Study On Visible-light-induced Alkyl Radical Aminocarbonylation

Both of Amide and α-ketoamide,as key frameworks,play an important role in pharmaceutical and synthetic chemistry.Thus,the development of mild and efficient strategies for the synthesis of these two classes of molecules is also the interest of scientists.Aminocarbonylation involving carbon monoxide is an important strategy for the construction of amides and α-ketoamides.Based on ionic-type and radical aminocarbonylation processes,this field has witnessed considerable advances.Amine carbonylation field,however,some problems still exist.First of all,most of the metalcatalyzed double carbonylation reactions are only applicable to alkyl amines with strong nucleophilicity,aromatic amines with weak nucleophilicity often result in poor selectivity and can only form amides in some cases.Besides,radical double carbonylation using alkyl halides,alkanes and potassium alkyl borate as alkyl radical precursors is an efficient strategy for the construction of α-ketoamides.However,due to the way in which free radicals are generated,the reaction usually needs to be carried out under the condition of heating or ultraviolet radiation.Taking these points into account,the range of radical precursors is still narrow,the milder radical generation modes is relatively scarce.Thirdly,there are few reports on the switchable aminocarbonylation of alkyl radicals.Finally,to our knowledge,four-component radical double carbonylation of weakly-nucleophilic aromatic amines is rarely reported.In recent years,strategies of photocatalysis and transition metal catalysis have been widely used in the field of organic synthesis.Under these two methodologies,we explored the aminocarbonylation reaction of alkyl radicals.Specific research contents are as follows:Firstly,a visible light-induced and copper-catalyzed radical aminocarbonylation of cycloketone oxime esters was developed.Several amides containing cyanoalkyl group was synthesized with medium to good yields.Control experiments show that the complex of copper,tripyridine ligand and amine is sensitive to visible light,which is the intrinsic factor that accelerates the reaction.On the other hand,the use of copper and ligands could regulate the chemoselectivity by avoiding direct C-N coupling and double carbonylation processes.Secondly,double carbonylation of alkyl radical precursors such as cyclobutanone oxime esters and phthalimide esters with amines was realized based on photoredox catalysis,generating the corresponding α-ketoamides in moderate to good yields.This strategy further expands the range of electrophiles of double carbonylation and also achieves double carbonylation of arylamines with good selectivity.In addition,adding DMAP to the reaction system,we could further regulate the chemoselectivity of aminocarbonylation,and achieve synthesis of amides with excellent chemoselectivity and yields.Based on control experiments and DFT calculations,we proposed a philicity regulation strategy and explained the chemoselectivity of this switchable carbonylation.Finally,a four-component double carbonylation reaction of Umemoto reagent,nonactivated alkenes,carbon monoxide and arylamines was successfully achieved.Without addition of metal catalysts and photosensitizer,α-ketoamides containing trifluoromethyl substituents could be obtained in moderate to good yields under irradiation of white LEDs.Control experiments show that Umemoto reagent and aromatic amine could form electron donor acceptor complex(EDA complex)in ethyl acetate solution.After exposure to light in the presence of carbon monoxide,it accelerated the single electron oxidation process of amines through intermolecular electron transfer pathway and promoted the generation of carbamoyl radicals.Cross-coupling of carbamoyl radicals with alkyl acyl radicals promotes the formation of α-ketoamides.