Theoretical Study On The Mechanism Of Transition Metal Rhodium-catalyzed Alkylation Of Indole With Cyclopropanol

There are plenty of indole derivatives in the nature.Most of them exist in the form of alkaloids owing to the unique chemical structure.Therefore,chemists are also very active in the research and development of indole derivatives,which are functionalized with indole as the basic skeleton.Synthetic indole derivatives are widely used in medicine,fine industry,agricultural production and other fields.The construction of C-C(alkyl)bonds by the activation C-H bonds with transition metals is one of the important methods for synthesizing indole derivatives.In this thesis,I conducted research on the alkylation reaction of indole with cyclopropanol,and found a reasonable reaction path through the use of quantum chemistry calculation methods.It provides new insights in this study are expected to be pertinent in other reaction systems involving combination C-H activation and ring-opening.The specific content is as follows:(1)The reaction features combination of indole's C-H activation and ring opening of cyclopropanol was studied with the aid of DFT calculations.With the reaction of rhodium-catalyzed N-pyrimidylindoline with 1-benzylcyclopropanol as an example to accomplish the alkylation,we found the order of C-H activation/ring opening is difficult to occur.Instead,the order of ring opening/C-H activation is predicted to be more reasonable,which circumvents the N?Rh bond breaking.The first cycle relates to the catalytic oxidation of cyclopropanol by Cu(?)to generate an intermediate product,the vinyl ketone.The mechanism mainly involves prior ring opening of cyclopropanol and b-H elimination.The second cycle relates to the product formation from the resultant intermediate product,in which the C-H activation of N-pyrimidylindoline,C=C bond insertion of the intermediate product and protonation are included.(2)The second work in the thesis extends the discussion of the regioselective alkylation of N-pyrimidinylindole and cyclopropanol at the C2 and C7 sites on the basis of the first work.When the pyrrole ring part of the indole skeleton of the substrate changes from a C-C bond to a C=C bond,the product undergoes a regioselective change from C7-alkylation to C2-alkylation.It is verified by calculation that the mechanism of the intermediate product vinyl ketone as a bridge between the two reaction cycles in the previous work is still applicable to this work.Calculations found that the C-H activation step on the indole ring is the key step to determine the regioselectivity.The reason is that the nucleophilicity of the indole ring C2 and C7 is different,which leads to the different activity of the C-H bond.The C2-H bond is easier to activate and break than the C7-H bond,resulting in the existence of only C2-alkylated indole products in the experiment.