1H and 13C NMR assignments of all three isomeric o-fluoronaphthaldehydes and three o-fluorophenanthrene aldehydes

Article abstract of DOI:10.1002/mrc.2523

Three isomeric o-fluoronaphthaldehydes, 9-fluorophenanthrene, and three previously unreported o-fluorophenanthrene aldehydes were analyzed in detail by multiple NMR techniques to provide unambiguous assignment of structures and resonances. The six aldehyd

Full text of DOI:10.1002/mrc.2523

Spectral Assignments and Reference Data
Received: 28 April 2009
Revised: 16 August 2009
Accepted: 21 August 2009
Published online in Wiley Interscience: 6 October 2009
(www.interscience.com) DOI 10.1002/mrc.2523
1H and 13C NMR assignments of all three
isomeric o-fluoronaphthaldehydes and three
o-fluorophenanthrene aldehydes
Carl A. Busacca,∗ Scot Campbell, Nina C. Gonnella and Chris H. Senanayake
Three isomeric o-fluoronaphthaldehydes, 9-fluorophenanthrene, and three previously unreported o-fluorophenanthrene
aldehydes were analyzed in detail by multiple NMR techniques to provide unambiguous assignment of structures and
resonances. The six aldehydes serve as the key starting materials for novel chiral ligands used in highly enantioselective
c
rhodium-catalyzed asymmetric hydrogenation reactions. Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Keywords: NMR; 1H NMR; 13C NMR; 19F NMR; HOESY; HMQC; HMBC; TOCSY; catalysis; chiral ligands
Introduction
combination of hydrogen bonding between the fluorine atom
and the formyl hydrogen and F–O repulsion strongly favors
this geometry. This isomerism has previously been studied in
o-FB by many analytical techniques including not only NMR[5] but
also infrared[6] and microwave spectroscopy.[7] In each case, the
O-trans form was found to be favored, and the current results are
in concert with these findings. Evidence for this geometry was also
found by analysis of the nuclear overhauser effect spectroscopy
(NOESY) and Rotational nuclear overhauser effect spectroscopy
(ROESY) spectra of aldehydes 1–3. In every case, no NOE from
the formyl proton to the ortho- or peri-proton was observed. In
contrast, these NOE’s were readily observed in commercial 1- and
2-naphthaldehyde.
We have recently developed chiral ligands (BIPI Ligands) for
the asymmetric hydrogenation of functionalized olefins that
proceed with near-perfect levels of enantioselectivity.[1] One of
the best members of this class is BIPI 153 (Scheme 1), which is
prepared in four chemical steps from 1-fluoro-2-naphthaldehde
(1). Significantly higher selectivity was observed with ligands
such as this possessing the naphthyl core, as opposed to those
with a phenyl core, such as BIPI 69, prepared analogously from
o-fluorobenzaldehyde (FB). In order to probe the explanation for
this enhanced enantioselectivity, we needed to prepare and test
theligandsderivedfromtheisomericfluoronaphthaldehydes. This
in turn required the rigorous structural and spectral assignment of
these fluoroarenes, which is the focus of this work.
Application of standard 2-D NMR techniques to fluoroaldehyde
1, whose structural assignment was not in question, allowed
complete 1H and 13C assignments (Table 1) to be made. The most
deshielded ring proton resonance in 1 was observed to be peri-
proton H8, in agreement with the known deshielding effect of
Results and Discussion
fluorine on the peri position in 1-fluoronaphthalene.[8] The 1-D 13
C
Lithiation of 2-fluoronaphthalene with sec-BuLi at −78 ◦C and
quenching with dimethylformamide[2] led to a 1 : 1 mixture of re-
gioisomericaldehydes2and3(Fig. 1),whichwereseparatedbyau-
tomatedcolumnchromatography(Combiflash,silicagel)eluting
withahexane/dichloromethanegradient.Phenanthrenealdehyde
4 was prepared by the analogous lithiation/formylation sequence
starting with 9-fluorophenanthrene,[3a] while aldehydes 5 and 6
were prepared by application of the same formylation method-
ology to 4-fluorophenanthrene and 2-fluorophenanthrene,[3b]
respectively.
data then furnished the J (C,F) coupling constants that we were
particularly interested in. Figure 2 collects this data in structural
form along with established J (C,F) data for 1-fluoronaphthalene
(7).[9] The most conspicuous difference in the comparison of
aldehyde 1 with 7 is the diminished value of 2J (C,F) for C2 in
aldehyde 1. The value has been reduced to 5.5 Hz from 20 Hz in
theparentsystem. Ithaspreviouslybeennoted[8] thatJ (C,F)canbe
severely attenuated by the presence of an electron-withdrawing
substituent in the coupling path between the fluorine atom and
the carbon of interest, as observed here. This attenuation may
extend to the 3J (C,F) value for C3 as well, where the coupling
The structural assignment of aldehydes 1–3 began with
19F heteronuclear overhauser effect spectroscopy (HOESY)
experiments.[4] Thistechniqueprovedtobeextremelypowerfulby
unambiguously identifying the ortho-proton (2,3) or peri-proton
(1) adjacent to the fluorine atom and thereby removing the un-
∗
Correspondence to: Carl A. Busacca, Departments of Chemical Development
certainty due to very similar values of the 1H–1H and 1H–19
F
and Analytical Sciences, Boehringer-Ingelheim Pharmaceuticals, Inc., 900
Ridgebury Rd, Ridgefield, CT 06877, USA.
E-mail: carl.busacca@boehringer-ingelheim.com
vicinal couplings. The HOESY experiments also provided imme-
diate structural information. For all three aldehydes, a strong
HOESY magnetization transfer to the aldehydic proton was ob-
served. This established the existence of a preponderance of the
‘O-trans’ form (as drawn in Fig. 1) for all aldehydes, in which a
Departments of Chemical Development and Analytical Sciences, Boehringer-
Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877,
USA
c
Magn. Reson. Chem. 2010, 48, 74–79
Copyright ꢀ 2009 John Wiley & Sons, Ltd.

1H and 13C NMR assignments
Scheme 1. Ligand Synthesis from Fluoroaldehydes.
Figure 2. J (C,F) couplings in 1 and 7.
transfer to a ring proton that was a dd was observed, while in the
other isomer, this correlation was to a proton which appeared as a
simpledinthe1Hspectrum.TheddhadtorepresentH3inaldehyde
2,whilethed,withonlycouplingto19F,wasH1ofaldehyde3.Addi-
tionalsupportforthisconclusioncamefromthe2-D19F–1HHMQC
spectra [optimized for J (C,F) = 10 Hz] for the two isomers. In one
aldehyde, heteronuclear multiple quantum correlation (HMQC)
correlations from F to two proton resonances each of which were
doublets was observed. This was thus aldehyde 3, with coupling
to H4 (4JHF = 7 Hz) and H1 (3JHF = 11.6 Hz) observed in the HMQC
spectrum. The most deshielded ring proton resonance in aldehyde
2 was the peri-proton, H8, at δ 9.27. This agrees with the known
deshielding zones created by an aromatic aldehyde.[10] Applying
this principle to aldehyde 3 also leads to the correct identification
ofH4asthemostdeshieldedringsignal.The13Cassignmentsagain
allowed us to evaluate the effect of the aldehyde substituent on nJ
(C,F) values for these systems in comparison to the parent system,
2-fluoronaphthalene (8). This data is collected in structural form,
as displayed previously for aldehyde 1, in Fig. 3. In aldehyde 2,
dramatic reductions in J (C,F) for electron-deficient carbons in the
coupling path is again observed for C1 (from 20 Hz to 3.4 Hz), and
C8a (from 9 Hz to 2.2 Hz). In aldehyde 3, the same phenomenon is
found for C3 and C4. A comparison of C3 in these isomers shows
that 3J (C,F) in 3 is significantly smaller than in 2. This agrees
with the known effect of ortho-substitution on this value.[8a,c] The
complete 1H and 13C assignments for aldehydes 2 and 3 are found
in Tables 2 and 3. The 19F resonances of 2 and 3 were observed at
δ −115.5 ppm and −122.9 ppm, respectively. On comparing the
physical properties of these three isomeric arenes, aldehyde 3 was
found to be the least soluble, and also to have the highest melting
point of the three isomers: 36 ◦C (1); 64 ◦C (2); 87 ◦C (3).
Figure 1. Fluorinated arylaldehydes 1–6.
Table 1. NMR data (CDCl3) for fluoroaldehyde 1
HMBC
No. δH ppma nJ (H,H) (Hz) δC (ppm) nJ (C,F) (Hz) correlation
1
NA
NA
7.80b
7.55
NA
7.83d
7.70
7.32
8.18d
NA
162.92
118.74
121.74
124.13
137.82
127.72
129.91
127.12
121.79
123.06
186.78
268
5.5
2
3
8.6
8.6
2.3
4.5
6.6
3.3
1,4a,9
4
1,2,4a,8a
4a
5
8.2
4,7,8,8a
4a,7,8
6
1.3, 6.9, 8.2
0.9, 6.9, 8.5
8.5
7
5,8a
8
6.7
15.5
8.8
1,4a,5,6,8a
8a
9
10.55c
2,3,4
a NA, not applicable.
b 4
J
J
= 6.6 SS.
(H,F)
c 4
= 0.72 Hz.
(H,F)
d Broad doublet.
We next investigated the novel fluorophenanthrene aldehydes
4–6, species with considerable added complexity relative to the
naphthalene structures previously described. Full 1H and 13C
assignments for 4–6 are found in Tables 4, 6, and 7. The melting
points of 4, 5, and 6 were 132 ◦C, 146 ◦C, and 116 ◦C, respectively.
In 4, two H spin systems, H1 to H4 and H5 to H8, are present
(Fig. 4). 19F HOESY allowed us to identify these two groups of
protons by determining initially as to which of the four doublets
has been reduced from 8 Hz in the parent to 2.3 Hz in 1. The 19
resonance of 1 was observed at δ −127.0.
F
We next carried out the detailed NMR analyses of aldehydes
2 and 3, whose structural assignments had not been made. The
HOESY experiments alone were found to be sufficient to correctly
assign the regioisomers. In one isomer, a HOESY magnetization
1
c
Magn. Reson. Chem. 2010, 48, 74–79
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

C. A. Busacca et al.
Table 3. NMR data (CDCl3) for fluoroaldehyde 3
nJ (H,H)
nJ (C,F)
HMBC
correlation
No.
δH ppma
(Hz)
δC (ppm)
(Hz)
1
7.65b
NA
112.21
160.14
124.08
131.93
129.61
129.91
126.25
129.74
127.15
136.94
187.49
19.6
255
13.0
2.7
2,3,4a,8,9
1,2,5,8a,9
2
3
NA
8.41c
4
4a
5
NA
7.99
7.53
7.64
7.84
NA
8.3
7.5, 8.3
7.5, 8.3
8.3
4,7,8a
4a,8
6
2.9
7
5,8a
8
4.9
9.9
5.5
1,4a,6,8a
8a
9
10.44
3,4,4a
a NA, not applicable.
b 3
J
J
= 11.6 Hz.
(H,F)
c 4
= 7.0 Hz.
(H,F)
Figure 3. J (C,F) couplings in 2, 3 and 8.
Table 4. NMR data (CDCl3) for fluoroaldehyde 4
nJ (H,H)
(Hz)
nJ (C,F)
(Hz)
HMBC
correlation
No.
δH (ppm)a
δC (ppm)
Table 2. NMR data (CDCl3) for fluoroaldehyde 2
1
9.34
7.71
7.67
8.63
NA
8.2
126.41
128.93
126.78
122.52
127.52
134.84
122.94
131.10
127.48
122.78
122.46
165.43
113.87
127.97
189.02
6.5
3,10
4,10a
nJ (H,H)
(Hz)
nJ (C,F)
(Hz)
HMBC
correlation
2
7.2, 8.2
7.2, 8.1
8.1
No.
δH ppma
δC (ppm)
3
1,4a,
4
2,4b,10a
1
NA
NA
7.30b
8.10c
NA
116.49
167.02
115.69
138.04
130.52
128.41
126.23
130.16
125.49
130.81
188.97
3.4
262
4a
4b
5
5.8
7.8
2.8
2
NA
3
9.0
9.0
25.6
11.3
1,2, 4a, 9
1,2,4a,5
8.66
7.86
7.73
8.31
NA
8.4
4a,7,8a,9
4b,7,8
6,8a,
4
6
7.5, 8.4
7.5, 8.1
8.1
4a
5
7
7.85
7.55
7.70
9.27d
NA
8.3
4,7
8
9.0
19.1
269
4b,6,9
6
7.6, 8.3
7.6, 8.7
8.7
1.8
4a,8
8a
9
7
5,6,8,8a
1,4a,5,6
NA
8
5.7
2.2
10
10a
11
NA
8a
9
NA
3.1
10.82
13.2
1,8a
10.94
15.6
10,10a
a NA, not applicable.
a NA, not applicable.
b 3
J
J
= 10.7 Hz.
(H,F)
c 4
= 5.6 Hz.
(H,F)
d Hi-res COSY shows coupling to H4, H5, H6.
effect reached its most extreme possible value with C10, where 2J
(C,F) is reduced to zero, from 20 Hz in the parent system. The ring
junction carbon C10a J (C,F) was also reduced from 15 Hz in the
parent to 3 Hz in phenanthrene aldehyde 4. The 19F resonances
of 4 and 7 were observed at δ −124.7 ppm and −122.0 ppm,
respectively (Table 8).
The most deshielded proton resonance in aldehyde 5, at δ
9.12, was found to be the peri-proton H5, as expected. HOESY
spectra showed a strong magnetization transfer from fluorine to
this proton, as expected from the close spatial proximity of the two
nuclei across the ‘bay’ region of 4-substituted phenanthrenes. 19F
HMQC showed a correlation to H5 as well. The 19F chemical shift
of aldehyde 5 was δ −116 ppm (Table 8), which appears at a lower
field than the isomeric and less sterically encumbered species 4
and 6. This is clearly a manifestation of the steric deshielding of 19F
resonances.[11a,b] Analysis of J (C,F) in 5 revealed the large (24 Hz)
4J (C,F) coupling of C5 to fluorine, which was anticipated by the
25 Hz value previously observed for the parent fluoroarene.[11c,d]
found in the 1H spectrum was H8. This key observation, along
with the total correlated spectroscopy (TOCSY) establishment of
sequential couplings, allowed the full 1H and 13C assignments to
be made (Table 4). The most deshielded ring proton resonance (δ
9.34) was found to be peri-proton H1, in complete agreement with
the chemical shift of the peri-proton in the isomeric aldehyde 2 (δ
9.27) described earlier. We wanted to again compare the effect of
the aldehyde substituent on nJ (C,F) values for the ring system, yet
the complete assignment of 9-fluorophenanthrene (9, m.p. 48 ◦C)
had not been previously reported. We therefore performed this
analysis as well, utilizing all of the techniques described above,
as shown in Table 5. The collected experimental J (C,F) values
for aldehyde 4 and the parent system are shown in structural
form in Fig. 4. As was observed for the three systems described
above,attenuationofJ(C,F)forcarbonswithelectron-withdrawing
groups in the coupling path was observed for aldehyde 4, yet this
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 74–79

1H and 13C NMR assignments
Table 5. NMR data (CDCl3) for fluoroarene 9
Table 7. NMR data (CDCl3) for fluoroaldehyde 6
nJ (H,H)
(Hz)
nJ (C,F)
(Hz)
HMBC
correlation
nJ (H,H)
(Hz)
nJ (C,F)
(Hz)
HMBC
correlation
No.
δH (ppm)a
δC (ppm)
No.
δH (ppm)a
δC (ppm)
1
7.84b
7.62b
7.63b
8.65b
NA
128.02
127.21
125.74
122.75
127.81
131.84
122.72
127.62
126.84
121.27
124.25
157.08
107.91
131.82
5.6
3,4a,10, 10a
4,10a
1
7.55b
NA
113.59
161.67
123.00
125.19
126.71
130.53
122.75
127.89
127.26
128.93
131.54
131.43
125.40
137.41
187.29
19.9
257.0
11.0
3.2
H4,10
H1,4
2
2
3
2.2
1,4a
3
NA
9.16c
H1
4
2,4b,10a
4
H1,11
H1,5,10
H6,9,4
H7
4a
4b
5
4a
4b
5
NA
NA
NA
8.70
7.75
7.69
8.22c
NA
8.2
4a,7,8,8a,9,10a
4b,8
8.67d
7.72
7.64
7.89d
NA
8.2
6
7.3, 8.2
7.3, 8.1
8.1
6
1.4, 8.0, 8.2
1.0, 7.9, 8.0
7.9
H8
7
5,8a
7
H5,8
8
5.9
19.8
252
4b,6,9
8
H6,9
8a
9
8a
9
H5,7,8,10
H8,10
H1
NA
7.40d
7.86
7.65
NA
9.0
9.0
10
10a
19.8
15.4
4a,8a,9
10
10a
11
3.5
9.3
5.5
NA
H4,9,10
H1,4
10.52
a NA, not applicable.
b Multiplet: coupling could not be determined due to severe overlap.
a NA, not applicable.
c Broad doublet.
b 3
J
J
= 11 Hz.
(H,F)
d 3
c 4
J
(H,F)
= 11.6 Hz.
= 6.8 Hz.
(H,F)
d Broad doublet.
Table 6. NMR data (CDCl3) for fluoroaldehyde 5
Table 8. 19F NMR data (CDCl3)
nJ (H,H)
(Hz)
nJ (C,F)
HMBC
correlation
Multiplicity nJ (H,F) (Hz)
No.
δH (ppm)a
δC (ppm)
(Hz)
Compound
δF (ppm)
1
7.74
8.02b
NA
8.3
8.3
124.89
123.78
119.13
164.99
121.53
128.58
127.58
128.15
127.67
128.97
132.72
131.70
126.15
138.90
187.35
4.4
3.2
8.8
H10
H1
1
2
3
4
5
6
9
−127.01
−115.44
−122.93
−124.74
−116.33
−122.90
−121.97
d (6.6)
dd (5.6, 10.7)
dd (7.0, 11.6)
s
2
3
H2,9,10
H1,2
4
NA
268
4a
4b
5
NA
8.9
4.5
H1,10
H8
d (6.2)
NA
dd (6.8, 11.0)
dd (1.2, 11.6)
9.12c
7.77
7.71
7.96
NA
8.5
23.6
2.2
H7
6
1.1, 8.1, 8.5
1.0, 7.9, 8.1
1.1, 7.9
H7
7
H6
8
H5,7,9,10
H7,8,9,10
H8,10
H1
The highest field carbon resonance in 6 was C1, at δ 113.59,
showing the effect of fluorine ortho-shielding previously observed
influorophenanthrene9andthenaphthylsystems.C1alsoshowed
an undiminished 2J (C,F) coupling of 19.9 Hz, while the analogous
two-bond coupling of C3, with the electron-withdrawing formyl
group in the coupling path, was reduced to 11 Hz. Observable
nJ (C,F) couplings in 6 were fewer in number (seven) than in the
isomeric phenanthrenes 4 (nine) and 5 (eleven), showing that
the phenanthrene A ring is influenced only weakly by a 2-fluoro
substituent.
8a
9
7.92
7.74
NA
8.8
8.8
10
10a
11
3.4
5.6
H2,9,10
H2
10.69
12.2
a NA, not applicable.
b 4
J
(H,F)
= 6.2 Hz.
c Broad doublet.
In summary, the complete 1H and 13C assignments
of all three possible o-fluoronaphthaldehydes, as well as
9-fluorophenanthrene and three novel, isomeric, o-fluoro-
phenanthrene aldehydes, have been determined. 19F–1H HOESY
2D spectra were used to determine that each of the aldehy-
des studied possessed the O-trans geometry between fluorine
and the formyl group. Critical spectroscopic trends observed in
these systems included shielding of 1H and 13C by o-fluorine,
1H deshielding by the formyl group, 1H deshielding by peri-
fluorine, steric deshielding of 19F, diminished J (C,F) values for
carbons with electron-withdrawing groups in the coupling path,
and through-space coupling of 13C and 19F in the phenanthrene
bay region.
2
The values of J (C,F) for C3 in 5 was diminished (8.8 Hz) by the
presence of the formyl group in the coupling path as previously
discussed, though this attenuation was less severe than in 4. Two-
bond coupling of the bay region quaternary carbon 4a to fluorine
was similarly reduced (8.9 Hz).
The study concluded with the analysis of fluoroaldehyde 6
(Table 7). The most deshielded proton resonance was bay proton
H4, at δ 9.16, while the most shielded resonance was H1 (δ
7.55), in agreement with the trends previously discussed. 19F
HOESY again revealed the O-trans geometry between fluorine and
the formyl proton, and the spatial proximity of bay protons H4
and H5 was readily apparent in the NOESY and ROESY spectra.
c
Magn. Reson. Chem. 2010, 48, 74–79
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C. A. Busacca et al.
points, 1H decoupled) were obtained using a 13C pulse width of 90
degrees, power-gated WALTZ-16 decoupling, a relaxation time of
0.5 s, and a spectral window 36 232 Hz. The data were processed
by zero filling to 64K complex points, applying a line broadening
of 1.0 Hz, Fourier transformed, phased for pure absorption and
baseline corrected using an automatically calculated fourth-order
polynomial function.
gHMQC was found to give sufficient resolution for the
assignment work needed, so that heteronuclear single quantum
correlation(HSQC)wasnotrequired.2-Dgradient-selected1H–13
C
gHMQC data were obtained (2K complex points in f2, 256 real
points along f1) using WALTZ-16 decoupling, a relaxation time of
2.0 spertransient, aspectralwidthof8680 Hzinf2 and36 219 Hzin
f1. Delays were used for a 1J (13C–1H) coupling constant of 145 Hz.
Successive free induction decay (FIDs) along f1 were acquired with
a constant receiver phase. These data were processed by zero
filling to 4K complex points in f2, 512 real points in f1, followed by
QSINEapodizationinbothdimensions, Fouriertransformationand
phasing to achieve pure absorption in both f1 and f2 dimensions.
2-D gradient-selected 1H–13C gHMBC data were obtained (2K
complex points in f2, 256 real points along f1) using WALTZ-16
decoupling, arelaxationtimeof1.5 spertransient, aspectralwidth
of8680 Hzinf2 and36 219 Hzinf1.AstandardBrukerheteronuclear
multiple bond correlation (HMBC) pulse program was used for all
samples using gradient pulses for selection. Delays were based
on a 1J (13C–1H) coupling constant of 145 Hz and an average
long range 2-bond/3-bond J (13C–1H) coupling constant of 4.5 Hz.
Successive FIDs along f1 were used with a constant receiver phase.
These data were processed by zero filling to 4K complex points
in f2, 512 real points in f1, followed by QSINE apodization in both
dimensions, Fourier transformation and phasing to achieve pure
absorption in both f1 and f2 dimensions.
2-D gradient-selected H–1H correlation spectroscopy (COSY)
1
Figure 4. J (C,F) couplings in 4–6 and 9.
data were obtained (2K complex points in f2, 256 real points along
f1) using a relaxation time of 1.5 s per transient, and a spectral
width of 8680 Hz in both dimensions. A 30 degree read pulse was
used. These data were processed by zero filling to 4K complex
points in f2, 512 real points in f1, followed by QSINE apodization in
both dimensions, Fourier transformation and phasing to achieve
pure absorption in both f1 and f2 dimensions.
Experimental
NMR spectra
The 1H NMR experiments were performed on a Bruker-Biospin
DRX600 spectrometer operating at 600.13 MHz and using a
Standard Bore 5 mm TXI (inverse triple resonance) XYZ gradient
probe. 13C NMR experiments were performed on the same
instrumentoperatingat150.92 MHz.19FNMR1Dand2Dcorrelated
experiments were performed on a Bruker AVIII 400 operating
at 376 MHz using a Standard Bore 5 mm BBFO (broad band
fluorine) Z gradient probe. The initial 1H and 13C assignments
were obtained using samples that were approximately 2 mM
in concentration. Samples were prepared by dissolution in about
0.6 mlCDCl3 (Aldrich, 99.9%D, Lot08204KB)followedbytransferto
a standard NMR tube (Wilmad, 535pp) for ana◦lysis. All experiments
were performed nonspinning at 303 or 298 K. 1H chemical shift
assignments are referenced to CDCl3 at 7.27 ppm. 13C chemical
shift assignments are referenced to CDCl3 at 77.00 ppm. 19F
chemical shift assignments are referenced to C6F6 at −162.3 ppm.
The 13C spectrum digital resolution for all samples was 0.5 Hz
1
2-D H–1H TOCSY data were obtained (2K complex points in
f2, 256 real points along f1) using a relaxation time of 1.0 s per
transient, and a spectral width of 8680 Hz in both dimensions.
A 60 ms spin lock time was used. Time proportional phase
incrementation was used to achieve quadrature detection in f1.
These data were processed by zero filling to filling to 4K complex
points in f2, 512 real points in f1, followed by QSINE apodization in
both dimensions, Fourier transformation, and phasing.
2-D 1H–1H NOESY data were obtained (2K complex points
in f2, 512 real points along f1) using a relaxation time of
1.5 s per transient, and a spectral width of 8680 Hz in both
dimensions. A 500 ms mixing time was used. Time proportional
phase incrementation was used to achieve quadrature detection
in f1. These data were processed by zero filling to 4K complex
points in f2, 1K real points in f1, followed by QSINE apodization in
both dimensions, Fourier transformation, and phasing. 2-D 1H–1H
ROESY data were obtained (2K complex points in f2, 512 real
points along f1) using a relaxation time of 1.5 s per transient,
and a spectral width of 8680 Hz in both dimensions. A 200 ms
mixing time was used. Time proportional phase incrementation
was used to achieve quadrature detection in f1. These data were
processed by zero filling to 4K complex points in f2, 1K real points
1
per point. One dimensional H data (32K complex points) were
obtained using a pulse width of 10 degrees, a relaxation time of
2.0 s, and a spectral width of 8680 Hz. The data were processed
by zero filling to 64K complex points, applying a line broadening
of 0.05 Hz, Fourier transformed, phased for pure absorption and
baseline corrected using an automatically calculated fourth-order
polynomial function. One dimensional 13C data (32K complex
c
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 74–79

1H and 13C NMR assignments
in f1, followed by QSINE apodization in both dimensions, Fourier
transformation, and phasing.
[3] (a) M. Zupan, J. Iskra, S. Stavber, J. Fluorine Chem. 1995, 70,
7; (b) A. De Meijere, Z. Z. Song, A. Lansky, S. Hyuda, K. Rauch,
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(d) R. P. Hughes,D. Zhang,A.J Ward,L. N. Zakharov,A. L. Rheingold,
J. Am. Chem. Soc. 2004, 126(19), 6169.
[5] (a) T. Schaefer, C. S. Takeuchi, Can. J. Chem. 1990, 68, 339;
(b) T. Drakenberg, R. Jost, J. M. Sommer, J. Chem. Soc. Perkin Trans. 2
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[6] T. Itoh, N. Akai, K. Ohno, J. Mol. Struct. 2006, 786, 39.
[7] J. L. Alonso, R. M. Villamanan, J. Chem. Soc., Farday Trans. 2 1989,
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[9] (a) B. F. Lutnaes, G. Luthe, U. A. T. Brinkman, J. E. Johansen, J. Krane,
Magn.Reson.Chem.2005,43,588;(b) I. D. Rae,J. A. Weigold,D. G. de
Kowalewski, R. R. Biekofsky, R. H. Contreras, Magn. Reson. Chem.
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2-D 19F–1H HOESY spectra were obtained (1K complex points
in f2, 128 real points along f1) using a relaxation time of 1.5 s per
transient, and a spectral width of 5597 Hz in the f2 dimension
and 33 333 Hz in the f1 dimension. A 700 ms mixing time was
used. States-time proportional phase incrementation was used to
achieve quadrature detection in f1. These data were processed by
zero filling to 1K real points in f1, followed by QSINE apodization
in both dimensions, Fourier transformation, and phasing.
2-D 19F–1H HMQC spectra were obtained (1K complex points
in f2, 256 real points along f1) using globally optimized alternating
phase rectangular pulse (GARP) decoupling, a relaxation time of
1.5 s per transient, a spectral width of 5597 Hz in f2 and 150 602 Hz
in f1. Delays were used for a J (19F–1H) coupling constant of 10 Hz.
Successive FIDs along f1 were acquired with a constant receiver
phase. Thesedatawereprocessedbyzerofillingto1Krealpointsin
f1, followed by QSINE apodization in both dimensions and Fourier
transformation and phasing.
[10] F. A. Bovey, Nuclear Magnetic Resonance Spectroscopy, Academic
Press: San Diego, 1988, p 115.p.
[11] (a) G. W. Gribble, D. J. Keavy, E. R. Olson, I. D. Rae, A. Staffa, T. E. Herr,
M. B. Ferraro, R. H. Contreras, Magn. Reson. Chem. 1991, 29, 422;
(b) W. R. Dolbier, Guide to Fluorine NMR for Organic Chemists, Wiley:
Hoboken, 2009, pp 12; (c) D. J. Sardella, E. Boger, Magn. Reson.
Chem. 1989, 27, 13; (d) D. J. Sardella, L. C. Hsee, Magn. Res. Chem.
1990, 28, 688.
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Magn. Reson. Chem. 2010, 48, 74–79
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