Synthesis of the dibenzopyrrocoline alkaloid skeleton: indolo[2,1-a]isoquinolines and related analogues

The indolo[2,1-a]isoquinoline and pyrrolo[2,1-a]isoquinoline nuclei have been synthesized from N-benzylindole or ethyl 1H-indol-1-ylacetate and N-benzylpyrrole precursors, respectively. Firstly, at C-2 of either the indole or pyrrole nucleus, aromatic rings containing a carbonyl substituent ortho to the newly formed biaryl axis were introduced using the Suzuki-Miyaura coupling reaction. Thereafter, under basic conditions the nucleophile that formed at the acidic methylene protons of the N-benzylindole, ethyl 1H-indol-1-ylacetate or N-benzylpyrrole intermediate reacted with the internal aromatic carbonyl to yield (after the expulsion of water) the title compounds. For example, exposure of ethyl 2-(2-(2-formylphenyl)-1H-indol-1-yl)acetate to potassium tert-butoxide resulted in the formation of ethyl indolo[2,1-a]isoquinoline-6-carboxylate. © 2007 Elsevier Ltd. All rights reserved.