Visible-Light Photocatalytic Remote Halo-difluoroalkylation of Thioalkynes

Abstract

Fluoroalkylated alkenes are of significant importance in life sciences and functional materials. The fluoroalkylation of alkynes offers an efficient method for the synthesis of functionalized fluoroalkylated alkenes. However, the current methods are often limited to 1,2-difunctionalization, while the remote fluoroalkylative difunctionalization of alkynes has been rarely developed. Herein, a novel visible-light-induced remote halo-difluoroalkylation of thioalkynes is realized with difluoroalkyl halides as the radical source, forming distally halogenated (Z)-fluoroalkylated alkenes in moderate to high yields with excellent regio-, stereo-, and site-selectivity. The notable features of this reaction include the mild reaction conditions, broad substrate scope, concurrent formation of three new chemical bonds, and a thermodynamically less stable (Z)-alkene, thus enabling it a highly attractive method for organic synthesis. It represents a new advance on the direct C-H bond halogenation. Preliminary mechanistic studies indicate a cascade radical process involving the heteroatom-induced β-fluoroalkylation of C-C triple bonds, intramolecular 1,5-hydrogen atom transfer (1,5-HAT), single electron transfer (SET) oxidation and halide addition.

Recent advances in hydrogen atom transfer induced C(sp3)–H functionalizations initiated by radical addition to alkynes

“…The authors demonstrated this strategy in the remote ketofluoroalkylation, hydroxytrifluoromethylation, and bromofluoroalkylation of heteroalkynes (Scheme 24b). 54 The mechanisms for these reactions were proposed as follows. The reduction of Umemoto's reagent or fluoroalkyl halides by excited photocatalysts provided a fluoroalkyl radical.…”

Sulfur in Waste‐Free Sustainable Synthesis: Advancing Carbon–Carbon Coupling Techniques

“…[111,112] Under photocatalytic reaction conditions, 1,5-HAT-mediated halogen transfer allows for a more complex radical cascade (Scheme 13b). [111,112] Regarding metal-catalyzed processes, it is to be noted that alkynyl sulfides predominantly exhibit high reactivity in the form of cationic intermediates (Scheme 14). This property has been applied in both intermolecular [113] and intramolecular hydroarylation reactions of alkynes.…”

Sulfur in Waste‐Free Sustainable Synthesis: Advancing Carbon–Carbon Coupling Techniques

“…[110] In addition to effective stabilization of cationic intermediates, alkynyl sulfides are excellent traps for electrophilic radicals and are capable of maintaining a halogen transfer radical addition chain reaction (Scheme 13a). [111,112] Under photocatalytic reaction conditions, 1,5-HAT-mediated halogen transfer allows for a more complex radical cascade (Scheme 13b). [111,112] Regarding metal-catalyzed processes, it is to be noted that alkynyl sulfides predominantly exhibit high reactivity in the form of cationic intermediates (Scheme 14).…”