The vicinal difluoro motif: The synthesis and conformation of erythro- and threo- diastereoisomers of 1,2-difluorodiphenylethanes, 2,3-difluorosuccinic acids and their derivatives

David O'Hagan,
Henry S. Rzepa,
Martin Schüler and
Alexandra M. Z. Slawin

Full Research Paper
Published 02 Oct 2006

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1. Graphical Abstract
2. Scheme 1: Synthesis of vicinal dimethyl difluorosuccinates. The conversion of the tartrates 1 with SF₄ and HF ...
  
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3. Scheme 2: Schlosser's route to vicinal erythro- or threo- difluoro alkanes 5 [13].
  
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4. Scheme 3: Halofluorination of electron-rich alkenes with in situ fluoride displacement generates vicinal difl...
  
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5. Scheme 4: Bromofluorination of stilbene [19].
  
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6. Scheme 5: Treatment of anti-14 with base generated the E-fluorostilbene 15 by an anti elimination mechanism.
  
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7. Scheme 6: Hypothesis for the predominent retention of configuration during fluoride substitution via phenoniu...
  
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8. Scheme 7: Proposed C-C bond rotation during the preparation of 14 from cis-stilbene.
  
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9. Figure 1: Crystal structure of erythro-13.
  
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10. Figure 2: X-ray structure of threo-13.
  
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11. Figure 3: Expanded regions of the second order AA'XX' spin systems in the ¹H-NMR (left) and ¹⁹F-NMR spectra (...
  
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12. Figure 4: NMR coupling constants and calculated relative energies (kcalmol^-1) of the staggered conformers of ...
  
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13. Scheme 8: Synthesis of erythro-19 via ozonolysis of erythro-13.
  
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14. Figure 5: X-ray structure of erythro-19.
  
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15. Figure 6: X-ray structure of threo-19.
  
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16. Scheme 9: Strategy for the preparation of diastereoisomers of erythro- and threo- 20.
  
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17. Figure 7: NMR (CDCl₃, RT) coupling constants of erythro- and threo- 2,3-difluoro-3-phenylpropionates 21.
  
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18. Figure 8: Newman projections showing the staggered conformations of erythro- and threo- 21.
  
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19. Figure 9: X-ray structure of methyl threo- 21.
  
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20. Figure 10: The preferred conformation of α-fluoroamides has the C-F and amide carbonyl anti-planar [29,30].
  
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21. Scheme 10: The synthesis of stereoisomers of erythro- and threo- 22. These isomers could be separated by chrom...
  
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22. Figure 11: X-ray structure of erythro-22.
  
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23. Figure 12: Crystal packing of erythro-22 clearly indicating intermolecular hydrogen bonding.
  
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24. Figure 13: X-ray structure of threo-22.
  
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25. Figure 14: The conformations of erythro- and threo- 23 are very different as a consequence of each conformatio...
  
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26. Figure 15: ³J_HF and ³J_HH coupling constants for the erythro (yellow) and threo (blue) diastereoisomers of the ...
  
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27. Figure 16: Newman projections of the three staggered conformations of the erythro and threo stereoisomers of t...
  
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28. Figure 17: The average coupling constant with no conformational bias. The limiting coupling constants J_g = 8 H...
  
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29. Figure 18: The observed ³J_HF coupling constants are an average over the rotational isomers.
  
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