The Formation Of C-C Bonds Via C-H Functionalization

To date,transition-metal-catalyzed C-H functionalization has emerged as a facile and robust approach to form C-C bonds.Its power originates in the ability to accomplish site-selective derivatization of inert C-H bonds without the need for prefunctionalized starting materials.Herein,this dissertation summarized the recent development on C-H oxidative-coupling methods and the use of directing groups(DGs)in the selective C-H bonds activation area.On this basis,several novel methodologies about site-and regio-selective C-C bond formation reactions based on the C-H activation mode are described in detail.First,a metal-free oxidative cross-coupling reaction of isochroman and indole derivatives was explored.In the presence of stiometric chemical oxidant DTBP,isochroman and related cyclic ether derivatives can be smoothly coupled with indoles at C3 position in satisfactory yields.This synthetically valuable procedure tolerates a broad range of substrates,which provides an alternative method to a-substituted cyclic ethers.Compared to the conventional total synthesis route,this methodology has distinct advantages of easily accessible starting materials,operational simplicity which represents an atom-economial catalytic pathway.Second,A nickel-catalyzed regioselective oxidative coupling of inactive C(sp3)-H bonds with indole derivatives was described.The divergent synthesis of C(sp3)-C(sp2)bonds which derived from 1,4-dioxane and indoles was achieved in 41-87%yields and excellent regioselectivity(up to 19:1 ratio)with DTBP as the oxidant.The nickel species and additives play pivotal roles on regioselectivity control though the exact reason is unclear.Mechanistic study indicated that the C-H bond cleavage proceeded via a single electron transfer mediated by nickel catalyst.This general procedure presents good functional group tolerance on indole derivatives.Thus,the synthetic sig1ificance on selective elaboration ofheteroaromatic stuctues is elear.Next,the regioselective fiuoroalkylation of quinolines catalyzed by copper was achieved with fluorinated sulfonate salts RfSO2Na(Rf=CF3,CF2H,C4F9,CsF11,and C6F13).With the assistance of 8-amido chelation,the selective fuctionalization of C-H bonds at the C5S-osition of quinolines was established using AIBN as oxidant.The formation of metal-chelated copper containing complex would affect the electron contribution in quinoline,which ends up with the regioselective fluoroalkyl radical addition to the C5-positions.Meanwhile,this reaction features a broad substrate scope,excellent functional group tolerance thus afforded the desired C5-fluoroalkylated quinoline deravatives in 17-89%yields.Experimental observations revealed a SET process might be involved.Finally,we report a palladiun-catalyzed directed arylation of protected thiols at y aliphatic sites.The key is to utilize Michael acceptors as a dual reagent to install a protecting/directing group on thiols via the thiol-Michael click reaction,which later can be easily removed under basic conditions.The C-H arylation proceeds with huge functional group tolerance and the deprotected thiols could be further transformed into other sulfur-containing compounds.This unique mode of activation could open the door for site-selective functionalizations of thiols or other sulftur-containing compounds at unactiveted positions.