Influence of relative configuration of disubstituted cyclopentanes and -hexanes on 13C shifts

Article abstract of DOI:10.1002/mrc.2261

¹³C shifts of disubstituted cyclopentane and cyclohexane derivatives were compared in dependence on the relative configuration of the two substituents. A diequatorial substitution correlates with deshielding compared to other substitution patterns. Some novel fluorinated cyclopentanes and -hexanes including their DFT calculation-assisted structure elucidation are described. Copyright

Full text of DOI:10.1002/mrc.2261

Note
Received: 10 March 2008
Revised: 22 April 2008
Accepted: 28 April 2008
Published online in Wiley Interscience: 9 July 2008
(
www.interscience.com) DOI 10.1002/mrc.2261
Influence of relative configuration of
disubstituted cyclopentanes and -hexanes on
13
C shifts
a ∗
a∗
a
Margit Winkler, † Norbert Klempier, Hansj o¨ rg Weber,
a
b
b
Katrin R. Gr u¨ nwald, Michaela Flock and Alk Dransfeld
13Cshiftsofdisubstitutedcyclopentaneandcyclohexanederivativeswerecomparedindependenceontherelativeconfiguration
of the two substituents. A diequatorial substitution correlates with deshielding compared to other substitution patterns. Some
novel fluorinated cyclopentanes and -hexanes including their DFT calculation-assisted structure elucidation are described.
Copyright ꢀc 2008 John Wiley & Sons, Ltd.
Keywords: NMR; 13C-NMR; relative configuration; cyclopentane; cyclohexane; fluorinated carbocycles; DFT calculation
Introduction
Analytical thin layer chromatography was carried out on Merck
Silica gel 60 F254 plates. Flash chromatography was performed on
Merck Silica gel 60, 230–400 mesh. Gas chromatographic analyses
were carried out on a HP5 column with an Agilent 6890N Network
GC system.
During our investigations on the biocatalytic preparation of
cyclic carboxylic acids and amides from the respective nitriles
we collected an ample set of disubstituted cyclopentane and
[
1–5]
cyclohexane derivatives.
The majority of these substances
represent new compounds which had to be fully characterized
including a thorough determination of the relative configuration
of their two substituents. Herein we present a synopsis of
spectroscopic properties ( C shifts) in correlation with relative
configurations of these compounds and the structural assignment
of novel fluorinated carbocyclic compounds.
Synthesis and characterization of novel compounds
(
± )-Trans-2-Fluorocyclohexanecarbonitrile (3p) was prepared
1
3
from (± )-cis-2-hydroxycyclohexanecarbonitrile 4a as follows: 1
equiv. of the alcohol was dissolved in CH2Cl2 and cooled to
◦
−
78 C; 2 equiv. of (diethylamino)sulfur trifluoride (DAST) was
Substituted cyclohexanes are a well-investigated substance
class with respect to configuration and conformation, the
added dropwise. The mixture was cooled for 15 min and stirred
overnight at RT. MeOH was added to destroy the excess of DAST,
and the organic layer was washed with NaHCO3 sat and HCl 2N. Af-
ter drying with Na2SO4 and evaporation, the product was purified
by silica gel chromatography and the fractions analyzed by GC.
Isolated yield: 8% of light yellow oil. The compound decomposes
[
6,7]
latter generally in more detail.
Recently, cis-disubstituted
cyclohexanes were the topic of a detailed investigation toward
[
8]
stereoelectronic and inductive effects. Less attention, however,
was focused on cyclopentane derivatives. Constantino et al.
contributed to this field with several studies toward spectroscopic
properties of cyclopentane derivatives bearing at least three
methyl groups and two different other substituents on the ring.[
◦
1
upon storage at −18 C within weeks. H NMR (CDCl3) δ 1.31–1.40
(m, 2H), 1.55–1.80 (m, 4H), 2.07 (m, 2H), 2.72 (m, 1H), 4.60 (dtd,
9]
13
3
1
H, J = 48.5, 8.7, 3.9 Hz); C NMR (CDCl3) δ 22.3 (d, JFC = 8.2 Hz,
3
2
C-4), 23.4 (C-5), 27.3 (d, JFC = 3.6 Hz, C-6), 30.7 (d, JFC = 18.2 Hz,
2
1
C-3), 34.5 (d, JFC = 21.1 Hz, C-1), 90.1 (d, JFC = 181.8 Hz, C-2),
3
1
19.3 (d, JFC = 0.1 Hz, CN).
Experimental
1
SpectrawererecordedonaVarianINOVA500[ H(499.82 MHz)and
C (125.68 MHz)] at a temperature of 300 K using approximately
1
3
∗
Correspondence to: Margit Winkler and Norbert Klempier, Institute of
OrganicChemistry, GrazUniversityofTechnology, A-8010Graz, Stremayrgasse
16, Austria. E-mail: mw60@st-andrews.ac.uk; klempier@tugraz.at
−
1
1
0 mg ml of the compounds dissolved in CDCl3 in 5-mm o.d.
◦
tubes, unless otherwise stated. The 90 pulses were the following:
1.1 µs for H and 8.0 µs for C. In all, 8 scans were accumulated
for H and 2000 for C. Chemical shifts are given on the δ scale.
1
13
1
†
Current address: School of Chemistry and Centre for Biomolecular Sciences,
University of St. Andrews, KY16 9ST St. Andrews, North Haugh, UK. E-mail:
mw60@st-andrews.ac.uk, Tel: +441334467254 Fax: +441334463808.
1
13
1
Resolution enhancement ( H; digital resolution usually 32, and
sometimes 64 K) was utilized when needed. DEPT, TOCSY1D, and
NOESY1D assisted in structure elucidation. All experiments were
performed through standard pulse sequences as suggested by the
manufacturer of the equipment. Shaped pulses for TOCSY1D and
NOESY1D (iBURP2) were created using PBox.
a Institute of Organic Chemistry, Graz University of Technology, A-8010 Graz,
Stremayrgasse 16, Austria
b Institute of Inorganic Chemistry, Graz University of Technology, A-8010 Graz,
Stremayrgasse 16, Austria
Magn. Reson. Chem. 2008, 46, 865–871
Copyright ꢀc 2008 John Wiley & Sons, Ltd.

M. Winkler et al.
Figure 1. General structures.
Figure 2. Configuration and conformation possibilities of disubstituted cyclohexanes.
(
± )-Cis-2-Fluorocyclohexanecarbonitrile (4p) was prepared
(± )-Trans-3-Fluorocyclopentanecarbonitrile (5p) was prepared
from (± )-cis-3-hydroxycyclopentanecarbonitrile 6a as described
from (± )-trans-2-hydroxycyclohexanecarbonitrile 3a as described
1
1
for 3p. Yield: 30% of light yellow oil. H NMR (CDCl3) δ 1.37–1.42
for 3p. Yield: 59% of viscous dark brown oil. H NMR (CDCl ) δ
3
(
3
1
m, 1H), 1.44–1.50 (m, 1H), 1.60–1.84 (m, 4H), 1.89–2.02 (m, 2H),
1.97–2.09 (m, 4H), 2.25–2.32 (m, 1H), 2.42 (m, 1H), 3.04 (m, 1H),
.01 (dm, 1H, J = 16.6 Hz), 4.66 (ddt, 1H, J = 47.9, 7.8, 3.9 Hz);
13
4
3
.88 (d, 1H, J = 53.7 Hz); C NMR (CDCl3) δ 26.2 (C-1), 28.8 (C-5),
3
3
C NMR (CDCl3) δ 21.5 (d, JFC = 6.7 Hz, C-4), 22.5 (C-5), 26.2
2
2
2.8 (d, JFC = 22.6 Hz, C-4), 39.0 (d, JFC = 22.6 Hz, C-2), 95.0 (d,
JFC = 174.2 Hz, C-3), 122.6 (CN).
3
2
(
d, JFC = 6.4 Hz, C-6), 29.4 (d, JFC = 19.2 Hz, C-3), 33.9 (d,
1
2
1
JFC = 18.2 Hz, C-1), 88.4 (d, JFC = 182.3 Hz, C-2), 119.3 (CN).
(
± )-Cis-3-Hydroxycyclopentanecarbonitrile (6a) was prepared
(± )-Trans-3-Hydroxycyclopentanecarbonitrile (5a) was pre-
1
and isolated as described for 5a. Yield: 63% of colorless oil. H
pared by Michael addition of CN as follows: 1 equiv. commercial
-cyclopenten-1-one in MeOH was added dropwise to a solution
NMR (CDCl3) δ 1.71–1.82 (m, 2H), 1.91–1.94 (m, 1H), 2.05–2.17 (m,
2
13
2
H), 2.23 (m, 1H), 2.42 (s, 1H, OH), 2.78 (m, 1H), 4.35 (m, 1H);
C
of 1.4 equiv. Et3NHCl and 1.2 equiv. of KCN in a 1 : 1 H2O/MeOH
mixture. MeOH was subsequently removed and the remaining
aqueous phase extracted with CH2Cl2 four times. After drying
with Na2SO4, (± )-3-cyanocyclopenten-1-one was isolated as pure
NMR (CDCl3) δ 26.0 (C-1), 29.0 (C-5), 35.2 (C-4), 40.1 (C-2), 72.7 (C-3),
23.6 (CN).
1
(
± )-Cis-3-Fluorocyclopentanecarbonitrile (6p) was prepared
from (± )-trans-3-hydroxycyclopentanecarbonitrile 5a as de-
yellow oil in 94% yield. 1 equiv. of (± )-3-cyanocyclopenten-1-one
scribed for 3p. Yield: 45% of viscous dark brown oil. 1H NMR
◦
was dissolved in MeOH, cooled to 0 C and treated with 1 equiv.
(CDCl3) δ 1.64–1.80 (m, 1H), 2.16–2.19 (m, 3H), 2.25–2.27 (m,
of NaBH4 in small portions. The mixture was stirred until complete
conversion at rt; 2 equiv. of acetic acid were added, the solvent was
removed and the residue taken up in NaHCO3 sat. The products (a
1
H), 2.31–2.34 (m, 1H), 2.85 (m, 1H, J = 7.8 Hz), 5.18 (dm, 1H,
1
3
J = 53.6 Hz); C NMR (CDCl3) δ 26.3 (C-1), 29.2 (C-5), 33.8
2
2
(
d, JFC = 22.6 Hz, C-4), 38.3 (d, JFC = 23.0 Hz, C-2), 94.7 (d,
3
1/69 mixture of 5a and 6a) were isolated by extraction into ethyl
1
JFC = 175.1 Hz, C-3), 122.6 (CN).
acetate, drying with Na2SO4 and evaporation. The diastereomers
were separated by silica gel chromatography. Yield: 21% of 5a
as colorless oil. H NMR (CDCl3) δ 1.56 (s, 1H, OH), 1.71 (m, 1H),
1
1
(± )-Trans-3-Fluorocyclohexanecarbonitrile (7p) was prepared
1
from (± )-cis-3-hydroxycyclohexanecarbonitrile 8a as described
1
.89–1.96 (m, 1H), 1.97–2.06 (m, 2H), 2.10 (m, 1H), 2.23–2.31 (m,
for 3p. Yield: 8% of colorless oil. H NMR (CDCl3) δ 1.48–1.69 (m,
1
3
H), 3.04 (m, 1H), 4.48 (s, 1H); C NMR (CDCl3) δ 25.9 (C-1), 28.9
4H), 1.75–1.93 (m, 1H), 2.14 (m, 1H), 2.85 (m, 1H), 4.82 (dm, 1H,
1
3
3
(C-5), 34.6 (C-4), 40.6 (C-2), 72.5 (C-3), 123.4 (CN).
J = 46.9 Hz); C NMR (CDCl3) δ 19.5 (d, JFC = 3.8 Hz, C-5), 24.2
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Copyright ꢀc 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 865–871

Relative configuration of disubstituted carbocyclic compounds
Table 1. 13C-chemical shifts for ring carbons of cyclopentane derivatives bearing substituents
Compound
R1
R2
C-α
C-β
C-γ
References
Trans 1a
Cis 2a
CN
CN
OH
OH
37.7
36.9
52.3
49.7
39.2
37.1
35.8
35.2
35.0
34.7
53.3
50.3
51.6
47.5
50.9
47.2
51.0
47.9
51.9
50.2
50.9
46.5
50.0
47.9
52.7
46.0
25.9
26.0
26.1
26.2
42.1
42.2
41.4
41.7
26.2
26.3
77.2
73.6
76.3
73.9
59.2
54.9
58.9
56.2
56.4
52.6
58.0
54.6
57.6
57.1
55.1
53.2
55.8
54.8
55.3
55.6
57.7
56.4
54.8
53.0
56.1
56.0
–
–
–
1
13
14
14
15
15
2
Trans 1c
Cis 2c
COOH
COOH
CN
OH
–
OH
–
Trans 1d
Cis 2d
NH2
–
CN
NH2
–
Trans 1g
Cis 2g
CN
NHTs
NHTs
NHBz
NHBz
NH2
–
CN
–
2
Trans 1j
Cis 2j
CN
–
2
CN
–
2
Trans 1e
Cis 2e
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
COOH
COOH
COOH
COOH
COOH
COOH
COOH
COOH
CN
–
16
16
3
NH2
–
Trans 1ha
Cis 2ha
Trans 1ka
Cis 2ka
Trans 1na
Cis 2n
NHTs
NHTs
NHBz
NHBz
NHBoc
NHBoc
NH2
–
–
2
–
2
–
2
–
4
–
16
16
17
3
Trans 1fb
Cis 2fb
–
NH2
–
Trans 1i
Cis 2i
Trans 1la
Cis 2la
NHTs
NHTs
NHBz
NHBz
NHBoc
NHBoc
OH
–
–
2
–
2
–
2
Trans 1o
Cis 2o
–
4
–
18
–
Trans 5a
Cis 6a
72.5
72.7
54.0
54.0
54.9
55.0
54.8
54.9
95.0
94.7
CN
OH
–
–
Trans 5g
Cis 6g
Trans 5ha
Cis 6ha
Trans 5i
Cis 6i
CN
NHTs
NHTs
NHTs
NHTs
NHTs
NHTs
F
–
5
CN
–
5
CONH2
CONH2
COOH
COOH
CN
–
5
–
5
–
5
–
5
Trans 5p
Cis 6p
–
–
CN
F
–
–
a
Determined in DMSO-d6.
Determined in D2O.
b
2
2
∗
13
(
C-1),28.9(C-6),30.1(d, JFC = 20.5 Hz,C-4),34.1(d, JFC = 21.4 Hz,
with the GIAO/B3LYP/6–31 + G method. The C NMR chemical
1
13
C-2), 87.5 (d, JFC = 171.0 Hz, C-3), 122.2 (CN).
shifts were obtained by referencing to tetramethylsilane (σ C =
(
± )-Trans-3-Cyanocyclohexyl benzoate (7q) was prepared by
190.9 ppm) calculated at the same level of theory. An error of
up to +4.6 ppm was established by validating against a set
of carbocyclic compounds with fluoro or cyano substituents.
The coupling constants were computed using the half-and-half
functional BHandHLYP as implemented in Gaussian 03 together
with IGLO-III basis sets.
standard benzoylation of a 90 : 10 cis/trans mixture of (± )-3-
hydroxycyclohexanecarbonitrile. Yield: 9% of 7q as a white solid
after chromatographic separation of the diastereomers on silica
1
gel. H NMR (CDCl3) δ 1.72–1.80 (m, 4H), 1.89 (m, 1H), 1.99–2.04
m, 2H), 2.20–2.23 (m, 1H), 2.98 (m, 1H), 5.35 (s like m, 1H), 7.45 (t,
(
2
1
3
H, J = 7.5 Hz), 7.58 (t, 1H, J = 7.5 Hz), 8.02 (d, 2H, J = 7.5 Hz);
C
NMR (CDCl3) δ 20.2, 24.9, 29.1, 29.6, 33.6, 68.8, 122.1, 128.7, 129.8,
30.4, 133.4, 165.6.
1
Results and Discussion
Disubstituted carbocyclic compounds have been in the center of
our interest for several years, especially carbonitriles, carboxam-
ides, and carboxylic acids with second substituents such as –OH,
–NH2, derivatives thereof, and –F (Fig. 1). The investigation of the
Computational details
Structure optimizations have been performed at the density
functional level of theory using the hybrid B3LYP functional
∗
13
together with 6–31 + G basis sets as implemented in Gaussian
C spectra of cis/trans pairs of these compounds clearly revealed
[
10]
[11] 13
0
3.
The magnetic shieldings of the nuclei were calculated
a trend
:
C shifts of the substituted carbons of disubstituted
Magn. Reson. Chem. 2008, 46, 865–871
Copyright ꢀc 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

M. Winkler et al.
Table 2. 13C-chemical shifts for ring carbons of cyclohexane derivatives bearing substituents
Compound
R1
R2
C-α
C-β
C-γ
C-δ
Configuratione
Reference
Trans 3a
Cis 4a
Trans 3ba
Cis 4bb
Trans 3d
Cis 4d
CN
CN
OH
OH
37.8
36.4
52.1
48.4
38.8
38.0
34.7
35.8
34.5
34.2
50.4
45.4
49.0
44.5
49.1
44.2
49.7
45.2
48.9
44.4
34.5
33.9
24.9
27.0
24.9
26.3
24.9/25.1
26.8
25.9
27.1
26.5
27.0
26.2
27.4
38.6
43.4
39.0
43.4
38.8
43.4
38.3
42.2
38.7
42.2
27.3
27.1
42.4
42.1
47.9
44.3
41.7
39.2
70.9
68.8
69.8
68.2
52.9
51.0
52.9
52.7
50.3
49.0
53.9
52.5
50.5
48.7
52.5
50.0
54.0
52.7
50.2
48.2
90.1
88.4
–
–
–
–
–
eq/eq
ax/eq
19
13
1
CONH2
CONH2
CN
OH
–
–
eq/eq
ax/eq
OH
–
–
13
15
15
4
NH2
–
–
eq/eq
ax/eq
CN
NH2
–
–
Trans 3g
Cis 4g
CN
NHTs
NHTs
NHBz
NHBz
NHTs
NHTs
NHBz
NHBz
NH2
–
–
eq/eq
ax/eq
CN
–
–
2
Trans 3j
Cis 4j
Trans 3ha
Cis 4ha
Trans 3ka
Cis 4ka
CN
–
–
eq/eq
ax/eq
2
CN
–
–
2
CONH2
CONH2
CONH2
CONH2
COOH
COOH
COOH
COOH
COOH
COOH
CN
–
–
eq/eq
ax/eq
3
–
–
2
–
–
eq/eq
ax/eq
2
–
–
2
Trans 3f
Cis 4f
–
–
eq/eq
eq/ax or ax/eq
eq/eq
ax/eq
20
20
4
NH2
–
–
Trans 3i
Cis 4i
Trans 3la
Cis 4la
NHTs
NHTs
NHBz
NHBz
F
–
–
–
–
2
–
–
eq/eq
ax/eq
eq/eqf
ax/eqf
ax/eq
2
–
–
2
Trans 3p
Cis 4p
–
–
–
CN
F
–
–
–
Trans 7a
Cis 8a
CN
OH
65.3
68.7
68.8
70.4
71.5
73.4
49.1
51.3
45.7
47.3
46.6
48.8
49.2
52.5
45.6
48.4
46.6
49.9
49.2
52.1
46.5
49.6
–
–
21
21
–
CN
OH
–
–
eq/eq
ax/eq
Trans 7q
Cis 8q
Trans 7rc
Cis 8rc
CN
OBz
–
–
CN
OBz
–
–
eq/eq
ax/eq
1
CN
OMosher
OMosher
NHTs
NHTs
NHBz
NHBz
NHCbz
NHCbz
NHTs
NHTs
NHBz
NHBz
NHCbz
NHCbz
NHTs
NHTs
NHCbz
NHCbz
OBz
–
–
21
21
5
CN
–
–
eq/eq
ax/eq
Trans 7g
Cis 8g
CN
–
–
CN
–
–
eq/eq
ax/eq
5
Trans 7j
Cis 8j
CN
–
–
5
CN
–
–
eq/eq
ax/eq
5
Trans 7s
Cis 8s
Trans 7ha
Cis 8ha
Trans 7ka
Cis 8ka
CN
–
–
5
CN
–
–
eq/eq
ax/eq
5
CONH2
CONH2
CONH2
CONH2
CONH2
CONH2
COOH
COOH
COOH
COOH
CN
–
–
5
–
–
eq/eq
ax/eq
5
–
–
5
–
–
eq/eq
ax/eq
5
Trans 7ta
Cis 8ta
–
–
5
–
–
eq/eq
ax/eq
5
Trans 7i
Cis 8i
–
–
5
–
–
eq/eq
ax/eq
5
Trans 7u
Cis 8u
–
–
5
–
–
eq/eq
eq/eq
ax/eq
5
Trans 9q
Cis 10q
Trans 9va
Cis 10va
Trans 9fd
Cis 10fd
Trans 9oa
Cis 10oa
–
70.4
70.0
73.0
69.6
52.5
51.8
48.7
47.4
22
22
1
CN
OBz
–
–
CONH2
CONH2
COOH
COOH
COOH
COOH
OBz
–
–
eq/eq
ax/eq
OBz
–
–
1
NH2
–
–
eq/eq
eq/ax or ax/eq
eq/eq
ax/eq
23
23
23
23
NH2
–
–
NHBoc
NHBoc
–
–
–
–
a
Determined in DMSO-d6.
Determined in CD3OD.
Determined in CCl4/CD3OD.
Determined in D2O.
b
c
d
e
f
According to A-value[6] comparison unless otherwise stated.
Calculated.
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Copyright ꢀc 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 865–871

Relative configuration of disubstituted carbocyclic compounds
1
2
2
3
3
Figure 3. The measured F–C spin coupling constants of 3p ( J 181.8 Hz, J 21.1 Hz, J 18.2 Hz, J 8.2 Hz, J 3.6 Hz) match the calculated coupling constants
of 3p eq/eq. The calculated δ 13C chemical shifts are given in parentheses.
1
2
2
3
3
Figure 4. The measured F–C spin coupling constants of 4p ( J 182.3 Hz, J 19.2 Hz, J 18.2 Hz, J 6.7 Hz, J 6.4 Hz) match the calculated coupling constants
of 4p ax/eq. The calculated δ 13C chemical shifts are given in parentheses.
Figure 5. BHandHLYP/IGLO-III calculated fluorine–carbon spin–spin coupling constants for 5p (left) and 6p (right). The measured F–C spin coupling
1
2
2
1
2
2
13
constants of 5p and 6p are ( J 174.2 Hz, J 22.6 Hz, J 22.6 Hz) and ( J 175.1 Hz, J 23.0 Hz, J 22.6 Hz), respectively. The calculated δ C chemical shifts
are given in parentheses.
Magn. Reson. Chem. 2008, 46, 865–871
Copyright ꢀc 2008 John Wiley & Sons, Ltd.
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M. Winkler et al.
carbocycles are shifted to higher parts per million values, the Conclusion
more equatorial substituents the ring carries. Thus, the 13C nu-
A series of disubstituted cyclopentane and cyclohexane deriva-
clei of 1,2-trans, 1,3-cis, and 1,4-trans disubstituted cyclohexanes
are deshielded compared to 1,2-cis, 1,3-trans, and 1,4-cis, respec-
tively. In 1,2 and 1,4-disubstituted cyclohexanes the diequatorial
arrangement corresponds to trans configuration and the 1,3 to
cis (Fig. 2). The shift differences are, on average, smaller for 1,3-
1
3
tives was investigated by comparison of the C shifts of their
substituted carbons. We observed a strong tendency of diequa-
1
3
torially substituted compounds to show deshielded C signals.
The implementation of these findings to the structural elucidation
of novel fluorinated carbocyclic nitriles enabled their complete
spectral assignment with the aid of DFT calculations. Especially,
[
12]
and 1,4- than for 1,2 substitution (up to 6.7 ppm). Cyclopentane
derivatives show the same trend (Table 1) although the conforma-
tional status of the two substituents is more complex compared to
cyclohexane derivatives, where equatorial and axial arrangements
are distinct.[
3
the comparison of calculated and experimental JFC coupling con-
stants enabled the final assignment. Thus, fluorinated carbocyclic
nitriles obey the general trend albeit in a less pronounced manner
than, for example, carbocyclic hydroxynitriles. These results en-
courage the configurational assignment of other diastereomeric
pairs of cyclohexanes and cyclopentanes by simple comparison of
9a]
For substances listed in Tables 1 and 2, 13C data for both the
cis and the trans forms were available either from this lab or
from the literature (only for very few diastereomer pairs of this
13
their C shifts.
1
3
series C data were available and, to our knowledge, the list
is comprehensive; see References). Unless otherwise stated, the
spectra were recorded in CDCl3.
Acknowledgements
The fluorinated compounds 3p–7p (Trans-7p is not included
in Table 2 because data for the corresponding cis isomer was
not available) take exceptional positions in this series. The
assignment of the relative configuration was aggravated due
to synthetic reasons – elimination and retention of configuration
were side reactions of the SN2-exchange procedure during
We thank Carina Illaszewicz-Trattner and Peter Plachota for
technical support.
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[
24]
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[
3
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[
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