Buchwald indoline synthesis

What is Buchwald indoline synthesis?

The Buchwald indoline synthesis, which is also referred to as the Buchwald indole-indoline ring synthesis, was first documented by Buchwald in 1991. This synthesis allows for the regiospecific production of 3,4-disubstituted indoline and indole derivatives. It involves the creation of a zirconocene-stabilized benzyne complex from N-allyl o-haloaniline, which then undergoes intramolecular olefin insertion to create a tricyclic indoline zirconacycle.

Buchwald indoline synthesis - Buchwald indole-indoline ring
Buchwald indoline synthesis

This zirconacycle then reacts with electrophiles or oxidizing agents to form indoline derivatives. If refluxed with ammonium formate in MeOH in the presence of Pd/C, the 3,4-disubstituted indoline derivatives can be converted into indole derivatives. Alternatively, the intermediate exo-methylene indoline derivative can be transformed into an indole derivative through an ene reaction.