DoE-Assisted Development of a 2H-MoS2-Catalyzed Approach for the Production of Indole Derivatives

2H-MoS2 is an appealing semiconductor because of its Earth-abundant nature, cheapness, and low toxicity. This material has shown promising catalytic activity for various energy-related processes, but its use in catalysis for C-C bond forming reactions towards useful organic compounds is still largely unexplored. The lack of examples in organic synthesis is mainly due to the intrinsic difficulties of using bulk 2H-MoS2 (e. g., low surface area), which implies the reliance on high catalytic loadings for obtaining acceptable yields. This makes the optimization process more expensive and tedious. Here, we report the development of a 2H-MoS2-mediated synthesis of valuable bis(indolyl)methane derivatives, using indoles and benzaldehydes as starting materials. Exploiting the Design of Experiments (DoE) method, we identified the critical parameters affecting the catalytic performance of commercial 2H-MoS2 powder and optimized the reaction conditions. Lastly, we demonstrated that the catalytic system has versatility and good tolerance towards functional group variations of the reagents.

Automated summary

2H-MoS2 is a promising semiconductor with earth-abundant nature, low toxicity, and low cost. Although it has demonstrated good catalytic activity in various energy-related processes, its application in catalysis for C-C bond forming reactions in organic synthesis remains largely unexplored. The challenges arise from the difficulty of using bulk 2H-MoS2 due to its low surface area, which requires high catalytic loadings for acceptable yields and makes the optimization process expensive and tedious. In this study, we developed a 2H-MoS2-mediated synthesis of valuable bis(indolyl)methane derivatives and optimized the reaction conditions using the Design of Experiments method.