The Synthesis Of3-trifluoromethyl-indazoles And One-pot Synthesis Of Halogenated2,3-dihydroquinolin-4(1H)-ones

Part one: Trifluoromethylated compounds are receiving increasing attentionbecause of the unusual and profound effects on physical properties imparted by theintroduction of the CF3into organic molecules.1H-indazole is a pharmaceuticallyimportant class of nitrogen-containing heterocycles with important biological andpowerful pharmacological activities. In this context, indazoles featuring atrifluoromethyl substitution are attractive targets with regard to their potentialbioactivity. However, although numerous synthesis of the indazole core has beendescribed, the efficient method for the construction of related indazoles bearing atrifluoromethyl group is still rare reported. We attempt to synthesizetrifluoromethylindazoles by [3+2] cycloaddition of CF3CHN2as a1,3-dipole witharynes. The reaction conditions such as the fluorides and its loading, additives,temperature, and solvents were optimized. Finally, fifteen3-trifluoromethyl-1H-indazoles were obtained in up to85%yields by using2.4equiv of CsF in thepresence of TEBAC in THF at25oC.Part two:2,3-Dihydroquinolin-4(1H)-one scaffolds are present in many naturaland unnatural compounds that exhibit important biological activities. Our group hasdeveloped a novel and efficient one-pot multi-step procedure for the facile synthesisof fluorinated2,3-dihydroquinolin-4(1H)-one derivatives from simple startingmaterials and under mild conditions. Then, this methodology was further extended toafford the corresponding chlorinated/brominated products of a fluorinated product.The structure of brominated product is different from the corresponding fluorinatedand chlorinated products which were confirmed by X-ray crystallography analysis. Tocontinue our previous work, we further focused our studies on the stereoselectivesynthesis of chlorinated and brominated2,3-dihydroquinolin-4(1H)-ones via one-potmulti-step transformation based on our previous work. Thirty-six products wereobtained in good yields and excellent diastereoselectivities. Based on these results, apotential reaction mechanism was proposed.