Reaccions intramolecualrs de radicals 2-indolilacilaplicació a la síntesi de compostos indòlics

Abstract

This thesis work is placed in the context of intramolecular reactions of 2- indolylacyl radicals. According with the initial objectives its structured in two parts. The first part focus attention to the cyclisation of 2-indolylacyl radicals under reductive conditions, using alkenes as radical acceptors to obtain structures related with natural products and medicinal compounds. In this first part: - A new annulation procedure based on intramolecular reactions of 2- indolylacyl radicals have been developed. This procedure provides straightforward access to cyclic ketones fused to 1,2-position of the indole nucleus. - A total synthesis of the (±)-guatambuine and a formal synthesis of olivacine alkaloid have been achieved. The second part of the work is placed in the context of intramolecuar reactions of 2-indolylacyl radicals with aromatic systems. In this second part: - The cyclization of 2-indolylacyl radicals under non reductive conditions (n-Bu6Sn2-h"v"to give efficiently tetracyclic phenyl indolyl ketones have been studied. - Regioselective cyclization of 2-indolylacyl radicals upon pyridines under non reductive conditions (n-Bu6Sn2-h"v" to give tetracyclic indolyl 4-pyridyl ketones have been studied. The effectiveness of this radical protocol is illustrated by a fast synthetic entry to ellipticine quinones. - The cyclisation of 3-(3-quinolyl)methyl-2-indolylacyl radicals under TTMSS-AIBN conditions have been studied. This cyclisation provides an efficient synthetic entry to calothrixin-related pentacycles, which are obtained in a different oxidation state depending on the substitution at the indole nitrogen. The synthesis of calothrixin B has been achieved from a radical precursor suitably protected at the indole nitrogen. - A new metal-free protocol for the cyclisation of 3-(3-quinolyl)methyl-2- indolylacyl radicals that illustrates the determinant role of AIBN in homolytic aromatic substitutions have been developed. "