Boryl Radicals-triggered Selective C-H Functionalization For The Synthesis Of Diverse Phenanthridine Derivatives

Boron chemistry is a very important part of today's chemistry.The discovery of organoboron radicals in the past decade has solved many shortcomings such as poor selectivity,strict conditions,and incompatibility of functional groups in the preparation of organoboron compounds by conventional methods.However,there are few types of boron radical precursors,and people lack understanding of their structure and properties.In addition,the special structure of borane leads to a large dissociation energy(BDE)of boron hydrogen bonds,so it is difficult to develop a simple boron radical precursor that allows the construction of carbon-boron bonds under mild conditions.Calculations show that the BED energy in N-heterocyclic carbene boron radicals is much smaller than that of borane,which makes the N-heterocyclic carbene boron radicals develop very rapidly.Currently,N-heterocyclic carbene boron radicals can be used to reduce xanthate,halogen and cyano group,what is more,it also can be used for homo-cracking substitution with a disulfide and radical polymerization of an electron-deficient olefin.In recent years,people have studied the new mode of boron radical reaction and found that 4-cyanopyridine can coordinate with diborane,and the BB bond is homogenized under the action of Lewis base,and then pyridine-boron radical can be generated which could reduce azo compounds and hydrazine.This topic is a summary of the literature on pyridine-boron radical reaction in recent years,and we found that ether solvents are necessary in the pyridine-boron radical reaction.We hypothesized that pyridine-boron radicals may may undergo ligand exchange in an ether solvent,and the ether-boron radical BED is greatly increased easily,which make the hydrogen can be extracted by utilizing boron radicals to achieve hydrocarbon-selective functionalization.Based on the above hypothesis,this paper further achieve the synthesis of phenidine derivative the important organic drug intermediates.The main research content is designed in the following three aspects:(1)The synthesized 2-isocyano-1,1'-biphenyl is used as a free radical carrier,4-cyanopyridine and boronic acid pinacol ester are added,and diethyl ether is used as a solvent to synthesize the target phenanthridine derivative.A large number of screens for the amount of 4-cyanopyridine required for the reaction,the amount of boronic acid pinacol ester,the type and amount of oxidizing agent,and were found.the yield was best when the use of 1 equivalent of 4-cyanopyridine,2 equivalents of boron,2 equivalents of 4- cyanopyridine N-oxide and 2 mL of diethyl ether solvent.(2)On the basis of using the optimal reaction conditions,we do the substrate expansion by using different 2-isocyano-1,1'-biphenyl,ethers,amines,and acetamides.The material was found to be very suitable,and the corresponding compound can be obtained in good yield,whether it is an electron-withdrawing substituent or an electron-donating substituent.(3)Through a series of controlled experiments,the reaction is indicated by a free radical route,and C-H bond cleavage may not be a determining step.After analyzing the reaction mixture for GC,it was found that 4-cyanopyridine was rapidly produced in the reaction.Based on the results of the control experiment,we proposed a possible mechanism of the reaction.Finally,we conclude that this paper developed a new mode of pyridine-boron radical reaction and successfully obtained important organic drug intermediates using this method.