Alkyl Radical Initiated Cyclization/Cascade for Synthesizing Lactam-Substituted Alkyl Sulfones

An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite (K2S2O5) as a connector is developed for the synthesis of various lactam-substituted alkyl sulfones. Notably, this process does not require a metal catalyst or metal powder reductant, highlighting its environmentally friendly features. The reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional groups. Furthermore, the biologically active molecules and commercially available drugs with a late-stage modification are also highly compatible with this transformation. Mechanistic studies revealed that the reaction proceeds through a single-step process involving intramolecular radical cyclization, "SO2" insertion, and external alkyl incorporation.