Theoretical Studies Of The Mechanism For Transition-Metal Catalyzed C-H Activation In The Presence Of Bidentate Directing Group

C-H bonds are widely present in various organic compounds.Formation of C-C bonds and C-heteroatom bonds via inert C-H activation is extremely challenging in the field of organic synthesis.At room temperature,the direct functionalization of the C-H bond at a specific position has dual challenges in terms of kinetics and thermodynamics,which has always been a difficult problem to be solved in organic synthetic chemistry.Transition metal catalyzed C-H activation has become a widely used synthesis strategy in organic synthesis chemistry.Improving the selectivity and reactivity of C-H activation has been the focus in this field.A directing group can be introduced into the reaction substrate,and the selective activation of adjacent C-H chemical bonds can be achieved through the coordination of heteroatoms with the central metal.Herein,two different types of Ni and Co-catalyzed C-H activation were studied by theoretical methods.The catalytic reaction mechanism and the role of the guiding group were discussed in depth.In order to compare the different roles of monodentate and bidentate directing groups,the mechanism of the cyclizations of aromatic amides with alkynes catalyzed by Ni(0)under the action of N,N-bidentate and monodentate amide NH guiding groups were studied seperately.In the reaction using bidentate-2-pyridylmethylamide as the directing group,the reaction mechanism includes the oxidative addition of N-H bond,alkyne insertion into Ni-H bond,the activation of C-H,and alkyne insertion into Ni-C(sp~2)and reduction elimination.Under the same reaction conditions,due to the lack of a remote N(sp~2)coordination site,the N-H activation reaction with monodentate NH as a guiding group is difficult to proceed.However,in the presence of a strong base,the deprotonation of the aromatic amide N-H can occur to form an amide anion,followed by coordination with the metal center.The reaction mechanism includes the oxidative addition of C(sp~2)-H,alkyne insertions into Ni-H and Ni-C bond,and reduction elimination.The C-H activation mechanisms in the above two types of reactions are found to be different.The C-H cleavage occurs via?-bond metathesis in the bidentate guide group and via oxidation addition mechanism in the monobidentate directing group.In addition,we also studied the insertion order of alkynes and the structural differences of nickel hydrides.Saturated three-membered naphthenic cycloalkanes with higher ring strain energy are ideal substrates for C-C bond cleavage.In recent years,the transition metal catalyzed C-C bond activation of cyclopropane derivatives has gained great progress.The ring-opening and cycloaddition reactions of cyclopropane derivatives have been studied previously.In addition to the release of high ring strain energy of methylene cyclopropane,its unsaturated double bond will also cooperate with the transition metal to catalyze the activation of C-H to further achieve C-C bond cleavage activation,thereby expanding the reaction range.We systematically studied the cyclization of aromatic amides with methylenecyclopropane catalyzed by Co(III)in the presence of N,N-bidentate directing group.The reaction mechanism mainly includes the following processes:N-H activation,C-H activation,alkenes insertion,?-C elimination,C-H activation,and reduction elimination.In addition,the different insertion directions of the C=C double bond of methylenecyclopropane will lead to different reaction paths,and?-C elimination and C-N reduction elimination of alkenes insertion intermediates may lead to two competing reactions.We explored the possibility of the above mechanism from the perspective of thermodynamics and kinetics,and the effect of different spin states of cobalt on the potential energy surface of the reaction.The research work of the above system will provide deep understanding of the unique reactivity of the 3d metals and the detail roles of directing group.Our results will be helpful for further design of new types of transition metal catalyzed C-H activation.