Sunlight Induced And Alternative Sc（OTf）₃ Catalyzed Remote C-H Halogenation Of Indoles

Aromatic heterocycles are one of the basic frameworks in the field of organic synthetic chemistry.Halogenated aromatic heterocycles can be used not only in the fields of flame retardants,fungicides,pharmaceutical pesticides,etc.,but also as important intermediates in various coupling reactions.Therefore,their synthetic methods have attracted much attention.The traditional aromatic heterocyclic halogenation requires high energy consumption and the use of toxic halogenation reagents.The organometallic-mediated or transition metalcatalyzed halogenation method can only activate the C-H bond at the ortho position of the guiding group,and has high reaction cost and high pollution.The photocatalytic halogenation reaction has developed in recent years,which pertinently solves the defects of transition metal catalyzed halogenation reaction,but need to use specific light sources and photocatalysts,and the site selectivity is poor.As a pure and infinite green energy,sunlight is the most ideal light source in photochemical reactions.However,the reported organic reactions mediated by sunlight are mainly used in photocatalytic oxidation reaction,photocatalytic cyclization reaction and photocatalytic olefin insertion reaction,the remote C-H bond halogenation reaction of aromatic heterocycles mediated by sunlight is not involved.In that invention,indole is used as a reaction substrate,and the selective halogenation reaction of the C-H bond at the C5 position of indole is realized unde the induction condition of Lewis acid or sunlight.It has the characteristics of mild conditions,low cost and environmental friendly.The details are as follows:(1)A general method for indole C5-position remote halogenation reaction catalyzed by Lewis acid Sc(OTf)3 is developed.Cheap N-halogenated succinimide is used as a halogen source,hexafluoroisopropanol is used as a reaction solvent,and bromo-and iodo-products at indole C5-position can be obtained with good yield and good regioselectivity.And the method has the advantages of wide substrate range,strong functional group tolerance and very important practical application and later functionalization potential.(2)On the basis of Lewis acid-catalyzed long-distance C-H bond halogenation of indole,we have successfully developed a sunlight-induced selective bromination reaction of indole at C5.An indole C5 bromination product with high regioselectivity was successfully obtained by reacting an indole substrate with NBS for 4-6 h under sunlight.No photocatalyst and oxidant are needed to be added in the whole reaction process,and the sunlight is used as an energy source,so that the energy consumption is reduced,and the method meets the current development concept of green environmental protection.In addition,the reaction features short time,high efficiency,simple operation,and low cost.A general method is provided for the halogenation reaction of the indole remote C-H bond.