Cyanation Reactions Of Alkenes And Indoles With Formamide As The Green Cyanogen Source

Nitrile constitutes a prevalent unit in numerous natural products,pharmaceuticals,and agrochemicals.It’s also particularly useful in organic synthesis as a versatile precursor to a range of functional groups such as amines,amides,aldehydes,amidines,ketones,and carboxylic acids.Therefore,various procedures for introducing the nitrile group onto organic compounds has been developed by employing different cyano sources.Currently,aliphatic nitriles compounds are mainly prepared by the cyanation of unsaturated hydrocarbons with HCN and metal cyanides.This cyanation requires an expensive Ni（0）catalyst.However,the Ni（0）catalyst is difficult to handle due to its sensitivity to moisture and oxygen,while hydrogen cyanide and metal cyanides are extremely toxic and volatile;which limits the application of alkene hydrocyanation in the multistep synthesis of more complex organic compounds.In order to solve these problems,the development of non-metal cyano source for the synthesis of nitriles is of great significance.This dissertation is consisted of two parts:In the first part of the study,we report a novel Ni（II）-catalyzed hydrocyanation of alkenes with formamide as a green cyano source,dehydrant,reductant and solvent,by generating the“CN”unit from the dehydration of formamide,from safe and readily available formamide.Excellent linear or branched regioselectivity,wide substrate scope,cheap and stable nickel salt as precatalyst,safe cyano source,slow generation of“CN”to obviate catalyst deactivation and convenient experimental operation would render this hydrocyanation attactive for laboratory synthesis of aliphatic nitriles.In the second part of the study,we report a novel Pd-catalyzed direct C₃-H bond functionalization reaction of indoles with formamide as a green cyano source.The difference between this scheme and the cyanation reaction of alkenes is that the reaction is an oxidation system,and the equivalent of copper is used as an oxidant to realize the cyanation of indole.This protocol avoids the use of highly toxic metal cyanide,The raw materials are commercially available,and this method has great application value.Our novel cyanation protocol has the following characteristic features:（1）direct cyanation of indole compounds under mild conditions;（2）various types of indole compounds are applicable,the indole compounds substituent function is maintained,which is beneficial for further transformations of the cyanation products.This reaction provides a new protocol for synthesis of 3-CN indole compounds.