Synthesis Of α-amino Cyclopentanones Via Pd-catalyzed Heteroaromatics Addition To Nitriles/α-iminol Rearrangement Sequences

The development of efficient α-iminol rearrangement is of high synthetic value,given the importance of the α-amino ketones in the synthesis of biologically relevant compounds.Thermally driven and acid catalyzed rearrangements of performed α-iminols constituted the main body of α-iminol rearrangement.However,extra synthetic steps were required to access α-iminols,which were prepared normally from the condensation between α-hydroxy aldehydes or ketones and amines,and not only need the more steps,but the obtained imine were liable to hydrolysis generally.Recently,transition-metal-catalyzed C-H bond additions to nitriles have witnessed remarkable advances.In these transformations,organometallic species generated by C-H bond activations attacked the CN bond of nitriles to provide the imine intermediates,which subsequently delivered either aryl ketone products or azaheterocycles.We have developed α-iminol rearrangement triggered by Pd-catalyzed C-H addition of nitriles to provided α-amino cyclopentanones under milder reaction conditions.The main research contents are as follows:(1)We have developed α-iminol rearrangement triggered by Pd-catalyzed C-H addition of electronic-rich heteroarenes to cyclobutanone-derived O-acyl cyanohydrins to provide α-amino cyclopentanones.With the optimized reaction conditions,a series of α-amino cyclopentanones were directly and effectively synthesized in an atomeconomic fashion.In addition,further synthetic transformations of products have also been demonstrated.(2)We have investigated α-iminol rearrangement triggered by Pd-catalyzed C-H addition of electronic-rich heteroarenes to cyclopentanone-derived O-acyl cyanohydrins to provide α-amino cyclohexanones.However,our research has certain challenges,and we can only get the target products with low yield.The further optimization of reaction conditions is still continuing.