Henry reaction of fluorinated nitro compounds

Article abstract of DOI:10.1016/j.jfluchem.2011.09.004

The Henry (nitroaldol) reaction of fluorinated nitro compounds with various aromatic aldehydes and a fluorinated aliphatic aldehyde to give β-fluoro-β-nitroalcohols which bearing a fluorinated quaternary carbon center was reported. The relative configuration of the major diastereoisomer of 2-fluoro-2-nitro-1-(4-nitrophenyl)-3-phenylpropanol (5bf) was determined by X-ray single crystal analysis.

Full text of DOI:10.1016/j.jfluchem.2011.09.004

Journal of Fluorine Chemistry 133 (2012) 108–114
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Henry reaction of fluorinated nitro compounds
a
a,
b,
Huawei Hu , Yangen Huang *, Yong Guo **
a
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Road, Shanghai 201620, China
b
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The Henry (nitroaldol) reaction of fluorinated nitro compounds with various aromatic aldehydes and a
Received 30 June 2011
fluorinated aliphatic aldehyde to give
carbon center was reported. The relative configuration of the major diastereoisomer of 2-fluoro-2-nitro-
-(4-nitrophenyl)-3-phenylpropanol (5bf) was determined by X-ray single crystal analysis.
ß 2011 Elsevier B.V. All rights reserved.
b-fluoro-b-nitroalcohols which bearing a fluorinated quaternary
Received in revised form 31 August 2011
Accepted 6 September 2011
Available online 16 September 2011
1
Dedicated to Professor Wei-Yuan Huang
on the occasion of his 90th birthday.
Keywords:
Henry reaction
Organocatalysis
Enantioselectivity
Aldehyde
Fluorine
1
. Introduction
fluorinated quaternary carbon center, which is highly desirable
motif in numerous drug molecules [22–25]. Fluoronitroalkane is
less studied as a monofluorinated synthetic synthon compared to
Since its discovery in 1895, the Henry (nitroaldol) reaction
becomes one of the most important carbon–carbon bond forming
reactions in organic synthesis. The resulted -nitroalcohol is
versatile intermediate in the synthesis of a variety of natural
products and medicinally important compounds [1–8]. While the
Henry reaction has been extensively studied in numerous
synthetic processes, few studies of halogenated nitroalkanes have
been reported [9].
fluoronitroester [26–29]. For a recent example, using
a-fluoro-a-
b
nitro esters, Zhao and their coworkers reported an organocatalytic
asymmetric Michael addition [28]. In contrast, few reactions of
fluoronitroalkane have been reported, to the best of our knowledge
[29]. Herein we report the Henry reaction of fluoronitroalkanes to
give
b-fluoro-b-nitroalcohols with a fluorine-containing quater-
nary carbon center in high yields.
Fluorine-containing compounds have attracted considerable
attention for introduction of fluorine to organic compounds can
drastically change both their biological and physical properties
2. Results and discussion
[
10–20]. It was reported that as many as 30–40% of agrochemicals
and 20% of pharmaceuticals including four of the top ten best-
selling drugs on market were estimated to contain fluorine [20,21].
Accordingly, the development of methodologies to incorporate
fluorine into organic molecules has attracted great attention
As shown in Tables 1 and 2, fluoronitroalkanes 3a–3e were
prepared via nitroalkanes 2a–2e starting from halides 1a to 1e
[30,31]. Reaction of 1-fluoro-1-nitroheptane 3a and benzaldehyde
4a was chosen as the model reaction to optimize the reaction
conditions. A variety of bases including organic and inorganic bases
were screened as the catalyst (Table 3, entries 1–8). It was found
that 1,1,3,3-tetramethylguanidine (TMG) was found to be the most
effective, giving product 5aa in 67% yield with a diastereoselec-
tivity of 30:70. Interestingly, The decrease in dosage of TMG from
recently [10–20]. We envisioned that the addition of
a-fluoroni-
troalkanes to carbonyl compounds to form fluorinated
b
-hydro-
xynitroalkanes could represent one of these important methods.
Moreover, the Henry reaction of fluoronitroalkane gives rise to
50 mol% to 30 mol% resulted similar yield and the same
diastereoselectivity (Table 3, entry 8 vs 9). The reaction conditions
were further optimized by changing the solvents (Table 4, entries
*
Corresponding author. Tel.: +86 21 67792612; fax: +86 21 67792608.
*
* Corresponding author. Tel.: +86 21 54925462; fax: +86 21 64166128.
1–5). Finally, THF (Table 4, entry 2) was found to be the preferential
E-mail addresses: hyg@dhu.edu.cn (Y. Huang), yguo@sioc.ac.cn (Y. Guo).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.09.004

H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
109
Table 1
Table 3
Synthesis of nitro compounds.
Effects of base catalysts.
X
a or b
NO
2
R1
R1
1
2
1
Entry
Substrate
R
X
Product
Temp (8C)
Yield (%)
a
a
a
1
2
3
4
1a
1b
1c
1d
n-C
6
H
13
I
2a
2b
2c
2d
r.t.
62
Entry
Cat.
CO
Yield (%)
Syn:anti
b
C
6
H
5
CH
2
I
60
60
a
1
2
3
4
5
6
7
8
K
2
3
38
36
45
35
60
26
29
67
70
26:74
26:74
23:77
46:54
31:69
57:43
44:56
30:70
30:70
Ph
Br
Br
À18
r.t.
45
a
Cs
2
CO
f-BuONa
Et
3
35
3
N
O
O
DBU
DABCOÁ6H
DIPEA
TMG
2
O
a
5
1e
Br
2e
r.t.
30
b
9
TMG
a
DABCO, triethylenediamine; DIPEA, ethyldiisopropylamine, TMG, tetramethylgua-
nidine.
NaNO
AgNO
2
/urea in DMF.
b
2
2
in H O.
a
19
Yields and Syn:anti determined by F NMR.
b
30% TMG was used.
Table 4
solvent in terms of the yield (67%). Reactions in other solvents,
such as CH Cl , EtOH, toluene and MeCN, gave lower yields.
After the optimal reaction condition was found (30 mol% of
TMG in THF), the diastereoselective Henry reactions of
Effects of the solvent.
2
2
a
-
fluoronitroalkanes 3a–3e and various aldehydes 4a–4h were
investigated. As summarized in Table 5, the Henry reaction
between
a-fluoronitroalkanes 3a/3b and different aromatic
aldehydes in the presence of 30 mol% TMG in THF at room
temperature led to desired products in moderate to good yield (40–
a
a
Entry
Solvent
CH CL
Yield (%)
Syn:anti
8
0%) (Table 5, entries 1–10). In general, aromatic aldehydes
bearing electron-withdrawing groups showed higher reactivity
than those with electron-donating groups. In contrast to
1
2
3
4
5
2
2
32
67
60
45
34
33:67
30:70
31:69
37:63
29:71
a
-
THF
EtOH
fluoronitroalkanes 3a/3b, compound 3c–3e seemed to be more
reactive since the reactions at ambient atmosphere produced a
complex mixture. However, when the reactions of 3c–3e were
carried out at a lower temperature (approximately À30 8C), the
reactions went smoothly to afford the nitroaldol products in 60–
toluene
MeCN
a
19
Determined by F NMR.
8
5% yields (Table 5, entries 11–15). Interestingly, some of the
the same reaction conditions, giving a 73% yield of the nitroaldol
product in a 27:73 diastereoselectivity. Both isomers except 5df of
nitroaldol products were obtained and fully characterized after a
careful separation by column chromatography on silica gel. Owing
nitroaldol products were unstable when subjecting to silica gel
chromatograph. The products 3c and aromatic aldehydes (e.g. p-
nitrobenzaldehyde) of retro Henry reaction were isolated. The
Henry reaction of fluoroalkylaldehyde was studied. 1-Fluoro-1-
phenyl-1-nitromethane 3c reacted smoothly with 5-chloro-
2
,2,3,3,4,4,5,5-octafluoropentanal 4i (Table 5, entry 12) under
Table 2
Monofluorination of nitro compounds.
Š
1
Entry
Substrate
R
Product
Yield (%)
1
2
3
4
2a
2b
2c
2d
n-C
6
H
13
3a
3b
3c
3d
82
80
75
76
6 5 2
C H CH
Ph
Fig. 1. X-ray structure of anti-5bf. Selected bond lengths ( A˚ ) and (torsion) angles (8):
O
O
F(1)–C(1) 1.358(19), N(1)–O(2) 1.209(2), N(1)–O(3) 1.216(2), N(1)–C(1) 1.542(2),
O(1)–C(2) 1.419(2), C(1)–C(9) 1.512(2), C(1)–C(2) 1.527(2); O(2)–N(1)–C(1)
1
1
18.85(16), O(3)–N(1)–C(1) 15.71(13), F(1)–C(1)–C(9) 110.32(15), F(1)–C(1)–C(2)
09.25(14), C(9)–C(1)–C(2) 117.09(14), F(1)–C(1)–N(1) 105.24(12), C(9)–C(1)–N(1)
5
2e
3e
73
108.35(13), C(2)–C(1)–N(1) 105.84(14), O(1)–C(2)–C(3) 111.90(15), O(1)–C(2)–
C(1) 104.72(14), C(3)–C(2)–C(1) 112.81(15), C(1)–C(9)–C(10) 112.89(13); F(1)–
C(1)–C(2)–O(1) À60.1(2).

1
10
H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
Table 5
Henry reaction of 1-fluoronitroalkanes to aldehydes catalyzed by TMG.
1
2
Entry
R CHFNO
2
R CHO
Temp
Product
1
2
a
b
3
R
4
R
Yield
Syn:anti
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3c
3c
3d
n-C
3
H
13
4a
4b
4c
4d
4e
4a
4b
4d
4f
Ph
r.t.
5aa
5ab
5ac
5ad
5ae
5ba
5bb
5bd
5bf
5bg
5ch
5ci
70(64)
75(65)
51(48)
52(45)
45(40)
63(65)
73(70)
47(43)
80(80)
62(60)
76(60)
70(62)
81(78)
30:70
34:66
28:72
31:69
34:66
35:65
37:63
34:66
39:61
35:65
18:82
27:73
4-CIC
6
H
4
r.t.
4-BrC
6
H
4
r.t.
4-MeC
3-OHC
6
H
H
4
r.t.
6
4
r.t.
Bn
r.t.
r.t.
r.t.
4-NO
2
C
6
H
4
r.t.
1
1
1
1
0
1
2
3
4g
4h
4i
4-FC
4-CF
6
H
4
r.t.
Ph
3
C
6
H
4
À30 8C
À30 8C
À30 8C
4 8
CIC F
c
4f
5df
43:57
O
O
1
4
5
3e
4f
À30 8C
À30 8C
5ef
70(69)
83(85)
50:50
43:57
1
3e
4h
5eh
a
b
c
19
Yields determined by F NMR using an internal standard and isolated yields in parentheses.
19
Determined by F NMR.
Downfield/upfield.
constant of tertiary fluorine and hydrogen geminal to the
hydroxyl, syn/anti isomers were determined (anti-isomer with
larger JHF or FH, see Section 4 for details).
3. Conclusion
In summary, a series of novel
a-fluoronitroalkanes were
prepared and applied to the Henry reaction with various
aldehydes. The desired products with fluorine-containing
a
quaternary center were obtained in good yields. This method
provides a practical method for the preparation of biologically
useful fluorinated derivatives. Asymmetry version of the reaction
is undergoing in our laboratory, and will be reported in due course.
4. Experimental
4.1. General information
All reagents were used as received from commercial sources,
Scheme 1. Newman projection of transition state.
unless specified otherwise, or prepared as described in the
literature. Melting points are measured on a Temp-Melt apparatus
1
and are uncorrected. H NMR spectra were recorded on a Bruker
to only one
a
-proton within our starting nitro compounds, a
AM 300 (300 MHz) spectrometer with TMS as an internal standard
1
9
quaternary carbon center was built in the final products, where
elimination of vicinal hydroxyl group would not happen.
(negative for upfield). F NMR spectra were recorded on a Bruker
AM 300 (282 MHz) with CFCl as an external standard (negative for
upfield). C NMR spectra were recorded on a Bruker AV-400
(100 MHz) spectrometer with CDCl as an internal standard
3
1
3
In order to determine the relative configuration of the newly
generated stereogenic center, X-ray single crystal analysis of one
major isomer of compound 5bf was carried out (Fig. 1). It was
found that F atom was anti to –OH group in 5bf. The anti-
selectivity in this reaction can be explained by steric hindrance
in the cyclic transition state, as can readily be seen in the
Newman projection (Scheme 1). According to the coupling
3
(negative for upfield). MS and HRMS were recorded on a
Hewlett–Packard HP-5989A spectrometer and a Finnigan MAT-
8483 mass spectrometer. Infrared spectra were measured with a
Perkin-Elmer 983 spectrometer. TLC analyses were performed on
silica gel plates (RP-18 WF254s, Merck, 0.25 mm), and column

H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
111
chromatography was performed using silica gel (mesh 300–400).
All solvents were purified by standard methods.
(30 mL) at 0 8C. The mixture was vigorously stirred for 1 h, and
then cooled to À17 8C to provide partial precipitation of the
nitronate. CH
2
Cl
2
(50 mL, pre-cooled to À78 8C) and Selectfluor
(
8.13 g, 23.0 mmol) were added in one portion. The cooling bath
4.2. General procedure and spectra data
was removed, and the mixture was vigorously stirred. The reaction
temperature was allowed to rise to 10 8C, at which point petroleum
ether (50 mL) was added, after stirring about 10 min, The mixture
was filtered through Celite, the organic layer were separated, and
the aqueous layer was extracted with portions of CH Cl –hexanes
4
4
.2.1. Preparation of nitro compounds [30,31]
.2.1.1. 1-Nitroheptane (2a). 2a: To a solution of 1-iodoheptane
(6.78 g, 30 mmol) in DMF (60 mL) was added NaNO
2
(3.5 g,
2
2
5
0 mmol). The mixture was stirred at r.t. for 6 h. The reaction
(1:1, 30 mL). The combined organic phases were dried over
anhydrous Na SO , filtered, concentrated, and the residue was
purified by distillation in vacuum or flash column chromatography
mixture was then poured into ice-water (60 mL) and layered over
with petroleum ether (100 mL). The aqueous phase was extracted
with petroleum ether (60 mL Â 3). Then the extracts were washed
with then with water (50 mL Â 2). The organic phase was dried over
2
4
on silica gel to give the corresponding products 3a–3e.
anhydrous Na
2 4
SO , filtered, concentrated, and the residue was
4.2.2.1. 1-Fluoro-1-nitroheptane (3a). Colorless oil (82% yield); bp.
1
distilled in vacuum. A colorless liquid 2a was obtained (2.70 g, 62%).
Colorless oil; bp. 73 8C/4.5 mmHg; H NMR (CDCl
J = 6.9 Hz, 3H), 1.22–1.46 (m, 8H), 1.95–2.08 (m, 2H), 4.38 (t,
J = 6.9 Hz, 2H).
75 8C/7.5 mmHg; H NMR (CDCl ):
d
0.89 (t, J = 6.6 Hz, 3H), 1.25–
3
1
19
3
):
d
0.88 (t,
1.60 (m, 8H), 2.05–2.22 (m, 2H), 5.80 (dt, J = 51, 5.4 Hz, 1H);
NMR (CDCl ):
À146.5 (dt, J = 50.2, 22.8 Hz).
F
3
d
4
.2.2.2. 1-Fluoro-2-phenylnitroethane (3b). Colorless oil (80%
1
4
.2.1.2. 2-Phenylnitroethane (2b). 2b: To a water solution (40 mL)
of (2-iodoethyl)benzene (4.68 g, 20 mmol) was added AgNO
3.06 g, 20 mmol) and the reaction flask was wrapped with
3
yield); bp.102 8C/4.5 mmHg; H NMR (CDCl ): d 3.30–3.58 (m,
19
2
2H), 5.94 (ddd, J = 50.6, 6.7, 3.8 Hz, 1H), 7.18–7.42 (m, 5H);
NMR (CDCl ):
À145.7 (dt, J = 50.5, 23.7 Hz).
F
(
d
3
aluminum foil to avoid light. After being stirred at 60 8C for 1.5 h,
the reaction mixture was filtered, extracted with EtOAc
4.2.2.3. 1-Fluoro-1-phenylnitromethane (3c). Colorless oil (75%
1
(
30 mL Â 3), and dried over anhydrous Na
2
SO
4
and the solvent
yield); bp.96 8C/7.5 mmHg;
H
NMR (CDCl ):
d
6.61 (d,
À139.9
3
1
9
was evaporated under reduced pressure. The crude products were
purified by flash column chromatography on silica gel (hexane:
J = 48.6 Hz, 1H), 7.55–7.59 (m, 5H); F NMR (CDCl ):
d
3
(d, J = 48.5 Hz).
EtOAc, 97:3) to afford 2b (1.8 g, 60%) as pale yellow liquid.
1
Pale yellow oil; H NMR (CDCl
3
):
d
3.31 (t, J = 7.2 Hz, 2H), 4.60 (t,
4.2.2.4. 2-(2-Fluoro-2-nitroethyl)-1, 3-dioxolane (3d). Pale yellow
1
J = 7.2 Hz, 2H), 7.18–7.37 (m, 5H).
oil (76% yield); 5% Et O in hexane; H NMR (CDCl ):
3
d
2.42–2.61 (m,
2
2
H), 3.91–4.02 (m, 4H), 5.12 (t, J = 4.2 Hz, 1H), 5.97 (ddd, J = 50.2,
1
9
4.2.1.3. Phenylnitromethane (2c). 2c: Benzyl bromide (5.1 g,
6.9, 4.2 Hz, 1H); F NMR (CDCl ):
18.6 Hz); C NMR (100 MHz, CDCl ): d 37.6 (d, J = 18.6 Hz), 65.1,
d
À146.2 (ddd, J = 50.5, 24.5,
3
1
3
3
5
0 mmol) was added to a stirred mixture of NaNO (3.5 g,
0 mmol) and urea (3.6 g, 60 mmol) in DMF (60 mL) at À18 8C.
2
3
65.3, 99.2 (d, J = 3.7 Hz), 108.4 (d, J = 238.7 Hz).
After stirring at À18 8C for 6 h, the reaction mixture was poured
into ice-water (60 mL) and layered over with petroleum ether
4.2.2.5. 4-Fluoro-4-nitrobut-1-ene (3e). Pale yellow oil (73% yield);
1
(
(
100 mL). The aqueous phase was extracted with diethyl ether
60 mL Â 3). Then the extracts were washed with 10% aqueous
5% Et O in hexane; H NMR (CDCl ):
3
d
2.84–2.97 (m, 2H), 5.13–5.23
2
(m, 2H), 5.70–5.94 (m, 3H).
sodium thiosulfate solution (20 mL Â 2) and water (50 mL Â 2) in
sequence. The organic phase was dried over anhydrous Na
2
SO
4
,
4.2.3. Typical experiment procedure for the nitro-aldol reaction of
fluoronitrocompounds with aldehydes
a-
filtered, concentrated, and the residue was distilled in vacuum (b.p.
1
7
5 8C/4.5 mmHg) to afford 2c (2.1 g, 45%) as colorless liquid.
H
To a solution of 1-fluoro-1-nitroheptane 3a (195 mg, 1.2 mmol)
in THF (5 mL) was added benzaldehyde 4a (106 mg, 1 mmol) and
TMG (35 mg, 0.3 mmol). The mixture was stirred at indicated
temperature overnight, and then neutralized by acetic acid. The
crude products were purified by flash column chromatography on
silica gel.
NMR (CDCl ): 5.44 (s, 2H), 7.45 (m, 5H).
3
d
4
.2.1.4. 2-(2-Nitroethyl)-1,3-dioxolane (2d). 2d: To a solution of
bromo compound (5.4 g, 30 mmol) in DMF (60 mL) was added
NaNO (3.5 g, 50 mmol). After stirring at r.t. for 6 h, the reaction
2
mixture was poured into ice-water (60 mL) and layered over with
petroleum ether (100 mL). The aqueous phase was extracted with
diethyl ether (60 mL Â 3). The organic phase was dried over
4.2.3.1. 2-Fluoro-2-nitro-1-phenyloctan-1-ol
(5aa). Syn-isomer:
Colorless oil. IR (neat) nmax 3426, 2954, 2931, 2870, 2852, 1558,
anhydrous Na
2
SO
4
, filtered, concentrated, and the residue was
1497, 1460, 1362, 1305, 1173, 1084, 1057, 844, 743, 712,
À1
1
purified by flash column chromatography on silica gel with 5% Et
2
1
O
699 cm
1.05–1.50 (m, 8H), 2.08–2.52 (m, 2H), 2.70 (d, J = 4.5 Hz, 1H), 5.15
; H NMR (300 MHz, CDCl ): d 0.86 (t, J = 6.6 Hz, 3H),
3
in hexane as eluent to afford 2d (1.5 g, 35%) as pale yellow oil. H
NMR (CDCl ): 2.40–2.47 (m, 1H), 3.85–4.02 (m, 4H), 4.51 (t,
J = 7.2 Hz, 2H), 5.03 (t, J = 3.6 Hz, 1H).
19
3
d
(dd, JH,F = 15.6 Hz, J = 4.5 Hz, 1H), 7.35–7.39 (m, 5H); F NMR
13
(282 MHz, CDCl ):
3
d
d
À138.0 (ddd, J = 33.0, 15.5, 6.2 Hz); C NMR
15.6 (CH ), 23.3 (d, J = 2.5 Hz, CH ), 24.1 (CH ),
30.3 (CH ), 33.0 (CH ), 34.5 (d, J = 21.2 Hz, CH ), 77.6 (d, J = 23.1 Hz,
(
100 MHz, CDCl
3
):
3
2
2
4.2.1.5. 4-Nitrobut-1-ene (2e). The procedure described above for
2
2
2
the preparation of 2d was followed. Theproduct 2eas pale yellow oil
CHOH), 122.6 (d, J = 249.9 Hz, CF), 129.2 (d, J = 1.9 Hz), 130.3,
131.2, 136.8; HRMS(ESI) calcd for C14H20ClFNO3 [M+Cl] :
304.1121, found: 304.1122.
À
was purified by flash column chromatography on silica gel with 5%
1
Et
2
O in hexane as eluent, yield: 30%; H NMR (CDCl
3
):
d
2.72–2.79
(m, 2H), 4.44 (t, J = 6.6 Hz, 2H), 5.13–5.23 (m, 2H), 5.70–5.84 (m, 1H).
Anti-isomer: white solid, Mp 42–44 8C. IR (KBr) nmax 3458, 2932,
2
859, 1569, 1495, 1456, 1362, 1172, 1058, 831, 738, 705, 620,
À1
1
4
.2.2. Preparation of
Solid KOH (82%, 1.6 g, 20 mmol) was added to a mixture of the
respective nitro compound (20 mmol), MeCN (15 mL) and H
a
-fluoronitro compounds [29,32,33]
580 cm
. H NMR (300 MHz, CDCl ): d 0.82 (t, J = 6.6 Hz, 3H),
3
1.01–1.50 (m, 8H), 1.52–1.71 (m, 1H), 2.04–2.16 (m, 1H), 2.83 (d,
J = 6.3 Hz, 1H), 5.22 (dd, JH,F = 20.4, 6.0 Hz, 1H), 7.38–7.42 (m, 5H);
2
O

1
12
H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
1
1
9
À
3
H22ClFNO [M+Cl] : 318.1278, found:
F NMR (282 MHz, CDCl
3
):
d
d
À145.1 (ddd, J = 32.8, 20.6, 6.2 Hz).
13.9 (CH ), 21.6 (d, J = 3.9 Hz, CH ),
), 32.8 (d, J = 21.3 Hz, CH ), 76.0 (d,
J = 22.9 Hz, CHOH), 122.0 (d, J = 246.5 Hz, CF), 127.6 (d, J = 1.6 Hz),
HRMS(ESI) calcd for C15
318.1276.
3
C NMR (100 MHz, CDCl
2.4 (CH ), 28.6 (CH
3
):
3
2
2
2
2
), 31.3 (CH
2
2
Anti-isomer: colorless oil. IR (neat)
1567, 1463, 1363, 1172, 1095, 1059, 1020, 825, 764 cm . H NMR
n
max 3440, 2957, 2931, 2859,
À1 1
+
1
2
28.6, 129.5, 135.2; HRMS(ESI) calcd for C14
92.1319, found: 292.1320.
H
20FNO
3
Na [M+Na] :
3
(300 MHz, CDCl ): d 0.83 (t, J = 7.2 Hz, 3H), 1.01–1.50 (m, 8H),
1.52–1.74 (m, 1H), 2.08–2.28 (m, 1H), 2.38 (s, 3H), 2.46 (d,
J = 6.0 Hz, 1H) 5.22 (dd, JH,F = 20.3, 6.3 Hz, 1H), 7.23 (d, J = 7.8 Hz,
1
9
4
.2.3.2. 2-Fluoro-2-nitro-1-(4-chlorophenyl)octan-1-ol (5ab). Syn-
isomer: white solid, Mp 62–63 8C. IR (KBr) max 3423, 2958,
931, 2871, 2851, 1557, 1497, 1464, 1362, 1172, 1092, 1057, 1015,
2H), 7.31 (d, J = 7.8 Hz, 2H); F NMR (282 MHz, CDCl
3
):
d
):
À145.5
13.9
), 31.3
), 76.4 (d, J = 19.6 Hz, CHOH), 122.5
1
3
n
(ddd, J = 33.8, 21.7, 7.3 Hz); C NMR (100 MHz, CDCl
3
d
2
8
(CH
(CH
3
2
), 21.2, 21.5 (d, J = 3.2 Hz, CH
), 34.2 (d, J = 21.1 Hz, CH
2 2 2
), 22.3 (CH ), 28.4 (CH
À1
1
55, 822, 795, 766, 698 cm . H NMR (300 MHz, CDCl
3
):
d
0.83 (t,
2
J = 6.0 Hz, 3H), 1.05–1.56 (m, 8H), 2.04–2.54 (m, 2H), 2.82 (s, 1H),
(d, J = 243.6 Hz, CF), 127.6 (d, J = 2.0 Hz), 129.6, 132.8, 139.6;
19
À
5
.15 (d, JH,F = 14.7 Hz, 1H), 7.22–7.45 (m, 5H); F NMR (282 MHz,
HRMS(ESI) calcd for C15
318.1274.
H
22ClFNO
3
[M+Cl] : 318.1272, found:
13
CDCl
3
):
d
À138.5 (ddd, J = 30.7, 13.8, 5.9 Hz); C NMR (100 MHz,
13.9 (CH ), 21.5 (d, J = 3.3 Hz, CH ), 22.4 (CH ), 28.5 (CH ),
), 32.6 (d, J = 21.2 Hz, CH ), 75.3 (d, J = 17.6 Hz, CHOH),
20.7 (d, J = 246.7 Hz, CF), 128.8, 128.9 (d, J = 1.7 Hz), 133.5, 135.5;
CDCl
3
1
3
):
d
3
2
2
2
1.3 (CH
2
2
4.2.3.5. 2-Fluoro-2-nitro-1-(3-hydroxyphenyl)octan-1-ol
(5ae). Syn-isomer: white solid, Mp 98–101 8C. IR (KBr) nmax 3312,
+
HRMS(ESI) calcd for C14
H
19ClFNO
3
Na [M+Na] : 326.0930, found:
2961, 2933, 2856, 1606, 1565, 1465, 1364, 1288, 1229, 1168, 1058,
À1
1
3
26.0924.
Anti-isomer: Colorless oil. IR (neat)
569, 1493, 1466, 1363, 1172, 1092, 1015, 826, 769 cm . H NMR
): 0.83 (t, J = 6.6 Hz, 3H), 1.01–1.50 (m, 8H),
.52–1.71 (m, 1H), 2.04–2.16 (m, 1H), 2.83 (d, J = 6.0 Hz, 1H), 5.23
873, 843, 794, 765 cm
. H NMR (300 MHz, CDCl ): d 0.87 (t,
3
n
max 3414, 2958, 2932, 2859,
J = 7.2 Hz, 3H), 1.05–1.56 (m, 8H), 2.13–2.56 (m, 2H), 2.65 (d,
J = 3.0 Hz, 1H), 4.86 (s, 1H), 5.12 (dd, JH,F = 15.8, 3.0 Hz, 1H), 6.81–
À1
1
1
1
9
(300 MHz, CDCl
3
d
6.95 (m, 3H), 7.20–7.25 (m, 2H); F NMR (282 MHz, CDCl
3
):
):
), 31.3
), 75.7 (d, J = 23.1 Hz, CHOH), 114.5,
116.5, 120.0 (d, J = 1.5 Hz), 121.8 (d, J = 245.7 Hz, CF), 129.9, 136.9,
d
d
1
3
1
À138.5 (ddd, J = 33.0, 16.6, 8.2 Hz); C NMR (100 MHz, CDCl
13.9 (CH ), 21.5 (d, J = 3.5 Hz, CH ), 22.4 (CH ), 28.5 (CH
(CH ), 32.8 (d, J = 21.1 Hz, CH
3
19
(dd, JH,F = 19.8, 6.0 Hz, 1H), 7.35–7.45 (m, 4H); F NMR (282 MHz,
3
2
2
2
13
CDCl
3
):
d
À145.5 (ddd, J = 31.9, 20.0, 5.9 Hz). C NMR (100 MHz,
13.9 (CH ), 21.5 (d, J = 2.7 Hz, CH ), 22.3 (CH ), 28.4 (CH ),
), 34.1 (d, J = 20.9 Hz, CH ), 75.7 (d, J = 20.3 Hz, CHOH),
22.1 (d, J = 239.1 Hz, CF), 129.0, 129.1 (d, J = 2.1 Hz), 134.3, 135.6;
2
2
CDCl
3
1
3
):
d
3
2
2
2
+
1.2 (CH
2
2
155.7; HRMS(ESI) calcd for C14
found: 308.1265.
4
H20FNO Na [M+Na] : 308.1269,
+
HRMS(ESI) calcd for C14
26.0933.
H
19ClFNO
3
Na [M+Na] : 326.0930, found:
Anti-isomer: white solid, Mp 103–105 8C. IR (KBr)
nmax 3312,
3
2961, 2933, 2857, 1607, 1564, 1465, 1364, 1288, 1230, 1058, 873,
À1
1
7
94, 766 cm . H NMR (300 MHz, CDCl
3
): d 0.83 (t, J = 6.6 Hz, 3H),
4
.2.3.3. 2-Fluoro-2-nitro-1-(4-bromophenyl)octan-1-ol (5ac). Syn-
isomer: white solid, Mp 61–63 8C. IR (KBr) max 3419, 2956,
931, 2851, 1557, 1493, 1463, 1361, 1173, 1076, 1055, 1011, 854,
0.98–1.50 (m, 8H), 1.51–1.70 (m, 1H), 1.94–2.16 (m, 1H), 5.20 (d,
19
n
J
H,F = 20.4 Hz, 1H), 6.86–7.00 (m, 3H), 7.26–7.32 (m, 1H); F NMR
(282 MHz, CDCl ):
À145.8 (ddd, J = 34.7, 21.4, 5.9 Hz); HRMS(ESI)
calcd for C14 20FNO
2
8
1
3
d
À1
1
+
20, 765 cm . H NMR (300 MHz, CDCl
3
):
d
0.86 (t, J = 6.9 Hz, 3H),
H
4
Na [M+Na] : 308.1269, found: 308.1273.
.05–1.56 (m, 8H), 2.03–2.52 (m, 2H), 2.82 (s, 1H), 5.14 (d,
J
H,F = 14.7 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H);
4.2.3.6. 2-Fluoro-2-nitro-1,3-diphenylpropan-1-ol (5ba). Syn-iso-
mer: white solid, Mp 118–120 8C. IR (KBr) max 3445, 3026,
1557, 1496, 1454, 1432, 1360, 1208, 1166, 1081, 1052, 1029, 844,
19
F NMR (282 MHz, CDCl
C NMR (100 MHz, CDCl
), 28.5 (CH ), 31.3 (CH
J = 23.7 Hz, CHOH), 121.7 (d, J = 246.3 Hz, CF), 123.7, 129.2 (d,
3
):
d
d
À138.4 (ddd, J = 33.6, 15.8, 7.9 Hz);
13.9 (CH ), 21.5 (d, J = 3.1 Hz, CH ),
), 32.6 (d, J = 21.1 Hz, CH ), 75.3 (d,
n
1
3
3
):
3
2
À1
1
2
2.4 (CH
2
2
2
2
753, 742, 710, 700 cm
J = 4.2 Hz, 1H), 3.56–3.81 (m, 2H), 5.30 (dd, JH,F = 16.4, 4.2 Hz, 1H),
. H NMR (300 MHz, CDCl ): d 2.72 (d,
3
19
J = 1.5 Hz), 131.6, 134.1; HRMS(ESI) calcd for C14
[
H
19BrClFNO
3
7.14–7.17 (m, 2H), 7.25–7.29 (m, 3H), 7.38–7.42 (m, 5H); F NMR
À
13
M+Cl] : 382.0226, found: 382.0229.
(282 MHz, CDCl
(100 MHz, CDCl
3
):
):
d
d
À139.0 (ddd, J = 31.0, 15.5, 10.4 Hz); C NMR
39.0 (d, J = 21.1 Hz, CH ), 76.0 (d, J = 22.1 Hz,
Anti-isomer: Colorless oil. IR (neat)
n
max 3418, 2957, 2931, 2871,
3
2
À1
1
2
858, 1568, 1489, 1466, 1362, 1170, 1074, 1011, 824, 767 cm . H
NMR (300 MHz, CDCl ): 0.83 (t, J = 6.3 Hz, 3H), 1.01–1.50 (m, 8H),
.52–1.71 (m, 1H), 2.04–2.16 (m, 1H), 2.78 (s, 1H), 5.23 (d,
CHOH), 121.0 (d, J = 248.0 Hz, CF), 127.6 (d, J = 1.5 Hz), 128.1,
3
d
128.6, 128.7, 129.6, 130.2, 130.7 (d, J = 1.3 Hz), 134.9; HRMS(ESI)
À
1
calcd for C15
H
14ClFNO
3
[M+Cl] : 310.0652, found: 310.0655.
J
H,F = 20.1 Hz, 1H), 7.31 (d, J = 7.8 Hz, 2H), 7.56 (d, J = 7.8 Hz, 2H);
Anti-isomer: white solid, Mp 78–80 8C. IR (KBr)
nmax 3512, 3068,
19
F NMR (282 MHz, CDCl
C NMR (100 MHz, CDCl
), 28.4 (CH ), 31.2 (CH
J = 20.3 Hz, CHOH), 121.9 (d, J = 248.4 Hz, CF), 123.9, 129.4 (d,
3
):
):
d
d
À145.1 (ddd, J = 33.0, 20.6, 7.3 Hz).
13.9 (CH ), 21.5 (d, J = 11.3 Hz, CH ),
), 34.1 (d, J = 21.6 Hz, CH ), 75.8 (d,
2913, 1560, 1496, 1457, 1420, 1367, 1290, 1204, 1150, 1049, 1026,
1
3
À1
1
3
3
2
834, 784, 739, 697 cm
. H NMR (300 MHz, CDCl ): d 2.70 (d,
3
2
2.3 (CH
2
2
2
2
J = 6.6 Hz, 1H), 3.04 (dd, J = 14.5, 10.7 Hz, 1H), 3.45 (dd, J = 33.0,
14.5 Hz, 1H), 5.33 (dd, JH,F = 18.3, 6.9 Hz, 1H), 7.08–7.12 (m, 2H),
1
9
J = 2.1 Hz), 132.0, 134.7; HRMS(ESI) calcd for C14
[
H
19BrClFNO
3
7.24–7.27 (m, 3H), 7.44–7.48 (m, 5H); F NMR (282 MHz, CDCl
3
3
):
):
À
13
M+Cl] : 382.0227, found: 382.0229.
d
d
À144.8 (ddd, J = 33.0, 18.6, 10.4 Hz); C NMR (100 MHz, CDCl
40.3 (d, J = 20.1 Hz, CH
2
), 76.4 (d, J = 20.5 Hz, CHOH), 121.4 (d,
4
.2.3.4. 2-Fluoro-2-nitro-1-(4-tolyl)octan-1-ol (5ad). Syn-isomer:
max 3428, 2955, 2931, 2856,
557, 1463, 1362, 1173, 1094, 1057, 1021, 851, 758, 762,
J = 248.7 Hz, CF), 127.7 (d, J = 2.0 Hz), 128.2, 128.7, 129.0, 129.8,
À
white solid, Mp 50–51 8C. IR (KBr)
n
130.1, 130.3, 135.6; HRMS(ESI) calcd for C15
310.0652, found: 310.0654.
H
14ClFNO
3
[M+Cl] :
1
7
1
À1
1
12 cm
3
. H NMR (300 MHz, CDCl ): d 0.86 (t, J = 6.9 Hz, 3H),
.05–1.56 (m, 8H), 2.16–2.54 (m, 5H), 2.55 (d, J = 4.2 Hz, 1H), 5.14
4.2.3.7. 2-Fluoro-2-nitro-1-(4-chlorophenyl)-3-phenylpropan-1-ol
(5bb). Syn-isomer: white solid, Mp 84–86 8C. IR (KBr) max 3444,
(dd, JH,F = 16.1, 4.5 Hz, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.25 (d,
n
1
9
J = 7.8 Hz, 2H);
J = 33.0, 15.5, 7.1 Hz); C NMR (100 MHz, CDCl
2
3
F NMR (282 MHz, CDCl
3
):
d
À138.4 (ddd,
3065, 3027, 2917, 1598, 1558, 1495, 1455, 1429, 1361, 1220, 1152,
13
À1 1
3
):
d
13.9 (CH
3
),
),
1090, 1055, 1014, 878, 851, 798, 750, 708 cm . H NMR (300 MHz,
1.2, 21.6 (d, J = 3.1 Hz, CH
2.9 (d, J = 21.1 Hz, CH
2
), 22.4 (CH
2
), 28.6 (CH
2
), 31.3 (CH
2
CDCl
3
): d 2.84 (d, J = 4.2 Hz, 1H), 3.51–3.78 (m, 2H), 5.28 (dd,
2
), 75.9 (d, J = 22.5 Hz, CHOH), 122.1 (d,
J
H,F = 15.8, 4.2 Hz, 1H), 7.13–7.17 (m, 2H), 7.24–7.32 (m, 3H), 7.38–
1
9
J = 237.6 Hz, CF), 127.4 (d, J = 2.0 Hz), 129.3, 132.2, 139.4;
7.42 (m, 4H); F NMR (282 MHz, CDCl
3
):
d
À138.5 (ddd, J = 33.0,

H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
113
1
3
À1
1
1
6.6, 8.2 Hz); C NMR (100 MHz, CDCl
CH ), 75.3 (d, J = 23.2 Hz, CHOH), 120.9 (d, J = 247.7 Hz, CF), 127.6
d, J = 1.5 Hz), 128.2, 128.8, 129.1 (d, J = 1.5 Hz), 129.2, 130.2, 130.6
3
):
d
39.0 (d, J = 20.9 Hz,
851, 835, 785, 748, 710, 698 cm
.
H NMR (300 MHz, CDCl
3
):
d
2
2.74 (d, J = 3.6 Hz, 1H), 3.57–3.78 (m, 2H), 5.30 (dd, JH,F = 16.2,
1
9
(
(
[
4.5 Hz, 1H), 7.05–7.44 (m, 9H); F NMR (282 MHz, CDCl
3
):
d
d, J = 1.5 Hz), 133.5, 135.7; HRMS(ESI) calcd for C15
M+Cl] : 344.0262, found: 344.0264.
H
13Cl
2
FNO
3
À137.9 (ddd, J = 30.0, 16.4, 10.4 Hz, 1F), À111.0 to À111.12 (m, 1F);
À
13
3 2
C NMR (100 MHz, CDCl ): d 39.1 (d, J = 20.6 Hz, CH ), 75.3 (d,
Anti-isomer: colorless oil. IR (neat)
n
max 3555, 3066, 3034, 2934,
J = 22.5 Hz, CHOH), 115.7 (d, J = 21.5 Hz, CHaron), 120.8 (d,
J = 248.4 Hz, CF), 128.1, 128.7, 129.6 (dd, J = 8.5, 2.0 Hz, CHaron),
130.2 (d, J = 1.0 Hz, CHaron), 130.6 (Caron), 130.7 (d, J = 3.5 Hz, Caron),
1
7
706, 1570, 1496, 1465, 1362, 1261, 1162, 1090, 1048, 1015, 837,
À1
1
74, 749, 724, 700 cm
3
. H NMR (300 MHz, CDCl ): d 2.83 (d,
J = 6.6 Hz, 1H), 2.98–3.12 (m, 1H), 3.46 (dd, J = 23.2, 14.7 Hz, 1H),
163.4 (d, J = 249 Hz, CFaron); HRMS(ESI) calcd for C15
[M+Cl] : 328.0558, found: 328.0553.
H
13ClF
2
NO
3
À
5
.30 (dd, JH,F = 17.4, 6.3 Hz, 1H), 7.08–7.12 (m, 2H), 7.25–7.29 (m,
19
3
H), 7.40–7.44 (m, 4H); F NMR (282 MHz, CDCl
3
):
d
À145.5 (ddd,
): 40.2 (d,
), 75.5 (d, J = 20.9 Hz, CHOH), 121.0 (d, J = 248.4 Hz,
CF), 128.3, 128.7, 129.0 (d, J = 2.3 Hz), 129.2, 130.0, 130.6 (d,
Anti-isomer: white solid, Mp 87–90 8C. IR (KBr)
nmax 3590, 3031,
13
J = 31.9, 17.4, 11.3 Hz); C NMR (100 MHz, CDCl
J = 20.3 Hz, CH
3
d
2918, 1614, 1566, 1516, 1455, 1429, 1363, 1227, 1145, 1070, 989,
À1
1
2
880, 846, 805, 743, 702 cm . H NMR (300 MHz, CDCl ): d 2.69 (d,
3
J = 6.6 Hz, 1H), 3.07 (dd, J = 14.7, 11.4 Hz, 1H), 3.46 (dd, J = 32.4,
J = 1.4 Hz), 133.9, 135.8; HRMS(ESI) calcd for C15
H
13Cl
2
FNO
3
15.0 Hz, 1H), 5.31 (dd, JH,F = 17.7, 6.6 Hz, 1H), 7.10–7.49 (m, 9H);
À
19
[
M+Cl] : 344.0262, found: 344.0263.
F NMR (282 MHz, CDCl
À110.6 to À100.8 (m, 1F); C NMR (100 MHz, CDCl
3
):
d
À142.1 (ddd, J = 33.0, 17.5, 11.3 Hz),
13
3
): d 40.3 (d,
4.2.3.8. 2-Fluoro-2-nitro-1-(4-tolyl)3-phenylpropan-1-ol
J = 20.1 Hz, CH ), 75.5 (d, J = 21.1 Hz, CHOH), 116.1 (d, J = 21.6 Hz,
2
(
5bd). Syn-isomer: white solid, Mp 67–70 8C. IR (KBr)
n
max 3445,
CHaron), 121.1 (d, J = 246.0 Hz, CF), 128.3 (CHaron), 128.7 (CHaron),
129.6 (dd, J = 8.5, 2.0 Hz, CHaron), 130.0 (CHaron), 130.1 (Caron),
1
7
606, 1569, 1511, 1431, 1364, 1228, 1155, 1045, 837, 810, 744,
À1
1
02 cm
.
H NMR (300 MHz, CDCl
3
):
d
2.35 (s, 3H), 2.67 (d,
131.3 (d, J = 3.5 Hz, Caron), 163.5 (d, J = 252 Hz, CFaron); HRMS(ESI)
À
J = 3.6 Hz, 1H), 3.52–3.78 (m, 2H), 5.26 (dd, JH,F = 16.8, 3.6 Hz, 1H),
calcd for C15
H
13ClF
2
NO
3
[M+Cl] : 328.0558, found: 328.0555.
1
9
13
7
.15–7.32 (m, 9H); F NMR (282 MHz, CDCl
NMR (100 MHz, CDCl ): 21.2 (CH ), 39.1 (d, J = 21.1 Hz, CH
d, J = 22.1 Hz, CHOH), 121.1 (d, J = 248.5 Hz, CF), 127.5 (d,
J = 1.4 Hz), 128.0, 128.7, 129.4, 130.2 (d, J = 1.3 Hz), 130.8 (d,
3
):
d
À137.9 (m);
C
3
d
3
2
), 75.9
4.2.3.11. 2-Fluoro-2-nitro-1-(4-trifluoromethylphenyl)-2-ethanol
(5ch). Anti-isomer [34]: white solid, Mp 80–83 8C. IR (KBr)
3501, 2926, 1621, 1572, 1453, 1420, 1327, 1230, 1169, 1129, 1073,
(
n
max
À1
1
J = 1.4 Hz), 132.0, 139.7; HRMS(ESI) calcd for
C
16
H
16ClFNO
3
1019, 995, 947, 845, 817, 746, 723, 695 cm . H NMR (300 MHz,
CDCl ): 2.84 (d, J = 6.9 Hz, 1H), 5.99 (dd, JH,F = 22.4, 6.0 Hz, 1H),
7.25–7.60 (m, 9H); F NMR (282 MHz, CDCl
À
[
M+Cl] : 324.0808, found: 324.0802.
3
d
1
9
Anti-isomer: white solid, Mp 78–80 8C. IR (KBr)
nmax 3440, 3035,
3
):
J = 22.6 Hz, 1F), À62.5 (s, 3F); C NMR (100 MHz, CDCl
J = 19.5 Hz, CHOH), 119.8 (d, J = 247 Hz, CF), 123.7 (q, J = 272 Hz,
CF ), 125.1 (q, J = 3.8 Hz), 125.2 (d, J = 9.6 Hz), 128.3, 128.8 (d,
d
À148.2 (d,
1
3
2
7
1
5
922, 1607, 1569, 1514, 1456, 1369, 1225, 1185, 1037, 831, 806, 741,
3
): d 76.2 (d,
À1 1
3
02 cm . HNMR (300 MHz, CDCl ): d2.39 (s, 3H), 2.60 (d, J = 6.9 Hz,
H), 3.02 (dd, J = 14.6, 10.5 Hz, 1H), 3.44 (dd, J = 33.0, 14.8 Hz, 1H),
.29 (dd, JH,F = 18.6 Hz, J = 6.9 Hz, 1H), 7.08–7.12 (m, 2H), 7.24–7.28
3
J = 1.4 Hz), 130.4, 130.7 (q, J = 32.7 Hz), 131.2, 138.8; HRMS(ESI)
1
9
À
(m, 5H), 7.34–7.38 (m, 2H); F NMR (282 MHz, CDCl
3
):
21.3 (CH
), 76.3 (d, J = 20.1 Hz, CHOH), 121.5 (d,
d
À142.9
calcd for C15
H
11ClF
4
NO
3
[M+Cl] : 364.0369, found: 364.0369.
1
3
(
4
ddd, J = 33.0, 18.3, 10.1 Hz); CNMR (100 MHz, CDCl
0.3 (d, J = 20.1 Hz, CH
3
):
d
3
),
2
4.2.3.12. 6-Chloro-1,3,3,4,4,5,5,6,6-nonafluoro-1-nitro-1-phenyl-
J = 248.7 Hz, CF), 127.6 (d, J = 2.0 Hz,), 128.1, 128.7, 129.7, 130.1 (d,
hexan-2-ol (5ci). Syn-isomer: white solid, Mp 50–52 8C. IR (KBr)
J = 1.0 Hz), 130.4, 132.6 (d, J = 1.0 Hz), 139.8; HRMS(ESI) calcd for
n
max 3519, 1581, 1499, 1455, 1362, 1193, 1133, 976, 846, 817, 764,
À
À1
1
C
16
H
16ClFNO
3
[M+Cl] : 324.0808, found: 324.0803.
708, 692, 656 cm
.
3
H NMR (300 MHz, CDCl ): d 3.21 (d,
J = 11.1 Hz, 1H), 5.58 (td, J = 20.7, 11.3 Hz, 1H), 7.45–7.55 (m,
1
9
4
.2.3.9. 2-Fluoro-2-nitro-1-(4-nitrophenyl)-3-phenylpropan-1-ol
5bf). Syn-isomer: white solid, Mp 103–105 8C. IR (KBr) max 3564,
064, 2918, 1607, 1553, 1518, 1470, 1432, 1348, 1226, 1178, 1075,
3H), 7.68–7.73 (m, 2H); F NMR (282 MHz, CDCl
3
):
d
À144.7 to
(
n
À144.9 (m, 1F), À125.3 to À112.3 (m, 6F), À67.9 to À68.2 (m, 2F);
1
3
3
8
3
7
C NMR (100 MHz, CDCl ): d 70.8 (q, J = 25.1 Hz, CHOH), 105–125
3
À1
1
72, 800, 734, 700 cm . H NMR (300 MHz, CDCl
3
):
d
3.1 (s, 1H),
(m), 118.3 (d, J = 248.8 Hz, CF), 124.9 (dd, J = 10.1, 2.3 Hz), 129.0 (d,
J = 1.9 Hz), 129.4 (dd, J = 22.1, 1.9 Hz), 131.7; HRMS(ESI) calcd for
[M+Cl] : 453.9665, found: 453.9687.
Anti-isomer: colorless oil. IR (neat)
1499, 1455, 1360, 1193, 975, 846, 809, 761, 706, 692 cm . H NMR
.50–3.80 (m, 2H), 5.44 (d, JH,F = 14.7 Hz, 1H), 7.11–7.32 (m, 5H),
1
9
À
.63 (d, J = 10.2 Hz, 2H), 8.24 (d, J = 10.2 Hz, 2H);
F NMR
C
12
H
7
Cl
2
F
9
NO
3
1
3
(
(
282 MHz, CDCl
100 MHz, CDCl
3
):
):
d
d
À136.2 (ddd, J = 31.9, 13.3, 9.3 Hz); C NMR
38.9 (d, J = 20.7 Hz, CH ), 74.8 (d, J = 22.7 Hz,
nmax 3511, 3072, 2924, 1581,
À1 1
3
2
CHOH), 120.6 (d, J = 247.1 Hz, CF), 123.7, 128.3, 128.7, 128.8 (d,
(300 MHz, CDCl
8.1 Hz, 1H), 7.45–7.57 (m, 3H), 7.67–7.74 (m, 2H); F NMR
(282 MHz, CDCl ):
À144.8 (td, J = 23.7, 11.5, Hz, 1F), À125.1 to
À118.0 (m, 6F), À67.7 (tm, J = 13.2 Hz, 2F); C NMR (100 MHz,
CDCl ): 70.1 (dt, J = 25.4, 21.2 Hz, CHOH), 105–125 (m), 116.2 (d,
3
): d 2.89 (d, J = 8.1 Hz, 1H), 5.65 (ddd, J = 24.3, 18.0,
19
J = 2.0 Hz), 130.0, 130.1 (d, J = 1.2 Hz), 141.9, 148.6; HRMS(ESI) calcd
À
for C15H13ClFN O
2 5
[M+Cl] : 355.0503, found: 355.0505.
3
d
1
3
Anti-isomer: white solid, Mp 107–109 8C. IR (KBr)
nmax 3445,
3
8
070, 2924, 1606, 1571, 1523, 1456, 1350, 1223, 1153, 1080, 1042,
3
d
À1
1
63, 833, 780, 732, 702 cm . H NMR (300 MHz, CDCl
3
):
d
3.05 (d,
J = 251.2 Hz, CF), 125.4 (d, J = 9.7 Hz), 129.2 (d, J = 1.9 Hz), 130.0 (d,
J = 7.2 Hz, 1H), 3.16–3.27 (m, 1H), 3.53 (dd, J = 30.2, 14.7 Hz, 1H),
J = 22.3 Hz), 131.7 (d, J = 1.0 Hz); HRMS(ESI) calcd for
À
5
2
.39(dd, JH,F = 15.2, 7.2 Hz, 1H), 7.08–7.32(m, 5H), 7.65(d, J = 7.8 Hz,
C
12
H
7
Cl
2
F
9
NO
3
[M+Cl] : 453.9665, found: 453.9687.
19
H), 8.30 (d, J = 7.8 Hz, 2H); F NMR (282 MHz, CDCl
3
):
d
À139.1
13
(
m); C NMR (100 MHz, CDCl
3
):
d
2
40.2 (d, J = 20.1 Hz, CH ), 74.8 (d,
4.2.3.13. 3-(1,3-Dioxolan-2-yl)-2-fluoro-2-nitro-1-(4-nitrophenyl)-
J = 22.1 Hz, CHOH), 120.6 (d, J = 243.1 Hz, CF), 123.9, 128.5, 128.7 (d,
propan-1-ol (5df). Syn-anti mixture: white solid, Mp 103–106 8C. IR
J = 2.0 Hz), 128.9, 129.7, 130.1 (d, J = 1.2 Hz), 142.2, 148.6;
(KBr)
1141, 1014, 953, 937, 821, 741, 642 cm
CDCl ): 2.51–2.77 (m, 2H), 3.47 (d, J = 6.0 Hz, 0.6H), 3.83 (d,
nmax 3396, 3116, 2897, 1576, 1521, 1493, 1416, 1349, 1261,
À
À1
1
HRMS(ESI) calcd for C15H13ClFN O
2 5
[M+Cl] : 355.0503, found:
. H NMR (300 MHz,
3
55.0497.
3
d
J = 4.5 Hz, 0.4H), 3.87–4.06 (m, 4H), 5.11 (t, J = 4.8 Hz, 0.6H), 5.24 (t,
J = 4.8 Hz, 0.4H), 5.37 (dd, J = 15, 6.0 Hz, 0.6H), 5.41 (dd, J = 18.3,
4.5 Hz, 0.4H), 7.55 (d, J = 8.4 Hz, 0.8H), 7.62 (d, J = 8.4 Hz, 1.2H),
4
.2.3.10. 2-Fluoro-2-nitro-1-(4-fluorophenyl)-3-phenylpropan-1-ol
5bg). Syn-isomer: white solid, Mp 78–80 8C. IR (KBr) max 3451,
079, 2920, 1608, 1570, 1512, 1452, 1431, 1363, 1227, 1163, 990,
(
n
1
9
3
8.20–8.28 (m, 2H); F NMR (282 MHz, CDCl
3
):
d
À135.8 (td,

1
14
H. Hu et al. / Journal of Fluorine Chemistry 133 (2012) 108–114
1
3
J = 18.3, 13.5 Hz, 0.4F), À136.9 (dt, J = 23.6, 15.3 Hz, 0.6F); C NMR
123.7 (q, J = 272 Hz), 125.8 (q, J = 3.7 Hz), 126.0 (d, J = 4.1 Hz),
(
100 MHz, CDCl
3
):
d
38.1, 65.2, 74.7, 99.1, 120.5, 123.7, 128.6,
128.2, 131.8 (q, J = 32.7 Hz), 139.3; HRMS(ESI) calcd for
À
À
141.3, 148.6; HRMS(ESI) calcd for
51.0395, found: 351.0388.
C
12
H
13ClFN
2
O
7
[M+Cl] :
C
12
H
11ClF NO
4 3
[M+Cl] : 328.0369, found: 328.0363.
3
Acknowledgments
4
.2.3.14. 2-Fluoro-2-nitro-1-(4-nitrophenyl)pent-4-en-1-ol
5ef). Syn-isomer: white solid, Mp 65–66 8C. IR (KBr) max 3374,
115, 2920, 1607, 1568, 1522, 1434, 1357, 1316, 1240, 1202, 1082,
(
n
We are grateful for the financial support from the National
Natural Science Foundation of China (No. 21172241) and Shanghai
Science and Technology Commission (11ZR1445700). This work
was also supported by the Key Laboratory of Organofluorine
Chemistry, Shanghai Institute of Organic Chemistry, and SIOC.
3
1
CDCl
À1
1
053, 1014, 989, 941, 864, 784, 739 cm
): 2.93–3.01 (m, 1H), 3.05–3.21 (m, 2H), 5.21–5.29 (m, 2H),
.37 (dd, JH,F = 14.4, 3.2 Hz, 1H), 5.63–5.68 (m, 1H), 7.59 (d,
. H NMR (300 MHz,
3
d
5
1
9
J = 8.4 Hz, 2H), 8.22 (d, J = 8.4 Hz, 2H); F NMR (282 MHz, CDCl
3
d
):
):
2
), 74.5 (d, J = 23.2 Hz, CHOH), 120.4 (d,
1
3
À137.1 (ddd, J = 31.0, 14.4, 9.3 Hz); C NMR (100 MHz, CDCl
7.1 (d, J = 20.5 Hz, CH
3
d
3
References
J = 246.2 Hz, CF), 122.8, 126.3 (d, J = 4.2 Hz), 128.7 (d, J = 1.8 Hz),
1
3
À
41.7, 148.6; HRMS(ESI) calcd for
05.0346, found: 305.0339.
C
11
H
11ClFN
2
O
5
[M+Cl] :
[
1] N. Ono, The Nitro Group in Organic Synthesis, Wiley-VCH, New York, 2001.
[2] J. Boruwa, N. Gogoi, P.P. Saikia, N.C. Barua, Tetrahedron: Asymmetry 17 (2006)
315–3326.
3
Anti-isomer: white solid, Mp 85–87 8C. IR (KBr)
nmax 3508, 3116,
[3] C. Palomo, M. Oiarbide, A. Laso, Eur. J. Org. Chem. (2007) 2561–2574.
2
9
2
5
2
918, 1605, 1564, 1515, 1426, 1351, 1174, 1144, 1092, 1047, 990,
[4] Y. Sohtome, Y. Hashimoto, K. Nagasawa, Adv. Synth. Catal. 347 (2005) 1643–1648.
À1
1
39, 829, 781, 744, 721 cm . H NMR (300 MHz, CDCl
3
):
d
2.50–
[5] C. Palomo, M. Oiarbide, A. Mielgo, Angew. Chem. Int. Ed. 43 (2004) 5442–5444.
[
[
[
6] S. Gao, G. Xi, N. Li, C. Wang, J. Ma, Chin. J. Org. Chem. 30 (2010) 1811–1819.
7] F.A. Luzzio, Tetrahedron 57 (2001) 915–945.
8] G. Rosini, R. Ballini, Synthesis (1988) 833–847.
.59 (m, 1H), 2.86–3.00 (m, 1H), 3.26 (s, 1H), 5.16–5.26 (m, 2H),
.40 (d, JH,F = 18.0 Hz, 1H), 5.55–5.64 (m, 1H), 7.63 (d, J = 8.4 Hz,
1
9
H), 8.26 (d, J = 8.4 Hz, 2H); F NMR (282 MHz, CDCl
3
):
):
d
d
À144.3
[9] G. Blay, V. Hern a´ ndez-Olmos, J.R. Pedro, Chem. Commun. (2008) 4840–8482.
10] R.D. Chambers, Fluorine in Organic Chemistry, Blackwell Publishing Ltd./CRC
Press, Boca Raton, FL, 2004.
11] T. Hiyama, Organofluorine Compounds, Chemistry and Applications, Springer-
Verlag, Berlin, 2000.
13
[
[
(ddd, J = 31.3, 18.9, 9.3 Hz); C NMR (100 MHz, CDCl
3
37.1 (d,
2
J = 20.5 Hz, CH ), 74.5 (d, J = 20.9 Hz, CHOH), 120.7 (d, J = 247.9 Hz,
CF), 123.1, 125.8 (d, J = 3.7 Hz), 128.8 (d, J = 1.8 Hz), 142.3, 148.6;
À
HRMS(ESI) calcd for C11
05.0338.
H
11ClFN
2
O
5
[M+Cl] : 305.0346, found:
[12] P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004.
[13] V.A. Soloshonok, Fluorine-Containing Synthons, ACS Symposium Series 911,
Oxford University Press, Washington, DC, 2005.
3
[14] K. Uneyama, Organofluorine Chemistry, Blackwell Publishing, Oxford, 2006.
4
.2.3.15. 2-Fluoro-2-nitro-1-(4-trifluorophenyl)pent-4-en-1-ol
5eh). Syn-isomer: colorless oil. IR (neat) max 3546, 3088, 2925,
646, 1570, 1420, 1326, 1170, 1130, 1069, 1018, 937, 859, 781,
[15] K. Muller, C. Faeh, F. Diederich, Science 317 (2007) 1881–1886.
[16] M. Schlosser, Angew. Chem. Int. Ed. 37 (1998) 1496–1513.
[17] D. O’Hagan, Chem. Soc. Rev. 37 (2008) 308–319.
[18] S. Purser, P.R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 37 (2008) 320–
330.
(
n
1
7
5
À1
1
3
23 cm . H NMR (300 MHz, CDCl ): d 2.92–3.22 (m, 3H), 5.20–
[19] K.L. Kirk, Org. Process Res. Dev. 12 (2008) 305–321.
.33 (m, 3H), 5.60–5.74 (m, 1H), 7.52 (d, J = 7.8 Hz, 2H), 7.50 (d,
19
[20] D. O’Hagan, J. Fluorine Chem. 131 (2010) 1071–1081.
21] A.M. Thayer, Chem. Eng. News 84 (2006) 15–24.
[22] J. Ma, D. Cahard, Chem. Rev. 104 (2004) 6119–6146.
J = 7.8 Hz, 2H); F NMR (282 MHz, CDCl
3
):
3.3, 8.2 Hz, 1F), À63.1 (s, 3F); C NMR (100 MHz, CDCl
d, J = 20.9 Hz, CH ), 74.5 (d, J = 23.2 Hz, CHOH), 120.6 (d,
J = 247.0 Hz, CF), 122.6 (d, J = 1.0 Hz), 123.7 (q, J = 272.2 Hz, CF ),
25.5 (q, J = 3.7 Hz), 126.6 (d, J = 4.6 Hz), 128.0 (d, J = 1.9 Hz), 131.6
q, J = 32.5 Hz), 138.8; HRMS(ESI) calcd for 11ClF NO
d
À136.0 (ddd, J = 31.9,
[
13
1
(
3
): 37.1
d
[
[
[
23] A.M.R. Smith, K.K.M. Hii, Chem. Rev. 111 (2011) 1637–1656.
24] K. Shibatomi, Synthesis (2010) 2679–2702.
25] M. Bella, T. Gasperi, Synthesis (2009) 1583–1614.
2
3
1
[26] Y. Takeuchi, K. Nagata, T. Koizumi, J. Org. Chem. 52 (1987) 5061–5063.
[27] Y. Takeuchi, K. Nagata, T. Koizumi, J. Org. Chem. 54 (1989) 5453–5459.
[28] H. Cui, P. Li, X. Wang, Z. Chai, Y. Yang, Y. Cai, S. Zhu, G. Zhao, Tetrahedron 67 (2011)
(
[
C
12
H
4
3
À
M+Cl] : 328.0369, found: 328.0366.
Anti-isomer: colorless oil. IR (neat)
574, 1418, 1326, 1170, 1130, 1069, 1018, 937, 879, 850, 781,
312–317.
n
max 3543, 3089, 2928, 1645,
[29] R.A. Kunetsky, A.D. Dilman, M.I. Struchkova, P.A. Belyakov, V.A. Tartakovsky, S.L.
Ioffe, Synthesis (2006) 2265–2270.
[30] R. Ballini, L. Barboni, G. Giarlo, J. Org. Chem. 69 (2004) 6907–6908.
1
7
3
5
À1
1
3
03 cm . H NMR (300 MHz, CDCl ): d 2.48–2.56 (m, 1H), 2.81–
[31] N. Kornblum, H.O. Larson, R.K. Blackwood, D.D. Mooberry, E.P. Oliveto, G.E.
.00 (m, 2H), 5.15–5.26 (m, 2H), 5.36 (dd, JH,F = 18.0, 6.6 Hz, 1H),
.54–5.63 (m, 1H), 7.57 (d, J = 7.8 Hz, 2H), 7.70 (d, J = 7.8 Hz, 2H);
Graham, J. Am. Chem. Soc. 78 (1956) 1497–1501.
[32] W. Peng, J.M. Shreeve, Tetrahedron Lett. 46 (2005) 4905–4909.
[33] P. Butler, B.T. Golding, G. Laval, H.L. Khouzani, R.R. Karimib, M.M. Sadeghib,
Tetrahedron 63 (2007) 11160–11166.
1
9
F NMR (282 MHz, CDCl
3
):
F), À63.3 (s, 3F); C NMR (100 MHz, CDCl
), 75.3 (d, J = 20.0 Hz, CHOH), 121.0 (d, J = 247.5 Hz, CF), 122.8,
d
À143.7 (ddd, J = 31.9, 17.8, 7.9 Hz,
13
1
CH
3
d
): 38.5 (d, J = 20.5 Hz,
[
34] Syn-isomer (d
F
: À139.2 ppm, d, JFH = 20.6 Hz) was observed but without separa-
2
tion.