Computational Study Of Mechanism Of Transition Metal-catalyzed C-H And C-O Bond Activation Reactions

Transition metal-catalyzed reactions have been in the spotlight of synthetic community for the last two decades,and the C-H and C-O activation reactions are both widely explored and developed.Despite that the mechanisms of these reactions are of great importance,many still yet remain to be discovered.This dissertation mainly consists of two mechanistic studies on two very different reaction systems,as shown below.1.Mechanisms and Origins of Chemo-and Regioselectivities of Ru(?)-catalyzed Decarboxylative C-H Alkenylation of Aryl Carboxylic Acids with AlkynesThe mechanisms,chemo-and regioselectivities of Ru(?)-catalyzed decarboxylative C-H alkenylation of aryl carboxylic acids with alkynes were investigated with density functional theory(DFT)calculations.The catalytic cycle involves sequential carboxylate-directed C-H activation,alkyne insertion,decarboxylation and protonation.The facile tether-assisted decarboxylation step directs the intermediate towards the desired decarboxylative alkenylation,instead of typical annulation and double alkenylation pathways.The decarboxylation barrier is very sensitive to the tether length,and only the seven-membered ring intermediate can selectively undergo the designed decarboxylation,suggesting a tether-dependent chemoselectivity.This tether-dependent chemoselectivity also applies to the alkyl tethers.In addition,the polarity of sol,vent is found to control the chemoselectivity between the decarboxylative alkenylation and[4 + 2]annulation.Solvent with low polarity(toluene)favors the decarboxylation pathway,leading to the decarboxylative alkenylation.Solvent with high polarity(methanol)favors the ionic stepwise C-O reductive elimination pathway,leading to the[4 + 2]annulation.To understand the origins of regioselectivity with asymmetric alkynes,the distortion/interaction analysis was applied to the alkyne insertion transition states,and led to a predictive frontier molecular orbital model.The asymmetric alkynes selectively use the terminal with the larger HOMO orbital coefficient to form the C-C bond in the insertion step.2.Mechanism and Origins of Ligand-controlled Stereoselectivity of Ni-Catalyzed Suzuki-Miyaura Coupling with Benzylic EstersNickel catalysts have shown unique ligand control of stereoselectivity in the Suzuki-Miyaura cross-coupling of boronates with benzylic pivalates and derivatives involving C(sp3)-O cleavage.The SIMes ligand produces the stereochemically inverted C-C coupling product,while the PCy3 ligand delivers the retained stereochemistry.We have explored the mechanism and origins of the ligand-controlled stereoselectivity with density functional theory(DFT)calculations.The oxidative addition determines the stereoselectivity with two competing transition states,an SN2 back-side attack type transition state that inverts the benzylic stereogenic center,and a concerted oxidative addition through a cyclic transition state which provides stereoretention.The key difference between the two transition states is the substrate-nickel-ligand angle distortion;the ligand controls the selectivity by differentiating the ease of this angle distortion.For the PCy3 ligand,the nickel-ligand interaction involves mainly ?-donation,which does not require a significant energy penalty for the angle distortion.The facile angle distortion with PCy3 ligand allows the favorable cyclic oxidative addition transition state,leading to the stereoretention.For the SIMes ligand,the extra d-p back donation from nickel to the coordinating carbene increases the rigidity of nickel-ligand bond,and the corresponding angle distortion is more difficult.This makes the concerted cyclic oxidative addition unfavorable with SIMes ligand,and the back-side SN2-type oxidative addition delivers the stereoinversion.