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.chusov
gmail.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.
DOI: 10.1021/acs.orglett.2c02807
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Abstract
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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proposed mechanism
scale-up experiment
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.
Key Words
reductive amination, sodium hypophosphite, green chemistry
ID: J54-Y2022
