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Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Tröger's Base: A Comparative Spectroscopic and Computational Study.

Runarsson, Ögmundur LU ; Benkhäuser, Christian; Christensen, Niels Johan; Artacho Ruiz, Josep LU ; Ascic, Erhad; Harmata, Michael; Snieckus, Victor; Rissanen, Kari; Fristrup, Peter and Lützen, Arne, et al. (2015) In Journal of Organic Chemistry 80(16). p.8142-8149
Abstract
The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in... (More)
The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2. (Less)
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publication status
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Journal of Organic Chemistry
volume
80
issue
16
pages
8142 - 8149
publisher
The American Chemical Society
external identifiers
  • pmid:26244379
  • wos:000360103000032
  • scopus:84939783025
ISSN
1520-6904
DOI
10.1021/acs.joc.5b01236
language
English
LU publication?
yes
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c2b83bbb-b72d-4ad5-bc6c-5267d573664c (old id 7844660)
date added to LUP
2015-09-13 20:36:34
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2017-09-24 03:15:06
@article{c2b83bbb-b72d-4ad5-bc6c-5267d573664c,
  abstract     = {The first reported twisted bis-lactam, a racemic Tröger's base (TB) analogue (2), was resolved into its enantiomers on a chiral stationary phase HPLC column. The absolute configuration of (+)-2 was determined to be (R,R)-2 by comparing experimental and calculated vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra. The absolute configuration of (-)-2 was determined by comparing experimental and calculated electronic circular dichroism (ECD) spectra. The corresponding theoretical spectra were calculated using the lowest energy conformation of (R,R)-2 and (S,S)-2 at the B3LYP/6-31G(d,p) level of theory. The absolute configuration of (+)-2 was also determined to (R,R)-2 by anomalous X-ray diffraction (AXRD) in a chiral space group P212121 using Cu-irradiation resulting in a very low Flack parameter of -0.06(3), despite the heaviest element being an oxygen atom, thus unambiguously confirming the results from the spectroscopic studies. We conclude that, for the Tröger's base (TB) analogue (2), we may rank the reliability of the individual methods for AC determination as AXRD ≫ VCD > ECD, while the synergy of all three methods provides very strong confidence in the assigned ACs of (+)-(R,R)-2 and (-)-(S,S)-2.},
  author       = {Runarsson, Ögmundur and Benkhäuser, Christian and Christensen, Niels Johan and Artacho Ruiz, Josep and Ascic, Erhad and Harmata, Michael and Snieckus, Victor and Rissanen, Kari and Fristrup, Peter and Lützen, Arne and Wärnmark, Kenneth},
  issn         = {1520-6904},
  language     = {eng},
  number       = {16},
  pages        = {8142--8149},
  publisher    = {The American Chemical Society},
  series       = {Journal of Organic Chemistry},
  title        = {Resolution and Determination of the Absolute Configuration of a Twisted Bis-Lactam Analogue of Tröger's Base: A Comparative Spectroscopic and Computational Study.},
  url          = {http://dx.doi.org/10.1021/acs.joc.5b01236},
  volume       = {80},
  year         = {2015},
}