Synthesis 2015; 47(18): 2819-2825
DOI: 10.1055/s-0034-1380430
special topic
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Total Synthesis of Tylophorine through a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane

Yousuke Yamaoka*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Marie Taniguchi
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Ken-ichi Yamada
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
,
Kiyosei Takasu*
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan   Email: yyamaoka@pharm.kyoto-u.ac.jp   Email: kay-t@pharm.kyoto-u.ac.jp
› Author Affiliations
Further Information

Publication History

Received: 28 April 2015

Accepted after revision: 12 May 2015

Publication Date:
01 July 2015 (online)

Abstract

The asymmetric total synthesis of phenanthroindolizidine alkaloid (–)-tylophorine was achieved by asymmetric transfer hydrogenation of a cyclic imine. The cyclic imine with a pendant phenanthrene core was synthesized by a TfOH-promoted domino ring-contraction/ring-opening sequence of a cyclobutanol bearing an azide group, which was constructed by a formal [2+2] cycloaddition of a 2′-vinyl-1,1′-biaryl-2-yl ketone enolate. Catalytic asymmetric hydrogenation of the cyclic imine intermediate allowed the late-stage construction of the asymmetric center.

Supporting Information

 
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