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Synlett 2007(4): 0607-0610  
DOI: 10.1055/s-2007-970747
LETTER
© Georg Thieme Verlag Stuttgart · New York

Fragmentation of 4-Sulfonylbicyclo[3.1.0]hexan-2-ones as the Key Step in the Enantioselective Synthesis of (1R)-cis-Chrysanthemic Acid Involving Desymmetrization of 3,3,6,6-Tetramethylbicyclo[3.1.0]hexane-2,4-dione

Alain Krief*, Adrian Kremer
Laboratoire de Chimie Organique de Synthèse, Facultés Universitaires N.-D. de la Paix, 61 Rue de Bruxelles, Namur 5000, Belgium
Fax: +32(81)724536; e-Mail: alain.krief@fundp.ac.be;
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Publication History

Received 6 December 2006
Publication Date:
21 February 2007 (online)

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Abstract

t-BuOK-H2O (7.6:2.3) in THF or DMSO allows the efficient Grob-type fragmentation of 4-sulfonyl-bicyclo[3.1.0]hexan-2-ones which cannot be achieved by potassium hydroxide in DMSO as we originally described.

Key words

ring opening - retro-aldol - nucleophiles - lithiation - chirality

    References and Notes

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  • 1d

    Readily available from dimethyl dimedone.
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  • 11a

    Compound 10a: [α]D 20 -20 (c 1.20, CHCl3).

  • 11b

    Compound 11a exo : [α]D 20 +12.5 (c 1.22, CHCl3).

  • 11c

    Compound 1a Ms-exo : [α]D 20 +55.1 (c 1.11, CHCl3).

  • 11d

    Compound 2a: [α]D 20 +81.7 (c 1.0, CHCl3).

  • 11e

    Compound 12a exo : [α]D 20 +4.9 (c 1.32, MeOH).

  • 11f

    Compound 2a: [α]D 20 +82.2 (c 1.0, CHCl3).

7

Once we found a good method for the fragmentation reaction, we performed the synthesis of scalemic 2a as originally planned by Prof. Nigel Simpkins and informed him. We thank Prof. Nigel Simpkins, School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK for his kindness.

8

These results as well as those on the whole series of stereoisomers disclosed on Scheme [1] will be reported later. For example, we confirmed that the very labile endo-mesylate 1a Ms- endo does not produce chrysanthemic acid 2a neither under conditions A nor optimized conditions B or C.1a,4

12

Norberg, B.; Wouters, J.; Krief, A.; Kremer, A. Acta Crystallogr., Sect. C, to be published.