Geometry determination of tetrasubstituted stilbenes by proton NMR spectroscopy

Article abstract of DOI:10.1016/j.tetlet.2005.04.001

A simple spectroscopic method was applied to determine the geometry of tetrasubstituted alkenes. The observation of the ⁵J-coupling constants in proton NMR spectra on the ¹³C satellite signals could confirm the previous misassignment of 2,3-diphenylbutene. Hence, the (E)-isomer showed a 1.5 Hz coupling constant, whereas the (Z)-isomer showed a 1.1 Hz coupling constant. Based on this new assignment and a stereospecific preparation, we also propose a revision concerning the NMR data of 2,3-diphenyl-2,3-butanediol.

Full text of DOI:10.1016/j.tetlet.2005.04.001

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 3793–3795
Geometry determination of tetrasubstituted stilbenes by
proton NMR spectroscopy
Viviana S. Flux a´ , Titus A. Jenny and Christian G. Bochet*
Department of Chemistry, University of Fribourg, 9 Chemin du Mus e´ e, CH-1700 Fribourg, Switzerland
Received 22 February 2005; revised 30 March 2005; accepted 1 April 2005
Available online 16 April 2005
Abstract—A simple spectroscopic method was applied to determine the geometry of tetrasubstituted alkenes. The observation
5
13
of the J-coupling constants in proton NMR spectra on the C satellite signals could confirm the previous misassignment of
,3-diphenylbutene. Hence, the (E)-isomer showed a 1.5 Hz coupling constant, whereas the (Z)-isomer showed a 1.1 Hz coupling
constant. Based on this new assignment and a stereospecific preparation, we also propose a revision concerning the NMR data
2
of 2,3-diphenyl-2,3-butanediol.
Ó 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
precludes a direct observation of both NOE effects and
coupling constants. Special NMR techniques, such as
carbon-edited NOESY sequences, have been developed
for this case, but tested so far only on polyaromatic
The geometry of 1,2-disubstituted alkenes is routinely
determined by proton NMR spectroscopy, through the
vicinal coupling constant J. For tetrasubstituted alk-
3
1
hydrocarbons. We report here a quick and simple
enes, the observation of NOE effects or the coupling
between more distant protons is required, for example,
the J constant (Scheme 1).
method to determine the geometry around the double
bond in tetrasubstituted stilbene derivatives, and con-
firm the misassignment of the alkene geometry in the
5
2,3-diphenyl-2-butene previously published.
R1
R2
R1
R2
R3
H
R4
2. Results and discussion
H
H
H
H
H
In the course of a structure–activity study of Tamoxifen
analogues, we had to prepare both 2,3-diphenyl-2-butene
stereoisomers, and ascertain unambiguously their stereo-
chemistry. We chose the simple synthetic sequence
described in Scheme 2.
3J
5J
1
Scheme 1. Geometry determination of alkenes by H NMR.
Non-spectroscopic methods, such as chemical derivati-
zation, are often tedious and X-ray quality crystals are
not always available.
The addition of methylmagnesium bromide to benzil
gave a 90:10 mixture of erythro (meso) and threo (dl)
2,3-diphenyl-2,3-butanediol, which was then converted
into the desired olefins by an Eastwood deoxygen-
In the specific case of symmetrical tetrasubstituted alk-
enes, however, the substituents are related by either a
C -axis for the (E)-isomer or a plane for the (Z)-isomer.
2
–4
ation.
A 94:6 mixture of two olefin isomers was
obtained. The near perfect match between the isomer
ratios of diols and olefins, together with the known reac-
tion mechanism, confirmed the stereospecificity of the
reductive elimination.
2
Hence, the isochronism between the coupling partners
Keywords: Synthesis; Stilbene; NMR.
*
1
13
Corresponding author. Tel.: +41 263008758; fax: +41 263009738;
e-mail: christian.bochet@unifr.ch
Based on comparison of the H and C NMR chemical
shifts of the methyl groups with literature values, we
0
040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.04.001

3794
V. S. Flux a´ et al. / Tetrahedron Letters 46 (2005) 3793–3795
O
OH
Me
MeMgBr
THF
R2
2
O
R1
1
1
2
2
a: R =Me, R =OH
1
2
b: R =OH, R =Me
Me
Me
Me
(
MeO) CH
3
+
BzOH, ∆
Me
3
a
3b
Scheme 2. Simple access to tetrasubstituted stilbenes.
initially assigned 3a as the (Z)-isomer (1.89 ppm and
5.1 ppm, Harom at 7.2–7.4 ppm) and 3b as the (E)-iso-
mer (2.19 ppm and 21.4 ppm, Harom at 6.9–7.1 ppm).
However, simple qualitative inspection of the structures
would predict the opposite assignment. Indeed, the aro-
matic protons in 3a should have usual chemical shifts
1
3
2
Scheme 4. Coupling constants of 3b C-satellites.
5
mer and 3b is the (Z)-isomer. This confirms that the
literature values are erroneous. The same conclusion
was also found by Andersson on the basis of chemical
derivatization and X-ray diffraction analysis. Since
2,4
the reductive elimination is stereospecific, we can also
conclude that the threo isomer is diol 2a (d of the methyl
group at 1.54 ppm) and the erythro is 2b (d of the methyl
group at 1.62 ppm). The assignment from the recent
literature is in this case correct, but older data are
10,11
contradictory.
(
shielding, especially for the ortho protons, by the influ-
around 7.3 ppm), whereas 3b should show a significant
9
6
ence of the nearby aromatic ring. MM2 molecular
modelling confirmed this prediction, showing a skewed
conformation between the two rings (Scheme 3).
5
Moreover, NMR data in a different solvent also showed
4
the reversed assignment. Finally, the addition of an
excess of Grignard reagent to benzil is known to give
In conclusion, a quick and simple known, but frequently
overlooked, spectroscopic method was used to differen-
tiate between E and Z tetrasubstituted olefins. This
technique, however, should be used with confidence only
when both isomers are available, since the differences be-
tween the coupling constants are small and in the range
of substituent effects. This study extends the warning on
the assignment of 2,3-diphenylbutene also to 2,3-diphen-
7
preferentially an erythro stereochemistry. Since the
deoxygenation is stereospecific, the major erythro diaste-
reoisomer 2b should hence lead to a (Z)-alkene. These
discrepancies prompted us to investigate more closely
the NMR data.
12
We took advantage of the well-resolved and intense
methyl signals to avoid the tedious synthesis of isotopi-
cally enriched compounds. Hence, we turned our atten-
tion to the naturally occurring carbon isotope, and
13
yl-2,3-butanediol.
1
3
1
observed the C-satellite signals in the H NMR spec-
trum. The isomer 3a revealed quartet sidebands with a
J coupling constant of 1.5 Hz for the 2.01 ppm signal,
Acknowledgements
5
We thank Mr. Felix Fehr for his assistance in recording
the NMR spectra. The support from the Swiss National
Science Foundation (grant 620-066063) is gratefully
acknowledged.
whereas 3b showed a coupling constant of 1.1 Hz on
the multiplet satellite of the 2.32 ppm peak (Scheme 4).
These values are in total agreement with data measured
8
for 2-butenes. Thus, we conclude that 3a is the (E)-iso-
References and notes
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3
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248–2249.
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. G u¨ nther, H. NMR-Spektoscopie, 2nd ed.; Georg Thieme:
Stuttgart, 1983.
5
6
1
Scheme 3. MM2 structures of 3a and 3b.

V. S. Flux a´ et al. / Tetrahedron Letters 46 (2005) 3793–3795
3795
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3
12. Final NMR data (Bruker Avance 500, in CDCl ) for
1
compound 3a: H: 1.89 (6H), C: 25.1; compound 3b: H:
13
1
1
3
2.19 (6H), C: 21.4.
1
0. Maruyama, K.; Katagiri, T. J. Am. Chem. Soc. 1986, 108,
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1. The melting points quoted for the meso- and the (À)-
6
13. Final NMR data (Bruker Avance 500, in CDCl ) for
3
1
compound 2a: H: 1.54 (6H); compound 2b: H: 1.62 (6H),
1
1
1
3
isomers have to be considered as correct, since they are
C: 143.78, 127.27, 126.90, 126.88, 78.57, 25.11.