Synthesis Of Multi-Substituted Pyridine And Indole Derivatives Based On The Catellani Reaction

Heterocycles are important integral components of natural products,pharmaceuticals,pesticides,spices and dyes.Therefore,how to efficiently obtain polysubstituted heterocycles is of great importance that chemical scientists must focus on.Whereas transition metal catalysis is a widely used C-H activation strategy,palladium-catalyzed C-H activation of heterocycles is often limited by catalyst poisoning or side reactions.The Catellani-type C-H functionalization,which is a palladium-catalyzed and norbornene-mediated coupling process,can achieve ortho C-H activation,and the ipso-position can be introduced with a variety of functional groups via traditional cross coupling.It has advantages of low cost,good functional group tolerance,broad substrates range,simple and mild method.Since Catellani reported first in 1996,the application of Catellani-type reaction in arenes has been full-blown,while the application of heterocyclic systems is relatively rare.Under the circumstance of palladium-catalyzed/norbornene-mediated,we developed a method to efficiently build multiple C-C bonds on the pyridine,quinoline and indole substrates by one-pot process.It is further proved that the Catellani-type reaction can effectively overcome the limitation in C-H activation of heterocycles and established multiple C-C bonds formation based on a simple and mild condition.Based on a large amount of literature,the mechanism of Catellani-type reaction applied to 3-iodopyridine substrate was speculated.In this paper,a series of iodide linear paraffins were used as alkylating agents,and acrylates were used as alkylation reagents.The functional group tolerance of those nitrogen-containing heterocyclic substrates was also studied in detail.Finally,ortho-alkylation/ipso-alkenylation were achieved in moderate to good yields.All this series of products were characterized by ¹H-NMR,¹³C-NMR and mass spectrometry.