Sodium Hypophosphte as an Available and Green Reagent for Reductive Amination Reaction

Sustainable development of mankind in various fields and areas of science, from biology to materials science, requires continuous development and improvement of methods for synthesis of chemical molecules. Atom-economy and environmental safety of the corresponding processes are important aspects. One of the most important classes of organic compounds are amines. They find their application in various spheres of human life - medicines, pesticides, dyes. Sodium hypophosphite (NaH2PO2) is a widely available reagent and a large-tonnage product of the chemical industry. According to the European Union's chemicals regulator, it is a safe compound for both humans and the environment. However, the use of this reagent in organic synthesis has been very poorly investigated. In this work we have achieved our goals: we have developed a method of reductive amination using an accessible, cheap, safe reagent - sodium hypophosphite. The wide applicability of this method for various types of amines and carbonyl compounds with acceptable (52-86%) isolated yields was shown. The method showed high selectivity and tolerance for easily reduced functional groups such as NO2, CN, OBn, Br, and C=C. A 200-fold scalability of reaction conditions, low E factor values (0.98), and synthesis of the drug Ladastene were demonstrated.