Synthesis Of Dihydrobenzofurans/dihydroindoles By Intramolecular Friedel-crafts Reaction Of Aryloxyl-/Arylamino-substituted Propargylic Alcohols

Dihydrobenzofurans and dihydroindoles derivatives are universally used as important intermediates in organic synthesis for their high donor ability and activity.They are important structural moieties found in various functional materials and biologically active molecules.Although many viable methods for construction of dihydrobenzofurans and dihydroindoles have been developed,they always suffer from the use of expensive transition-metal catalysts or multistep preparation of the starting materials.Thus,the development of a new strategy for the direct synthesis of dihydrobenzofurans and dihydroindoles from readily available starting materials has important research value.Propargylic alcohols include both terminal acetylenes and hydroxyl functional groups which can take part in several reactions.It’s a high reaction activity intermediate in the synthesis.We can use suitable nucleophiles to trap the allenic carbocation intermediates which can be produced in situ by the Meyer-Schuster rearrangement of propargylic alcohols to form allenes availably.Several heterocyclic and carboncyclic compounds were also gained via Friedel-Crafts from propargylic alcohols.In this paper,the phenol-and amine-substituted propargylic alcohols are synthesized firstly.Then,dihydrobenzofurans and dihydroindoles were synthesized by the Intramolecular Friedel-Crafts Reaction when the propargylic alcohols were catalyzed by FeCl3.Part 1:We synthesized twelve kinds of aryloxides and arylamines from a variety of substituted phenol and N-tosyl amines as the starting materials which react with propargyl bromide.Part 2:16 Phenol-and amine-substituted propargylic alcohols were gained by the reaction of aryloxide and arylamine with ethyl Grignard reagent and ketones.Part 3:11 dihydrobenzofurans and dihydroindoles were synthesized by the Intramolecular Friedel-Crafts Reaction of phenol-and amine-substituted propargylic alcohols using FeCl3 as the catalyst.According to the experiment,the optimal reaction conditions are as follows:phenol-and amine-substituted propargylic alcohols as the starting materials,dioxane as the solvent,1 equiv of FeCl3 as the catalyst,CaH2 as the desiccant at 40 ℃ for 4h under N2,the reaction yield up to 94%.In conclusion,we developed a versatile and direct strategy for the construction of dihydrobenzofurans and dihydroindoles via intramolecular Friedel-Crafts reaction of aryloxyl-and arylamino-substituted using inexpensive FeCl3 as the catalyst under the mild reaction conditions.