Paired Electrolysis for Decarboxylative Cyanation: 4-CN-Pyridine, a Versatile Nitrile Source
Gadde Sathish Kumar, Prashant S. Shinde, Haifeng Chen, Krishnamoorthy Muralirajan, Rajesh Kancherla and Magnus Rueping*
*KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia,
Email: magnus.rueping
kaust.edu.sa
G. S. Kumar, P. S. Shinde, H. Chen, K. Muralirajan, R. Kancherla, M. Rueping, Org. Lett., 2022, 24, 6357-6363.
DOI: 10.1021/acs.orglett.2c01897
see article for more reactions
Abstract
4-CN-pyridine is an effective cyanation reagent under catalyst-free, paired electrochemical reaction conditions. Mechanistic studies support a nucleophilic reaction pathway, and the cyanation protocol can be applied to diverse substrates including N,N-dialkyl anilines, indole derivatives and amino acids (via decarboxylative cyanation).
see article for more examples
General Procedure for cyanation of amine derivatives
In an argon-filled glove box electrochemical cell equipped with an anode, cathode (1×1.5 cm), and stir bar was charged with 0.3 mmol (33 mg) of 4-CN pyridine, 0.2 mmol of amines, K2CO3 (0.4 mmol). Anhydrous CH3CN (4 mL) and TBABF4 (0.4 mmol, 0.1M) were added to the reaction mixture and stirred for another 10 minutes before starting the electrolysis. The power supply was connected and the reaction was carried out for 8 h at 4 mA constant current. After the reaction is completed, the mixture was transferred to a 100 mL separating funnel, and electrodes were washed with ethyl acetate. Then H2O (20 mL) was added and the mixture was extracted with EtOAc (20 mL) three times. The combined organic layer was washed with H2O (20 mL) and brine (20 mL). The organic layer was dried with anhydrous MgSO4, then concentrated under a vacuum. The product was purified by flash column chromatography on silica gel using hexane/EtOAc as eluent. [Column chromatography done by using Interchim PuriFlash®215 automatic purification system (silica SI-HC, 25 µM, F0040 was used), ethyl acetate/petroleum ether eluent (20-35% of EA in petroleum ether) was used].
Key Words
α-aminonitriles, pyrrolidines, morpholines, electrochemistry
ID: J54-Y2022
