Sodium Hypophosphite as a Bulk and Environmentally Friendly Reducing Agent in the Reductive Amination
Fedor Kliuev, Anton Kuznetsov, Oleg I. Afanasyev, Sofiya A. Runikhina, Ekaterina Kuchuk, Evgeniya Podyacheva, Alexey A. Tsygankov and Denis Chusov*
*A.N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Moscow 119991, Russian Federation, Email: denis.chusovgmail.com
F. Kliuev, A. Kuznetsov, O. I. Afanasyev, S. A. Runikhina, E. Kuchuk, E. Podyacheva, A. A. Tsygenkov, D. Chusov, Org. Lett., 2022, 24, 7717-7721.
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The nontoxic, stable, environmentally benign, and easily available NaH2PO2 promotes reductive amination with E factors around 1. The reaction demonstrated a great compatibility with a wide range of functional groups.
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General procedure for the substrate scope study
A 12 mL glass tube with a screw-cap wrapped by sealing tape (to avoid oxidation of chemicals in air, but on a scale-up experiment there is no difference between sealing with a septum and refluxing) was charged with stirring bar, sodium hypophosphite monohydrate (0.5 equiv., 0.5 mmol), amine (1.25 equiv., 1.25 mmol) and carbonyl compound (1 equiv., 1 mmol). The tube was placed into a preheated oil bath (at the indicated temperature) and stirring was continued for 19 h. Then the tube was cooled down to the room temperature. The reaction mixture was washed with 3 mL of DCM, placed into an ultrasonic bath for 10 minutes and then centrifugated (10 minutes, 8000 rpm). The residue was purified by column chromatography or vacuum distillation.