Synthèse de composés polyhétérocycliques par une réaction de couplage pallado-catalysée et de composés polycycliques à système rigide via la réaction d'addition-cyclisation

Abstract

We prepared, in the first part of our work, the original heterocyclic derivatives by palladiumcatalyzed direct heteroarylation reaction of heteroarenes by chloride derivatives heteroarylsulfonyl. The use of the catalytic system PdCl2 (CH3CN)2/Li2CO3 in middle 1,4-dioxane, developed in the laboratory of Professor H. Doucet, proved to be the most suitable for the preparation, in one phase, of poly–heterocycliques compounds. Thus, we first synthesized a series of original heterocyclic derivatives (14 compounds) by a coupling reaction involving the chloride thiophen-3-sulfonyl carrier of various groups (halogen, alkyl or ester) in position α of the sulfur atom as the arylating agent, and hetero aryl groups such as Nmethyl-1H-pyrrole, furan and substituted benzofuran and benzothiophene. Then, we have extended the reaction to the use of heterocyclic rings having as the heteroatom nitrogen (methyl N-methyl-1H-pyrrol-2-carboxylate and pyridine) bearing a chlorosulfonyl group in C-5 pyrrole and meta position of pyridine as arylating agents. We used as substrates N-methyl-1Hpyrrole and 2-butylfurane. Analysis of the overall results suggest that the presence of n-butyl group at C-2 furan (donor group) '' deactivate '' C-H bonds in the heterocyclic ring. In a second approach, we addressed the coupling of 4-(3-methyl-1H-pyrrazol-1-yl)benzen-1- chlorosulfonyl, with two hetero five-membered, N-methyl-1H-pyrrole and 2-methylthiophene, under the same conditions. The arylation reaction is successful and leads to the expected coupling products. Finally, we have completed our investigations on the reaction pallado-catalyzed arylation by a conventional coupling between the 2-(5-bromothiophen-2-yl)-1-methyl-1H-pyrrole with 2-ethyl (isopropyl)-4-methylthiazole. To do this we used PdCl(C3H5)(dppb) as catalyst (2 mol%) in the excess presence of KOAc (3 equiv.) in refluxing DMA: tricyclic compounds are obtained. In the second part, a series of heterocyclic compounds poly-rigid system (fused), derivatives of 2,3-disubstituted-thieno[2,3-b]quinoxaline was prepared (13 compounds) by a reaction of additioncyclisation acid-catalysed of benzaldehyde derivatives in the 3-methylquinoxalin-2-thione. The results of this study show that a substrate / aldehyde / acid 1: 2.2: 2 is the most appropriate, and sulfuric acid is the most effective. Yields are good in the majority of the feedback we have achieved. All the formulated products were identified by conventional spectroscopic methods (1H-NMR, 13C-NMR), and for most further analysis such as elementary analysis and another MS mass spectrometry were performed.