Heteroarylation of Organophosphonium Salts with Indoles in Water: Synthesis of Symmetrical and Unsymmetrical 3,3'-Bisindolylmethane Derivatives

Abstract

A method for the synthesis of symmetrical and unsymmetrical 3,3'-bis(indolyl)methanes (3,3'-BIMs) has been developed through the direct heteroarylation of indolyl-containing di(hetero)aryl phosphonium salts with indole derivatives in aqueous media. This metal-free reaction proceeds smoothly under mild conditions, eliminating the need for hazardous solvents and expensive additives/catalysts typically used in conventional synthesis routes, thereby highlighting the synthetic practicality and efficiency of the process. The success of this approach is largely attributed to the role of water as a promoter, facilitating the C-P bond functionalization of the phosphonium salts. Furthermore, the reaction demonstrates a broad substrate scope, good functional group tolerance, and excellent scalability. Moreover, the protocol can also be extended to the synthesis of triindolylmethane compound and diarylmethylated indole.