Synthesis of Indoles by Palladium-Catalyzed Reductive Cyclization of β-Nitrostyrenes with Phenyl Formate as a CO Surrogate

Abstract

The reductive cyclization of suitably substituted organic nitro compounds by carbon monoxide is a very appealing technique for the synthesis of heterocycles because of its atom efficiency and easiness of separation of the only stoichiometric byproduct CO₂, but the need for pressurized CO has hampered its diffusion. We have recently reported on the synthesis of indoles by reductive cyclization of o-nitrostyrenes using phenyl formate as a CO surrogate, using a palladium/1,10-phenanthroline complex as catalyst. However, depending on the desired substituents on the structure, the use of β-nitrostyrenes as alternative reagents may be advantageous. We report here the results of our study on the possibility to use phenyl formate as a CO surrogate in the synthesis of indoles by reductive cyclization of β-nitrostyrenes, using PdCl₂(CH₃CN)₂ + phenanthroline as the catalyst. It turned out that good results can be obtained when the starting nitrostyrene bears an aryl substituent in the alpha position. However, when no such substituent is present, only fair yield of indole can be obtained because the base required to decompose the formate also catalyzes an oligo-polymerization of the starting styrene. The reaction can be performed in a single glass pressure tube, a cheap and easily available piece of equipment.