtained in the synthesis of the natural products were similar to those previously described in the literature, however, unlike the literature our synthesis involved a reduced number of steps to obtain the desired product. In the optimization step of Åkermark-Knölker reaction, we first applied palladium (II) acetylacetonate instead of palladium (II) acetate. Moreover, with the achieved results the possible mechanism of this reaction was proposed. Additionally, after several attempts, dimethylchromenos were obtained from aminophenols using prenal and phenylboronic acid, which will be useful in the synthesis of other carbazoles, such as Clauraila B.

Compostos heterociclos estão muito presentes em nossas vidas, desde processos biológicos até em fármacos. Dentre esses compostos, os carbazóis, vem ultimamente se mostrando promissores como alternativa terapêutica para diversas doenças, principalmente para o câncer. Muitos carbazóis são produtos naturais, como é o caso das Claurailas A-D. Baseando-se na estrutura da Clauraila A, esse trabalho propôs o desenvolvimento de uma biblioteca de análogos desse alcaloide a fim de prospecção biológica. Para a síntese da Clauraila A foram estudadas condições ideais da ciclodeidrogenação da diarilamina precursora desse alcaloide, através da reação de Åkermark-Knölker. Para a obtenção dessa diarilamina, foi realizado uma otimização da reação de aminação de Buchwald-Hartwig. Com o processo otimizado, foram obtidos diversos carbazóis, com diferentes padrões de substituição, em rendimentos bons à moderados, entre eles estão os produtos naturais 6-metoximurraianine e Clausenal. O rendimento global obtido na síntese desses produtos naturais e da Clauraila A são semelhantes aos previamente descritos na literatura, no entanto, em nosso trabalho foi realizada a síntese deste alcaloide em número reduzido de etapas. Durante o processo de otimização da reação de Åkermark-Knölker foi demonstrado, pela primeira vez, o uso de acetilacetonato de paládio como fonte de paládio II alternativa ao acetato de paládio. Além disso, com esses resultados foi possível inferir o possível mecanismo dessa reação. Adicionalmente, após tentativas por diversas alternativas sintéticas, foram obtidos compostos dimetilcromenos a partir de aminofenóis utilizando prenal e ácido fenilborônico, que podem ser úteis na síntese de outros carbazóis, como a Clauraila B. / Heterocyclic molecules are very important class of compounds in biological processes and drugs designing. Among all of them, carbazoles show great applicability for treatment of several diseases, especially against cancer. Many carbazoles are natural products, and one of our interests is Clauraila A. This work is based on the Clauraila A structure to development of a library of carbazoles for biological applications. The optimal conditions of the Åkermark-Knölker cyclodehydrogenation of diarylamine was studied to obtaind the carbazole core. The diarylamines were obtained by the optimized Buchwald-Hartwig amination reaction. This synthetic strategy was used to obtain the range of carbazoles, with different substituents in good and moderate yields, including natural products 6-methoxymurrayanine and Clausenal. The overall yield obtained in the synthesis of the natural products were similar to those previously described in the literature, however, unlike the literature our synthesis involved a reduced number of steps to obtain the desired product. In the optimization step of Åkermark-Knölker reaction, we first applied palladium (II) acetylacetonate instead of palladium (II) acetate. Moreover, with the achieved results the possible mechanism of this reaction was proposed. Additionally, after several attempts, dimethylchromenos were obtained from aminophenols using prenal and phenylboronic acid, which will be useful in the synthesis of other carbazoles, such as Clauraila B.

Nesta tese são apresentados, em dois capítulos, os resultados da reatividade química de quinoxalinas e os estudos visando à síntese de quinona natural, a vegfrecina. Modificações específicas em estruturas privilegiadas, padrões estruturais relevantes para bioatividade, representam uma alternativa viável na busca de novos ligantes para alvos macromoleculares. Neste cenário, as quinoxalinas apresentam destacada importância no âmbito da química medicinal, sendo assim é de grande importância o desenvolvimento de metodologias de funcionalização que conduzam a diversidade molecular deste núcleo. Neste contexto, foram realizadas reações de ativação C - H, como uma estratégia para a síntese de derivados vinil quinoxalinicos, com base na abordagem de Fujiwara-Moritani. Os resultados obtidos com este estudo indicaram que a densidade eletrônica das olefinas utilizadas neste estudo foi determinante para o rendimento reacional. Assim, as reações envolvendo olefinas ricas em elétrons, resultaram em maior rendimento do produto alquenilado, alcançando 89%. A deoxidação ocorreu em rendimentos de 43 - 54%, levando a ampliação da coleção de compostos desenvolvidos neste projeto. Os compostos aqui desenvolvidos foram testados quanto à atividade antimicobacteriana, entretanto, nenhum deles apresentou resultados promissores. O segundo capítulo desta tese abordou a síntese da Vegfrecina, que possui seletividade de inibição dos receptores do fator de crescimento endotelial vascular (VEGFR), bloqueando a ativação de VEGFR-1 e VEGFR-2 e, consequentemente, interferindo na vascularização, proliferação e metástase tumoral. Nossa estratégia utilizou o intermediário chave 6-Bromo-5,8-dimetoxi-2,2-dimetil-2,3-dihidroquinazolin-4(1H)-ona em reações de aminação de Buchwald Hartwig com três anilinas diferentes. Embora tenhamos obtido três intermediários sintéticos inéditos, em bons rendimentos, a etapa de oxidação não foi promissora, impossibilitando a obtenção da Vegfrecina e de seus análogos. / The study of chemistry reactivity of quinoxalines and the study aiming total syntheses of natural quinone, vegfrecine, are shown in this thesis in two chapters. The specific modifications privileged scaffold represents a promising way following for new macromolecular ligands targets. Considering the great importance of quinoxaline core in medicinal chemistry, the development of efficient methodologies in orther to obtain molecular diversity have attracted large attention. In this context, using Fujiwara-Moritani approach the C-H activation reactions were performed as good strategy in synthesis of vinyl- quinoxaline derivatives. Our results indicated the importance of olefin electron density in the reaction yields. In this way, reactions involving high electron density olefines, results in the high alkenilated products, achieving 89% of yield. The deoxygenation process occurred in yields of 43 until 54. The compounds obtained were tested against Mycobacterium tuberculosis, however no primissing results were observed. The second chapter in this thesis show our attempt to total synthesis of Vegfrecine, that have inhibitory activity of vascular endothelial growth factor receptor (VEGFR), Our strategy used the 6-bromo-5,8-dimethoxy-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-one in Buchwald Hartwig reaction with three different olefins. Although these new synthetic intermediates were obtained with good yield, the last step of oxidation didn\'t work. Therefore, it was not possible to obtain the Vegfrecine and its analogous.

Résumé: Le travail rapporté dans cette thèse concerne le développement de nouvelles réactions organométalliques pour la création de liaisons C-S dans des systèmes complexes.Dans Le premier chapitre, nous rapportons une méthode originale de bioconjugation de peptides et protéines dans l'eau à température ambiante. La méthode a été appliquée avec succès à la bioconjugation de l'anticorp Trastuzumab.Le deuxième chapitre est consacré à l'étude de la réactivité des alpha ou béta thiosucres dans le couplage de Buchwald-Hartwig-Mitiga avec différent partenaires électrophiles.Dans un premier sous chapitre, nous rapportons une réaction inattendue de couplage de thiosucres avec le précatalyseur G3-Xanthphos pour conduire à de 2-aminobiphenyl glycosides bifonctionnels. La reaction a lieu à température ambiante et dans l'eau et produit des atropidiastéréomères stables.Dans une seconde partie de ce travail, nous décrivons une méthode originale d'accès à benzothiapinones et benzoxathiapinones glycosylées.Cette méthode fait intervenir un couplage de thiosucres avec des aryls iodés ayant un ester en ortho, suivi d'une lactonisation (ou lactimisation) pour conduire aux produits cyclisés.L'avant dernière partie de ce travail, concerne la synthèse de polysaccharides via une réaction de couplage de 2-iodo glycals avec des thiosucres de configuration définie.Ce travail se termine par l'application de couplage de thiosucres à la synthèse de Carbènes N-Hétérocycliques thioglycosylés (NHCs) hydrosolubles. / Abstract: The work reported in this thesis concerns the development of new organometallic reactions for the creation of C-S bonds in complex systems.In the first chapter, we report an original method of bioconjugation of peptides and proteins in water at room temperature. The method has been successfully applied to the bioconjugation of the antibody Trastuzumab.The second chapter is devoted to the study of the reactivity of alpha or beta-thiosugars in the Buchwald-Hartwig-Mitiga coupling with different electrophilic partners.In a first sub-chapter, we report an unexpected reaction of thiosugar coupling with the G3-Xanthphos precatalyst to yield bifunctional 2-aminobiphenyl glycosides. The reaction takes place at room temperature and in water and produces stable atropidiastereomers.In a second part of this work, we describe an original method of access to glycosylated benzothiapinones (and benzoxathiapinones).This method involves thiosugar coupling with iodinated aryls having an ortho ester, followed by lactonization (or lactimization) to yield cyclized products.The last part of this work concerns the synthesis of polysaccharides via a coupling reaction of 2-iodo glycals with thiosugars of defined configuration.This work ends with the application of thiosugar coupling to the synthesis of water-soluble thioglycosylated N-Heterocyclic Carbenes (NHCs) .

[pt] Neste trabalho foi desenvolvida a síntese de novos análogos do tipo N-tosil-aza-carbapterocarpanos com potencial ação antiproliferativa em linhagens de leucemia e mama.Os compostos aza-carbapterocarpanos e espiro-iso-indolinas, foram preparados através de abordagens sintéticas distintas e classificadas em Grupo I e II respectivamente. A etapa chave para obtenção dos compostos do grupo I foi a reação de aza-arilação do tipo Heck catalisada por paládio a partir de tetralonas comerciais e N-tosil-iodoanilinas substituídas previamente sintetizadas. Três moléculas deste grupo foram avaliadas quanto a sua ação antiproliferativa em linhagens de leucemia e mama. Dentre estas, o composto N-tosil-aza-carbaptercarpeno apresentou IC50 = 1,93 (mais ou menos) 0,88 micrômetros, 2,18 (mais ou menos) 1,47 micrômetros e 2.89 (mais ou menos) 0,92 micrômetros nas linhagens de leucemia K562, lucena-1 e FEPS, respectivamente, e na linhagem de mama MDA-MB-231 IC50=33.37 (mais ou menos) 3.98 micrômetros. Por outro lado, o composto aza-carbapterocarpeno foi inativo nestas mesmas linhagens, indicando que na ausência do grupo arilsulfonamida a ação antileucêmica não ocorre. Os compostos do grupo II, denominados espiro iso-indolinas, foram sintetizados através da adição diastereosseletiva de organomagnesío às N-terc-butano-sulfiniliminas quirais, seguida de uma aminação de Buchwald-Hartwig intramolecular catalisada por paládio. As N-terc-butano-sulfiniliminas foram obtidas através de tetralonas, cromanonas e tiocromanonas comerciais em uma reação de condensação com as N-tert-butanosulfinamidas comerciais em micro-ondas em uma abordagem livre de solvente utilizando tetraetóxido de titânio. Após as reações de adição nucleofílica com organomagnésio, remoção do auxiliar quiral e ciclização intramolecular, os compostos forma obtidos enantiomericamente puros e foram avaliados em linhagens de leucemia K562 e FESP. Embora estes compostos tenham apresentado baixa potência frente às linhagens testadas (IC50 entre 31,85 mais ou menos 3.0 micrômetros e 77,58 (mais ou menos) 5.76 micrômetros), pôde-se observar que há diferenças relevantes entre os enantiômeros, assim o como apresentam sensibilidade colateral, atuando em linhagens multiresitentes. / [en] In this work, the synthesis of new N-tosyl aza-carbapterocarpane analogues with potential antiproliferative action in leukemia and breast cell lines was developed. The aza-carbapterocarpanes and spiro-isoindolines compounds were prepared using different synthetic approaches and classified in Group I and II respectively. The key step for obtaining group I compounds was the palladium catalyzed Heck-type azaarylation reaction from commercially synthesized substituted tetralones and substituted N-tosyl iodoanilines. Three compounds of this group were evaluated for their antiproliferative action in leukemia cell lines and breast cancer cells lines. The compound N-tosyl-aza-carbaptercarpene presented IC50 = 1,93 0,88 , 2,18 (plus or minus) 1,47 micrometers e 2.89 (plus or minus) 0,92 micrometers. On the other hand, the aza-carbapterocarpene compound was inactive in these same lines, suggesting the role of the absence of the arylsulfonamide group for the antileukemic activity does not occur .The group II, denominated spiroisoindolines, were synthesized by diastereoselective addition of organomagnesium to chiral N-tert-butane sulfinylimines, followed by a palladium catalyzed intramolecular Buchwald-Hartwig amination. The N-tert-butane sulfinylimines were obtained through commercial tetralones, chromanones and thiochromanones by the condensation reaction with commercial N-tert-butanesulfinamides in a solvent free sistem using titanium tetraethoxide. After nucleophilic addition reactions with organomagnesium, chiral auxiliary removal and intramolecular cyclization, the compounds were obtained enantiomerically pure and were evaluated in K562 and FESP leukemia lines. Although these compounds presented low potency compared to the tested lines (IC50 between 31.85 (plus or minus) 3.0 micrometers and 77.58 (plus or minus) 5.76 micrometers), it was observed that there of them present relevant differences between enantiomers as soon as collateral sensitivity, acting in leukemia multiresistent cell lines.