Study On The Asymmetric Synthesis Of CF₃-Containing Benzohexaheterocyclic Heterocyclic Compounds

Heterocyclic compounds are widely present in nature,and their applications are constantly expanding.Benzo-six-membered heterocycle is one of the major representatives in this large heterocyclic family,most of which could be widely used as important bioactive molecules and pharmaceutical intermediates in medical,agricultural and material fields.Many CF₃-containing benzohexacyclic heterocyclic compounds have special medicinal value and have been used in clinical diagnosis and treatment.However,the asymmetric synthesis of such CF₃-containing heterocyclic compounds is very limited.Therefore,the asymmetric introduction of CF₃-into benzo-six-membered heterocyclic compounds is still a challenge.We introduced CF_3-into the 2-position of benzo-six-membered nitrogen-,oxygen-and sulfur-containing compounds through organic catalytic asymmetric methods to give a series of CF₃-containing heterocyclic compounds in excellent yields and stereoselectivities.Firstly,we introduced CF₃ asymmetrically into chromanes by squaramides-catalyzed cascade reaction of2-hydroxychalcones withβ-CF₃-nitroalkenes to obtain the reaction products bearing three contiguous stereogenic centers in up to 96%yields and 99%ee.Secondly,we introduced CF₃asymmetrically into thiochromanes by squaramides-catalyzed Michael-Aldol reaction of2-mercaptobenzaldehyde withβ-CF₃ enones to afford the reaction products in up to 91%yields and 97%ee.Thirdly,the squaramides-catalyzed Michael-Aldol reaction of2-mercaptobenzaldehyde withβ-indole-β-CF₃ enones introduced asymmetrically both CF₃ and indole into thiochromanes and afforded the products in up to 88%yields and 96%ee.Finally,the thioureas-catalyzed cascade reaction of 2-aminochalcones withβ-CF₃-nitroalkenes gave the CF₃-containing tetrahydroquinolines in up to 94%yields and 99%ee.Our study provides simple and efficient synthesis methods for the asymmetric introduction of CF₃ into benzo-six-membered heterocyclic compounds,which is of great value in the synthesis of those kinds of compounds.