Synthesis Of Novel Indole Derivatives

Indole compounds is heterocyclic alkaloid derivatives,widely exists in many kinds of natural compounds,biological active compounds and pharmacological active substances,which has significant biological activity.Fluorine is one of the halogen elements.Compared with other halogen,fluorine has unique chemical properties.Fluorine is able to replace the hydrogen or other atom in the bioactive molecules,improving their metabolic pathways and metabolism velocity in different degrees.In some circumstances,fluorine can influence the bioavailability and biological selectivity of drugs.This paper analysis the development prospect of indole derivatives and fluoride drugs,summarize the synthesis methods of quaternary 3,3-Disubstituted 2?Oxindoles,planning to design novel indole derivatives with fluorine,in order to construct a chiral center with fluorine,which can be further develop to be a new indole derivative drugs.This research is aimed at finding new synthesis method for specific indole derivatives,which is environmentally friendly,can be conducted under mild reaction condition,and has higher yield.Currently Selectfluor is the most representative and commonly used fluoride reagent,which is multifunctional as a reactant.Considering the varied abilities of Selectfluor,we believe that Selectfluor is capable to be the reactant which can generate novel indole derivatives.Using selectfluor as reaction media,we can now synthesis a variety of 3,3-disubstituted-2-oxindole derivatives from the corresponding 2-subsituted-indoles.After that we tried to optimize the reaction condition and expand the substrates,and then we successfully synthesis a series of 3,3-disubstituted-2-oxindole derivatives.The best condition we found is that using 1.2 equiv of Selectflour as reactant,acetonitrile as solvent,carrying out under room temperature.The yield of N-methy-3-methy-3-hydroxymethyl-2-oxoindole achieve 76%.The next step is the substrates expansion.We use different functional groups to substitute the N-position,C2 position,C3-positon,and the hydrogen in the indolic Ar ring.The result tells us that this reaction can be widely used in most kind of different substituted substrates to get the corresponding products with satisfactory yield.It's noteworthy that when we used 3-bromo-2-hydroxymethylindole as the substrate,fluorine will replace the bromine atom,and a novel quaternary 3,3-disubstituted-2-oxindole is formed.In conclusion,we have found a new synthesis method to synthesize 3,3-disubstituted 2-oxindole products using 2-subtituted indole substrates.This method is free from metal catalyst or organic catalyst,which means that it allows the reaction conduct under mild condition.We have successfully synthesized a series of 3,3-disubstituted-2-oxidation indole derivatives through the oxidation rearrangement reaction.In addition,we found a new way to introduce fluorine into the quaternary center.A range of 3-fluoro-3-hydroxymethyl-2-oxindole products were got.This method is meaningful to organofluorine chemistry.