Chem. Pharm. Bull., 53(8),952-957, August 2005

Regular Articles

Asymmetric Synthesis by the Intramolecular Haloetherification Reaction of Ene Acetal: Discrimination of Prochiral Dienes in Cyclohexane Systems

Hiromichi FUJIOKA,^* Naoyuki KOTOKU, Yoshinari SAWAMA, Hidetoshi KITAGAWA, Yusuke OHBA, Tsung-Lung WANG, Yasushi NAGATOMI, and Yasuyuki KITA^*

Graduate School of Pharmaceutical Sciences, Osaka University; 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. * To whom correspondence should be addressed. e-mail: fujioka@phs.osaka-u.ac.jp

A novel asymmetric synthesis of the cyclohexane derivative functionalized by some substituents has been developed from the diene acetals (1), prepared from the corresponding diene aldehyde and (+)-hydrobenzoin. The treatment of 1 with NBS in the presence of MeOCH₂CH₂OH predominantly afforded 2 in a stereoselective manner. Subsequent alkylation of the methoxyethoxy group produced the optically active cyclohexene compounds (3) in good yields. The stereoselective chemical modification of the remaining olefin in 3 was made by OsO₄-oxidation.

Key words desymmetrization; cyclohexa-1,4-diene; intramolecular haloetherification; (+)-hydrobenzoin; ene acetal