Skeletal diversity-oriented synthesis of cycloheptatriene[b]indole, spiro-cyclopentene[b]indole and carbazole derivatives via Pd-catalyzed domino reaction involving indolyl allene intermediates

Abstract

Herein, we report a Pd-catalyzed, base-controlled divergent cyclization strategy for the synthesis of polycyclic indole derivatives. Utilizing 3-propargyl indoles and ortho-iodophenyl-ynones as substrates, the reaction pathway can be tuned by the choice of a base: (1) with DIPA, the reaction proceeds through Pd-catalyzed cross-coupling, propargylic Alder ene-type reaction (1,8-H transfer), and indole-migrative cyclization to afford cycloheptatriene[b]indole scaffolds; (2) NIS was incorporated into the reaction system with the purpose of capturing the indole-allene intermediate, and it successfully yielded spiro cyclopentene[b]indole derivatives; (3) alternatively, DBU promotes a distinct pathway involving Pd-catalyzed cross-coupling, propargyl–allenyl isomerization (1,3-H transfer), [4 + 2] cycloaddition and aromatization to generate carbazole scaffolds. The proposed reaction mechanism is supported by experimental investigations.