Cyclization of indoles and enol ethers with alkynes catalyzed by platinum and gold

Identifier:  TDX:800

Handle:  https://hdl.handle.net/20.500.11797/TDX800

Authors:  Ferrer Llabrés, Catalina

Abstract:
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