Visible Light-Induced Cascade Cyclization Of Unsaturated Oxime Esters:Access To Fluorine-Containing Pyrrolines

Pyrroline scaffolds are widely spread in bio-active natural products and drug molecules.Therefore,pyrroline is of great significance in the field of natural product synthesis.Recently,the use of unsaturated oxime esters in N-containing heterocycle synthesis has been one of the important strategies for the construction of heterocycle skeletons,especially for the pyrroline ones.The incorporation of fluorine-containing groups（such as trifluoromethyl and trifluoromethanesulfonyl）into pharmaceutical molecules can effectively enhance the metabolic stability and lipophilicity,which is beneficial for the absorption and delivery of drugs.Therefore,the incorporation of trifluoromethyl into molecules has been of great research significance in pharmaceutical chemistry.As an important commercially available fluorine-containing reagent,sodium trifluoromethanesulfinate has been widely used in the synthesis of fluorine-containing compoundsThis thesis aims to construct fluorine-containing pyrroline skeletons and synthesizes CF₃-,CF₃SO₂-substituted pyrroline derivatives via visible light catalysis strategy,and thus eventually to get some lead molecules with potential biological activity and provide useful explorations for the design and synthesis of new pharmaceuticals.This thesis mainly includes the following two parts:（1）Visible light-induced cascade cyclization/trifluoromethylation of unsaturated oxime estersVisible light-induced transition-metal-free cascade cyclization/trifluoromethylation of unsaturated oxime esters has been developed in this part.The optimal reaction conditions were established by the screening of reaction parameters,such as catalysts,solvents,and light sources.Under the optimized conditions,various CF₃-tethered pyrrolines were synthesized in high yields.This method features mild reaction conditions,easily available reagents and the gram-scale synthesis.Additionally,the product could undergo facile reduction by the treatment with DIBAL-H to generate pyrrolidine derivative.Based on the results of radical-trapping and emission quenching experiments,a possible mechanism was proposed.（2）Visible light-induced cascade cyclization/trifluoromethylation of unsaturated oxime estersThis part has developed a synergistic catalytic system with photocatalyst and copper,and established a visible light-induced cascade cyclization/trifluoromethanesulfonylation of unsaturated oxime esters from the same raw materials via chemo-selective control.Under the optimized conditions,a series of CF₃SO₂-tethered pyrrolines were synthesized in moderate to good yields.The gram-scale reaction could also be carried out smoothly.A plausible reaction mechanism was proposed based on the results of radical-trapping experiments.