Buchwald Indoline Synthesis

Abstract This reaction is a regiospecific synthesis of 3,4‐disubstituted indoline and indole derivatives. It involves the generation of a zirconocene‐stabilized benzyne complex from N ‐allyl o ‐haloaniline, which undergoes intramolecular olefin insertion to a tricyclic indoline zirconacycle and then reacts with electrophiles or oxidating agents to give indoline derivatives. Refluxing with ammonium formate in MeOH in the presence of Pd/C, the indole derivatives are formed and these derivatives can be further transformed into indole via ene reaction. This reaction requires only a catalytic amount of zirconocene and has been applied to the synthesis of a variety of molecules containing indole or indoline scaffolds. The rection has been further extended to other kinds of indoline and indole derivatives from an aryl Grignard reagent, an olefin, a primary amine, and the air‐stable titanocene Cp 2 TiCl 2 . Besides this, 2‐( o ‐halo‐phenyl)ethylamine can be directly converted into indoline via various methods. Even secondary amides and carbamates can be intramolecularly mounted onto aromatic nucleus, giving a variety of benzo‐heterocycles.