Palladium-Catalyzed Direct C-2 Arylation of Indoles with Aryl Halides in Aqueous Medium

Abstract

A newly developed, efficient catalytic system for direct C2-arylation of indoles with aryl halides in aqueous medium under mild conditions (80 °C) is reported. These procedures are free of toxic solvents, and exhibit improved yields and high chemo- and ­regioselectivity.

Key words

arylation - indole - aqueous medium - green chemistry - synthetic method

• References and Notes

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• 15 General Procedure for Direct C-2 Arylation of Indoles in Aqueous Medium: Pd(Amphos)₂Cl₂ (0.005 mmol), NaOH (0.375 mmol), tetrachlorophthalic anhydride (TCPA; 0.375 mmol) and indole 1 (0.250 mmol) were weighed into a microwave vial at r.t. Aryl halide (0.375 mmol), EtOH (0.10 mL) and H₂O (0.50 mL) were then added by syringe. The resulting solution was allowed to stir at 80 °C for 24 h. Upon completion, the reaction mixture was diluted with EtOAc (4.0 mL), filtered through a bed of silica gel layered over Celite, The volatiles were removed in vacuo to afford the crude product. The extent of conversion was determined by GC–MS. Further column chromatography on silica gel afforded the pure desired product 2.