Study On The Synthesis Of Fluoro-containing Indole Derivatives By Dehydrative Coupling Reactions Of Fluoroalkylated Indolyl Alcohols

Alkaloids are a class of very important nitrogen-containing heterocyclic organic compounds,many of which have a wide range of biological activities.Among many alkaloids,indole alkaloids have become a research hotspot because of their wide sources and good biological activity.At the same time,indole alkaloids are also common structural units in natural products and drug molecules.Many compounds containing indole structural units show a wide range of biological activity,such as anticancer,antibacterial and anti-inflammatory.Among them,bisindole are widely used in many fields such as medicine,pesticide and materials.Many compounds containing bisindoles show a series of unique bioactives.On the other hand,fluorine atoms have the characteristics of large electronegativity and small atomic radius.Introducing fluorine atoms or fluorine-containing groups into organic molecules can significantly change their physical and chemical properties and physiological activities.However,the number of natural fluorinated indole derivatives is limited,so it is of great significance to develop a simple,regioselective and mild method to construct fluorinated indole derivatives.Based on this,the thesis have carried out the following two research topics:(1)a green and practical protocol for regioselective dehydrive Friedel-Crafts arylation of trifluorinated3-indolyl(2-thiophenyl)methanols with 2-substituted indoles(2)a green and practical catalyst-free approach for the synthesis of 2-phosphoryl-3-monofluorovinylindoles.Although people have synthesized various bisindole compounds,there is still few study on asymmetric bisindole compounds that incorporate trifluoromethyl groups into heterocyclic rings.Herein,we demonstrate a green and practical protocol for regioselective dehydrive Friedel-Crafts arylation of trifluorinated 3-indolyl(2-thiophenyl)methanols with 2-substituted indoles,forging a diverse array of thiophene-based bisindole derivatives bearing various functional groups using DBSA as the catalyst in water.Notably,the present protocol features operational simplicity,exceptional regioselectivity,mild reaction conditions,and environmental benignity.We also put forward the plausible mechanism of the reaction through a series of control experiments.As the most abundant element in nature,phosphorus is widely used in various fields.Combining it with indole alkaloids has very important research value,but the synthesis of C2-phosphono substituted fluoroalkene indole has not been reported.We herein describe a green and practical catalyst-free approach for the synthesis of 2-phosphoryl-3-monofluorovinylindoles via a cascade regioselective dehydrative phosphorylation/stereoselective defluorination process starting from easily accessible difluoromethylated3-indolylmethanols and H-phosphine oxides.Notably,this protocol features catalyst-and additive-free conditions,excellent regio-and stereospecificity,broad substrate scope,and environmental benignity.On the basis of the above experimental results and previous reports,a plausible reaction mechanism is proposed for this catalyst-free transformation.The paper develops a new method for constructing fluorine-containing or phosphono indole using difluoro and trifluoromethyl indole alcohol,which enriches and expands the research of indole alkaloids and has certain academic significance and potential value.