关键词: 光氧化还原, 三氟乙氧基化, 胺化, 烯烃

The trifluoroethoxy group represents a valuable fluorinated building block with high metabolic stability and remarkable lipophilicity. It has been successfully incorporated into the molecular frameworks of numerous important pharmaceuticals and agrochemicals. In light of these advantages, the development of efficient and practical strategies for the incorporation of the trifluoroethoxy group has emerged as a prominent research hotspot in modern synthetic chemistry. In this work, an efficient and mild visible-light redox-catalyzed radical trifluoroethoxylation/amination difunctionalization reaction of alkenes with N-trifluoroethoxy benzotriazolium triflate has been successfully developed, providing a new and effective pathway for the precise synthesis of β-trifluoroethoxyamine compounds. This method exhibits good functional group tolerance and a wide substrate scope, being compatible with various common electron-donating and electron-withdrawing functional groups. Among them, nitriles, benzamides, and benzenesulfamides have all been confirmed as suitable nitrogen-centered nucleophiles, which can participate in the reaction smoothly. In addition, this method can also be applied to the late-stage structural modification of drug molecules. The products obtained from the reaction can be derivatized into structurally diverse fluorine-containing derivatives through subsequent functional group transformation reactions, which fully verifies the practical application value of such products in organic synthesis. Preliminary mechanistic studies indicate that this reaction may proceed via a radical pathway. The general procedure for this photoredox-catalyzed radical trifluoroethoxylation/amination of alkenes is as follows: To a mixture of alkene (0.1 mmol), N-trifluoroethoxy benzotriazolium reagent (0.2 mmol), tris(2,2′-bipyridyl)ruthenium(II) chloride hexahydrate (4 mol%) in a 6 mL vial was added nitrile (1.0 mL). The vessel was evacuated and backfilled with Ar three times. The tube was screw-capped and stirred at room temperature under irradiation with 30 W blue LEDs (distance approximate 2 cm) for 5 h. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel using a mixture of petroleum ether and ethyl acetate as the eluents to afford the desired products.

Key words: photoredox, trifluoroethoxylation, amination, alkene