Synthesis of 6-methyl-6 H-indolo[3,2- c]isoquinoline and 6-methyl-6 H-indolo[2,3- c]isoquinoline: two new unnatural isoquinoline isomers of the cryptolepine series

Abstract

11 H-indolo[3,2- c]isoquinoline has been synthesized in two steps starting from 4-bromoisoquinoline and 2-bromoaniline via a selective Buchwald–Hartwig reaction followed by a Pd-catalyzed intramolecular direct arylation involving C(sp 2)–H activation. The synthesis of 7 H-indolo[2,3- c]isoquinoline was achieved by a combination of a Suzuki reaction with an intramolecular nitrene insertion reaction starting from 4-bromoisoquinoline and {2-[(2,2-dimethylpropanoyl)amino]phenyl}boronic acid. Selective methylation of the tetracyclic skeletons yielded the title compounds 6-methyl-6 H-indolo[3,2- c]isoquinoline and 6-methyl-6 H-indolo[2,3- c]isoquinoline, which have never been described in the literature before.