Rhodium-catalyzed Regioselective C4-H Activation And Olefination Of Indoles

The indole is one of the most ubiquitous heterocycle exhibiting a wide range of biological activities and is one of the most important structural motif found in natural products and pharmaceuticals.As a result,great effort has been made to develop synthetic methods for the direct functionalization of indoles over the past decades.Transition-metal catalyzed direct C-H bond functionalization has emerged as a versatile strategy in organic chemistry,which avoided the prefunctionalization of the substrates.From the viewpoint of green chemistry,direct C-H bond functionalization becomes the preferred method for the preparation of indole derivatives.However,the functionalization of indoles at N1,C2 and C3 position is easy to achieve,the functionalization of indoles on the benzene ring(C4-C7 positions)is hard,which may provide new challenges and opportunities for the development of functionalization of indoles.Based on our previous research interest in trifluoroacetylation of indoles,in this paper,3-trifluoroacetylindole was used as the substrate,namely trifluoroacetyl group as the directing group,and acrylate was used as the olefination reagent to realize the direct C4-olefination of Indoles.The effect of the molar ration,solvents,catalysts and its loading,additives and its loading and the reaction temperature on the reaction was discussed.The results demonstrated that the reaction proceeded smoothly in the presence of [Rh Cp*Cl2]2(5 mol%)with Ag Sb F6(10 mol%)and Cu(OAc)2·H2O(2.0 equiv)as the additives in DCE for 8 h at 120 oC providing the target product in 83.4% yield.A series of target products were synthesized under the optimized conditions.The reaction system provides a new approach to the direct functionalization of indoles on the benzene ring.