Mechanistic Insights Into C–H Insertion And Related Reaction Of Metal Carbene

In rencent years,the active intermediate metal-carbene which is generated from transition-metal-catalyzed decomposition of diazo compound,inserted into X-H?X=C,N,O,Si,S,B,etc.?bond is one of the most useful synthesis methods for constructing of carbon-carbon bonds and carbon-heteroatom bonds.It has an important application value in the fields of synthesizing pivotal compounds such as natural products,pharmaceutical molecules,especially in asymmetric synthesis.However,this kind of synthesis methods has some shortcomings widely,such as narrow substrate range,low chiral selectivity.It prompts researchers to deeply understand the mechanism of this kind of reaction,then reasonably guide the optimization of reaction and develop new catalysts of high efficiency,which has become the urgent issue to be settled in this field.This paper mainly applys the density functional theory,systematically investigating:?1?The C-H insertion reaction of 1-phenylpyrrolidine cooperatively catalyzed by a dirhodium?II?complex and chiral spirophosphoric acid;?2?The C-H insertion reaction of indole catalyzed by Cu?acac?₂ complex;?3?The three component reaction based on N-H insertion asymmetrically catalyzed by chiral Rh?I?compounds.The main conclusions were obtained by systematically calculating and investigating,and could be summarized as follows:1.The C-H insertion reaction catalyzed by Cu?I?or Rh?II?compounds,both proceeded through enol intermediates.This conclusion can be further extended and applied to explain the three component reaction based on N-H insertion catalyzed by Rh?I?,indicating that the mechanism based on our investigation has a certain degree of universality,and can turn into important basic theory reference for the further development in this field.2.The reason why reaction?1?yielded asymmetric catalytic products is that the chiral phosphoric acid and metal have a strong electrostatic interaction,ensuring the existance of chiral phosphoric acid always around the metal complex.Having seperated from metal,the enol intermediate can be rapidly trapped by phosphoric acid.Owing to the asymmetric steric hindrance effect,it brings about a larger difference in the corresponding activation energy of R-type and S-type products obtained by subsequent[1,3]-H shift,resulting in the formation of asymmetric products.3.The enol intermediate generated by reaction?2?underwent a ligand exchange with diazoacetates.Then,the[1,3]-H shift reaction of achiral enol lead to the product being racemate,which well explained the observation of experiment.4.The reaction?3?also produced enol intermediates,but,when they dissociated from metal,they rapidly coordinated with the Cl coordination atoms of chiral catalyst via hydrogen bond,to build a chiral center of greater steric hindrance.Which could asymmetry induced the third component enter,and it is the key to the realization of the three component asymmetry.