Double Arylation of Diynes and Alkynylation of Functionalized Heteroaryl Halides by a Practical Heck Reaction in an Ionic Liquid

Abstract

The efficient palladium-catalyzed alkynylation of electron-rich bromoheteroarenes, incorporating deactivating electron-donating methyl and methoxy groups, and the (hetero)arylation of diynes, take place in the imidazolium ionic liquid [BMIM][BF₄], as a highly polar non-volatile solvent. This method may constitute a sustainable alternative to classical solvents such as dioxane, DMF, NMP, or DMAc. New enynes are formed in the presence of a system encompassing a copper-free palladium catalyst, triphenylphosphine as ligand, and various inexpensive bases. The enyne molecules reported are selectively synthesized in high yields and are mostly unprecedented.

Key words

arylation - diynes - heteroarenes - palladium - ionic liquid

References and Notes

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15

Typical procedure: The catalyst was prepared as a solid mixture of [Pd(allyl)Cl]₂ (6.3 mg, 0.034 mmol of Pd) and Ph₃P (26.9 mg, 0.102 mmol), and degassed for 15 min in a 20 mL Schlenk tube equipped with a magnetic stirrer bar and a reflux condenser. Under argon, were added the heteroaryl halide (either solid or liquid, 3.42 mmol) and [BMIM][BF₄] (3 mL). The mixture was further degassed under reduced pressure for 10 min. The Schlenk tube was heated in an oil bath at 60 ˚C to give a red solution. The vessel was removed from the heating bath and, to the ionic liquid solution, was then added pyrrolidine (0.35 mL, 292 mg, 4.1 mmol) and the terminal alkyne (4.1 mmol). The resulting mixture was heated at 100 ˚C for 4 h under argon and, after extraction with diethyl ether (4 × 5 mL), the product was purified by silica gel chromatography (ethyl acetate-heptane, 1:9) to give the enyne compound. The recovered ionic liquid can be reused without treatment for further catalytic couplings, after removal of ether traces by simple evaporation under vacuum. Reloading of triphenylphosphine may be necessary after three runs due to a partial organic extraction, no amine salt removal was done during this recycling.

16

Copies of ^¹H and ^¹³C NMR spectra of products 1-22 and detailed assignment are reported as Supporting Information.