Photoredox Catalyzed Iminyl Radical-Mediated C-C Bond Cleavage/Addition/Oxidation Cascade For Synthesis Of Ketonitriles

Due to their ubiquity in natural products and drug molecules,the synthesis of N-containing molecules has always been the focus of synthetic chemists.Compared with the well-developed ionic type of reactions for their synthesis,the study and application of radical strategy in the synthesis of N-containing molecules and are still under rapid development.Therefore,the research on N-centered radical chemistry offers more ideas and methods in terms of bond disconnection and reaction design.Over the last decade,visible-light-promoted photoredox catalysis,has been established as a powerful tool for generation of diverse radical species under mild condition,and has also been widely applied in N-centered radical chemistry.In this context,various oxime esters are regarded as the ideal iminyl radical precursors because of their weak BDE of the N-O bonds.In this paper,on the basis of our previous works on iminyl radicals,we utilized cyclobutanone oxime esters as the iminyl radical precursors,and developed an efficient C-C bond cleavage/radical addition/Kornblum oxidation cascade reaction.This reaction provides a generally applicable approach to a series of diversely functionalized ketonitriles.Notably,traditional thermal methods for their synthesis usually require toxic cyano source or highly sensitive organometallic reagents.After systematic optimizations of reaction conditions,we have confirmed the optimal conditions of this cascade reaction:fac-Ir(ppy)3 as the photocatalyst,DMSO as the solvent and oxidant,under the irradiation of 7 W blue LED,reacting at room temperature for 10-24 h.The corresponding desired ketonitrile products could be isolated with 32-90%yields.Meanwhile,cycloketone oxime esters of different ring size were further tested,delivering the corresponding ketonitriles with different lengths of carbon chain in good yields.Finally,based on the literatures and control experiments,we proposed a possible reaction pathway for the reaction.All the desired products have been fully characterized by means of 1H-NMR,13C-NMR,and HRMS.The results of the above research have been published on Chemical Communication.(2018,54,12262-12265)...