Study On Multi-step Radical Tandem Reaction Via C-H Functionalization

Compared with the traditional coupling reaction,C-H functionalization reaction has a number of advantages.Because it needn't pre-functionalization of the substrate,shortens the reaction step,reduces energy consumption,and improves the efficiency of the use of atoms,this strategy is more in line with the state of green chemical requirements.Based on the dissociation of C-H bond,we can realize the transformation to other C-X bonds(X = C,O,N,P,S,B,halogen,etc.),and finally we can synthesis a series of complex molecules.It must be noted that the use of radical multi-step tandem reaction to complete the relevant synthesis is a hot spot in chemical field.At present,such radical multi-step tandem reaction based on C-H bond functionalization has played a positive and far-reaching role in drug synthesis,material design and development.Therefore,this paper focuses on this special free radical reaction.The contents were listed as below:1.Metal-free radical cyclization of vinyl isocyanides with ether via functionalization of C(sp3)-H Bond.In this chapter,a DBU-promoted cascade C(sp3)-H bond functionalization of ethers and radical cyclization reaction of vinyl isocyanide was reported.The reaction tolerated a wide range of substrates and could be performed under simple conditions.This reaction involved two new C(sp3)-C(sp2)and C(sp2)-C(sp2)bonds formations,which provides a straightforward and atom-economical access to multi-functionalized isoquinolines from readily available starting materials.2.Cascade alkylarylation of substituted N-allylbenzamides for the construction of isoquinolinone derivatives.In this chapter,a mertal-free cascade functionalization of unactivated C(sp3)-H bonds and cyclization reactions of N-substituted allylbenzamides were developed.The reaction involved cleavage of the C(sp3)-H bond,alkylation and intramolecular cyclization,affording the 4-alkyl-substituted dihydroisoquinolin-1(2H)-one derivatives with moderate to good chemical yield.The substituent on the C=C double bond was found to play a key role for the formation of the desired products.Also,N-methacryloylbenzamides worked well in the current reaction,which provides an easy way for the preparation of alkyl-subsituted isoquinoline-1,3(2/H,4H)-diones.3.Visible-light photoredox catalyzed oxidative/reductive cyclization reaction of N-cyanamidealkenes for the synthesis of sulfonated quinazolinones.In this chapter,an efficient photocatalytic oxidative/reductive cyclization reaction of N-cyanamidealkenes with arylsulfinic acids or arylsulfonyl chlorides has been reported,which proceeds through the C-S,C-C and C-N bonds formation.Both the oxidative and reductive cyclization reactions obey the Baldwin's rule definitely,resulting in sulfonated quinazolinones with excellent yields.The photocatalytic reaction was conducted under mild conditions with broad substrate compatibility,which provides a new strategy for the synthesis of sulfonated quinazolinones.Furthermore,one-pot procedure to achieve terminal alkenes has also been explored by elimination of the obtained sulfonated quinazolinones under basic condition.4.NIS-initiated spirocyclopropanation of styrenes with 1,3-dicarbonyl compound for the synthesis of spirocyclopropanes.In this chapter,we developed an efficient cascade spirocyclopropanation reaction between 1,3-dicarbonyl compounds and styrenes,which proceeded through cleavage of a C(sp3)-H bond of(2H)-indne-1,3-dione,iodination,coupling with styrene,second iodination,and intramolecular cyclization.These reactions could be carried out at room temperature and tolerated a wide range of substrates,resulting in good to excellent chemical yields.This process demonstrates a multistep radical reaction for functionalization of 1,3-dicarbonyl compounds and also represents a new strategy for preparation of spirocyclopropane.5.Metal-free nitroxyl radical-mediated ?-C(sp3)-H amination of saturated ketones with heteroaryl halides.In this chapter,we have developed a TEMPO-mediated direct ?-amination reaction of saturated ketone with the design of heteroaryl halides as amide precursors,which proceeds through a cascade ?-aminoxylation,Cope-like elimination,and aza-Michael addition sequence to afford ?-amino ketone derivatives with excellent yields.In addition,we exquisitely realized a case of oxygenation reaction by employing TEMPO as an oxygen source.Furthermore,TEMPO has been demonstrated to act as an oxidant,an a-aminoxylation reagent,a ?-hydrogen acceptor and an in situ base.Meanwhile,further studies concerning the mechanism of this reaction are currently underway in our laboratory.