Difluoro(phenylchalcogen)methylation of aldehydes, ketones, and imines with S-, Se-, and Te-containing reagents PhXCF2H (X = S, Se, Te)

Article abstract of DOI:10.1016/j.jfluchem.2011.08.007

A series of sulfur-, selenium- and tellurium-containing (phenylchalcogen)difluoromethylation reagents PhSCF₂H (1a), PhSeCF₂H (1b), and PhTeCF₂H (1c) were prepared, and their relative reactivity towards aldehydes, ketones,

Full text of DOI:10.1016/j.jfluchem.2011.08.007

Journal of Fluorine Chemistry 135 (2012) 45–58
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Difluoro(phenylchalcogen)methylation of aldehydes, ketones, and imines
with S-, Se-, and Te-containing reagents PhXCF2H (X = S, Se, Te)
*
Mingyou Hu, Fei Wang, Yanchuan Zhao, Zhengbiao He, Wei Zhang, Jinbo Hu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A series of sulfur-, selenium- and tellurium-containing (phenylchalcogen)difluoromethylation reagents
PhSCF2H (1a), PhSeCF2H (1b), and PhTeCF2H (1c) were prepared, and their relative reactivity towards
aldehydes, ketones, and imines was investigated. Compared to the former developed (phenylchalco-
gen)difluoromethylation reagents, these reagents are relatively easily available and more atom-
economical in fluoroalkylation reactions. It was found that the efficient nucleophilic (phenylchalco-
gen)difluoromethylation of aldehydes, ketones, and imines could be achieved with 1a–1c. Reagents 1a
and 1b showed better reactivity than 1c toward carbonyl compounds and imines, and PhOCF2H (1d) was
found to be unable to undergo similar fluoroalkylation reactions.
Received 24 June 2011
Received in revised form 9 August 2011
Accepted 10 August 2011
Available online 13 September 2011
Dedicated to Professor Wei-Yuan
Huang on the occasion of his 90th birthday.
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
(Phenylchalcogen)difluoromethylation
Fluorine
Difluoromethylation
Nucleophilic fluoroalkylation
Diastereoselectivity
1. Introduction
Recently, inspired by the importance of introducing a (phe-
nylthio)difluoromethyl [11], (phenylseleno)difluoromethyl [12],
Nucleophilic fluoroalkylation with (fluoroalkyl)silanes RfSiR3
(such as the Ruppert-Prakash reagent, TMSCF3) has become one of
the widely used methods for the synthesis of fluorinated organic
compounds (Eq. (1)) [1,2]. Another class of nucleophilic fluoroalk-
ylation agents are hydrofluorocarbons (RfH), which, under the
treatment of a proper base, generate the fluoroalkyl anions Rfꢀ that
act as real nucleophilic fluoroalkylating species (Eq. (2)) [3,4]. The
hydrofluorocarbon reagents include trifluoromethane (CF3H) and
other polyfluoroalkanes [5], diethyl difluoromethanephosphonate
[6], difluoromethyl phenyl sulfone (PhSO2CF2H) [7], fluoromethyl
phenyl sulfone (PhSO2CH2F) [8], and fluorobis(phenylsulfonyl)-
methane [9], among others. The advantage of using RfH as
fluoroalkylating agents lies in the fact that the functionalization of
C–H bond is the most atom-economical way in organic synthesis
[10].
or (phenyltelluro)difluoromethyl group [13] into organic mole-
cules, we were interested in developing PhSCF2H (1a), PhSeCF2H
(1b), and PhTeCF2H (1c) as efficient nucleophilic (phenylchalco-
gen)difluoromethylation reagents. It should be mentioned that,
both (phenylthio)difluoromethylation and (phenylseleno)difluor-
omethylation with PhSCF2SiMe3 and PhSeCF2SiMe3 have been
previously described [11,12], while the similar (phenyltelluro)di-
fluoromethylation has never been reported. Furthermore, to the
best of our knowledge, the nucleophilic (phenylchalcogen)difluor-
omethylation with PhXCF2H (X = S, Se, Te) reagents (1a–c) has
never been reported, although compounds 1a–c have been known
for decades [13,14]. In this paper, we wish to disclose the efficient
nucleophilic (phenylthio)-, (phenylseleno)-, and (phenyltelluro)-
difluoromethylation of aldehydes, ketones, and imines with S-, Se-,
and Te-containing reagents PhXCF2H (X = S, Se, Te).
Eþ
Rf ꢀSiR3acꢀtiv!atorRf ꢀE
(1)
(2)
2. Results and discussion
Eþ
Rf ꢀHꢀ!Rf ꢀE
base
A
series of difluoromethylation reagents PhSCF2H (1a),
PhSeCF2H (1b) and PhTeCF2H (1c) were prepared by using
previously known methods [13,14]. Then, we carried out the
(phenylseleno)difuoromethylation reactions by using benzalde-
hyde (2a) as a model compound with PhSeCF2H (1b). The reaction
conditions were initially based on the previously reported ones
* Corresponding author. Tel.: +86 21 54925174; fax: +86 21 64166128.
E-mail addresses: jinbohu@sioc.ac.cn, jinbohu@mail.sioc.ac.cn (J. Hu).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.08.007

46
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
Table 1
(Phenylseleno)difuoromethylation of benzaldehyde (2a) with reagent 1b.
O
OH
CF2SePh
Base, Solvent
Temp
H
PhSeCF2H
1b
2
4a
.
Entry
Base
Solvent
Temp (8C)
Time (h)
1b:2:base
Yield (%)a
1
2
LiHMDS
n-BuLi
THF
ꢀ78
ꢀ78
ꢀ50
ꢀ50
ꢀ78
ꢀ30
0–5
rt
0.5
0.5
1
1:1:2
0b
0b
57c
57c
0
THF
1:1:2
3
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
DMF
DMF
THF
1:1:2
4
3
1:1:2
5
0.5
2
1:1:2
6
DMF
DMF
DMF
THF
1:1.5:2
1:1.5:2
1:1.5:2
1:1.5:2
1:1.5:2
1:1.5:2
1:1:4
21
20
3
7
2
8
2
g
0–5
rt
2
37
3
86c
58c
10
11
12
DMSO
DMF
DMF
2
ꢀ50
2
ꢀ50
2
Yield was based on 19F NMR of a sample from the crude reaction mixture using PhCF3 as an internal standard.
When the temperature up to room temperature, there was still no product monitored.
Isolated yield.
a
b
c
with PhSO2CF2H reagent [15]. When we used n-BuLi and LiHMDS
important role in the reaction. When the base was changed to
potassium hydroxide (KOH), and the temperature was increased
from 0 8C to room temperature, the reaction (in DMF) gave the
product 11a in 71% isolated yield (Table 4, entry 14). Encouraged
by this result, we further investigated the substrate scope of
(LiN(SiMe3)2) as bases at ꢀ78 8C (or room temperature) in THF, the
reaction failed to give the desired product, as monitored by 19F
NMR (Table 1, entry 1–2). When t-BuOK was employed, we found
that the reaction took place at ꢀ50 8C, and further optimization
revealed that DMF was the best solvent at ꢀ50 8C (Table 1, entries
3–12). The reaction typically completed within 2 h.
Table 2
With the optimized condition, a variety of aldehydes as
substrates have been investigated, and the results are summarized
in Table 2. For those aldehydes with electron-donating substi-
tuents on the aromatic ring (such as 4-methoxy and 4-dimethy-
lamino benzaldehyde), the yields were generally high (Table 2,
entries 2 and 3). But for the alkyl substituted benzaldehyde, the
yield was much lower since a significant amount of starting
materials were unreacted (Table 2, entry 9). For electron-
withdrawing substituents on the aromatic ring, the yields were
relatively low due to the serious side reaction (Cannizzaro
reaction) of the aldehydes (Table 2, entries 4 and 5), which was
consistent with the previous report [16]. For reagent 1c, the anion
intermediate is unstable to some extent, and much lower yields
were obtained (entries 1, 3, 5–7, 9 and 10).
Encouraged by the aforementioned results, we examined the
reaction of these reagents with ketones, and the results were listed
in Table 3. As ketones possess relatively lower reactivity than
aldehydes, the yields dropped sharply with the decrease of the
anion stability (PhSCF2ꢀ > PhSeCF2ꢀ > PhTeCF2ꢀ). However, in
most cases when reagents 1a and 1b were used, the corresponding
products were obtained in satisfactory yields regardless of the
electronic nature of the substituents on the aromatic ring (Table 3).
It is worth noting that although reagents 1a–c could react with
non-enolizable aldehydes and ketones, they did not react
efficiently with enolizable carbonyl compounds under the
aforementioned conditions. Therfore, we chose acetone as a model
substrate to further optimize the reaction conditions. It was found
that, when LiHMDS and n-BuLi were employed as bases, no matter
what the temperature and solvent were, there were no target
products observed (Table 4, entries 3–6 and 11). However, when
KHMDS was used, the product was observed in 30% yield
(monitored by 19F NMR), whereas in the case of NaHMDS, only
6% yield of product was formed (Table 4, entries 7–10). These
results indicated that the metal counterion of the base may play an
(Phenylchalcogen)difluoromethylation of different aldehydes with reagents 1a–c.
O
OH
t-BuOK (2 equiv), DMF
PhXCF2H
+
R
H
R
CF2XPh
-50 oC, 2 h
1 equiv
1.5 equiv
3 or 4 or 5
1a-c
2
X = S, Se, Te
.
Entry
1
Substrate
Product
Yield (%)a
R = Ph (2a)
3a X5S
4a X5Se
5a X5Te
3b X5S
4b X5Se
3c X5S
94
86
76
91
92
79
91
72
28
91
72
75
54
94
73
91
75
35
68
83
61
34b
47
94
94
49
2
3
R = 4-(Me2N)C6H4 (2b)
R = 4-(MeO)C6H4 (2c)
4c X5Se
5b X5Te
3d X5S
4d X5Se
3e X5S
4e X5Se
5c X5Te
3f X5S
4
5
R = 2-BrC6H4 (2d)
R = 4-CIC6H4 (2e)
6
7
R = 4-BrC6H4 (2f)
5d X5Te
3g X5S
4f X5Se
5e X5Te
3h X5S
4g X5Se
3i X5S
R = 2-Naphthyl (2g)
8
9
R = 2,5-(MeO)2C6H3 (2h)
R = 4-MeC6H4 (2i)
4h X5Se
5f X5Te
3j X5S
10
R = t-Butyl (2k)
4j X5Se
5g X5Te
a
Isolated yield.
b
There were still lots of starting materials left.

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
47
Table 3
acidic than PhSeCF2H (1b) and PhTeCF2H (1c). This is in
consistent with the previous report that for -substituted
(Phenylchalcogen)difluoromethylation of different ketones with reagents 1.
a
methyl carbanions XCH2ꢀ, the higher period substituents X
substantially decrease the proton affinity (PA) of XCH2ꢀ, whereas
lower period substituents are less effective in reducing the
basicity of XCH2ꢀ [17]. It shꢀould be noted that we found that all of
three carbanions PhXCF2 (X = S, Se, Te) tend to undergo
O
HO
t-BuOK (2 equiv), DMF
CF2XPh
R2
PhXCF2H
+
R1
R2
R1
-50 oC, 2 h
1 equiv
1
1.5 equiv
6
7 8
,
9
or
decomposition (presumably via
Furthermore, we extended the present nucleophilic (phenyl-
chalcogen)difluoromethylation reactions to imines. At the outset,
a-elimination) (Table 6).
X = S, Se, Te
.
Entry
Substrate
R1
R2
Product
Yield (%)a
we
utilized
N-benzylidene-4-methylbenzenesulfonamide
(PhCH55NTs) as a model substrate and t-BuOK as a base, to react
with PhSeCF2H (1b) at ꢀ50 8C in DMF. However, no desired
product was observed by 19F NMR. Thereafter, we chose N-tert-
butylsulfinyl imine (PhCH55NSOt-Bu) (13a) as a model substrate,
and trace amount of product 15a was observed by 19F NMR. When
we increased the temperature to ꢀ30 8C, the reaction proceeded
smoothly to give the product 15b in 80% isolated yield and with
98:2 diastereomeric ratio (Table 7, entry 2). Further investigation
disclosed that the temperature scope could be ranged from ꢀ40 to
ꢀ30 8C, and with this reaction condition, we examined the
reaction with a variety of structurally diverse N-tert-butylsulfinyl
imines (Table 7). It was found that, while both PhSCF2H (1a) and
PhSeCF2H (1b) were able to efficiently undergo nucleophilic
addition to sulfinimines 13 to afford corresponding PhSCF2- and
PhSeCF2-containing chiral imines 14 (or 15) in good yields and
with high diastereoselectivity, the similar reactions with
PhTeCF2H (1c) were not successful. It is worth noting that we
found that PhOCF2H (1d) could not undergo similar (phenyloxo)
difluoromethylation reaction with aldehydes, ketones and imines
under similar aforementioned conditions.
1
2
3
6a
6b
6c
Ph
Ph
7a X5S
96
88
96
82
79
79
66
92
79
36
94
60
89
91
28
82
91
8a X5Se
7b X5S
8b X5Se
7c X5S
C6H4
Ph
C6H4
4-CIC6H4
8c X5Se
9a X5Te
7d X5S
8d X5Se
9b X5Te
8e X5Se
9c X5Te
7e X5S
4
6d
Ph
4-BrC6H4
5
6
6e
6f
Ph
Ph
4-FC6H4
4-MeOC6H4
8f X5Se
9d X5Te
7f X5S
7
6g
Ph
4-PhC6H4
8g X5Se
a
Isolated yeild.
(phenylchalcogen)difluoromethylation of enolizable ketones, and
the results are summarized in Table 5. It was found that both
acyclic and cyclic enolizable ketones could react with PhSCF2H (1a)
and PhSeCF2H (1b) in moderate to excellent yields. It should be
mentioned that when we tried the similar KOH-mediated reaction
between ketones and PhTeCF2H (1c), no desired product was
observed.
To probe the relative acidity of 1a–c, we conducted the H/D
excange experiments of 1a–c in KOH/D2O/DMF. The data are
shown in Table 6, which suggest that the PhSCF2H (1a) is less
3. Conclusions
In conclusion, we have developed efficient nucleophilic
(phenylchalcogen)difluoromethylation of aldehydes, ketones,
and imines with PhSCF2H (1a), PhSeCF2H (1b), and PhTeCF2H
(1c). It was found that reagents 1a and 1b showed better reactivity
Table 4
The reaction between 1a and enolizable ketones.
O
OH
CF2SPh
Base (2 equiv)
PhSCF2H
+
Solvent, Temp, 3 h
1 equiv
2 equiv
1a
10
11a
.
Entry
Base
Solvent
Temp (8C)
Yield (%)a
1
2
t-BuOK
t-BuOK
LiHMDS
LiHMDS
LiHMDS
LiHMDS
KHMDS
KHMDS
NaHMDS
NaHMDS
n-BuLi
DMF
ꢀ50
0b
DMF
25
Trace
0b
3
THF/HMPA
THF/HMPA
THF/HMPA
DMF
ꢀ78
4
0
0b
5
25
0b
6
0
0b
7
THF
ꢀ50 to rt
ꢀ50 to rt
ꢀ50 to rt
ꢀ50 to rt
ꢀ78
0b
8
DMF
30
0b
9
THF
10
11
12
13
14
DMF
6
THF/HMPA
DMF
0b
K2CO3
ꢀ50 to rt
ꢀ50 to rt
0 to rt
0b
KOH
DMF
27
71c
KOH
DMF
Yield were determinded by 19F NMR using PhCF3 as an internal standard.
No desired product was formed.
a
b
c
Isolated yield after the reaction mixture was stirred for 13 h.

48
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
Table 5
The reaction of 1a (or 1b) with enolizable ketones.
OH
O
KOH(20equiv),DMF
0 oC~rt,13 h
R1
R2
CF2XPh
PhXCF2H
+
R1
10
2 equiv
R2
X = S 1a
X = Se 1b
1 equiv
11 12
or
.
Entry
1
Substrate
Reagent
Product
Yield (%)a
71
1a
HO
O
CF2SPh
11a
10a
2
3
1b
1a
83
97
HO
CF2SePh
12a
O
HO
CF2SPh
11b
10b
4
5
1b
1a
60
94
HO
CF2SePh
12b
HO CF2SPh
O
11c
10c
6
7
1b
55
HO CF2SePh
12c
HO CF2SPh
1a
1b
53
29
O
11d
10d
8
HO CF2SePh
12d
a
Isolated yeild.
Table 6
The deuterium-labeling experiments with reagents 1a–1c.
DMF
PhXCF2H
1 equiv a
D2O
KOH
PhXCF2D
rt, 1 h
20 equiv
50 equiv
(X = S, Se, Te)
X
Resultb
PhXCF2H (%)
PhXCF2D (%)
Decomposed (%)
S
36
6
23
50
35
41
44
58
Se
Te
7
aThe starting material was employed on 0.2 mmol scale.
b
Determined by 19F NMR PhCF3 as an internal standard. All reactants were added in one portion.

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
49
Table 7
The reaction of 1a (or 1b) with N-tert-butylsulfinyl imines.
.
Entry
1
Reagent
Substrate
Product
Yield (%)a
58
drb
1a
ꢂ87:13
2
3
4
5
1b
1a
1b
1a
80
76
73
33
ꢂ98:2
ꢂ94:6
ꢂ94:6
ꢂ91:9
6
7
8
1b
1a
1b
52
72
71
ꢂ99:1
ꢂ95:5
ꢂ91:1
9
1a
1a
43
72
ꢂ78:22
ꢂ97:3
10
11
12
1b
1b
63
52
ꢂ96:4
–
a
Isolated yield based on the main isomer.
Determined by 19F NMR.
b
than 1c toward carbonyl compounds and imines, and PhOCF2H
(1d) was unable to undergo similar fluoroalkylation reactions.
4.1. Typical procedure for preparation of reagents 1
The reagents 1 were prepared following reported methods [13].
4. Experimental
4.2. General procedure for reaction of 1 (PhXCF2H, X = S, Se, Te) with 2
and 6
All reactions and manipulations were performed using standard
Schlenk techniques. Unless otherwise mentioned, solvents were
purchased from commercial sources and purified before using. THF
was distilled from sodium benzophenone ketyl. DMF, DMSO and
HMPA were distilled over CaH2 under nitrogen atmosphere. Other
reagents were purchased from commercial sources and used as
received. 1H NMR spectra were recorded on Bruker 300 or Mercury
300 spectrometers with Me4Si as internal standard. 19F NMR
spectra were recorded on Bruker 300 or Mercury 300 spectro-
meters with CFCl3 as external standard. 13C NMR spectra were
recorded on Avance 500 or DPX-400 spectrometers. Mass spectra
were obtained on a spectrometer. High-resolution mass data were
recorded on a high-resolution mass spectrometer in the EI, ESI or
MALDI mode.
Under a nitrogen atmosphere, to a stirred solution of PhSeCF2H
(1b) (414 mg, 2.0 mmol) and benzaldehyde (2a) (318 mg,
3.0 mmol) with 3 mL DMF in a Schlenk tube, t-BuOK (448 mg,
4.0 mmol) (dissolved in 2 mL DMF) was added dropwise at ꢀ50 8C.
The mixture was stirred at this temperature for 2 h. Then quenched
with saturated aqueous ammonium chloride or brine, the reaction
mixture was extracted with Et2O (3 ꢁ 10 mL). The combined
organic layer was washed with H2O (2 ꢁ 10 mL), followed by brine
(10 mL), dried over MgSO4 and concentrated under vacuum. The
residue was purified by flash chromatography with ethyl acetate/
petroleum ether (1:10) as eluent to give 520 mg 4a as a colorless
oil. Yield 86%.

50
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
4.2.1. 2,2-Difluoro-1-phenyl-2-(phenylthio)ethanol (3a)
(d, J = 210.3 Hz, 1F), ꢀ85.3 (dd, J = 211.5 Hz, J = 11.5 Hz, 1F). The
characterization datawereconsistent withthe previous report [11a].
4.2.6. 1-(4-Bromophenyl)-2,2-difluoro-2-(phenylthio)ethanol (3f)
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.47–7.31 (m, 8H), 4.98 (m, 1H), 2.82 (d, J = 4.0 Hz, 1H). 19F
NMR (CDCl3, 282 MHz):
d 7.57 (d, J = 7.0 Hz,
d
ꢀ81.1 (dd, J = 209.5 Hz, J = 8.1 Hz, 1F),
ꢀ84.8 (dd, J = 209.5 Hz, J = 11.0 Hz, 1F). The characterization data
Colorless oil; 1H NMR (CDCl3, 300 MHz):
4.95 (m, 1H), 2.79 (d, J = 3.1 Hz, 1H). 19F NMR (CDCl3, 282 MHz):
d 7.57–7.25 (m, 9H),
were consistent with the previous report [18].
d
ꢀ81.1 (dd, J = 211.3 Hz, J = 7.1 Hz, 1F), ꢀ85.2 (dd, J = 210.4 Hz,
J = 10.2 Hz, 1F). The characterization data were consistent with the
previous report [11a].
4.2.2. 1-(4-(Dimethylamino)phenyl)-2,2-difluoro-2-
(phenylthio)ethanol (3b)
4.2.7. 2,2-Difluoro-1-(naphthalen-2-yl)-2-(phenylthio)ethanol (3g)
Yellow oil; IR (film): 3420, 3060, 2890, 2805, 1615, 1526, 1475,
1441, 1356, 1230, 1189, 1159, 1054, 981, 819,787,751, 691 cmꢀ1. 1H
White solid; 1H NMR (CDCl3, 300 MHz):
(m, 3H), 7.60–7.32 (m, 8H), 5.17 (m, 1H), 2.83 (d, J = 3.7 Hz, 1H). 19
NMR (CDCl3, 282 MHz):
d 7.96 (s, 1H), 7.87–7.85
NMR (CDCl3, 300 MHz):
6.70 (d, J = 6.7 Hz, 2H), 4.89 (t, J = 9.6 Hz, 1H), 2.95 (s, 6H). 19F NMR
(CDCl3, 282 MHz):
ꢀ82.1 (dd, J = 207.2 Hz, J = 9.1 Hz, 1F), ꢀ84.1
(dd, J = 207.3 Hz,J = 11.1 Hz, 1F).13CNMR(CDCl3, 100 MHz):
151.1,
d 7.57 (d, J = 7.1 Hz, 2H), 7.41–7.31 (m, 5H),
F
d
ꢀ80.8 (dd, J = 209.5 Hz, J = 7.3 Hz, 1F),
d
ꢀ84.2 (dd, J = 210.3 Hz, J = 11.1 Hz, 1F). The characterization data
d
were consistent with the previous report [11a].
136.4, 132.1, 129.7, 129.3, 129.0, 128.8, 126.4, 122.8, 112.1, 76.3 (t,
J = 26.4 Hz), 40.4. MS (EI, m/z, %): 309 (M+, 12.44), 150 (100.00).
HRMS (EI): Calcd. for C16H17F2ONS: 309.0999; found: 309.0990.
4.2.8. 1-(2,5-Dimethoxyphenyl)-2,2-difluoro-2-(phenylthio)ethanol
(3h)
4.2.3. 2,2-Difluoro-1-(4-methoxyphenyl)-2-(phenylthio)ethanol (3c)
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.41–7.31 (m, 5H), 6.90 (d, J = 8.6 Hz, 2H), 4.94 (m, 1H), 3.80 (s,
3H), 2.80 (d, J = 4.1 Hz, 1H). 19F NMR (CDCl3, 282 MHz):
(dd, J = 208.4 Hz, J = 8.2 Hz, 1F), ꢀ84.6 (dd, J = 208.5 Hz, J = 10.6 Hz,
1F). The characterization data were consistent with the previous
report [19].
d 7.57 (d, J = 7.1 Hz,
Yellow oil; IR (film): 3448, 3061, 3001, 2945, 2836, 1590, 1502,
1465, 1441, 1220, 1179, 1157, 1046, 989, 815, 751, 692 cmꢀ1 1H
.
d
ꢀ81.7
NMR (CDCl3, 300 MHz):
3H), 6.96 (s, 1H), 6.86 (m, 2H), 5.24 (m, 1H), 3.87 (m, 1H), 3.82 (s,
1H), 3.77 (s, 1H). 19F NMR (CDCl3, 282 MHz):
ꢀ81.0 (dd,
J = 205.5 Hz, J = 8.4 Hz, 1F), ꢀ84.8 (dd, J = 205.3 Hz, J = 13.4 Hz, 1F).
13C NMR (CDCl3, 100 MHz):
153.7, 152.0, 136.4, 132.7, 129.7,
d 7.60 (d, J = 7.7 Hz, 2H), 7.42–7.32 (m,
d
d
4.2.4. 1-(2-Bromophenyl)-2,2-difluoro-2-(phenylthio)ethanol (3d)
129.2, 129.0, 126.4, 124.4, 115.3, 115.1, 112.6, 73.4 (t, J = 26.6 Hz),
56.4, 55.8. MS (EI, m/z, %): 326 (M+, 21.49), 167 (100.00). HRMS
(EI): Calcd. for C16H16F2O3S: 326.0788; found: 326.0793.
4.2.9. 2,2-Difluoro-2-(phenylthio)-1-p-tolylethanol (3i)
Yellow oil; IR (film): 3417, 3063, 1591, 1570, 1474, 1440, 1157,
1125, 1062, 984, 845, 749, 691 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
7.72–7.54 (m, 4H), 7.45–7.35 (m, 4H), 7.25–7.15 (m, 1H), 5.53 (m,
1H), 2.77 (d, J = 4.4 Hz, 1H). 19F NMR (CDCl3, 282 MHz):
ꢀ79.8
(dd, J = 212.7 Hz, J = 5.1 Hz, 1F), ꢀ87.1 (dd, J = 212.7 Hz, J = 13.4 Hz,
1F). 13C NMR (CDCl3, 100 MHz):
136.5, 134.9, 132.9, 131.7, 130.5,
130.0, 129.9, 129.2, 127.6, 125.8, 124.3, 74.1 (t, J = 26.4 Hz), 40.4.
MS (EI, m/z, %): 345 (M+, 2.06), 185 (100.00), 187 (98.79). HRMS
(EI): Calcd. for C14H11F2BrOS: 343.9682; found: 343.9686.
d
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.41–7.11 (m, 7H), 4.95 (m, 1H), 3.00 (m, 1H), 2.36 (s, 1H). 19
NMR (CDCl3, 282 MHz):
d 7.57 (d, J = 7.1 Hz,
d
F
d
ꢀ81.5 (dd, J = 209.6 Hz, J = 8.0 Hz, 1F),
ꢀ84.6 (dd, J = 208.3 Hz, J = 11.3 Hz, 1F). The characterization data
were consistent with the previous report [19].
4.2.5. 1-(4-Chlorophenyl)-2,2-difluoro-2-(phenylthio)ethanol (3e)
4.2.10. 1,1-Difluoro-3,3-dimethyl-1-(phenylthio)butan-2-ol (3j)
White solid; 1H NMR (CDCl3, 300 MHz):
(m, 7H), 4.97(m,1H), 2.71 (s, 1H). 19FNMR (CDCl3,282 MHz):
d
7.58(m, 2H), 7.41–7.37
ꢀ81.2
Colorless oil; IR (film): 3474, 3062, 2961, 2913, 2876, 1475,
1441, 1168, 1063, 1023, 977, 932, 875, 747, 705, 691 cmꢀ1. 1H NMR
d

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
51
(CDCl3, 300 MHz):
(m, 1H), 2.24 (d, J = 7.3 Hz, 1H), 1.00 (s, 9H). 19F NMR (CDCl3,
282 MHz):
ꢀ72.4 (d, J = 208.9 Hz, 1F), ꢀ83.5 (dd, J = 209.2 Hz,
J = 18.6 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
136.6, 134.2, 131.4,
129.8, 129.0, 126.4 (t, J = 2.3 Hz), 80.2 (t, J = 25.2 Hz), 35.1, 26.8. MS
(EI, m/z, %): 246 (M+, 37.01), 57 (100.00). HRMS (EI): Calcd. for
C12H16F2OS: 246.0890; found: 246.0894.
d
7.55 (d, J = 7.3 Hz, 2H), 7.38–7.27 (m, 3H), 3.52
J = 6.5 Hz, 1F), ꢀ84.7 (dd, J = 211.7 Hz, J = 14.8 Hz, 1F). 13C NMR
(CDCl3, 100 MHz): d 137.3, 134.8, 132.9, 130.5, 129.9, 129.7, 129.4,
d
129.3, 129.2, 127.6, 126.40, 126.37, 124.3, 123.82, 123.78, 123.4,
74.8 (t, J = 25.1 Hz). MS (EI, m/z, %): 391 (M+, 5.10), 187 (100.00).
HRMS (EI): Calcd. for C14H11BrF2OSe: 391.9127; found: 391.9131.
d
4.2.15. 1-(4-Chlorophenyl)-2,2-difluoro-2-(phenylselanyl)ethanol
(4e)
4.2.11. 2,2-Difluoro-1-phenyl-2-(phenylselanyl)ethanol (4a)
White solid; m.p. 80–81 8C; IR (film): 3573, 3089, 3069, 3046,
2897, 1592, 1578, 1485, 1475, 1438, 1407, 1196, 1051, 969, 743,
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.32–7.15 (m, 8H), 4.81 (m, 1H), 3.01 (s, 1H). 19F NMR (CDCl3,
282 MHz):
J = 208.4 Hz, J = 12.4 Hz, 1F). The characterization data were
consistent with the previous report [12].
d 7.52 (d, J = 7.3 Hz,
691, 606 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
7.63 (d, J = 6.9 Hz, 2H),
7.43–7.30 (m, 7H), 4.92 (m, 1H), 2.70 (d, J = 3.9 Hz, 1H). 19F NMR
(CDCl3, 282 MHz):
ꢀ78.3 (dd, J = 211.6 Hz, J = 8.3 Hz, 1F), ꢀ83.2
(dd, J = 210.8 Hz, J = 12.4 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
d
ꢀ78.2 (dd, J = 208.5 Hz, J = 8.3 Hz, 1F), ꢀ82.2 (dd,
d
d
137.2, 135.1, 133.5, 129.6, 129.4, 129.3, 129.2, 128.6, 126.4, 123.6,
76.2 (t, J = 24.1 Hz). MS (EI, m/z, %): 347 (M+, 10.76), 141 (100.00).
HRMS (EI): Calcd. for C14H11ClF2OSe: 347.9632; found: 347.9634.
4.2.12. 1-(4-(Dimethylamino)phenyl)-2,2-difluoro-2-
(phenylselanyl)ethanol (4b)
4.2.16. 2,2-Difluoro-1-(naphthalen-2-yl)-2-(phenylselanyl)ethanol
(4f)
Yellow solid; m.p. 48–50 8C; IR (film): 3425, 3057, 2889, 2805,
1615, 1579, 1477, 1439, 1357, 1189, 1159, 1059, 966, 742, 692,
White solid; 1H NMR (CDCl3, 300 MHz):
d7.83 (s, 1H), 7.75–7.67
600 cmꢀ1
.
1H NMR (CDCl3, 300 MHz):
d
7.65 (d, J = 6.9 Hz, 2H),
7.38–7.30 (m, 5H), 6.70 (d, J = 9.2 Hz, 2H), 4.87 (t, J = 11.5 Hz, 1H),
2.96 (s, 6H), 2.64 (s, 1H). 19F NMR (CDCl3, 282 MHz):
ꢀ79.0 (dd,
J = 204.6 Hz, J = 9.5 Hz, 1F), ꢀ81.2 (dd, J = 205.6 Hz, J = 11.6 Hz, 1F).
13C NMR (CDCl3, 100 MHz):
151.1, 137.2, 130.1, 129.3, 129.1,
(m, 3H), 7.55–7.38 (m, 5H), 7.30–7.16 (m, 3H), 5.02 (m, 1H), 2.85 (s,
1H). 19F NMR (CDCl3, 282 MHz): ꢀ78.1 (dd, J = 209.7 Hz, J = 8.4 Hz,
1F), ꢀ81.9 (dd, J = 209.6 Hz, J = 11.3 Hz, 1F). The characterization
data were consistent with the previous report [20].
d
d
128.7, 127.1, 124.3, 124.1, 122.7, 112.1, 77.0 (t, J = 25.3 Hz), 40.4.
MS (EI, m/z, %): 357 (M+, 5.20), 150 (100.00). HRMS (EI): Calcd. for
C16H17F2NOSe: 357.0443; found: 357.0438.
4.2.17. 1-(2,5-Dimethoxyphenyl)-2,2-difluoro-2-
(phenylselanyl)ethanol (4 g)
4.2.13. 2,2-Difluoro-1-(4-methoxyphenyl)-2-(phenylselanyl)ethanol
(4c)
Yellow oil; IR (film): 3448, 3058, 3001, 2941, 2836, 1613, 1578,
.
1500, 1439, 1278, 1179, 1156, 1045, 978, 813, 742, 591 cmꢀ1 1H
NMR (CDCl3, 300 MHz):
5H), 6.94 (s, 1H), 6.85 (s, 1H), 5.22 (m, 1H), 3.88 (m, 1H), 3.81 (s,
1H), 3.76 (s, 1H). 19F NMR (CDCl3, 282 MHz):
ꢀ78.3 (dd,
J = 204.5 Hz, J = 8.2 Hz, 1F), ꢀ82.0 (dd, J = 203.9 Hz, J = 14.5 Hz, 1F).
13C NMR (CDCl3, 100 MHz):
153.7, 151.9, 137.2, 130.0, 129.3,
129.1, 127.0, 124.4, 124.3, 124.0, 115.22, 115.15, 112.6, 74.0 (t,
J = 26.0 Hz), 56.3, 55.8. MS (EI, m/z, %): 374 (M+, 10.90), 167
(100.00). HRMS (EI): Calcd. for C16H16F2O3Se: 374.0233; found:
374.0237.
d 7.68 (d, J = 6.8 Hz, 2H), 7.41–7.25 (m,
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.38–7.24 (m, 5H), 6.89 (d, J = 8.9 Hz, 2H), 4.90 (m, 1H), 3.80 (s,
3H), 2.76 (s, 1H). 19F NMR (CDCl3, 282 MHz):
J = 207.4 Hz, J = 8.1 Hz, 1F), ꢀ82.3 (dd, J = 208.9 Hz, J = 12.9 Hz, 1F).
The characterization data were consistent with the previous report
[20].
d 7.64 (d, J = 7.3 Hz,
d
d
ꢀ78.9 (dd,
d
4.2.14. 1-(2-Bromophenyl)-2,2-difluoro-2-(phenylselanyl)ethanol
(4d)
4.2.18. 2,2-Difluoro-2-(phenylselanyl)-1-p-tolylethanol (4h)
Colorless oil; IR (film): 3418, 3060, 1591, 1569, 1475, 1439,
1392, 1154, 1063, 968, 742, 691, 598 cmꢀ1 1H NMR (CDCl3,
.
Yellow oil; IR (film): 3436, 3058, 3031, 2921, 1614, 1578, 1477,
1439, 1381, 1157, 1061, 967, 741, 691, 601 cmꢀ1. 1H NMR (CDCl3,
300 MHz):
7.33 (m, 4H), 7.25–7.18 (m, 1H), 5.48 (m, 1H), 2.83 (d, J = 4.4 Hz,
1H). 19F NMR (CDCl3, 282 MHz):
ꢀ77.1 (dd, J = 212.7 Hz,
d 7.69 (d, J = 6.4 Hz, 3H), 7.53 (d, J = 8.2 Hz, 1H), 7.43–
300 MHz):
d 7.63 (d, J = 7.3 Hz, 2H), 7.37–7.26 (m, 5H), 7.16 (d,
J = 7.6 Hz, 2H), 4.88 (m, 1H), 2.81 (d, J = 3.1 Hz, 1H), 2.34 (s, 1H). 19
F
d

52
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
NMR (CDCl3, 282 MHz):
d
ꢀ78.6 (dd, J = 208.7 Hz, J = 9.3 Hz, 1F),
691, 645 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
7.39–7.22 (m, 7H), 4.83 (m, 1H), 2.73 (d, J = 3.6 Hz, 1H). 19F NMR
(CDCl3, 282 MHz):
–73.2 (dd, J = 228.1 Hz, J = 9.1 Hz, 1F), ꢀ77.8 (dd,
J = 227.6 Hz, J = 11.3 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
141.4,
135.1, 133.8, 129.4, 129.3, 129.1, 128.5, 120.4, 117.3, 110.4, 77.9 (t,
J = 23.6 Hz). MS (EI, m/z, %): 396 (M+, 37.27), 77 (100.00). HRMS (EI):
Calcd. for C14H11F2OClTe: 396.9525; found: 396.9528.
d 7.82 (d, J = 6.9 Hz, 2H),
ꢀ82.3 (dd, J = 208.3 Hz, J = 12.3 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
d
139.1, 137.3, 132.3, 129.8, 129.5, 129.3, 129.2, 129.1, 127.7,
d
126.8, 123.9, 123.8, 76.9 (t, J = 24.0 Hz), 21.3. MS (EI, m/z, %): 328
(M+, 6.71), 121 (100.00). HRMS (EI): Calcd. for C15H14F2OSe:
328.0174; found: 328.0176.
d
4.2.19. 1,1-Difluoro-3,3-dimethyl-1-(phenylselanyl)butan-2-ol (4i)
4.2.23. 1-(4-Bromophenyl)-2,2-difluoro-2-(phenyltellanyl)ethanol
(5d)
Yellow oil; IR (film): 3479, 3060, 2961, 2912, 2876, 1580, 1478,
1439, 1370, 1165, 1063, 971, 868, 739, 691 cmꢀ1. 1H NMR (CDCl3,
White solid; m.p. 92–94 8C; IR (film): 3565, 3081, 1693, 1587,
300 MHz):
1H), 2.33 (d, J = 7.7 Hz, 1H), 1.06 (s, 9H). 19F NMR (CDCl3,
282 MHz):
ꢀ68.7 (d, J = 205.4 Hz, 1F), ꢀ81.6 (dd, J = 205.4 Hz,
J = 20.4 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
137.3, 132.7, 129.74,
129.71, 129.4, 129.1, 126.7, 124.5, 81.2, 35.3, 26.7 (t, J = 2.9 Hz). MS
(EI, m/z, %): 294 (M+, 6.87), 57 (100.00). HRMS (EI): Calcd. for
d 7.71 (d, J = 6.9 Hz, 2H), 7.44–7.32 (m, 3H), 3.60 (m,
1484, 1471, 1433, 1402, 1220, 1132, 1099, 1074, 1036, 962, 816,
759, 737, 692, 647 cmꢀ1
.
1H NMR (CDCl3, 300 MHz):
d
7.81 (d,
d
J = 7.4 Hz, 2H), 7.49–7.22 (m, 7H), 4.81 (m, 2H), 2.73 (d, J = 3.2 Hz,
d
1H). 19F NMR (CDCl3, 282 MHz):
d–72.9 (dd, J = 229.1 Hz, J = 4.5 Hz,
1F), ꢀ77.5 (dd, J = 229.1 Hz, J = 11.2 Hz, 1F). 13C NMR (CDCl3,
100 MHz): d 141.4, 134.3, 131.5, 129.4, 129.3, 123.3, 110.4, 77.9 (t,
C
12H16F2OSe: 294.0334; found: 294.0333.
J = 23.4 Hz). MS (EI, m/z, %): 441 (M+, 40.93), 77 (100.00). HRMS
(EI): Calcd. for C14H11F2OBrTe: 441.9024; found: 441.9022.
4.2.20. 2,2-Difluoro-1-phenyl-2-(phenyltellanyl)ethanol (5a)
4.2.24. 2,2-Difluoro-1-(naphthalen-2-yl)-2-(phenyltellanyl)ethanol
(5e)
Yellow oil; IR (film): 3434, 3065, 1574, 1474, 1454, 1434, 1141,
.
1019, 997, 958, 843, 735, 692, 587 cmꢀ1 1H NMR (CDCl3,
300 MHz):
1H), 2.75 (s, 1H). 19F NMR (CDCl3, 282 MHz):
J = 224.9 Hz, J = 9.0 Hz, 1F), ꢀ77.1 (dd, J = 225.0 Hz, J = 12.5 Hz, 1F).
13C NMR (CDCl3, 100 MHz):
141.4, 135.5, 129.3, 129.2, 129.1,
128.4, 127.7, 110.7, 78.5 (t, J = 23.8 Hz). MS (EI, m/z, %): 364 (M+,
50.00), 77 (100.00). HRMS (EI): Calcd. for C14H12F2OTe: 363.9919;
found: 363.9922.
d
7.83 (d, J = 6.7 Hz, 2H), 7.44–7.21 (m, 8H), 4.85 (m,
Yellow solid; m.p. 69–71 8C; IR (film): 3418, 3051, 1573, 1472,
1433, 1362, 1298, 1138, 1086, 1038, 994, 954, 867, 777, 729, 689,
d
ꢀ73.1 (dd,
560 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
7.93 (s, 1H), 7.82–7.79 (m,
5H), 7.51–7.16 (m, 7H), 5.02 (m, 1H), 2.84 (s, 1H). 19F NMR (CDCl3,
282 MHz):
ꢀ72.8 (dd, J = 224.8 Hz, J = 9.2 Hz, 1F), ꢀ76.4 (dd,
J = 225.9 Hz, J = 12.4 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
141.3,
d
d
d
133.7, 132.9, 129.3, 129.2, 128.3, 128.2, 127.8, 127.3, 126.6, 126.4,
124.9, 110.7, 78.7 (t, J = 23.6 Hz). MS (EI, m/z, %): 414 (M+, 38.44),
157 (100.00). HRMS (EI): Calcd. for C18H14F2OTe: 414.0075; found:
414.0078.
4.2.21. 2,2-Difluoro-1-(4-methoxyphenyl)-2-(phenyltellanyl)ethanol
(5b)
4.2.25. 2,2-Difluoro-2-(phenyltellanyl)-1-p-tolylethanol (5f)
Yellow oil; IR (film): 3438, 3054, 2837, 1612, 1574, 1513, 1473,
1435, 1251, 1177, 1033, 997, 957, 832, 785, 736, 692, 586 cmꢀ1. 1H
White solid; m.p. 63–65 8C; IR (film): 3527, 3067, 2897, 1512,
NMR (CDCl3, 300 MHz):
d 7.84 (d, J = 7.3 Hz, 2H), 7.38–7.21 (m, 5H),
1473, 1433, 1376, 1238, 1143, 1074, 1040, 969, 953, 814, 734, 725,
6.88 (d, J = 8.7 Hz, 2H), 4.85 (m, 1H), 3.80 (s, 1H), 2.73 (d, J = 4.1 Hz,
689, 554 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
7.84 (d, J = 7.2 Hz, 2H),
1H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ73.8 (dd, J = 222.9 Hz, J = 8.8 Hz,
7.39–7.14 (m, 7H), 4.83 (m, 1H), 2.75 (d, J = 2.5 Hz, 1H), 2.35 (s, 3H).
1F), ꢀ76.8 (dd, J = 223.7 Hz, J = 12.3 Hz, 1F). 13C NMR (CDCl3,
19F NMR (CDCl3, 282 MHz):
d
ꢀ73.4 (dd, J = 224.0 Hz, J = 9.1 Hz, 1F),
100 MHz):
d 160.3, 141.3, 129.3, 129.2, 129.0, 127.6, 110.8, 78.2 (t,
ꢀ76.9 (dd, J = 223.7 Hz, J = 12.1 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
d
J = 23.6 Hz). MS (EI, m/z, %): 394 (M+, 11.71), 137 (100.00). HRMS
141.4, 139.1, 132.5, 129.3, 129.1, 127.6, 117.9 (t, J = 210.7 Hz), 110.7,
78.5(t,J = 22.8 Hz),21.3.MS(EI,m/z,%):378(M+,40.54),121(100.00).
HRMS (EI): Calcd. for C15H14F2OTe: 378.0075; found: 378.0077.
(EI): Calcd. for C15H14F2O2Te: 394.0024; found: 394.0022.
4.2.22. 1-(4-Chlorophenyl)-2,2-difluoro-2-(phenyltellanyl)ethanol
(5c)
4.2.26. 1,1-Difluoro-3,3-dimethyl-1-(phenyltellanyl)butan-2-ol (5g)
White solid; m.p. 66–68 8C; IR (film): 3566, 3064, 1594, 1573,
1486, 1471, 1433, 1406, 1217, 1132, 1075, 1036, 963, 821, 763, 736,
Yellow oil; IR (film): 3459, 3055, 2956, 2875, 1574, 1475, 1435,
1369, 1155, 1058, 1018, 999, 864, 731, 691 cmꢀ1. 1H NMR (CDCl3,

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
53
300 MHz):
1H), 2.40 (d, J = 8.3 Hz, 1H), 1.05 (s, 9H). 19F NMR (CDCl3, 282 MHz):
ꢀ62.6 (d, J = 218.2 Hz, 1F), ꢀ76.7 (dd, J = 218.7 Hz, J = 23.6 Hz,
d
7.94 (d, J = 7.1 Hz, 2H), 7.42–7.24 (m, 3H), 3.63 (m,
NMR (CDCl3, 300 MHz):
(CDCl3, 282 MHz):
100 MHz): d 149.2, 139.9, 139.2, 136.8, 131.1, 129.9, 129.6 (t,
J = 2.1 Hz), 129.0, 128.5, 128.2, 127.6 (t, J = 2.4 Hz), 122.6, 98.7, 81.4
(t, J = 24.0 Hz). MS (EI, m/z, %): 294 ([MꢀPhSOH]+, 0.83), 261
(100.00). HRMS (EI): Calcd. for [C20H15BrF2OS–PhSCF2]: 260.9915;
found: 260.9916.
d
7.59–7.33 (m, 14H), 3.11 (s, 1H). 19F NMR
d
ꢀ77.5 (s, 1F), ꢀ77.6 (s, 1F). 13C NMR (CDCl3,
d
1F). 13C NMR (CDCl3, 100 MHz):
d
141.3, 129.2, 129.1, 111.9, 83.3 (t,
J = 23.4 Hz), 35.4, 26.6. MS (EI, m/z, %): 344 (M+, 12.00), 57 (100.00).
HRMS (EI): Calcd. for C12H16F2OTe: 344.0232; found: 344.0227.
4.2.27. 2,2-Difluoro-1,1-diphenyl-2-(phenylthio)ethanol (7a)
4.2.31. 2,2-Difluoro-1-(4-methoxyphenyl)-1-phenyl-2-
(phenylthio)ethanol (7e)
White solid; 1H NMR (CDCl3, 300 MHz):
7.42–7.28 (m, 9H), 2.90 (s, 1H). 19F NMR (CDCl3, 282 MHz):
(s, 2F). The characterization data were consistent with the previous
report [11a].
d 7.62–7.54 (m, 6H),
d
ꢀ77.4
White solid; m.p. 70–71 8C; IR (film): 3421, 3074, 3001, 2841,
1605, 1509, 1474, 1450, 1375, 1247, 1177, 1089, 1058, 1035,
905, 837, 817, 742, 691, 597 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d
4.2.28. 9-(Difluoro(phenylthio)methyl)-9H-fluoren-9-ol (7b)
7.61–7.51 (m, 6H), 7.39–7.31 (m, 6H), 6.87–6.84 (m, 2H), 3.78 (s,
1H), 3.11 (s, 1H). 19F NMR (CDCl3, 282 MHz):
NMR (CDCl3, 100 MHz):
d
ꢀ77.3 (s, 2F). 13C
d
159.4, 140.5, 136.7, 134.2, 132.5,
131.3, 129.8, 129.2, 129.1, 129.0, 128.2, 128.0, 127.8, 126.5,
113.3, 81.5 (t, J = 23.5 Hz), 52.2. MS (EI, m/z, %): 246
([MꢀPhSOH]+, 1.42), 213 (100.00). HRMS (EI): Calcd. for
C
21H18F2O2S: 372.0996; found: 372.1002.
4.2.32. 1-(Biphenyl-4-yl)-2,2-difluoro-1-phenyl-2-
Colorless oil; IR (film): 3431, 3061, 1607, 1475, 1451, 1441,
1344, 1155, 1054, 994, 890, 838, 824, 769, 748, 732, 690 cmꢀ1. 1H
(phenylthio)ethanol (7f)
NMR (CDCl3, 300 MHz):
d 7.69 (t, J = 7.7 Hz, 4H), 7.46 (t, J = 6.9 Hz,
2H), 7.38–7.22 (m, 7H), 2.90 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ83.2 (s, 2F). 13C NMR (CDCl3, 100 MHz):
d 142.8, 141.2, 136.6,
132.4, 130.5, 129.8, 129.5, 128.8, 128.3, 126.1, 125.8, 120.2, 84.9 (t,
J = 23.5 Hz). MS (EI, m/z, %): 340 (M+, 4.72), 181 (100.00). HRMS
(EI): Calcd. for C20H14F2OS: 340.0733; found: 340.0735.
4.2.29. 1-(4-Chlorophenyl)-2,2-difluoro-1-phenyl-2-
White solid; m.p. 86–87 8C; IR (film): 3538, 3059, 3031, 1600,
1487, 1448, 1405, 1334, 1149, 1053, 1018, 903, 815, 764, 698,
637 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d 7.69–7.55 (m, 10H),
(phenylthio)ethanol (7c)
7.45–7.31 (m, 9H), 3.14 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ77.3 (s, 2F). 13C NMR (CDCl3, 100 MHz):
d 149.2, 141.0, 140.4,
140.2, 139.2, 136.7, 139.8, 129.8, 129.0, 128.8, 128.3, 128.2 (t,
J = 2.1 Hz), 128.1, 127.8 (t, J = 2.2 Hz), 127.5, 127.1, 126.7, 98.7,
81.5 (t, J = 24.8 Hz). MS (EI, m/z, %): 259 ([MꢀPhSCF2]+,
100.00). HRMS (EI): Calcd. for C26H20F2OS: 418.1203; found:
418.1206.
White solid; m.p. 58–59 8C; IR (film): 3571, 3450, 3056, 1592,
1491,1474,1447,1439,1404,1173,1093,1062,1039,1019,896,807,
750,700 cmꢀ1. 1HNMR(CDCl3, 300 MHz):
d
7.59–7.51(m, 6H), 7.40–
ꢀ77.5 (s, 1F),
d140.0, 138.8, 136.7, 134.4,
4.2.33. 2,2-Difluoro-1,1-diphenyl-2-(phenylselanyl)ethanol (8a)
7.28 (m, 8H), 3.13 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ77.6 (s, 1F). 13CNMR (CDCl3, 100 MHz):
131.0, 129.9, 129.4, 129.2, 129.1, 128.5, 128.20, 128.18, 128.0, 127.8,
127.7, 126.1, 81.4 (t, J = 24.2 Hz). MS (ESI, m/z, %): 399.0 ([M+Na]+).
HRMS (ESI): Calcd. for [C20H15ClF2OS]: 399.0388; found: 399.0392.
4.2.30. 1-(4-Bromophenyl)-2,2-difluoro-1-phenyl-2-
(phenylthio)ethanol (7d)
White solid; m.p. 122 8C; IR (film): 3434, 3073, 3056, 1598,
1582, 1491, 1448, 1341, 1169, 1150, 1053, 1038, 1012, 897, 810,
741, 634, 615 cmꢀ1
.
1H NMR (CDCl3, 300 MHz):
d
7.60 (m, 6H),
7.38–7.32 (m, 9H), 3.12 (s, 1H). 19F NMR (CDCl3, 282 MHz):
ꢀ74.5
(s, 2F). 13C NMR (CDCl3, 100 MHz):
140.2, 137.5, 132.3, 129.4,
d
d
129.19, 129.15, 129.0, 128.3, 128.2, 128.1, 127.9, 127.70, 127.68,
127.66, 126.1, 124.5, 82.0 (t, J = 22.1 Hz). MS (EI, m/z, %): 390 (M+,
1.14), 183 (100.00). HRMS (EI): Calcd. for C20H16F2OSe: 390.0334;
found: 390.0331.
Colorless oil; IR (film): 3542, 3060, 1588, 1488, 1475, 1448,
.
1441, 1397, 1337, 1148, 1053, 1020, 901, 801, 751, 691 cmꢀ1 1H

54
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
4.2.34. 9-(Difluoro(phenylselanyl)methyl)-9H-fluoren-9-ol (8b)
676, 614 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d 7.62–7.53 (m, 6H),
7.38–7.27 (m, 6H), 6.99 (t, J = 9.0 Hz, 2H), 3.14 (s, 1H). 19F NMR
(CDCl3, 282 MHz):
(CDCl3, 100 MHz):
d
d
ꢀ74.7 (d, 2F), ꢀ113.8 (m, 1F). 13C NMR
162.6 (d, J = 248.3 Hz), 140.1, 137.5, 135.9,
129.8, 129.7, 129.5, 129.1, 128.5, 128.2, 127.6, 115.0, 114.8, 81.7
(t, J = 22.7 Hz). MS (EI, m/z, %): 407 (M+, 1.08), 201
(100.00). HRMS (EI): Calcd. for C20H15F3OSe: 408.0240; found:
408.0240.
White solid; m.p. 58 8C; IR (film): 3436, 3060, 1608, 1477, 1451,
4.2.38. 2,2-Difluoro-1-(4-methoxyphenyl)-1-phenyl-2-
1439, 1336, 1150, 1063, 1022, 990, 907, 875, 824, 768, 744,
620 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d 7.67 (t, J = 8.0 Hz, 4H), 7.46
(phenylselanyl)ethanol (8f)
(t, J = 6.8 Hz, 2H), 7.38–7.17 (m, 7H), 2.90 (s, 1H). 19F NMR (CDCl3,
282 MHz):
d
ꢀ81.1 (s, 2F). 13C NMR (CDCl3, 100 MHz):
d 142.7,
141.3, 137.3, 130.5, 129.2, 129.1, 128.8, 128.3, 126.2, 125.8, 125.7,
124.2, 123.1, 120.22, 120.15, 85.5 (t, J = 22.1 Hz). MS (EI, m/z, %):
388 (M+, 2.95), 181 (100.00). HRMS (EI): Calcd. for C20H14F2OSe:
388.0178; found: 388.0170.
White solid; m.p. 83 8C; IR (film): 3401, 3071, 1605, 1508, 1475,
1451, 1378, 1294, 1246, 1178, 1153, 1072, 1057, 907, 838, 815,
738, 691 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d 7.67–7.52 (m, 6H),
4.2.35. 1-(4-Dhlorophenyl)-2,2-difluoro-1-phenyl-2-
(phenylselanyl)ethanol (8c)
7.44–7.28 (m, 6H), 6.88 (d, J = 9.6 Hz, 2H), 3.82 (s, 3H), 3.14 (s, 1H).
19F NMR (CDCl3, 282 MHz):
100 MHz):
d
ꢀ74.4 (s, 2F). 13C NMR (CDCl3,
d
159.5, 140.4, 137.4, 132.5, 132.3, 129.40, 129.35,
129.0, 128.9, 128.3, 128.0, 127.7, 127.6, 126.3, 124.6, 113.4, 81.8 (t,
J = 22.6 Hz), 52.2. MS (EI, m/z, %): 246 ([MꢀPhSeOH]+, 2.08), 213
(100.00). HRMS (EI): Calcd. for C21H18F2O2Se: 420.0440; found:
420.0441.
White solid; m.p. 63 8C; IR (film): 3535, 3060, 1594, 1578, 1492,
1448, 1402, 1333, 1147, 1093, 1016, 901, 793, 742, 691, 643 cmꢀ1
.
1H NMR (CDCl3, 300 MHz):
3.12 (s, 1H). 19F NMR (CDCl3, 282 MHz):
(CDCl3, 100 MHz):
d 7.62–7.50 (m, 6H), 7.40–7.25 (m, 8H),
4.2.39. 1-(Biphenyl-4-yl)-2,2-difluoro-1-phenyl-2-
d
ꢀ73.9 (s, 2F). 13C NMR
(phenylselanyl)ethanol (8g)
d
149.2, 139.8, 138.5, 137.4, 134.4, 129.5, 129.2
(t, J = 2.1 Hz), 129.1, 128.5, 128.2, 127.5 (t, J = 2.1 Hz), 124.2, 81.7 (t,
J = 21.5 Hz). MS (EI, m/z, %): 423 (M+, 0.94), 217 (100.00). HRMS
(EI): Calcd. for C20H15ClF2OSe: 423.9945; found: 423.9944.
4.2.36. 1-(4-Bromophenyl)-2,2-difluoro-1-phenyl-2-
(phenylselanyl)ethanol (8d)
Brown oil; IR (film): 3537, 3058, 3031, 1599, 1579, 1487, 1448,
.
1405, 1334, 1147, 1055, 1009, 903, 804, 763, 697, 631 cmꢀ1 1H
NMR (CDCl3, 300 MHz):
3.17 (s, 1H). 19F NMR (CDCl3, 282 MHz):
(CDCl3, 100 MHz):
d 7.67–7.53 (m, 10H), 7.44–7.23 (m, 9H),
d
ꢀ74.5 (s, 2F). 13C NMR
d
141.1, 140.5, 140.2, 139.2, 137.5, 132.3,
129.4, 129.3, 129.1, 128.9, 128.4, 128.3, 128.2, 128.1, 127.7,
127.6, 127.2, 126.8, 124.6, 82.0 (t, J = 22.8 Hz). MS (EI, m/z, %): 312
([Mꢀ(4-Ph)Ph]+, 0.32), 259 (100.00). HRMS (EI): Calcd. for
[C26H20F2OSe–PhSeCF2]: 259.1123; found: 259.1127.
Colorless oil; IR (film): 3535, 3059, 1579, 1488, 1448, 1397,
.
1333, 1147, 1055, 1013, 900, 791, 741, 691, 639 cmꢀ1 1H NMR
(CDCl3, 300 MHz):
(m, 6H), 3.06 (s, 1H). 19F NMR (CDCl3, 282 MHz):
J = 22.8 Hz, 2F). 13C NMR (CDCl3, 100 MHz):
139.8, 139.1, 137.4,
d
7.51 (t, J = 8.5 Hz, 4H), 7.37 (s, 4H), 7.32–7.18
d
ꢀ74.7 (d,
4.2.40. 1-(4-Chlorophenyl)-2,2-difluoro-1-phenyl-2-
d
(phenyltellanyl)ethanol (9a)
137.4, 131.1, 129.5 (t, J = 3.1 Hz), 129.1, 128.5, 128.2, 127.5 (t,
J = 2.1 Hz), 124.2, 122.7, 81.7 (t, J = 21.6 Hz). MS (EI, m/z, %): 467
(M+, 1.11), 263 (100.00). HRMS (EI): Calcd. for C20H15BrF2OSe:
467.9440; found: 467.9445.
4.2.37. 2,2-Difluoro-1-(4-fluorophenyl)-1-phenyl-2-
(phenylselanyl)ethanol (8e)
Yellow oil; IR (film): 3522, 3054, 1491, 1474, 1435, 1337, 1162,
.
1137, 1054, 1016, 997, 899, 828, 783, 735, 692 cmꢀ1 1H NMR
(CDCl3, 300 MHz):
d 7.82 (d, J = 7.3 Hz, 2H), 7.55–7.47 (m, 4H),
7.40–7.21 (m, 8H), 3.16 (s, 1H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ70.7
(s, 1F), ꢀ70.8 (s, 1F). 13C NMR (CDCl3, 100 MHz):
d 141.6, 139.8,
138.5, 134.4, 129.3, 129.23, 129.21, 128.6, 128.33, 128.28, 127.5,
121.0 (t, J = 320.6 Hz), 111.8, 81.4 (t, J = 20.6 Hz). MS (EI, m/z, %):
473 (M, 7.89), 217 (100.00). HRMS (EI): Calcd. for C20H15ClF2OTe:
473.9842; found: 473.9840.
White solid; m.p. 64–65 8C; IR (film): 3434, 3055, 1604, 1511,
1493, 1438, 1339, 1245, 1169, 1058, 1012, 902, 794, 756, 692,

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
55
4.2.41. 1-(4-Bromophenyl)-2,2-difluoro-1-phenyl-2-
ammonium chloride or brine, extracted with Et2O (3 ꢁ 10 mL). The
combined organic layer was washed with H2O (2 ꢁ 10 mL),
followed by brine (10 mL), dried over MgSO4 and concentrated
under vacuum. The residue was purified by flash chromatography
with ethyl acetate/petroleum ether (1:20) as eluent to give 77 mg
11a as a colorless oil. Yield 71%.
(phenyltellanyl)ethanol (9b)
4.3.1. 1,1-Difluoro-2-methyl-1-(phenylthio)propan-2-ol (11a)
White solid; m.p. 62–63 8C; IR (film): 3380, 3054, 1487, 1433,
1393, 1136, 1154, 1011, 901, 821, 781, 735, 691 cmꢀ1 1H NMR
.
(CDCl3, 300 MHz):
3.14 (s, 1H). 19F NMR (CDCl3, 282 MHz):
1F). 13C NMR (CDCl3, 100 MHz):
141.6, 139.7, 139.0, 131.2,
129.54, 129.51, 129.32, 129.29, 128.6, 128.3, 127.5, 122.7, 120.8 (t,
J = 318.1 Hz), 111.8, 82.2 (t, J = 19.0 Hz). MS (EI, m/z, %): 517 (M,
8.90), 263 (100.00). HRMS (EI): Calcd. for C20H15BrF2OTe:
517.9337; found: 517.9331.
d
7.81 (d, J = 7.3 Hz, 2H), 7.55–7.22 (m, 12H),
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.43–7.35 (m, 3H), 2.17 (s, 1H), 1.45 (s, 6H). 19F NMR (CDCl3,
282 MHz):
d 7.62 (d, J = 7.5 Hz,
d
ꢀ70.8 (s, 1F), ꢀ70.9 (s,
d
d
ꢀ85.9 (s, 2F). The characterization data were
consistent with the previous report [19].
4.3.2. 1,1-Difluoro-2-methyl-1-(phenylthio)butan-2-ol (11b)
4.2.42. 2,2-Difluoro-1-(4-fluorophenyl)-1-phenyl-2-
(phenyltellanyl)ethanol (9c)
Yellow oil; IR (film): 3445, 3062, 2981, 2944, 2885, 1475, 1441,
.
1384, 1278, 1146, 1097, 1061, 1015, 967, 927, 749, 691 cmꢀ1 1H
NMR (CDCl3, 300 MHz):
d 7.55 (d, J = 6.4 Hz, 2H), 7.35–7.27 (m,
3H), 1.93 (s, 1H), 1.72 (m, 2H), 1.31 (s, 3H), 0.95 (t, J = 7.2 Hz, 3H).
19F NMR (CDCl3, 282 MHz):
100 MHz):
d
ꢀ84.7 (s, 2F). 13C NMR (CDCl3,
d
136.7, 132.3 (t, J = 287.7 Hz), 129.7, 129.0, 126.2, 77.1
(t, J = 22.8 Hz), 29.1, 20.4, 7.4. MS (EI, m/z, %): 232 (M, 12.01), 73
(100.00). HRMS (EI): Calcd. for C11H14F2OS: 232.0733; found:
232.0736.
Yellow solid; m.p. 125–126 8C; IR (film): 3444, 3058, 1651,
1602, 1508, 1474, 1448, 1235, 1163, 1136, 1054, 902, 837, 736,
693 cmꢀ1 1H NMR (CDCl3, 300 MHz):
. d 7.82 (d, J = 6.8 Hz, 2H),
7.55–7.23 (m, 10H), 6.97 (t, J = 8.7 Hz, 2H), 3.22 (s, 1H). 19F NMR
4.3.3. 1-(Difluoro(phenylthio)methyl)cycloheptanol (11c)
(CDCl3, 282 MHz):
NMR (CDCl3, 100 MHz):
d
ꢀ70.5 (s, 1F), ꢀ70.7 (s, 1F), ꢀ113.6 (m, 1F). 13
C
d 162.5 (d, J = 247.2 Hz), 141.6, 140.0,
135.8, 132.7, 132.5, 130.0, 129.8, 129.7, 129.31, 129.27, 128.5,
128.4, 128.3, 127.5, 121.3 (t, J = 321.6 Hz), 115.1, 114.9, 111.9, 82.1
(t, J = 20.7 Hz). MS (EI, m/z, %): 458 (M, 1.92), 201 (100.00). HRMS
(EI): Calcd. for C20H15F3OTe: 458.0137; found: 458.0139.
White solid; m.p. 42–43 8C; IR (film): 3440, 3061, 2929, 2860,
1474, 1462, 1441, 1199, 1138, 1045, 987, 941, 919, 748, 691 cmꢀ1
.
4.2.43. 2,2-Difluoro-1-(4-methoxyphenyl)-1-phenyl-2-
1H NMR (CDCl3, 300 MHz):
3H), 2.09–1.61 (m, 13H). 19F NMR (CDCl3, 282 MHz):
2F). 13C NMR (CDCl3, 100 MHz):
136.7, 132.9 (t, J = 293.4 Hz),
d
7.62 (d, J = 7.2 Hz, 2H), 7.42–7.37 (m,
ꢀ85.4 (s,
(phenyltellanyl)ethanol (9d)
d
d
129.7, 129.0, 128.9, 126.4, 79.5 (t, J = 22.2 Hz), 39.6, 29.6, 22.1. MS
(EI, m/z, %): 272 (M, 5.82), 113 (100.00). HRMS (EI): Calcd. for
C14H18F2OS: 272.1046; found: 272.1040.
4.3.4. 1-(Difluoro(phenylthio)methyl)cyclohexanol (11d)
Yellow solid; m.p. 100 8C; IR (film): 3389, 3064, 2839, 1603,
1506, 1473, 1450, 1376, 1294, 1244, 1177, 1141, 947, 904, 807,
733, 691 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d 7.84 (d, J = 7.3 Hz, 2H),
7.56–7.22 (m, 10H), 6.84 (d, J = 9.2 Hz, 2H), 3.79 (s, 3H), 3.09 (s, 1H).
19F NMR (CDCl3, 282 MHz):
100 MHz):
129.0, 128.3, 128.1, 127.7, 121.7, 113.5, 82.2 (t, J = 20.4 Hz), 55.2.
MS (EI, m/z, %): 470 (M, 0.82), 213 (100.00). HRMS (EI): Calcd. for
d
ꢀ70.5 (s, 2F). 13C NMR (CDCl3,
Yellow oil; 1H NMR (CDCl3, 300 MHz):
7.31–7.28 (m, 3H), 1.77–1.10 (m, 11H). 19F NMR (CDCl3, 282 MHz):
d
7.55 (d, J = 6.2 Hz, 2H),
d
159.5, 141.5, 140.2, 132.6, 132.2, 129.8, 129.2, 129.1,
d
ꢀ87.6 (s, 2F). The characterization data were consistent with the
C21H18F2O2Te: 470.0337; found: 470.0332.
previous report [11a].
4.3. General procedure for reaction of 1 (PhXCF2H, X = S, Se) with 10
4.3.5. 1,1-Difluoro-2-methyl-1-(phenylselanyl)propan-2-ol (12a)
Under a nitrogen atmosphere, to a stirred solution of PhSCF2H
(1a) (80 mg, 0.5 mmol) and acetone (10a) (56 mg, 1.0 mmol) with
5 mL DMF in a Schlenk tube, KOH (82%) (560 mg, 10.0 mmol) was
added in one portion at 0 8C. The mixture was stirred at this
temperature for 1 h, then gradually warm to room temperature.
After 13 h, the reaction was quenched with saturated aqueous
Yellow oil; IR (film): 3400, 3060, 2986, 2958, 2870, 1651, 1477,
1439, 1200, 1092, 1058, 1022, 979, 942, 825, 742, 692 cmꢀ1 1H
.
NMR (CDCl3, 300 MHz):
d 7.71 (d, J = 6.2 Hz, 2H), 7.41–7.31 (m,

56
M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
3H), 2.35 (s, 1H), 1.43 (s, 6H). 19F NMR (CDCl3, 282 MHz):
(s, 2F). MS (EI, m/z, %): 266 (M, 11.81), 82 (100.00). HRMS (EI):
d
ꢀ81.7
J = 7.2 Hz, 1H), 1.27 (s, 9H). 19F NMR (CDCl3, 282 MHz):
J = 205.0 Hz, J = 10.2 Hz, 1F), ꢀ79.8 (dd, J = 205.0 Hz, J = 11.0 Hz,
1F). The characterization data were consistent with the previous
report [11b].
d
ꢀ78.5 (dd,
Calcd. for C10H12F2OSe: 266.0021; found: 266.0023.
4.3.6. 1,1-Difluoro-2-methyl-1-(phenylselanyl)butan-2-ol (12b)
4.4.2. (Rs)-N-[(S)-2,2-difluoro-1-(4-methoxyphenyl)-2-
(phenylthio)ethyl]-2-methylpropane-2-sulfinamide (14b)
Yellow oil; 1H NMR (CDCl3, 300 MHz):
7.40–7.33 (m, 3H), 2.05 (s, 1H), 1.75 (m, 2H), 1.35 (s, 3H), 1.01 (t,
J = 6.7 Hz, 3H). 19F NMR (CDCl3, 282 MHz):
d 7.71 (d, J = 6.4 Hz, 2H),
d
ꢀ80.5 (s, 1F), ꢀ80.7 (s,
1F). The characterization data were consistent with the previous
report [12].
White solid; 1H NMR (CDCl3, 300 MHz):
d 7.53 (d, J = 6.6 Hz,
2H), 7.32–7.43 (m, 5H), 6.91 (d, J = 8.7 Hz, 2H), 4.79 (td,
J = 9.9 Hz, J = 7.2 Hz, 1H), 7.80 (s, 3H), 3.71 (d, J = 7.2 Hz, 1H),
4.3.7. 1-(Difluoro(phenylselanyl)methyl)cycloheptanol (12c)
1.25 (s, 9H). 19F NMR (CDCl3, 282 MHz):
d
ꢀ78.0 (dd,
J = 205.2 Hz, J = 10.7 Hz, 1F), ꢀ80.6 (dd, J = 205.2 Hz,
J = 10.4 Hz, 1F). The characterization data were consistent with
the previous report [11b].
Yellow oil; IR (film): 3440, 3059, 2928, 2858, 1579, 1477, 1439,
4.4.3. (Rs)-N-[(S)-1-(4-chlorophenyl)-2,2-difluoro-2-
1198, 1130, 1046, 1022, 989, 932, 826, 739, 691 cmꢀ1 1H NMR
.
(phenylthio)ethyl]-2-methylpropane-2-sulfinamide (14c)
(CDCl3, 300 MHz):
2.06–1.98 (m, 3H), 1.87–1.52 (m, 10H). 19F NMR (CDCl3, 282 MHz):
–81.3 (s, 2F). 13C NMR (CDCl3, 100 MHz):
137.5, 131.7 (t,
d 7.71 (d, J = 6.8 Hz, 2H), 7.42–7.30 (m, 3H),
d
d
J = 255.6 Hz), 129.3, 129.0, 124.2, 80.0 (t, J = 20.7 Hz), 35.7, 29.6,
22.1. MS (EI, m/z, %): 320 (M, 13.41), 113 (100.00). HRMS (EI):
Calcd. for C14H18F2OSe: 320.0491; found: 320.0492.
White solid; 1H NMR (CDCl3, 300 MHz):
d 7.53 (dd, J = 8.1 Hz,
4.3.8. 1-(Difluoro(phenylselanyl)methyl)cyclohexanol (12d)
J = 1.5 Hz, 2H), 7.33–7.42 (m, 7H), 7.81 (td, J = 10.8 Hz, J = 7.8 Hz,
1H), 3.80 (d, J = 7.8 Hz, 1H), 1.26 (s, 9H). 19F NMR (CDCl3,
282 MHz):
d
ꢀ79.0 (dd, J = 207.8 Hz, J = 9.3 Hz, 1F), ꢀ79.7 (dd,
J = 207.8 Hz, J = 11.2 Hz, 1F). The characterization data were
consistent with the previous report [11b].
Colorless oil; 1H NMR (CDCl3, 300 MHz):
2H), 7.35–7.23 (m, 3H), 1.83–1.76 (m, 3H), 1.64–1.01 (m, 8H). 19
NMR (CDCl3, 282 MHz):
ꢀ83.1 (s, 2F). The characterization data
were consistent with the previous report [12].
d 7.63 (d, J = 7.6 Hz,
4.4.4. (Rs)-N-[(S)-2,2-difluoro-1-(naphthalene-2-yl)-2-
F
(phenylthio)ethyl]-2-methylpropane-2-sulfinamide (14d)
d
4.4. General procedure for reaction of 1 (PhXCF2H, X = S, Se) with 13
Under a nitrogen atmosphere, to a stirred solution of PhSeCF2H
(1b) (104 mg, 0.5 mmol) and PhCH55NSOt-Bu (13a) (165 mg,
0.75 mmol) with 3 mL DMF in a Schlenk tube, t-BuOK (112 mg,
1.0 mmol) (dissolved in 2 mL DMF) was added dropwise at ꢀ30 8C.
The mixture was stirred at ꢀ40 to ꢀ30 8C for 2 h, then quenched
with saturated aqueous ammonium chloride or brine, extracted
with Et2O (3 ꢁ 10 mL). The combined organic layer was washed
with H2O (2 ꢁ 10 mL), followed by brine (10 mL), dried over MgSO4
and concentrated under vacuum. The residue was purified by flash
chromatography with ethyl acetate/petroleum ether (1:5) as
eluent to give 168 mg 15a as a white solid (the product was the
main isomer, and the other isomer was not obtained). Yield 80%
(based on the main isomer).
White solid; 1H NMR (CDCl3, 300 MHz):
7.48–7.54 (m, 5H), 7.31–7.43 (m, 3H), 5.00 (td, J = 10.8 Hz,
J = 7.5 Hz, 1H), 3.91 (d, J = 7.5 Hz, 1H), 1.27 (s, 9H). 19F NMR
d 7.81–7.91 (m, 4H),
(CDCl3, 282 MHz):
d
ꢀ77.9 (dd, J = 206.4 Hz, J = 10.1 Hz, 1F),
ꢀ79.5 (dd, J = 206.4 Hz, J = 11.3 Hz, 1F). The characterization
data were consistent with the previous report [11b].
4.4.5. (Rs)-N-[(S)-2,2-difluoro-1-(furan-2-yl)-2-(phenylthio)ethyl]-
2-methylpropane-2-sulfinamide (14e)
4.4.1. (Rs)-N-[(S)-2,2-difluoro-1-phenyl-2-(phenylthio)ethyl]-2-
methylpropane-2-sulfinamide (14a)
White solid; 1H NMR (CDCl3, 300 MHz):
d 7.56 (dd, J = 7.2 Hz,
J = 1.2 Hz, 2H), 7.53–7.46 (m, 4H), 6.48 (d, J = 3.3 Hz, 1H), 6.39
(dd, J = 3.0, 1.8 Hz, 1H), 4.85–4.94 (m, 1H), 3.95 (s, 1H), 1.27 (s,
9H). 19F NMR (CDCl3, 282 MHz):
J = 10.7 Hz, 1F), ꢀ80.1 (dd, J = 206.4 Hz, J = 10.4 Hz, 1F). The
characterization data were consistent with the previous report
[11b].
d
ꢀ79.2 (dd, J = 206.4 Hz,
White solid; 1H NMR (CDCl3, 300 MHz):
7.31–7.45 (m, 8H), 4.83 (td, J = 10.8 Hz, J = 7.8 Hz, 1H), 3.79 (d,
d 7.51–7.54 (m, 2H),

M. Hu et al. / Journal of Fluorine Chemistry 135 (2012) 45–58
57
4.4.6. (Rs)-N-[(S)-1,1-difluoro-3,3-dimethyl-1-(phenylthio)butan-2-
22.5. MS (ESI, m/z, %): 474 (M++Na). HRMS (ESI): calcd. for
C18H20ClF2NO2SSeNa: 468.00392; found: 468.00399.
yl]-2-methylpropane-2-sulfinamide (14f)
4.4.10. (Rs)-N-[(S)-N-(2,2-difluoro-1-(naphthalen-2-yl)-2-
(phenylselanyl)ethyl)]-2-methylpropane-2-sulfinamide (15d)
White solid; 1H NMR (CDCl3, 300 MHz):
7.34–7.45 (m, 3H), 3.61 (d, J = 8.4 Hz, 1H), 3.45–3.55 (m, 1H), 1.33
(s, 9H), 1.15 (s, 9H). 19F NMR (CDCl3, 282 MHz):
d 7.55–7.59 (m, 2H),
d
ꢀ67.0 (dd,
J = 204.1 Hz, J = 6.2 Hz, 1F), ꢀ76.6 (dd, J = 204.1 Hz, J = 14.7 Hz, 1F).
The characterization data were consistent with the previous report
[11b].
Yellow solid; m.p. 155 8C; IR (film): 3445, 3318, 3054, 2953,
2923, 1466, 1438, 1367, 1071, 1015, 969, 861, 747 cmꢀ1 1H NMR
.
(CDCl3, 300 MHz):
(m, 6H), 5.02 (m, 1H), 3.96 (d, J = 7.8 Hz, 1H), 1.30 (s, 9H). 19F NMR
(CDCl3, 282 MHz):
ꢀ74.8 (dd, J = 205.0 Hz, J = 10.9 Hz, 1F), ꢀ77.2
(dd, J = 205.0 Hz, 12.5 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
137.2,
d 7.89 (m, 4H), 7.62 (d, J = 6.7 Hz, 2H), 7.54–7.27
4.4.7. (Rs)-N-[(S)-2,2-difluoro-1-phenyl-2-(phenyselanyl)ethyl]-2-
d
methylpropane-2-sulfinamide (15a)
d
133.1, 129.5, 129.2, 128.9, 128.4, 127.7, 126.9, 126.6, 125.3, 66.6 (t,
J = 23.9 Hz), 57.2, 22.6. MS (ESI, m/z, %): 490 (M++Na). HRMS (ESI):
calcd. for C22H23ClF2NOSSeNa: 484.05854; found: 484.05884.
4.4.11. (Rs)-N-[(S)-N-(1,1-difluoro-3,3-dimethyl-1-
White solid; m.p. 132–134 8C; IR (film): 3179, 1578, 1475,
(phenylselanyl)butan-2-yl)]-2-methylpropane-2-sulfinamide (15e)
1439, 1096, 1064, 996 cmꢀ1. 1H NMR (CDCl3, 300 MHz):
d
7.61 (d,
J = 6.9 Hz, 2H), 7.25–7.40 (m, 8H), 4.80–4.90 (m, 1H), 3.86 (d,
J = 7.5 Hz), 1.26 (s, 9H). 19F NMR (CDCl3, 282 MHz):
ꢀ76.3 (dd,
J = 206.3 Hz, J = 11.8 Hz, 1F), ꢀ77.4 (dd, J = 206.9 Hz, J = 12.1 Hz,
1F); 13C NMR (CDCl3, 100 MHz):
137.0, 135.1, 129.4, 129.2,
d
d
White solid; m.p. 87 8C; IR (film): 3352, 3060, 2964, 1471, 1371,
129.1, 128.8, 128.3, 125.8 (t, J = 298.0 Hz), 124.0, 66.3 (t,
J = 22.3 Hz), 57.0, 22.4; MS (ESI, m/z): 474 (M++Na). EA calcd.
for C18H21F2NOSSe: C, 51.92; H, 5.08; N, 3.36; found: C, 51.96; H,
4.92; N, 3.18.
1233, 1159, 1097, 1071, 968, 877, 746 cmꢀ1 1H NMR (CDCl3,
.
300 MHz):
J = 8.5 Hz, 1H), 3.52 (m, 1H), 1.35 (s, 9H), 1.13 (s, 9H). 19F NMR
(CDCl3, 282 MHz):
ꢀ62.5 (d, J = 202.3 Hz, 1F), ꢀ74.3 (dd,
J = 202.7 Hz, J = 17.8 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
137.4,
d 7.67 (m, J = 6.8 Hz, 2H), 7.44–7.32 (m, 3H), 3.66 (d,
d
d
4.4.8. (Rs)-N-[(S)-N-(2,2-difluoro-1-(4-methoxyphenyl)-2-
129.4, 129.1, 124.8, 70.5 (t, J = 22.9 Hz), 57.6, 34.8, 28.1 (t,
J = 2.9 Hz), 23.1. MS (ESI, m/z, %): 420 (M++Na). HRMS (ESI): calcd.
for C16H25F2NOSSeNa: 414.07419; found: 414.07383.
(phenylselanyl)ethyl)]-2-methylpropane-2-sulfinamide (15b)
4.4.12. (S)-N-(2,2-difluoro-1,1-diphenyl-2-(phenylselanyl)ethyl)-2-
methylpropane-2-sulfinamide (15f)
Yellow solid; m.p. 105–107 8C; IR (film): 3445, 3321, 3000,
2958, 2835, 1612, 1516, 1471, 1307, 1255, 1184, 1069, 972,
741 cmꢀ1
.
1H NMR (CDCl3, 300 MHz):
d
7.63 (d, J = 6.7 Hz, 2H),
7.44–7.30 (m, 5H), 6.90 (d, J = 8.6 Hz, 2H), 4.81 (m, 1H), 3.81 (s, 3H),
3.76 (d, J = 6.9 Hz, 1H), 1.27 (s, 9H). 19F NMR (CDCl3, 282 MHz):
ꢀ75.1 (dd, J = 204.4 Hz, J = 11.3 Hz, 1F), ꢀ77.7 (dd, J = 204.4 Hz,
J = 12.2 Hz, 1F). 13C NMR (CDCl3, 100 MHz):
160.3, 137.1, 129.7,
White solid; m.p. 117–118 8C; IR (film): 3319, 3049, 2966, 1446,
d
1369, 1143, 1075, 1061, 911, 850, 743 cmꢀ1 1H NMR (CDCl3,
.
300 MHz):
1.24 (s, 9H). 19F NMR (CDCl3, 282 MHz):
1F). 13C NMR (CDCl3, 100 MHz):
139.1, 137.9, 137.3, 130.4, 130.0,
d
7.62–7.56 (m, 4H), 7.45–7.23 (m, 11H), 4.79 (s, 1H),
d
d
ꢀ70.4 (s, 1F), ꢀ70.5 (s,
129.5, 129.2, 127.3, 124.3, 114.3, 65.9 (t, J = 22.6 Hz), 57.0, 55.3,
22.5. MS (MALDI, m/z, %): 447 (M+). HRMS (ESI): calcd. for
d
129.5, 129.1, 128.8, 128.1, 128.0, 57.2, 22.9. MS (ESI, m/z, %): 516
(M++Na). HRMS (ESI): calcd. for C24H25F2NOSSeNa: 510.07419;
found: 510.07495.
C
19H24F2NO2SSe: 442.07151; found: 442.07048.
4.4.9. (Rs)-N-[(S)-N-(1-(4-chlorophenyl)-2,2-difluoro-2-
(phenylselanyl)ethyl)]-2-methylpropane-2-sulfinamide (15c)
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (20772144, 20825209, 20832008) and the
Chinese Academy of Sciences for financial support.
Yellow solid; m.p. 94–96 8C; IR (film): 3324, 3058, 2987, 2958,
References
1596, 1495, 1477, 1437, 1086, 1014, 974, 741 cmꢀ1 1H NMR
.
(CDCl3, 300 MHz):
(m, 1H), 3.83 (d, J = 7.8 Hz, 1H), 1.26 (s, 9H). 19F NMR (CDCl3,
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ꢀ76.8 (dd, J = 208.3 Hz, J = 12.1 Hz, 1F), ꢀ77.7 (dd,
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