Identificador: TDX:800
Autores: Ferrer Llabrés, Catalina
Resumen:
Indole is a structure present in a large number of alkaloids and natural products with important pharmaceutically properties. Although a variety of methods have been developed to sythesize derivatives of this heterocycle and to modify its substitution pattern, new methods that provide indole derivatives are still of high interest in organic chemistry. An interesting way to obtain indole derivatives could be the catalytic hydroarylation of alkynes, although this method has not been widespread developed, until now.We have found that the intramolecular hydroarylation of alkynes using recently developed cationic gold(I) complexes allows the synthesis of seven membered ring indole derivatives by a 7-exo-dig cyclization process. Interestingly, AuCl3 promotes the formation of eight membered rings by an unusual 8-endo-dig cyclization. In some cases, we have also observed the formation of allenes or tetracyclic derivatives with gold(I), as a result of a fragmentation reaction. Based on experimental results, a mechanism has been proposed to explain the formation of these compounds. This mechanism involves a C-C bond formation at C-3 followed by a 1,2-migration in a Friedel-Craft type reaction.We have also developed the intermolecular reaction between indoles and alkynes catalyzed by gold, giving rise to a wide range of different products.In the second chapter of this Thesis the methodology developed for the cyclization of indoles with alkynes has been applied to the study of the total synthesis of the family of natural products lundurines A-D. This products contain an indoloazocine unit and by the cyclization of the appropiate substrate the tetracyclic core of the lundurines has been synthetized.Another topic of my Doctoral Thesis is the study of the reaction of enol ethers with alkynes. A methodology for the synthesis of 3-oxa-biciclo[4.1.0]hept-4-enes catalyzed by Pt(II) and Au(I) has been developed The general mechanism of Pt(II)-, Pd(II)-, and Au(I)-catalyzed reactions between alkynes and alkenes has been demonstrated in the context of 1,6-enyne cyclization. Accordingly cyclopropyl metal carbenes formed in the 6-endo-dig cyclization may evolve to form seven-membered ring intermediates. This has been achieved for the first time by using highly electrophilic platinum(II) and gold(I) complexes. Gold(I) also triggers a remarkable rearrangement of certain enynes leading to complex cyclic systems. This reaction also proceeds via a seven-membered ring intermediate.Finally, the mechanism for the cyclization of alkynyl imines catalyzed by Cu(I) to give pyrroles originally proposed by Gevorgyan has been corrected. Based on this new mechanistic proposal, we have carried out a study for the synthesis of 3-substitud pyrroles.
Repositori URV