The Mechanism Of The X-H Insertion Reaction Catalyzed By Transition-metal

Development of fast,atom-economic and asymmetrically selective construction of C-O and C-N bonds is of great scientific significance and widely promising applications in the construction of organic molecules,natural products and drug molecules,etc.However,it is known that transition-metal catalyzed asymmetric activation encounters problems such as low selectivity and limited substrates.Density Function Theory(DFT),with which reaction mechanisms as well as that how electrical and molecular structure of ligands tunes the mechanisms could be probed,will provide fundamental theoretical data and thoughts on design of novel,effective chiral catalysts.The mechanisms of asymmetric and symmetric X-H bond insertion reaction were studied respectly by using the density functional theory(DFT)method,including(1)themechanisticinsightintoasymmetricN-H insertionreactioncatalyzed byRh(II);(2)the mechanistic insight into symmetric O-H insertionreactioncatalyzed by Cu(I);(3)the mechanistic insight into asymmetric O-H insertionreactioncatalyzed by Cu(I).All the calculations are based on the density functional theory method and the commercial Gaussian 09 software package.Considering the effect of solvent,SMD theory was also used.Through calculation analysis,the main conclusions are as follows:(1)The results of the mechanisticstudy of Rh(II)catalyzedasymmetric N-H insertionreaction show thatthe reaction begins with thenucleophilic amine attacking at the carbenoid,forming a metal-associated ammonium ylide firstfollowed by a rapid proton transfer to afford a metal-associated enamine intermediate.Subsequently,the enamine intermediate dissociates from the metal and yield a more stable seven-membered-ring conformation via an intramolecular hydrogen-bond exchange.Formation of theenamine intermediate requires an overall barrier of 5.7 kcal/mol and is exergonic by 5.1 kcal/mol.Calculations also demonstrated that,the conversion of the achiral enamine into the N-Hinsertion product can be facilitated efficiently by the dirhodium catalyst.Meanwhile,in the presence of the spiro chiral phosphoric acid,the asymmetric proton induction of enamine is greatly favored,requiring an activation free energy of 6.0 kcal/mol to afford the major R-product.(2)The results of the mechanisticstudy of Cu(I)catalyzedsymmetric O-H insertionreaction show thatthe nucleophilic attack of methanol at the in situ generated Cu(I)carbenoid gives a Cu(I)-enol intermediate followed by a ligand exchange step to liberate free enol.Then,a[1,3]-proton shift of free enol can occur smoothly by using a methanol dimmer as the proton transfer catalyst,which has an overall barrier of 18.5 kcal/mol.Further calculations indicate that this mechanism is also suitable for the chiral Cu(I)-based catalysts such as Cu(I)-bisoxazoline and-Pybox.Our calculations also suggest that for the asymmetric O-H insertion,the free enol pathway should be avoided.And it can be explained by the steric hindrance of the ligand.It is consistent to the experimental observations.(3)The results of the mechanisticstudy of Cu(I)catalyzedsymmetric O-H insertionreaction show thatthe nucleophilic attack of water at the in situ generated Cu(I)carbenoid gives a Cu(I)-enol intermediate,which has an overall barrier of 13.8kcal/moland then followed by a ligand control step to liberate product.Firstlythe hydrogen and nitrogen atoms of Cu(I)-enol intermediate form into chemical bond under the control of N atom of the ligandto ensure the chiral of the intermediates,which has an overall barrier of 5.3 kcal/mol.Secondly,Cu(I)-oxonium ylide can occur by using a water dimmer as the catalyst also under the control of ligand.The reaction barrier is 17.4kcal/mol.Finally,the asymmetric catalytic O-H insertion reaction complete under the control of N atom and C atom cooperatively,which has an overall barrier of14.9 kcal/mol.Therefore,the accomplishment ofasymmetric O-H insertion catalyzed by Cu(I)-(S_a,S,S)-Ph-spirobox is attributed to the electronic and steric effects,which are tuned by the coordination of ligands.