Platinum-Catalyzed Friedel-Crafts-Type C-H Coupling-Allylic Amination Cascade to Synthesize 3,4-Fused Tricyclic Indoles

Abstract

A novel platinum-catalyzed cascade cyclization reaction was developed by intramolecular Friedel-Crafts-type C-H coupling of aniline derivatives with a propargyl carbonate unit-allylic amination sequence. Treatment of various propargyl carbonates tethered to meta-aniline derivatives with a Pt(dba)3/DPEphos catalyst system afforded the corresponding 3,4-fused tricyclic 3-alkylidene indolines in 42-99% yield, which were transformed into 3,4-fused indole derivatives by reaction with trifluoroacetic acid. The reaction products exhibited antiproliferative activities against cancer cells, but not normal cells, revealing the potential usefulness of this reaction for medicinal chemistry.

Keywords: C−H activation; antitumor agents; cascade reactions; heterocycles; platinum.