Stereoselective generation and use of <i>α</i> -fluorovinyl radicals via mesolytic cleavage of the C(sp2)–S bond of <i>α</i> -fluorovinyl sulfoximines

Abstract An unusual configurational stability of the α-fluorovinyl radical holds significant potential to synthesize valuable monofluoroalkenes, bioisosteres of amides, in a stereoselective fashion. However, the lack of a suitable precursor for this radical, generated in a stereoselective manner, has hindered its application to the stereoselective synthesis of monofluoroalkenes. Herein, we report the stereoselective generation of the α-fluorovinyl radical, which reacts with disulfide to form α-fluorovinyl sulfides. This method hinges on two key reactions: stereoselective condensation of N-pivaloyl fluoromethyl sulfoximine with an aldehyde to form α-fluorovinyl sulfoximine, and a substitution radical-nucleophilic unimolecular (SRN1)-type reaction involving the nontrivial mesolytic cleavage of the C(sp2)–S bond of the resulting α-fluorovinyl sulfoximines. The generation of the α-fluorovinyl radical was supported by a density functional theory calculation, the Arrhenius equation, and the stereospecificity of the substitution with retention of its original stereochemistry.