Synthesis of the 3-Aza[9]metacyclophane System by Oxidative Cleavage of a 3-Aza[6](1,7)naphthalenophane Derivative

Abstract

Reaction of 10,11-dimethoxy-1,4,5,6-tetrahydro-7,9-ethano-3-benzazecine-3(2H)- carbonitrile (3) with ozone at -78°, followed by destruction of the ozonide with dimethyl sulfide, gave, in 82% yield, 15-formyl-12,13-dimethoxy-8-oxo-4-azabicyclo[9.3.1]pentadeca-1(15), 11,13-triene-4-carbonitrile (4), a representative of the new 3-aza[9] metacyclophane system. The precursor (3) was obtained by cyanogen bromide-induced eliminative ring destruction of 8,9-dimethoxy-2,3,5,6,10,11,11a,11b-octahydro-1H-benzo[de] pyrido [3,2,1-ij] quinoline (2) in 96% yield. An attempt to make the analogous precursor for the 3-aza[8] metacyclophane system was unsuccessful due to a preferred nucleophilic attack by bromide ion. Reduction of (4) with sodium tetrahydroborate gave 8-hydroxy-15-( hydroxymethyl )-12,13-dimethoxy-4- azabicyclo [9.3.1]pentadeca-1(15),11,13-triene-4-carbonitrile (5) in 79% yield.