Organocatalytic Michael Addition of β-Ketoesters and Ethenesulfonyl Fluoride: Access to Chiral δ-Sultones via SuFEx Chemistry

Sultones have been gaining popularity within medicinal chemistry due to their vast biological activity; however, access to chiral δ-sultones remains limited. In this study, we have developed an organocatalyzed Michael addition reaction between β-ketoesters and ethenesulfonyl fluoride using a bifunctional thiourea catalyst. This methodology resulted in 11 Michael adducts in yields up to 99% and enantioselectivities up to 84%. Subsequent cyclization under sulfonyl fluoride exchange conditions afforded seven novel chiral δ-sultones in low to moderate yields, generally preserving the enantioselectivity. This work presents an innovative strategy for efficiently synthesizing chiral δ-sultones.