Construction of Medium- and Large-Sized Cyclic β-Keto Esters (or Nitriles) via One-Pot Three-Carbon Ring Expansion of Carbocyclic β-Keto Esters and Its Application to the Synthesis of (-)-Muscone

Article abstract of DOI:10.1021/jo00290a009

A one pot, three-carbon ring expansion involving intramolecular aldol condensation and subsequent retro-aldol cleavage is induced by treatment of β-keto esters with potassium tert-butoxide in dimethyl sulfoxide to afford functionalized 8-,9-,10-, and 15-membered rings, respectively.The stereochemistry of intermediate 21 was established to be a cis-fused carbocyclic ring system with the methyl ketone in the cis position.The mechanism for the three-carbon ring expansion is explained by considering the dual function of the electron-withdrawing group (EWG).An iterativering expansion was accomplished by the facile conversion of 8 to 20.Application of this ring expansion method to the synthesis of (-)-muscone further attests to the generality of this reaction.