Novel Conversion of Furans and Indols Based on Dearomatization/Aromatization and CuH-catalyzed 3-Hydroindolines Formation from o-Alkynylnitroarene

Author:Peng Hui

Supervisor:yin biao lin


Degree Year:2019





Furan and indole compounds are widely distributed in nature.As a cheap and easily available starting material,we can convert them into a new class of cyclized products with various functional groups by destroying their aromatic structure by chemical methods.The skeleton of these dearomatized cyclized compounds is widely present in natural products,drug molecules with biological activities,and has extremely important application value.Therefore,furan and indole compounds,as important synthetic blocks,have attracted more and more attention in the chemical and industrial fields.At the same time,furans and indols have low aromaticity,and as an important part of dearomatization research,they have maked remarkable achievements in recent years.Despite this,it is still a challenging task to seek a new dearomatization conversion reaction of furans and indols.Our group has long been committed to aromatization research,and has made considerable efforts and accumulated a lot of experience in this field.Therefore,We hope to develop a new method of dearomatization/rearomatization conversion of furans and indoles based on previous studies.Specifically,furan and indol form a highly active intermediate by dearomatization,which has a tendency to rearomatization,and then uses this driving force to complete the relevant conversion.Copper-hydrogen catalyzed reaction is an important part of modern organic chemistry.Under mild conditions,catalytic system of inexpensive copper with environmentally friendly silane can efficiently realize the reductive coupling reaction of unsaturated olefins(alkynes)with electrophilic amine reagents.The copper-hydrogen catalyzed amination reaction usually uses an aniline and a hydroxylamine compound as an amine source.However,the copper hydrogen catalyzed amination reaction using nitro group as both amine and oxygen source was rarely repoted.Therefore,the development of amination of nitroarene using nitro as both nitrogen and oxygen source is of great significance and value in the field of organic chemical synthesis research.In this paper,we investigation on novel conversion of furan and indol based on dearomatization/rearomatization and CuH-catalyzed 3-hydroindolines formation from o-alkynylnitroarene.The specific content is divided into five parts:In chapter two,we developed a furan oxidation dearomatization reaction based on ammonium cerium nitrate(CAN).The reaction is carried out at room temperature,and spiro-lactams was synthesized by reactions of furfurylamines with ynones oxidation by ammonium cerium nitrate.The product of rearomatization,polysubstituted pyrrole,can be obtained by controlling the amount of ammonium cerium nitrate.The reaction is simple in operation,and a good yield can be obtained by reacting in an air atmosphere for one hour,without using any oxidizing agent and additives except for ammonium cerium nitrate,and tolerating various functional groups.This reaction provides a simple,green route to the synthesis of spiro-lactams and polysubstituted pyrrole compounds.In chapter three,we report a one-pot protocol for the synthesis of dispiroacetals bearing a cyclobutane motif via tandem Achmatowicz rearrangement and acetalization of substituted furfuryl alcohol.The highly active dispiroacetals could subsequently undergo Lewis acid–catalyzed ring expansion and skeletal rearrangement to afford 6,7-dihydro-5H-benzofuran-4-ones in good yield.The method has short reaction time,simple operation and wide substrate scope,and promotes the development of a new reaction of furan.In chapter four,we developed a protocol for dearylmethylation of N-(Arylmethyl)carboxamides under metal-free condition in an aqueous medium at room temperature.This protocol involves methyl triflate-mediated successive C–C and C–N bond cleavages(Retro-Mannich reaction)induced by electrophilic dearomatization/rearomatization.Compared with the dearylmethylation reaction reported in the literature,the method has the characteristics of mild conditions and good substrate scope.In chapter five,a variety of Ugi adducts bearing a furan moiety were prepared.The Pd(0)-catalyzed intramolecular arylation of these compounds generate π-allylic palladium complexs that is postulated to initiate furans ring opening and afford polysubstituted indoles after β-hydride elimination.Rapid construction of potentially biologically active indoles by this method,and the molecular diversity was realizedIn chapter six,3-Hydroindolines and 2-aryl-3H-indol-3-ones were diasterospecifically synthesized via CuH-catalyzed intramolecular hydroxyamination of o-alkynylnitroarene in the presence of hydrosilane as the reductant.The protocol employs nitro as both nitrogen and oxygen sources for the intramolecular simultaneous construction of C-N and C-O bonds.Mild conditions,step economy,ready accessibility of the starting materials characterize the present transformation.