Immobilized Indolylboron as a Key Intermediate for Solid-Phase Synthesis of Bisindole Alkaloid Analogs

Immobilized indolylboron was easily prepared from resin-bound iodoindole and the subsequent Suzuki coupling reaction was used for the syntheses of bisindole alkaloid analogs.Solid-phase synthesis is regarded as a very efficient method for producing combinatorial libraries 1 and combining solid-phase synthesis with high-throughput screening has made a significant contribution for lead discoveries and optimization in pharmaceutical research.Contemporary synthetic reactions that use transition metals, particularly palladium, have been employed as well established methodologies for selective carbon-carbon bond forming reactions for solution-phase synthesis and for solid-phase synthesis. 2dole rings have been found in various biologically active molecules, like a simple arylindole and numerous studies have been done for the efficient construction and functionalization.We recently reported a solid-phase indole synthesis using a palladium catalyzed intramolecular alkenylation or amination. 3 Suzuki coupling 4 is one of the important palladium catalyzed cross-coupling reactions in medicinal chemistry and is suitable for synthesizing biaryl compounds.This reaction has been already applied to solid phase synthesis.5~7 Many of the reported works have treated the cross coupling of immobilized aryl halides with arylborons in solution and a limited number of examples were reported for the coupling reactions of immobilized arylmetals with free aryl halides in solution. 6,7From the viewpoint of coupling partners' availability, the latter seems to be attractive.In this paper, we wish to report the concise preparation of immobilized indolylboron and the subsequent arylation using palladium catalyst.The solid-phase synthesis of bisindole alkaloid analogs using resin-bound indolylboron was accomplished.