1. (1,5-Cyclooctadiene)(methoxy)iridium(I) dimer (505 mg, 0.76 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (409 mg, 1.52 mmol), and bis(pinacolato)diboron (13.4 g, 52.7 mmol) were dissolved in tertiary-butylmethyl ether (TBME, 135 mL) under nitrogen atmosphere. Catalyst solution was prepared.
2. The above catalyst solution (15 mL) was added to m-toluene dicarbonitrile (700 mg, 5.46 mmol) and the mixture was heated in a microwave reactor at 80 °C for 1 hour. The reaction was repeated 8 times and concentrated in vacuum after combining all the reaction mixtures.
3. Purification by rapid gradient chromatography using a hexane solution of 0-10% ethyl acetate as eluent gave 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalonitrile (5.6 g, 22.0 mmol). TLC: Rf 0.3 (hexane/ethyl acetate 4:1).
4. 4,6-Dichloropyrimidine (3.28 g, 22.0 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isobenzenedicarbonitrile (5.6 g, 22.0 mmol) and cesium carbonate (14.4 g, 44.2 mmol) were dissolved in 1,4-dioxane/water (9:1, 60 mL) and purged with nitrogen for Degas for 10 minutes. 5.
5. [1,1'-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (806 mg, 1.10 mmol) was added and the reaction mixture was stirred at 90 °C for 3 h. After cooling to room temperature, the reaction mixture was stirred at 90 °C for 3 h. The reaction mixture was then purged with nitrogen.
6. After cooling to room temperature, the reaction mixture was partitioned between water (250 mL) and ethyl acetate (150 mL), the organic phase was separated and the aqueous phase was extracted with ethyl acetate (2 x 150 mL). The organic phases were combined, dried with sodium sulfate and concentrated in vacuum.
7. Purification by rapid gradient chromatography using a hexane solution of 0-15% ethyl acetate as eluent afforded 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isophthalonitrile (1.70 g, 7.06 mmol) as a white solid.
