| 2,3-Fused dihydrobenzofuran structure widely exists in many natural products and biologically active substances,and is an important part of drug molecules.In particular,chiral 2,3-fused dihydrobenzofuranopyrrolidines have received extensive attention from chemists and pharmacologists due to their antimalarial,anti-inflammatory,and antibacterial activities.In this thesis,the application of dinuclear zinc catalysts in the dearomatization reaction has been developed.Catalytic asymmetric dearomatization[3+2]annulations of 2-nitrobenzofurans or 2-nitrobenzothiophenes with N-2,2,2trifluoroethylisatinimine were catalyzed by dinuclear zinc catalysts,generating chiral 2,3-fused dihydrobenzofuran(thiophene)compounds,bearing four consecutive chiral centers,including two quaternary stereogenic centers.Careful screening the reaction conditions(catalysts,solvents,temperature,catalyst loading,and additives),indicated the optimal reaction conditions as follows:10 mol%of catalyst,toulene as solvent,4 A molecular sieve as additive,25℃ for 36 h.Under the optimal condition,35 examples were examined with excellent diastereomer ratios(dr)of>20:1 and enantiomeric excess(ee)of up to 99%.This reaction could be performed on a gram scale,and the absolute configuration of product was confirmed by X-ray single crystal structure analysis.Finally,a possible mechanism was proposed.This is the first application of dinuclear zinc catalysts in catalytic asymmetric dearomatization reaction. |
