Title : CO From Our Worst Enemy to Our Best Friend: Pd-Catalyzed Reductive Cyclization of Beta-Nitrostyrenes Using Phenyl Formate as a CO Surrogate
Abstract:
The reduction of suitably substituted organic nitro compounds by CO, catalyzed by palladium-complexes, is a valuable method for the preparation of a variety of N-heterocyclic compounds. Despite the high efficiency of many of these reactions, the use of pressurized CO is a drawback since it requires the use of high-pressure equipment and CO lines and the presence of the corresponding safety measures. This limits the application of this kind of reactions as practical synthetic methods. In the aim of turning this kind of reaction into a “general tool” for the synthetic chemist, we developed a procedure based on the use of phenyl formate as an efficient in-situ CO surrogate. Recently, our group employed phenyl formate in the palladium-catalyzed reductive cyclization of 2-nitrostyrenes to afford indoles and in the reduction of nitroarenes in the presence of conjugated dienes to give oxazines. It was found that phenyl formate is the most effective CO source and the desired products were obtained with selectivities and yields that in most cases are higher than those previously reported using pressurized CO. The reaction can be performed in a glass pressure tube, a cheap equipment accessible to every laboratory. Here, we report our results regarding the use of phenyl formate as a CO surrogate in the synthesis of indoles by reductive cyclization of β-nitrostyrenes, catalyzed by PdCl2(MeCN)2 + 1,10-phenanthroline. It has been found that satisfactory results are obtained when the starting nitrostyrene has an aryl substituent at the alpha position. On the other hand, in the absence of such substituents, only moderate yields of indole have been achieved since the base required to degrade the formate can also catalyze the oligo-polymerization of the starting styrene.
Audience take-away:
- This work presents a one-step reaction to get indoles in excellent yields through the reductive cyclization reaction of β-Nitrostyrenes without the need of CO lines.
- The same reaction was used before to synthesize different heterocycles and fine chemicals which considered as a building block for valuable pharmaceutical and industrial compounds.
- The reaction can be performed in a single glass pressure tube, a cheap and easily available piece of equipment, so, we can avoid the use of autoclaves.
