Reductive Amination And Cyanation With Formamide

In many organic compounds,amines and nitriles occupy important positions.They are widely found in nature and play unique roles in chemical and pharmaceutical industries.Among them,N,N-dimethyl tertiary amines are used as ligands,organic catalysts,and assistant of flow phase in chromatography.Due to the highly scalable nature of cyano groups,aromatic nitriles are important intermediates in the synthesis of dyes,natural products,and pharmaceuticals.Their tremendous value in industrial production and theoretical research has attracted chemists to continuously developing new synthetic strategies.According to the existing literatures,N,N-dimethyl tertiary amines were synthesized mainly through the reductive amination strategies.Most of these strategies have problems of poor chemical selectivity or low atomic utilization.As a simple and common solvent,DMF has been reported to show partial reducibility and provide dimethylamine units.We have envisaged and developed a reductive amination method for aldehydes and ketones involved in DMF,with N,N-dimethyl tertiary amine as the product.The optimal condition is 2-naphthaldehyde(1a,0.2 mmol),Zn(OAc)2·2H2O(0.02 mmol,10 mol%),H2O(5.5 equiv),DMF(2a,0.5 mL)heated at 150 ? for 24 h under air.With excellent yields,simple post-processing operations,avoidance of precious metal catalysts and the complicated operation of column chromatography,this method shows a good application prospect.Due to the wide use of cyano groups in compound modification,chemists have been working on the development of new cyano sources in recent years.The existing methods still have the limitations of the use of toxic reagents and inefficient use of atoms.In theory,formamide only needs to lose a molecule of water to produce hydrocyanic acid,which acts as a cyanation reagen.In the previous exploration,we have detected that formamide can release HCN slowly and stably at a certain temperature in the presence of certain metals.On the other hand,the cyanation of arylboronic acid is one of the common methods for the synthesis of arylnitrile,which greatly encourages us to develop a method for synthesizing aronitrile from arylboronic acid using formamide as a cyano source.The optimal condition is 1-Naphthaleneboronic acid(4a,0.2 mmol),Cu(OAc)2(0.04 mmol,20 mol%),I2(1.2 equiv),Formamide(2d,1 mL)heated at 150 ? for 24 h under air.This method uses formamide as a new and green cyano source,which is easy to obtain raw materials,simple to feed,non-cyano anion directly involved,and the condition is relatively mild,which has great potential in the field of synthesis.