Mild, Fast, and Stereoselective Epoxide Opening by Ketone Enolate Anions. Application to Synthesis of the Norlignan Curculigine Gary H. Posner,* John P. Maxwell,† and Mehmet Kahraman Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, Maryland 21218
[email protected] Received December 18, 2002
We report here that (1) enolate anions of five- to seven-membered cycloalkanones nucleophilically open cyclopentene and cyclohexene oxides in 57-76% yields and with 4-8:1 diastereoselectivity; (2) enolate anions formed regiospecifically via kinetic deprotonation of 2-cyclohexenone and 2-cycloheptenone open cyclohexene oxide in 60-62% yields and with 32-95:1 diastereoselectivity; and (3) an aryl methyl ketone enolate anion opens a monosubstituted epoxide as the key step in a short synthesis of the γ-hydroxyketone (GHK) aglycon of the natural product curculigine. Introduction Nucleophilic enolate anions and electrophilic epoxides are fundamental building blocks in diverse carboncarbon bond-forming reactions, including synthesis of complex target molecules.1,2 Although ester3,4 (pKa 25) and amide5-7 (pKa 28) enolate anions nucleophilically open epoxides, ketone (pKa 20) enolate anions generally do not,3,8 probably as a result of their greater thermodynamic stability. The electrophilicity of epoxides can be enhanced, however, by various Lewis acids. Crotti and colleagues have studied this topic intensively,9 and they have applied especially Lewis acidic scandium triflate to facilitate ketone enolate anion opening of epoxides; typical reaction times are g18 h at room temperature. We reported recently in preliminary fashion a simple, mild (-78 °C) and rapid (
