Convenient catalytic synthesis and assignment of the absolute configuration of enantiomerically pure dihydronaphthalenes and their corresponding epoxides

Torsten Linker, Frank Rebien, Gábor Tóth, A. Simon, Jürgen Kraus, Gerhard Bringmann

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

In this paper we report on the synthesis and kinetic resolution of 1,2-dihydronaphthalenes by Jacobsen epoxidation, which proceeds smoothly with good selectivity (k(rel) = 6.3 - 9.1). The yields were conveniently adjusted by variation of the number of equivalents of MCPBA (m-chloroperoxybenzoic acid) as the terminal oxidant, to afford enantiomerically pure starting materials or epoxides after one recrystallization. Complete separation of the starting material and the epoxides was effected by HPLC with a chiral stationary phase. Interestingly, the Jacobsen epoxidations afford two diastereomers, whereas the reaction with MCPBA alone proceeds with high diastereoselectivity. This can be attributed to unfavorable steric interactions and a matched-mismatched pair in the transition states. The relative configuration of both diastereomers was elucidated by detailed NMR spectroscopy. Furthermore, the absolute configuration of all products was established unequivocally by comparison of experimental and calculated circular dichroism (CD) spectra. Since the epoxides can be transformed into the etoposide skeleton in only three steps, the kinetic resolution described herein offers simple access to optically active derivatives of these important anticancer drugs.

Original languageEnglish
Pages (from-to)1944-1951
Number of pages8
JournalChemistry - A European Journal
Volume4
Issue number10
DOIs
Publication statusPublished - Oct 1998

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Epoxidation
Epoxy Compounds
Kinetics
Acids
Dichroism
Oxidants
Nuclear magnetic resonance spectroscopy
Crystallization
Etoposide
Derivatives
Pharmaceutical Preparations

Keywords

  • Asymmetric catalysis
  • Circular dichroism
  • Epoxidations
  • Kinetic resolution
  • Quantum-chemical calculations

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Convenient catalytic synthesis and assignment of the absolute configuration of enantiomerically pure dihydronaphthalenes and their corresponding epoxides. / Linker, Torsten; Rebien, Frank; Tóth, Gábor; Simon, A.; Kraus, Jürgen; Bringmann, Gerhard.

In: Chemistry - A European Journal, Vol. 4, No. 10, 10.1998, p. 1944-1951.

Research output: Contribution to journalArticle

Linker, Torsten ; Rebien, Frank ; Tóth, Gábor ; Simon, A. ; Kraus, Jürgen ; Bringmann, Gerhard. / Convenient catalytic synthesis and assignment of the absolute configuration of enantiomerically pure dihydronaphthalenes and their corresponding epoxides. In: Chemistry - A European Journal. 1998 ; Vol. 4, No. 10. pp. 1944-1951.
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