Cascade carbopalladation-annulation approach toward polycylic derivatives of indole and indolizine
Natalia Chernyak, David Tilly, Zhou Li, and Vladimir Gevorgyan*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061, United States
E-mail:
[email protected]
Dedicated to William F. Bailey on the occasion of his 65th anniversary
Abstract
A convenient method for construction of polycyclic fused nitrogen-containing heterocycles has been developed. The methodology involves palladium-catalyzed intermolecular carbopalladation- annulation cascade reaction of haloaryl heterocyclic derivatives with different alkynes under relatively mild reaction conditions. Thus, the palladium-catalyzed cascade cyclization of bromophenyl derivatives of indolizine and indole with alkynes afforded tetracycles, possessing a newly formed fused six-membered ring. The reaction of 3-(2-iodobenzyl)-indoles with a variety of alkynes afforded polycyclic compounds with fused seven-membered rings. Annulation with unsymmetrical alkynes exhibited varied regioselectivity. Overall, this approach allows for quick and efficient assembly of polycyclic derivatives of indole and indolizine from easily available precursors.
Keywords: Heterocycles, annulation, palladium, alkynes
Introduction
Polycyclic derivatives of indole1 and indolizine2 are important scaffolds, widely found in natural and unnatural bioactive molecules. Thus, indole derivatives exhibit antioxidant and membrane stabilizing properties1a,b and also protect against chemical mediated chemotoxicity.1c Tricyclic and tetracyclic derivatives of indole, possessing seven-membered ring, are used as direct precursors in synthesis of antihistaminic and anti-inflammatory compounds.1h-k Heterocycles, possessing indolizine core have also found numerous applications in synthesis of biologically active compounds. In addition, partially or completely reduced indolizine analogs are widely used in synthesis of indolizidine alkaloids and related unnatural products.3 Moreover, polycyclic analogs of indole and indolizine have found a broad application as heterocyclic analogs of fluorene and indene in the synthesis of ligands for transition metal complexes.1d-g Although the numerous methods have
