A DFT Study On The Mechanism Of Palladium-catalysed Tandem Reaction Of Ortho-electron-deficient Alkynyl-substituted Aryl Aldehydes With Indoles

As a kind of important substance in chemistry,N-heterocyclic compounds are widely found in various natural compounds,among which indole derivatives are particularly prominent in drugs and bioactive compounds.Therefore,it is a hot topic for many researchers to study new efficient and environmentally friendly indole derivative synthesis methods.Among the various synthesis methods,the method using metal catalyst to synthesize indole derivatives is the most convenient and universal.The Pd（OAc）₂ has become the preferred catalyst for the synthesis of indole derivatives due to its rich sources,high catalytic yield,non-pollution and reusable advantages.Therefore,the application of Pd（OAc）₂ to catalyze the synthesis of indole derivatives is the most representative.Based on density functional theory,the series reaction mechanism of ortho-electron deficient alkyl substituted aromatic aldehydes with indoles catalyzed by Pd（OAc）₂ was systematically studied.The reaction potential surfaces associated with the catalytic cycle,involving alkynyl coordination,5-exo-dig cyclization,nucleophilic attack,concerted metalation deprotonation（CMD）,HOAc release,HOAc assisted ring opening step,and alkene insertion to ring rearrangement.The results show that Pd（II）ligands with alkynyl groups and Pd（II）ligands with oxygen atoms on aldehyde groups are two potential competitive reaction pathways.The fundamental reason for the interaction between alkenes and Pd（II）to promote the reaction was clarified.When the electron-withdrawing group is used in the cyclization reaction,its presence plays a key role in controlling the size of the ring.The above results can provide detailed theoretical guidance for the exploration of the relevant reaction mechanism.At the same time,it can also provide important reference for the design of catalyst.