Merging halogen atom transfer, ring-expansion and oxidation by electron-rich arenediazonium salts: modular assembly of cyclohexenone derivatives

Abstract

As fundamental structural scaffolds in numerous natural products and pharmaceutical molecules, the construction of cyclohexenone architectures has remained a pivotal focus in organic chemistry. However, established strategies to synthesize cyclohexenone derivatives via Dowd–Beckwith ring-expansion reaction invariably involve the use of transition metals and photoirradiation. Herein, we present a novel transition-metal- and photoirradiation-free pathway to access such structures from α-iodomethyl β-keto esters with electron-rich arenediazonium salts as inexpensive radical initiators and oxidants under mild reaction conditions. The unique aspect of this reactivity is the integration of halogen atom transfer, ring-expansion, and oxidation in one-pot. Further investigation reveals that this method is applicable for modifying complex biologically active molecules, such as epiandrosterone derivatives.