Elsevier

Tetrahedron

Volume 53, Issue 17, April 1997, Pages 6045-6056
Tetrahedron

Efficient Asymmetric Synthesis of the Four Diastereomers of Diphenacoum and Brodifacoum

https://doi.org/10.1016/S0040-4020(97)00254-8Get rights and content

Abstract

A highly stereo- and enantio-selective approach to the four stereoisomers of the rodenticides, diphenacoum and brodifacoum, is described. The key step involves the stereospecific formation of one of the crucial bonds in the molecular backbone, and is based on asymmetric organocopper 1,4-addition to chiral imides. Intramolecular cyclization of the resulting butanoate and coupling with 4-hydroxycoumarin, afford the title compounds © 1997 Elsevier Science Ltd.

Section snippets

EXPERIMENTAL

1H NMR spectra were recorded at ambient temperatures on a Bruker AM-300 spectrometer for solutions in CDCl3 or C6D6 with Me4Si as internal standard. IR spectra were recorded on a Unicam SP 100 spectrophotometer, using 0.1 cm sodium chloride solution cells. High and low resolution mass spectra were obtained on a Kratos MS-80 mass spectrometer. Melting points were measured on a Reichert hot-stage apparatus and are uncorrected. CD measurements were obtained for solutions in MeOH on a Jasco J-710

Acknowledgements

Financial support by the Foundation for Research Development, Pretoria and the ‘Sentrale Navorsingsfonds’ of this University is gratefully acknowledged.

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Cited by (20)

  • Measurement and analysis of diastereomer ratios for forensic characterization of brodifacoum

    2012, Forensic Science International
    Citation Excerpt :

    Approximately equal proportions of the diastereomers [2,3], measured in one case to be 11:9 trans:cis [5], were reported for coupling to the tetrahydronaphthol, while a ratio of approximately 1:5 was reported for coupling to the tetrahydronapthyl bromide [2,3]. More recently, an asymmetric brodifacoum synthesis was reported in which enantiospecific establishment of stereochemistry at the 3′ position was achieved by use of a chiral auxiliary during assembly of the tetrahydronapthone (tetralone) intermediate [6]. Reduction of the tetralone to the alcohol and coupling of 4-hydroxycoumarin yielded diastereomeric mixtures of single enantiomers with trans:cis ratios of 5:4 [6].

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