Rhodium-catalyzed Synthesis Of Polysubstituted Cyclopenta[b]dihydrobenzofurans

Cyclopenta[b]dihydrobenzofurans possesses a unique tricyclic structure that exists in many natural products such as aplysin, rocaglamide, silvestrol, and related compounds, which display a broad spectrum of bioactivities, and potential application value in biological medicine. To assemble this particular skeleton, the previous reports are less. In this paper, we developed an one- step method cyclization for the synthesis of multi-substituted cyclopenta[b]dihydrobenzofuran, which used rhodium as the catalyst,(E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one and diphenyl acetylene as the start material. This method is convenient with cheap raw materials, which consistent with the guiding ideology of atom economy, sustainable development and green chemistry.The main work of this paper includes the following parts:Firstly, we have taken a preliminary attempt to cyclopenta[b]dihydrobenzofuran,used(E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one and diphenyl acetylene as the start material. After a series of optimization of conditions( ligands, solvents, acids,alkali, temperature, etc.), we choosed the optimum reaction conditions: with 5 mol%[Rh(η5-C5Me5)Cl2]2 as a catalyst, adding 20 mol% AgSbF6, 2 equivalent Cu(OAc)2.H2 O, DCE solvent, 100 oC reaction temperature. The target product(3aR,8bR)-3,3a,8b-triphenyl-3a,8b-dihydro-1H-cyclopenta[b]benzofuran-1-one was obtained in 73% yield.Secondly, the reaction of various substituted(E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one and aryl alkyne were carried out under the optimized reaction conditions to test the reaction applicability. By synthesizing a series of multi-substituted cyclopenta[b]dihydrobenzofuran, we found that the reaction of wider range substrate has wide prospects.Finally, we carried out a lot of probing experiments to explore and reveal the reaction mechanism, and characterized the structure of quinoline products.In conclusion, we proposed a green method of synthesis of cyclopenta[b]dihydrobenzofuran, and a way of C-C bond cleavage, could provides experimental and theoretical basis for the research and development of other cyclopenta[b]dihydrobenzofuran derivatives and C-C bond cleavage.