Liu Yuanhong, research group of Shanghai Institute of organic chemistry, Chinese Academy of Sciences, made important progress in Ni catalyzed high efficiency hydrogen cyanide reaction of Alkynes

Nitriles are a kind of very important organic synthesis intermediates, which widely exist in medicine, pesticide, herbicide, pesticide, dye, perfume and natural products Organic nitriles can be converted into carboxylic acids, aldehydes, ketones, esters, amides, amines, tetrazoles and other nitrogen heterocyclic compounds Therefore, the synthesis of organic nitriles has attracted extensive attention and strong research interest Transition metal catalyzed hydrogen cyanidation of alkynes is considered to be one of the most direct and effective methods for the synthesis of alkenylcyanides However, there are still some limitations and shortcomings in this kind of reactions, such as the use of highly toxic and volatile hydrocyanic acid as the source of cyanogen, which is extremely dangerous in the laboratory and industrial production; the catalyst is easily inactivated by the poisoning of cyanide anion, and the reaction efficiency is often not high; the substrate universality and regional selectivity are not very good, etc Therefore, it is of great practical significance and application prospect to develop new catalytic systems and realize more efficient, safe and mild hydrogen cyanidation of alkynes catalyzed by transition metals, whether in laboratory synthesis or industrial application Liu Yuanhong, State Key Laboratory of metal organic chemistry, Shanghai Institute of organic chemistry, has been committed to the study of nickel catalyzed cyanation in recent years, and has realized the high-efficiency cyanation reaction of nickel catalyzed chloroaromatics / heteroaromatics with zinc cyanide with relatively low toxicity under mild conditions (org Lett 2017, 19, 2118) Later, they further expanded the research scope and successively realized the highly efficient cyanation of phenol derivatives and alkyl halogenated hydrocarbons (J org Chem 2018, 83, 14036; org Lett 2018, DOI: 10.1021/acs Orglett 8b03539) Recently, the research team applied zinc cyanide and green water to the hydrogen cyanide reaction of alkynes, and successfully realized the highly regioselective hydrogen cyanide reaction of terminal alkynes under mild conditions (j.am.chem.soc 2018, 140, 7385) The reaction has good substrate universality and functional group compatibility Both aryl terminal alkyne and non activated alkyl terminal alkyne can react under the reaction conditions, and halogen, hydroxy, amino, alkenyl and internal alkyne are all well compatible In addition, the reaction can also be applied to the late functional modification of complex drug molecules such as bucolizine derivatives and progesterone It should be pointed out that in this reaction system, zinc cyanide provides "cyanogen" source, while green water provides "hydrogen" source, avoiding the use of highly toxic and volatile hydrocyanic acid, which has the characteristics of simple operation, safety and efficiency, and provides an important application prospect for the laboratory synthesis and industrial production of alkenyl cyanogens In addition, the mechanism study further shows that the hydrogen on the product alkenyl cyanogen comes from water, and the reaction is mainly carried out in the way of CIS hydrogen cyanidation This new reaction mode will provide a new research idea for nickel catalyzed hydrogen functionalization of alkynes and olefins The first author of this paper is Zhang Xingjie, a doctoral student of Shanghai Institute of organic sciences The above research was supported by NSFC, the Ministry of science and technology, the strategic leading science and technology program of Chinese Academy of Sciences (category B), Shanghai Municipal Science and Technology Commission and Shanghai organic Research Institute.