JACS: nickel catalyzed [5 + 2] cycloaddition of benzothiophene and alkyne to synthesize 12 π electronic nonaromatic heptahydrobenzothiophene

It is of great significance to study the C-S bond cleavage and catalytic conversion of sulfur-containing aromatic compounds catalyzed by transition metals for understanding the mechanism of devulcanization Recently, Takuya kurahashi and seijiro Matsubara of Kyoto University reported the first official [5 + 2] cycloaddition reaction of 5-benzothiophene and alkyne catalyzed by nickel Seven benzothiophene (scheme 1b) was obtained by dearying This reaction enriches the synthesis of thermally metastable benzothiophene The in-situ X-ray absorption fine structure spectrum and density functional theory calculation confirmed the structure of the intermediate of thionickel substituted vinyl ring formed by the addition of C-S bond and nickel (0) oxidation Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b07948) (source: J am Chem SOC.) the reaction conditions were optimized with benzothiophene 1a and 4-octyne 2A as substrates (Table 1) The nickel catalyst was prepared in situ by the reaction of Ni (COD) 2 and ligand in toluene for 12 hours Through the selection of ligands, solvents and temperature, the author found that the target product 3AA could be obtained by the reaction of substrate with 30 mol% Ni (COD) 2 and 60 mol% PCY 3 in toluene at 30 ℃ for 120 hours with 87% yield (source: J am Chem SOC.) next, the author studied the nickel catalyzed cycloaddition of various benzothiophenes and alkynes (Figure 1) 3-hexyne and 6-dodecyl-ethyne can react smoothly Oxygen substituted alkynes with OME and OTBs can obtain the required seven membered rings in good yield Benzothiophene substituted by electron donor or electron acceptor also has good reactivity (source: J am Chem SOC.) at first, the author thought that the methoxy at C2 position of benzothiophene was necessary for the transformation, which could promote the oxidation addition of C-S bond and nickel (0) It has been shown that neither trifluoromethyl nor methyl substituted benzothiophene can react with alkynes by cycloaddition (Figure 2) In addition, ester group and non substituted benzothiophene do not react with alkynes under standard reaction conditions However, when exploring the substituent effect of benzothiophene at C2 position, the author found that fluorine substituted benzothiophene 4A also participated in the reaction with alkynes (Figure 3) 2-fluorobenzothiophene substituted by methoxy and siloxy can also react (source: j.am Chem SOC.) (source: j.am Chem SOC.) in order to understand the mechanism of the reaction, the author first tried to analyze the nickel complex produced by the oxidative addition of benzothiophene 1a and nickel (0) catalyst by X-ray single crystal analysis, but after purification and recrystallization, no high-quality crystal can be used for X-ray single crystal analysis Therefore, the author analyzed the reaction of Ni (0) catalyst with 1a in toluene by X-ray absorption fine structure (XAFS) The results of EXAFS are in good agreement with the theoretical model of thiovinyl ring 6a, and the R factor is 2.2% (Figure 4) The front edge peak in the X-ray absorption near edge structure (XANES) also indicates the formation of 6A EXAFS and XANES analysis confirmed that thiocycloethane 6A obtained from the reaction of benzothiophene 1A with nickel (0) catalyst is a reasonable key intermediate (source: J am Chem SOC.) finally, the author studied the reaction of benzothioheterocyclic heptane to naphthalene by the heat elimination of sulfur atom Benzothiophene 3AA can be converted to naphthalene 8AA in 86% yield after reaction at 110 ℃ for 24 hours These results show that the sulfur atom can be eliminated in situ during the nickel catalytic cycloaddition of benzothiophene and alkyne at high temperature, and the eliminated sulfur atom may inhibit the catalytic reaction through poisoning Sulfur will not be eliminated from benzothiophene when nickel catalyzed reaction is carried out at a lower temperature (i.e 30 ℃), so 12 π electronic non aromatic benzothiophene can be prepared, which is difficult to achieve through other reactions (source: J am Chem SOC.) conclusion: Kyoto University researchers have developed a method to prepare sulfur-containing seven membered 12 π electronic non aromatic benzothiophene by nickel catalyzed [5 + 2] cycloaddition of 10 π electronic aromatic thiophene ring and alkyne This reaction system provides the first example of nonaromatic compounds for the addition and cyclization of C-C unsaturated bonds and aromatic compounds.