Research On The Synthesis Of Benzofurans Via C-H Activation Of N-phenoxyacetamides

Background:Benzofuran core,as an important organic small molecule heterocyclic skeleton,is widely present in natural products,biologically active intermediates and agrochemicals.Therefore,related studies toward the efficient construction of this kind of heterocyclic compounds have become one of the research hotspots of the scientific researchers in modern organic synthesis.It is well-known that,the C-H bond is one of the most basic chemical bonds in the structure of organic compounds.In recent years,C-H functionalization have attracted widespread attention of organic chemists as C-H activation strategy can simplify the reaction raw materials,short the reaction process,and synthesize the target compounds in one-pot fashion.Especially,the direct construction of C-C bonds or C-X（X is heteroatom）bonds quickly and efficiently via the C-H activation strategy has become an important means for building numerous molecular skeletons with complex molecular structures and potential biological applications.Objective:To construct a series of small molecular benzofuran skeletons with potential medicinal values efficiently via the C-H activation strategy.Methods:（1）N-phenoxyacetamide and propargyl alcohol were used as model substrates with NaOAc as the additive,and the reaction was carried out in MeOH at room temperature for 24 h under iridium（III）-catalyzed reaction conditions to synthesize the target products.（2）N-phenoxyacetamide and methyl propionate were chosen as model substrates,and the reaction was carried out in MeOH at 50℃ for 48h under the base-mediated condition to synthesize the target products.Results:（1）Under simple and mild reaction conditions,a series of target benzofuran compounds were synthesized with good yield and specific regioselectivity.The structures of the obtained benzofuran products have been characterized by¹H-NMR,¹³C-NMR and mass spectra.（2）Under mild conversion conditions,a series of valuable 2-amino substituted trans-dihydrobenzofuran compounds were directly constructed with high atom economy and good diastereoselectivity.The structures of the synthesized 2-amino-substituted trans-dihydrobenzofuran compounds have been characterized by ¹H-NMR,¹³C-NMR and mass spectra.Conclusion:Through a redox neutral strategy and[3,3]-σrearranged C-H activation reactions,we have developed two methods for synthesizing the drug molecular skeleton of benzofurans efficiently and obtained a series of benzofurans and hydrobenzofuran derivatives,which provides a practical and more atom/step-economic route for the construction and transformation of this kind of structure.