Trapping of iminiums by the indole nucleus during catalytic hydrogenation of nitriles: a rapid synthesis of tetrahydro-β-carbolines

Abstract

Reductive self-condensation of indole acetonitrile upon catalytic hydrogenation over Pd·C in acetic acid yielded 1-(3-indolylmethyl)-1,2,3,4-tetrahydro-β-carboline. Hydrogenating 3,4-dimethoxyphenylacetonitrile failed to give tetrahydropapaverine, but a cross reaction between indole acetonitrile and 3,4-dimethoxyphenylacetonitrile allowed isolation of 1-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydro-β-carboline, which was otherwise prepared (76%) by catalytic hydrogenation of a mixture of tryptamine and 3,4-dimethoxyphenylacetonitrile. Besides an easy access to the yohimbane skeleton, the reaction opens the way to a useful general synthesis of tetrahydro-β-carbolines.