Li, Yaping, et al. Angewandte Chemie International Edition 59.23 (2020): 8907-8911.
Sodium dithionite (Na2S2O4) serves as a dual-functional reagent (SO2 source and radical initiator) in multicomponent decarboxylative sulfonylation, enabling efficient access to sterically bulky tertiary sulfones—key motifs in pharmaceuticals—without extra initiators.
Experimental Protocol: Redox-active esters (carboxylate-derived N-hydroxyphthalimide esters), Na2S2O4 (1:2 molar ratio to ester), and electrophiles (alkyl halides/phosphates) were reacted in DMF/CH3CN (2:1) with DIPEA (base), ZnCl2 (additive), and TBAB (phase transfer catalyst) at 120℃ under N2 for 15 h. Diverse carboxylic acids (natural products, drugs like ibuprofen) were tested.
Performance Evaluation: The reaction afforded tertiary sulfones in 32–79% yields, tolerating heteroatoms and sensitive functional groups. Kinetic studies confirmed decarboxylation (via single-electron transfer) as the rate-determining step. Na2S2O4's dual role simplified the process, avoiding toxic SO2 handling. Natural acids (abietic acid) and drug derivatives (naproxen) converted efficiently, with diastereoselectivity up to 13:1. This green, scalable method is ideal for drug discovery and fine chemical synthesis.