Diastereoselective and Regioselective Tunable Cascade Annulation of Prochiral Enone-Tethered Cyclohexadienones

We report a highly diastereoselective and regioselective base- and solvent-controlled cascade annulation of enone-tethered cyclohexadienones with nitroalkanes, affording diverse polycyclic scaffolds with up to six contiguous stereocenters. The use of the less nucleophilic base Et₃N favors the formation of bicyclic products, while DBU promotes the generation of tricyclic frameworks or highly strained fused tetracyclic cyclopropanes, depending upon the solvent. Mechanistic investigations indicate a reaction pathway involving sequential Michael additions followed by nucleophilic substitution of the nitro group. This strategy provides rapid access to structurally complex, highly functionalized polycycles with potential applications in synthetic and medicinal chemistry.