AGrâce à sa forte carbophilie, l’or est devenu en quelques années un métal de choix pour la formation de liaisons C-C et C-X (X = O, N, S). Par ailleurs, sa capacité à activer des hétéroatomes (acidité σ-Lewis) a été reconnue également et justifiée par de nombreux exemples de transformations de substrats carbonyles, imines, alcools π-activés et époxydes. Dans le contexte de la recherche de méthodes économiques et respectueuses de l'environnement dans le domaine de la chimie des ions N-acyliminiums, nous nous sommes intéressés à la capacité de l’or à promouvoir la formation des ions N-acyliminiums. Dans une première partie de ce travail, nous avons montré que l'acidité de type σ-Lewis de sels cationiques d’or (I) et (III) pouvait être exploitée pour catalyser efficacement la substitution nucléophile de divers alcoxy-et acétoxylactames, précurseurs d’ions N-acyliminiums. La réaction est compatible avec une large gamme de nucléophiles, incluant notamment l'allyltriméthylsilane, les éthers d'énols silylés, les arènes et les dérivés de méthylènes actifs. Dans un second temps, les deux caractères carbophile et oxophile des catalyseurs à l’or ont été combinés dans un processus cascade α-amidoalkylation/hydroarylation. Une seconde approche multicatalytique (acide de Brønsted – acide de Lewis) a ensuite été développée comme alternative pour pallier à certaines limites du système « tout or ». Ces séquences réactionnelles one-pot permettent d’accéder de façon rapide et efficace à un large panel de composés polycycliques fusionnés à partir de matières triviales. / AGold catalysts, as soft carbophilic Lewis acids, have rapidly develop and mature to become nowadays an outstanding tool for new C-C and C-X bonds (X = O, S, N) through π-bond activation. Moreover, its σ-Lewis acidity was also acknowledged and exemplified by numerous examples of carbonyl, imine, π-activated alcohol and epoxide activation. As part of our ongoing studies on N-acyliminium ion chemistry, we have been interested in using gold catalysts for N-acyliminium ion generation. First, we have shown that the σ-Lewis acidity of gold(I) and gold(III) could be exploited to efficiently catalyze the nucleophilic substitution reactions of various alkoxy- and acetoxylactams, precursors of N-acyliminium ions. The reaction was found to tolerate a wide range of nucleophiles, including allyltrimethylsilane, silyl enol ethers, arenes as well as active methylene derivatives. Next, gold catalysis was applied to cascade α-amidoalkylation/hydroarylation sequences unifying both the σ- and π-Lewis acid properties of gold complexes. Alternatively, Brønsted acid/Lewis acid multicatalysis approach has been alternatively developed to override some limitations featuring this unprecedented tandem intermolecular Friedel–Crafts/intramolecular hydroarylation sequence. This two complementary and highly efficient cascade sequences enable expedient access to complex fused polycyclic structures from trivial materials.

Syringolin A, a plant elicitor, was isolated in 1998 and has been identified as a potential anti-cancer compound based on its activity against proteasome. The unique structure of this natural product consists of a 12-membered diamide ring, formed by two non-proteinogenic amino acids 3,4-dehydrolysine and 5-methyl-4-amino-2-hexenoic acid, and a bis(valinyl)urea side chain which is connected to the macrocycle by a peptide bond. The construction of this challenging macrocylic core was achieved by a macrolactamization reaction using peptide coupling reagents BOP/HOAt, while the two (E)-configured double bonds in the ring were introduced by a Johnson-Claisen rearrangement and Wittig olefination respectively. Ru(bpy)3Cl2 which is an excellent visible light photoredox catalyst, has been extensively applied to organic syntheses in recent years. Although much research has focused on the study of the reductive quenching pathway, the oxidative quenching pathway has rarely been explored. Using persulfate as the electron acceptor, we have successfully developed a protocol for the oxidative functionalization of dialkylamides under mild reaction conditions. Further application has demonstrated a Friedel-Crafts amidoalkylation methodology applying various nucleophilic alcohols and arenes. The reaction can also be conducted under thermolysis condition without the photocatalyst, but requires elevated temperature. Both of the reactions generate N-acyliminium ion in situ as the key intermediate. The first example of photocatalytic halogenation has been achieved at room temperature using Ru(bpy)3Cl2 and polyhalomethanes (CBr4 and CHI3) as the electron acceptors. Excellent yields and high functional group tolerance have been established. Mechanistic studies indicate a single electron transfer (SET) pathway and the transformation is via a Vilsmeier-Haack type intermediate. Further expansion of this methodology to anhydride formation was achieved, providing a mild avenue for the synthesis of symmetric anhydrides. Furthermore, the use of a continuous flow reactor enabled the efficient large scale synthesis of anhydrides.

Made available in DSpace on 2015-07-22T20:49:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-06-24. Added 1 bitstream(s) on 2015-08-11T03:25:29Z : No. of bitstreams: 1 Publico-00299a.pdf: 807068 bytes, checksum: e4fb701e403dec161fff1eb2278518d5 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:29Z : No. of bitstreams: 2 Publico-00299a.pdf: 807068 bytes, checksum: e4fb701e403dec161fff1eb2278518d5 (MD5) Publico-00299b.pdf: 1749779 bytes, checksum: d8cc731e3f8410ce7bdb335a435143ec (MD5) / Neste trabalho, desenvolvemos uma nova metodologia para a obtencao estereosseletiva de pirrolidin-2-onas substituidas na posicao 5 atraves de adicao de sais de potassio de organotrifluoroboratos a cations N-aciliminio ciclicos. As reacoes de ƒ¿- amidoalquilacao envolvem lactamas derivadas do acido tartarico . (3R,4R)-3,4,5-tris- (acetoxi)-1-benzil-2-oxopirrolidin-3-il, (3R,4R,5R)-3,4-bis-(acetoxi)-5-hidroxi-1-benzil-2- pirrolidinona e sais de potassio de organotrifluoroboratos alquilicos, arilicos, heteroarilicos, alilicos e alquinilicos, fornecendo pirrolidin-2-onas substituidas na posicao ƒ¿ de 1 a-b, com rendimentos que variam de 63% a 87% e com diastereosseletividade de moderadas a boas, onde o diastereoisomero syn foi obtido preferencialmente nos casos onde o carbono nucleofilico tem hibridizacao sp e sp2 e ocorrendo a inversao da diastereosseletividade, isto e, preferencialmente o diastereoisomero anti nos casos de carbonos hibridizados sp3. A estereoquimica relativa syn/anti dos produtos majoritarios foi inferida atraves dos dados espectroscopicos de RMN de 1H e 13C. Os sais de heteroaril, aril, alquil e acetilênicos foram obtidos através da geração dos respectivos ânions organomagnésio e organolítio seguido pela adição de trimetilborato à baixa temperatura e posterior reação com KHF2 aquoso. / In this work, we developed a new methodology for the stereoselective acquisition of substituted pyrrolydin-2-ones in the 5 position through the addition of potassium organotrifluoroborate salts to cyclic N-acyliminium cations. The á-amidoalkylation reactions involve lactams derivative tartaric acid – (3R, 4R, 5R)-3,4-bis-(acetoxy)-5- hidroxy-1-benzyl-2-pyrrolydinone and alkyl, aryl, heteroaryl, allyl and alkynyl potassium organotrifluoroborate salts, providing substituted pyrrolydin-2-ones in the á position of 1 ab, with yield variable of 63% to 87% and diastereoselectivity of moderate to good, where the diastereoisomer syn were obtained preferentially in the cases where of the nucleophilic carbon have sp and sp2 hybridization and occurring the inversion of the diastereoselectivity, that is, preferentially the diastereoisomer anti in the case of carbon hybridization sp3. The relative stereochemistry syn/anti of the majority products were deduce through of the spectroscopic data of 1H and 13C NMR. The salts of heteroaryl, aryl, alkyl and acetylenes compounds were obtained through the generation of the respective organomagnesium and organolitium anions followed by the addition of trimethylborate at low temperature and further reaction with aqueous KHF2. / TEDE / BV UNIFESP: Teses e dissertações

La chimie des ions N-acyliminiums est un axe de recherche important dans le domaine de la chimie moderne. L’apport de la catalyse, avec l’utilisation de super acides de Lewis, a permis d’améliorer de nombreux processus synthétiques. Nous avons pu développer des réactions d’α-amidoalkylation catalytiques directes de cétones et d’aldéhydes. Ces réactions sont catalysées par des charges très faibles (0.5-2 mol%) du super acide de Lewis, le triflimidate d’étain IV Sn(NTf2)4 et donnent accès à une large gamme de structures carbonylées très intéressantes, avec de bons rendements. L’influence des différents paramètres gouvernant la réactivité et l’étendue de la méthode ont été étudiées. Par la suite, le potentiel synthétique des produits obtenus a été étudié. Deux stratégies de réactions intramoléculaires ont été testées à partir d’adduits alkylés judicieusement fonctionnalisés, en utilisant soit des catalyseurs à base d’or, soit des catalyseurs de métathèse, permettant d’atteindre quelques structures polycycliques. / AThe chemistry of N-acyliminiums ions is one important area of research in modern organic chemistry. Lewis superacid catalysis has contributed in the improvement of many synthetic processes. We have developed some direct α-amidoalkylation reactions starting from unmodified ketones and aldehydes. The reactions were catalyzed by the Lewis superacid tin IV triflimidate, Sn(NTf2)4, at a very low catalyst loading(0.5-2 mol%), providing access to a set of very interesting carbonylated structures in good yields. The influence of different parameters governing the reactivity and the scope of the reaction were studied. Thereafter, the synthetic potential of the obtained products was evaluated. Two intramolecular approaches from suitably functionalized alkylated products were tested using gold and metathesis catalysts, allowed access to some polycyclic structures.

Orientador: Ronaldo Aloise Pilli / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-08T12:16:22Z (GMT). No. of bitstreams: 1 Riston_JoseRoberto_M.pdf: 1975890 bytes, checksum: 83dd322a0b88c53adac5195340f43a5f (MD5) Previous issue date: 2006 / Resumo: Este trabalho trata de estudos visando à síntese estereosseletiva do alcalóide 275A (18, Figura 1). Esse alcalóide foi isolado por Daly e colaboradores da pele de pequenas rãs venenosas neotropicais da família Dendrobatidae em 1986. Sua estrutura possui um núcleo 1-azabiciclo[5.3.0]decano de grande importância sintética. Para construção desse núcleo utilizamos, principalmente, as reações de a-amidoalquilação e de metátese de olefinas de fechamento de anel (RCM), tendo como reagente inicial a (S) prolina (57) Esquema1 / Abstract: This work consists in studies toward the stereoselective synthesis of alkaloid 275A (18, Figure 1). This alkaloid was isolated by Daly and co-workers from the skin of neotropical poison little frogs of Dendrobatidae family in 1986. His structure has an 1-azabicyclo[5.3.0]decane nucleus of great synthetic importance. To construct this nucleus we used, mainly, a-amidoalkylation reactions and ring close metathesis (RCM), starting with (S) proline (57, Scheme 1) / Mestrado / Quimica Organica / Mestre em Química