Under nitrogen protection, 2-cyanothiophene (1 mmol) was dissolved in anhydrous THF (1.5 mL) in a flame-dried flask. TMPMgCl-LiCl (1.0 M solution of THF, 1.8 mL, 1.8 mmol) was slowly added dropwise at 25 °C and the reaction mixture was stirred for 2 h (for substrate 1a, it is recommended that the metallization time be kept within 1 h). The completion of the metallization reaction was monitored by GC analysis, and an aliquot of the reaction solution was taken and quenched with anhydrous THF solution of iodine (I2) to terminate the reaction. Subsequently, a solution of anhydrous THF (2 mL) with electrophilic reagent (2 mmol) was slowly added dropwise at 0 °C, and the temperature was raised to 25 °C to continue stirring for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated aqueous NaHCO3 solution. Extraction was carried out sequentially with NaHSO3 or NH4Cl solution (5 mL) and ethyl acetate (3 x 15 mL), the organic phases were combined and dried with anhydrous MgSO4. After filtration to remove the desiccant, the solvent was removed by distillation under reduced pressure to give the crude product 5-iodothiophene-2-carbonitrile.
