The Mechanistic Study Of The Transition Metal-catalyzed Annulation Reactions

N-heterocyclic compounds as structural motifs are often found in many organic materials,pharmaceuticals,synthetic intermediates and natural products.And it can also be used in many fields such as additives of preservatives,pigment and coatings.In recent years,transition metal-catalyzed annulation reactions were ranked among the most powerful and simple methods for the synthesis of these compounds,so it is of great significance to explore the catalytic process of this kind of annulation reactions.In this paper,the mechanism of Au-and Rh-catalyzed annulation reactions have been studied by the density functional theory?DFT?methods M062X.In the DFT calculations,we proposed the reasonable mechanisms of Au-and Rh-catalyzed annulation reactions through analysis of the isomers,transition states,reaction pathways and activation energy.The main results are as follows:1.The reaction mechanisms of the gold?I?-catalyzed cross-coupling reaction of aryldiazoacetate with vinyldiazoacetate leading to N-substituted pyrazoles have been theoretically investigated using density functional theory?DFT?calculations.Two possible reaction mechanisms were examined and discussed.Our results suggest that mechanism A is the preferred mechanism for the gold?I?-catalyzed annulation reaction of aryldiazoacetate and vinyldiazoacetate.The reaction mechanism A can be characterized by five steps:the formation of the gold carbenoid via the attack of catalyst to aryldiazoacetate?Step I?,nucleophilic addition of another reactant vinyldiazoacetate?Step II?,intramolecular cyclization?Step III?,hydrogen migration?Step IV?and catalyst elimination affording the final product N-substituted pyrazoles?Step V?.Step IV is found to be the rate-determining step with an overall free energy barrier of 28.3 kcal/mol.In addition,we also investigate the effects of different ligands?IPr and PPh₃?on the selectivity of the products and catalytic activity of the reaction.The results show that the ligands IPr and PPh₃ have the same selectivity to the products,but the ligands PPh₃ have more catalytic activity than IPr for the reaction.The present study may provide a useful guide for understanding these kinds of gold?I?-catalyzed cross-coupling reactions of diazo compounds.2.The reaction mechanisms of the rhodium?III?-catalyzed C-H activation/annulation between aromatic amides and??allenols leading to the formation of isoindolinones have been theoretically investigated using density functional theory?DFT?calculations.The results of our calculations showed that the detailed reaction mechanisms include 4 processes:N-H deprotonation and C-H activation,an??allenol double bond insertion and isomerization,?-H elimination and enol-keto tautomerism,and the formation of final product isoindolinone.In an??allenol double bond insertion and isomerization process?process 2?,we discussed the regioselectivity of the reaction.Two pathways?pathway I and pathway II?were considered:double bonds C4=C5?pathway I?or C3=C4?pathway II?of??allenols insertion into the Rh-C2 bond followed by isomerization.The free energy barrier for pathway I?22.8 kcal/mol?is lower than the pathway II?63.3 kcal/mol?,indicating that the C4=C5 of??allenols insertion into the Rh-C2 bond followed by isomerization?pathway I?is the preferred pathway for process 2.In the formation of final product isoindolinone?process 4?,three pathways?paths I-a,I-b and I-c?were studied.The results of our calculations have shown that the experimentally proposed paths I-a and I-b are kinetically unfavorable.Instead,we have identified a new path I-c as the lowest energy pathway,which include C-N reductive elimination and C-H reductive elimination.The C4=C5 bond of??allenols insertion step is found to be the rate-determining step with an overall free energy barrier of 24.6 kcal/mol.The present study is helpful for a better understanding of the related reaction mechanisms and provides significant implications for the future design of new catalytic systems.