Hydroamination-Heck Annulation Route to 3-Substituted Indoles

Significance

The reported procedure improves the existing catalytic heteroannulation methodologies for indoles. The existing methods, such as the Larock annulation (see book below), often fail for chloroanilines and the coupling with unsymmetrical alkynes leads to 2-substituted indoles. The reported process consists of a Ti-catalyzed hydroamination of alkynes with 2-chloroanilines, followed by Pd-catalyzed intramolecular aza-Heck reaction. This one-pot annulation selectively yields 3-substituted indoles (with unsymmetrical alkynes), thus complementing the Larock annulation. The yields range from moderate to good and functionalities such as ethers and halogens are well tolerated by the catalytic system.