Study Of The Functionalization Of C(sp~3)-H Bond Catalyzed By Cobalt Or Under Metal-Free Conditions

C（sp³）-H bond widely exists in organic compounds,and the dissociation of the C-H bond is extremely difficult due to the lack of the highest occupied orbital and the lowest unoccupied orbital for interacting with transition metals.Until now,the functionalization of C（sp³）-H bonds has always been dominated by the noble metal catalysts and the cost is relatively high.Therefore,the investigation of the C（sp³）-H bonds activation catalyzed by earth-abundant metals,especially for cobalt salt,and the functionalization of C（sp³）-H bonds under metal-free conditions,has high economical practicability.In this dissertation,a novel“cobalt/organic oxidant”catalytic system has been developed.Benzoxazines,indolines,and indoles were synthesized by cobalt-catalyzed selective functionalization of C（sp³）-H bonds.Meanwhile,the direct sulfonamidation of C（sp³）-H bonds to synthesize benzenesultam derivatives under metal-free conditions was achieved.The specific research contents are as follows:1.Synthesis of benzoxazine and indoline derivatives by cobalt catalyzed C（sp³）-H bond functionalization.In this work,a series of compounds Ar SO₂NHOR that contain N-O bonds were designed and synthesized,and a novel“cobalt/organic oxidant”catalytic system was developed.This strategy uses earth-abundant and easily Co（OAc）₂×4H₂O as the catalyst and Ar SO₂NHOR as an oxidantt,assisted by 2-picolinamide directing group,and through the selective functionalization of C（sp³）-H bond to access benzoxazine and indoline derivatives.This protocol features simple operation,low cost,mild conditions,and broad substrate scope.In addition,an organometallic Co（III）compound was synthesized and isolated,providing an experimental basis for further investigation of the reaction mechanism.A total of 30 benzoxazine derivatives and 18indoline derivatives were synthesized in this work,and the structures of the compounds were characterized by ¹H NMR,¹³C NMR,and HRMS.The specific structures of compounds 2q and 5 were confirmed by X-ray diffraction.2.Synthesis of indole derivatives by cobalt catalyzed C（sp³）-H bond functionalization.The sequential C-H bond activation of alkanes was achieved under the“cobalt/organic oxidant”catalytic system.The synthesis of 27 indole derivatives which containing various substituent groups was accomplished by using earth-abundant and commercially available Co（OAc）₂×4H₂O as the catalyst and Ar SO₂NHOR as the oxidant.The structures of the new compounds were characterized by ¹H NMR,¹³C NMR,and HRMS.This strategy features mild conditions and good functional group tolerance.The substrates containing primary or secondary inert C-H bonds were well compatible with this strategy.Moreover,the isolated dehydrogenation byproduct indicated that the reaction might undergo C（sp³）-H and C（sp²）-H bond activation.3.Direct C（sp³）-H bond sulfonamidation to synthesize benzosultam derivatives under metal-free conditionsThe metal-free C（sp³）-H bond functionalization strategy features low cost,high conversion efficiency,and environment friendly,which has attracted extensive interest from chemists.In this work,a total of 31 five-membered cyclic sulfonamide derivatives were successfully synthesized by using N-acetoxybenzenesulfonamide derivatives as the substrates.Moreover,the structures of the compounds were characterized by ¹H NMR,¹³C NMR,and HRMS.This strategy has the advantages of no heavy metal residues,high atom economy,and simple steps.The control experiments and DFT calculations were carried out,and further investigated the reaction mechanism.A plausible mechanism is proposed,which revealed that the reaction proceeds through a proton transfer coupled with the S_N2（PTS_N2）process.