Cyanoacetic Acid As A Cyanomethylation Agent: Cyanomethylation Of Amines, Carboxylic Acids And Alkenes

Cyano groups are commonly found in a variety of natural products and pharmaceutically active molecules. Therefore, methods to introduce the cyano group into an organic compound have been a topic of great interest to chemists. In recent years, following the development of the cyanomethylation strategy, a series of cyanomethylation agents have been exploited for use in this method. This article focus on cyanoacetic acid as a cyanomethylation agent participated in the reaction.This article is divided into two parts:Firstly, Bu₄NI catalyzed cyanomethylation reaction of amines and carboxylic acids.A transition-metal-free catalytic system for the cyanomethylation of amines and carboxylic acids was developed using cyanoacetic acid as a masked electrophile. The mild conditions and simplicity of the procedure provide a valuable method for the construction of α-aminonitriles and cyanomethyl esters. This method utilizes easily available procursors and enjoys a broad substrate scope as well as functionality tolerance.Secondly, transition-metal catalyzed oxidation cyanomethylation of alkenes.In this reaction, cyanoacetic acid is envisioned as a cyanomethylation agent to react with alkenes using Co（acac）₂ as a catalyst and tBuOOH as an oxidant. We have successfully developed the oxidation cyanomethylation of alkenes. Regrettably, the yield of this reaction is still relatively low.