First cross-coupling reactions on halogenated 1H-1,2,4-triazole nucleosides

Reaction Scheme


C-O activation of mesylates by a palladium catalyst and subsequent cross-coupling with potassium cyclopropyltrifluoroborate have been achieved with high yield. Both electron-enriched and electron- deficient aryl mesylates are suitable electrophilic partners for the Suzuki-Miyaura reaction. The scope was successfully extended to heteroaryl mesylates with yields up to 94%.



A Biotage microwave vial was charged with Pd(OAc)2 (1.1 mg, 5.0 ?mol), RuPhos (4.7 mg, 10 ?mol), naphthalen-1-yl methanesulfonate (55.5 mg, 0.25 mmol), cyclopropyl trifluoroborate (47.2 mg, 0.33 mmol), and K3PO4 (382 mg, 1.80 mmol). The test tube was sealed with a cap lined with a disposable Teflon septum , evacuated under vacuum, and purged with argon three times. A t-BuOH/H2O mixture (1.25 mL/1.25 mL) was added under argon. The reaction mixture was heated to 110 _C for 4 h before cooling to room temperature. The reaction mixture was extracted with EtOAc (3 2 mL) and then dried (MgSO4). The solvent was removed in vacuo, and the crude product was purified by preparative silica gel chromatography (elution with hexanes/CH2Cl2 80/20) to give 2a in 87% yield (36.6 mg) as a colorless oil.



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