A Novel and General Synthetic Pathway to Strychnos Indole Alkaloids:  Total Syntheses of (−)-Tubifoline, (−)-Dehydrotubifoline, and (−)-Strychnine Using Palladium-Catalyzed Asymmetric Allylic Substitution

Miwako Mori,* Masato Nakanishi, Daisuke Kajishima, and Yoshihiro Sato
Contribution from the Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
J. Am. Chem. Soc., 2003, 125 (32), pp 9801–9807
DOI: 10.1021/ja029382u
Publication Date (Web): July 17, 2003
Copyright © 2003 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, mori@pharm.hokudai.ac.jp

Abstract

Abstract Image

A method of palladium-catalyzed asymmetric allylic substitution for synthesizing 2-substituted cyclohexenylamine derivatives was established. Treatment of a 2-silyloxymethylcyclohexenol derivative with ortho-bromo-N-tosylaniline in the presence of Pd2dba3·CHCl3 and (S)-BINAPO in THF afforded a cyclohexenylamine derivative with 84% ee in 80% yield. The Heck reaction was carried out to produce an indolenine derivative in good yield. Using this method, we synthesized indolenine derivative 7, which was recrystallized from EtOH to give an optically pure compound. From this compound, tetracyclic ketone 13, which should be a useful intermediate for the synthesis of indole alkaloids, could be synthesized. The total syntheses of (−)-dehydrotubifoline, (−)-tubifoline, and (−)-strychnine were achieved from 13. All ring constructions for the syntheses of these natural products were achieved using a palladium catalyst.

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History

  • Published In Issue August 13, 2003
  • Received November 18, 2002

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