Benzomorphan related compounds. XIV. Synthesis of 2-(2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines and cyclization to pyrrolo[3,2-f]morphans

The synthesis of 2-{2-pyrrolylmethyl)- and 2-(2-indolylmethyl)tetrahydropyridines by condensation of 2-cyanopyridines with appropriate pyrrole or indole derivatives followed by ketone reduction, quaternization and sodium borohydride reduction are described. The acid-induced cyclization of 2-(2-pyrrolylmethyl)tetrahydropyridines affords 4,5,6,7,8,9-hexahydro-4,8-methanopyrrolo2,3-d]azocine systems (pyrrolo3,2-f]-morphans), although the method fails with N-benzyl substituted pyrroles. The acid treatment of 2-(2-indolylmethyl)tetrahydropyridines and of 2-indolyl tetrahydro-2-pyridyl ketones is not a suitable procedure for the preparation of indolo3,2-f]morphans, because of the protonation of indole nucleus or carbonyl group, respectively.