| This thesis describes the development of a novel, simple and efficient synthetic method for the preparation of variously functionalized and substituted indoles. This was achieved by the conjugate addition of N-formyl- o-haloanilines to acetylenic sulfones, esters and ketones. The resulting enamine adducts were then cyclized to the desired indoles by an intramolecular arylation reaction employing catalytic copper(II) acetate in DMF under ligand-free conditions without the need for exclusion of air and moisture. The reaction proceeds by reduction of Cu(II) to Cu(I) by formate ion produced by hydrolysis of the solvent, followed by the formation of a coordination complex with the enamine and ultimately ring-closure. Thus, the enamine intermediate itself serves as the ligand in the catalytic conversion of itself into the indole product. The structure of the coordination complex was verified in one example by X-ray crystallography. This methodology was further applied to the copper-catalyzed solid phase organic synthesis (SPOS) of indoles, as well as to the total synthesis of the HN-1 reverse transcriptase inhibitor L-737,126, and the cannabinoid agonist pravadoline. |
