Diversified Fluoroalkylation of Alkenes Using Quaternary Fluoroalkyl Alcohols as the Fluoroalkylating Reagents.

Given the widespread presence of fluoroalkyl functionalities in bioactive molecules, the development of fluoroalkylation reactions with bench-stable and easy-to-use fluoroalkylating reagents is highly desirable. In addition, realization of mono-, di-, tri-, or polyfluoroalkyation usually requires distinct types of fluoroalkylating reagents under different or even harsh reaction conditions, and a universal method to accomplish different hydrofluoroalkylation of alkenes is lacking. Herein, the use of quaternary fluoroalkyl alcohols is reported as the universal fluoroalkylating reagents to readily facilitate mono-, di-, tri-, or polyfluoroalkylation of a wide range of alkene substrates in high yields. Moreover, a cascade reaction of hydrofluoroalkylation followed by intramolecular fluoroalkylation facilitates the construction of a variety of high-value complex heterocycles bearing diverse fluoroalkyl functionalities from alkenes. Mechanistic studies suggest that a proton-coupled electron transfer (PCET) process may be involved through a radical-generating pathway. The utility of this method is showcased by the late-stage fluoroalkylation of various high-value complex molecules derived from either natural products or drug-like compounds. Of note is that a continuous-flow system is amenable to this homogeneous photoredox conditions, thereby opening up a possibility of using this protocol to realize large-scale manufacturing of fluoroalkyl products with industrial interests.