A novel method for the asymmetric synthesis of 4,4-disubstituted 2-cyclopentenones from optically active 1-chlorovinyl p-tolyl sulfoxides and its application to the asymmetric total synthesis of (+)-α-cuparenone

✍ Scribed by Tsuyoshi Satoh; Masaaki Yoshida; Yasuhiro Takahashi; Hiroyuki Ota

• Publisher: Elsevier Science
• Year: 2003
• Tongue: English
• Weight: 411 KB
• Volume: 14
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/s0957-4166(02)00797-8

✦ Synopsis

Enantiomerically pure 1-chlorovinyl p-tolyl sulfoxides having two different substituents at the 2-position were synthesized from unsymmetrical ketones and (R)-(-)-chloromethyl p-tolyl sulfoxide in three steps. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium at -78°C to room temperature gave optically active 2-amino-1-cyano-5,5-disubstituted-1,3-cyclopentadienes in high yields with very high asymmetric induction from the stereogenic center of the sulfoxide moiety. A mechanism for the asymmetric induction is proposed. The products were treated with phosphoric acid in acetic acid at reflux temperature to give enantiomerically pure 4,4-disubstituted 2-cyclopentenones in good yields. As an application of this synthetic method, a relatively short (seven steps) total asymmetric synthesis of (+)-a-cuparenone from methyl 4-methylphenyl ketone is described.