Efficient synthesis of unsymmetrical S-(bromodifluoromethyl)diarylsulfonium salts for electrophilic bromodifluoromethylating reagents

Article abstract of DOI:10.1039/c2nj40255f

A series of unsymmetrical S-(bromodifluoromethyl)diarylsulfonium salts 1 were readily synthesized by treatment of corresponding (bromodifluoromethyl) arylsulfoxides 2 and substituted benzenes 3 with triflic anhydride in moderate to good yields. The unsymmetrical sulfonium salts 1 with different aryl groups having electron-donating or electron-withdrawing substituents can be nicely constructed depending on the choice of 2 and 3. Bromodifluoromethylation of alkynes was evaluated by using the selected diarylsulfonium salts 1 to provide the desired bromodifluoromethylated alkynes in moderate to good yields.

Full text of DOI:10.1039/c2nj40255f

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PAPER
Efficient synthesis of unsymmetrical
S-(bromodifluoromethyl)diarylsulfonium salts for electrophilic
bromodifluoromethylating reagentsw
Guokai Liu, Satoru Mori, Xin Wang, Shun Noritake, Etsuko Tokunaga and
Norio Shibata*
Received (in Montpellier, France) 2nd April 2012, Accepted 4th June 2012
DOI: 10.1039/c2nj40255f
A series of unsymmetrical S-(bromodifluoromethyl)diarylsulfonium salts 1 were readily
synthesized by treatment of corresponding (bromodifluoromethyl)arylsulfoxides 2 and substituted
benzenes 3 with triflic anhydride in moderate to good yields. The unsymmetrical sulfonium salts
1 with different aryl groups having electron-donating or electron-withdrawing substituents can be
nicely constructed depending on the choice of 2 and 3. Bromodifluoromethylation of alkynes was
evaluated by using the selected diarylsulfonium salts 1 to provide the desired
bromodifluoromethylated alkynes in moderate to good yields.
Introduction
Therefore, the bromodifluoromethylation of common organic
molecules could potentially be the strategy after trifluoro-
methylation for the development of novel pharmaceuticals and
agrochemicals. In addition to this, bromodifluoromethylated
compounds have another advantage as intermediates, which can
be derived into gem-difluoromethylene compounds (–CF2–)7 or
compounds having a terminal difluoromethyl group (–CHF2).8
In 2011, Xiao et al. reported the synthesis of a symmetrical
S-(bromodifluoromethyl)diphenylsulfonium salt for electrophilic
bromodifluoromethylating reagent from sodium bromodifluoro-
methanesulfinate, benzene and triflic anhydride in dichloro-
methane.9 Although it is a simple, one-pot procedure, the
method cannot be applied to the synthesis of structurally fine-
tuned, unsymmetrical S-(bromodifluoromethyl)diarylsulfonium
salts which might give improved results in electrophilic
bromodifluoromethylation processes that at present give only
modest yields. Indeed, for trifluoromethylation, the unsymmetrical
reagents have much more success than symmetrical ones.4a,j–l
Prakash et al. also show the success of unsymmetrical reagents
for mono- and ditrifluoromethylation reactions.5a,6a Magnier and
co-workers reported electrophilic bromodifluoromethylating
reagents based on a sulfoximine skeleton.10 However, the reagents
performed ineffectively in the bromodifluoromethylating reaction.
Herein, we disclose the efficient synthesis of a series of unsym-
metrical S-(bromodifluoromethyl)diarylsulfonium salts 1 as electro-
philic bromodifluoromethylating reagents by treatment of aryl
bromodifluoromethylsulfoxides 2 with substituted benzenes in the
presence of triflic anhydride. S-(Bromodifluoromethyl)(2-bromo-
phenyl)(2,3,4,5-tetramethylphenyl)sulfonium triflate 1i0 was found
to be most effective for the electrophilic bromodifluoromethylation
of alkynes amongst the 5 novel unsymmetrical diarylsulfonium salts
prepared (Scheme 1).
Fluoro-organic compounds play an important role in the
development of pharmaceuticals, agrochemicals, and advanced
materials.1 According to a survey, around 20% of drugs on the
market contain fluorine(s) and more than 30% of crop protec-
tion agents are organofluorine compounds.2 Among several
strategies for the synthesis of organofluorine compounds, the
direct introduction of a fluoromethyl group into common non-
fluorinated organic molecules is principally advantageous since
the method can be performed at a later stage of the total
synthesis of target compounds. The direct fluoromethylation
of organic compounds can be approached by nucleophilic,
radical, and electrophilic ways.3 Over the past two decades,
electrophilic fluoromethylation has attracted considerable
attention.4–6 A series of electrophilic fluoromethylation reagents
have been extensively designed and synthesized, including for
trifluoromethylation (+CF3),4 difluoromethylation (+CHF2)5
and monofluoromethylation (+CH2F)6 reactions. As a part
of our research program for the development of direct fluoro-
methylation reactions and the synthesis of biologically attractive
organofluorine compounds, we required electrophilic bromodi-
fluoromethylating reagents (+CBrF2). While only dozens of
organofluorine compounds are available in nature, more than
1600 naturally occurring organobromine compounds have
been found, in particular from marine sources, and a large
number of these organobromines are biologically attractive.
Nagoya Institute of Technology - Frontier Materials,
Nagoya 4668555, Japan
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2nj40255f
c
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groups on Ar2H 3 promoted the reaction while electron-with-
drawing groups on Ar2H 3 intensely decrease the reactivity.
The problem of synthesis of diarylsulfonium salts having
electron-withdrawing groups can be overcome by the use of
a different combination of sulfoxides with electron-withdrawing
groups and benzene derivatives. Thus, p-nitrophenyl sulfoxide 2b,
when reacted with 1,3,5-trimethoxybenzene 3h, gave the reagent 1h
in 49% (entry 9). Interestingly, o-bromophenyl sulfoxide 2c
reacted with 3i and 3j in high yields (71% and 76%, respectively;
entries 10 and 12).
Scheme 1 Synthesis of unsymmetrical S-(bromodifluoromethyl)diaryl-
sulfonium salts 1.
Results and discussion
With these S-(bromodifluoromethyl)diarylsulfonium salts 1 in
hand, the electrophilic bromodifluoromethylation of acetylides
was examined. Optimization of the reaction was first conducted
using p-methoxyphenylacetylene (4a) as a model substrate,
and sulfonium salts (tetrafluoroborates or triflates), 1a, 1a0, 1h,
1i and 1i0 were taken as examples, resulting in the protocol
summarized in Table 2, which shows that sulfonium salt 1i0
had the highest reactivity and gave the desired product 5a in
isolated yield of 72% under the optimized reaction conditions
(entry 5). The reason of the better reactivity of triflate 1i0 than
tetrafluoroborate 1i for the transformation of 4a to 5a is not
clear. The similar counteranion effect is also observed for the
monofluoromethylation reagent.6b It might be the difference of
solubility of 1i and 1i0 (1i0 is a bit more soluble in organic
solvent than 1i), although it is not certain. Subsequently, with
the best reaction conditions, we screened the scope of acetylenes
with 1i0 as a bromodifuoromethylating reagent. The results are
summarized in Table 3. All the arylalkynes 4 proceeded with
good yields. Heteroaryl alkyne 4j also is tolerated with a
Synthesis of a series of unsymmetrical S-(bromodifluoromethyl)-
diarylsulfonium salts 1 were examined by the reaction of
aryl bromodifluoromethylsulfoxides with substituted benzene
derivatives in the presence of triflic anhydride at 0 1C to room
temperature. The starting aryl bromodifluoromethyl sulfoxides
were readily prepared from the corresponding sodium aryl-
thiolates with dibromodifluoromethane followed by oxidation
using m-CPBA in good overall yields. All the salts were
obtained as triflates and they were converted into tetrafluoro-
borates . The results are summarized in Table 1.
First, the reaction of bromodifluoromethyl phenyl sulfoxide 2a
and various benzene derivatives (Ar2H 3) having electron-donating
or electron-withdrawing groups was examined. 1,2,3,4-Tetramethyl-
benzene (3a, entry 1), 1,3,5-trimethylbenzene (3f, entry 7) and 1,3,5-
trimethoxybenzene (3g, entry 8) were smoothly reacted with 2a in
good to excellent yields. A mixture of o-methoxy and p-methoxy
isomers 1b was obtained in 89% yield when the reaction of 2a was
carried out with anisole (3b, entry 3). A longer reaction time of 48 h
was required for the reaction of 2a with fluorobenzene (3c, entry 4).
The single, p-substituted S-(bromodifluoromethyl)-p-fluorophenyl-
phenylsulfonium salt 1c was obtained. However, the reaction of 2a
with p-dibromobenzene (3d) or p-dinitrobenzene (3e) failed
(entries 5 and 6). These results indicate that electron-donating
Table 2 Optimization of bromodifluoromethylating reactiona
Table 1 Synthesis of unsymmetrical S-(bromodifluoromethyl) -diaryl-
sulfonium saltsa
Entry
2
Ar1
Ar2H 3
t/h
1
Yieldb
1
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2c
2c
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-NO2Ph
o-BrPh
o-BrPh
o-BrPh
1,2,3,4-Me4Ph 3a
1,2,3,4-Me4Ph 3a
MeO-Ph 3b
F-Ph 3c
1,4-Br2Ph 3d
1,4-(NO2)2Ph 3e
1,3,5-Me3Ph 3f
1,3,5-(MeO)3Ph 3g
1,3,5-(MeO)3Ph 3h
1,2,3,4-Me4Ph 3i
1,2,3,4-Me4Ph 3i
1,3,5-(MeO)3Ph 3j
12
12
10
48
48
48
10
12
12
17
17
3
1a
1a0
1b
1c
1d
1e
1f
1g
1h
1i
1i0
1j
62
66
89
81
NR
NR
72
89
49
68
71
76
2c
3d
4e
5
Entry
1 (equiv.)
n-BuLi (eq.)
Yieldb
6
7
8
1
2
3
4
5
6
7
1a (1.3)
1a0 (1.3)
1b (1.3)
1i (1.3)
1i0 (1.3)
1i0 (1.0)
1i0 (1.0)
1.2
1.2
1.2
1.2
1.2
1.0
1.2
66
57c
37
46c
72
21
39
9f
10
11c
12c
a
a
The reaction of 2 with 3 (1.5 equiv.) was carried out in the presence
of Tf2O (1.5 equiv.) in CH2Cl2 at 0 1C to room temperature. For
detailed reaction conditions, see the ESI. Isolated yield. TfO salt.
Lithium acetylides were first generated in the reaction of 4 with
n-BuLi at ꢀ78 1C. Then the bromodifluoromethylating agent 1 was
added and the reaction system was stirred for 1 h at ꢀ78 1C, and then
warmed to room temperature. For detailed reaction conditions, see the
b
c
d
The product is a mixture of o-methoxy and p-methoxy derivatives
e
which cannot be separated. Fluorobenzene was used as the solvent.
ESI. Isolated yield. Determined by 19F NMR using trifluorotoluene
b
c
f
5.0 equiv. Tf2O was used.
as the internal standard.
c
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Table 3 Scope of alkynes
performed in oven-dried glassware under a positive pressure
of nitrogen. Reaction mixtures were stirred magnetically.
Solvents were transferred via syringe and were introduced into
the reaction vessels though a rubber septum. All of the
reactions were monitored by thin-layer chromatography
(TLC) carried out on 0.25 mm Merck silica-gel (60-F254).
The TLC plates were visualized with UV light and 7%
phosphomolybdic acid or KMnO4 in water/heat. Column
chromatography was carried out on a column packed with
silica-gel 60 N spherical neutral size 63–210 mm. The 1H-NMR
(300 MHz) and 19F-NMR (282.3 MHz) spectra was recorded
on a Varian Mercury 300. The 13C-NMR (150.9 MHz) was
recorded on a Bruker Avance 600. Chemical shifts (d) are
reported in parts per million and coupling constants (J) are in
hertz. All the melting points are uncorrected. Mass spectra
were recorded on a SHIMADZU GCMS-QP5050A. Infrared
spectra were recorded on a JASCO FT/IR-200 spectrometer.
a
Determined by 19F NMR using trifluorotoluene as the internal
b
standard. Isolated yield.
General procedure for the preparation of
moderate yield (58%), but aliphatic alkyne, hept-1-yne (4f)
gave the desired product 5f in low yield (28%).
(bromodifluoromethyl)arylsulfoxide 2. Method A
To a solution of aryl bromodifluoromethylsulfide in dichloro-
methane, m-CPBA (1.0 equiv.) was added in four portions
over a period of four hours at 0 1C, and the mixture was stirred
overnight at room temperature. The resulting solution was
quenched with saturated aqueous NaHCO3, and the aqueous
layer was extracted twice again with dichloromethane. The
combined extracts were washed with water and brine, and
dried over anhydrous Na2SO4. After the drying agent was
filtered off and the solvent was removed in vacuum, the residue
was directly subjected to the silica-gel column chromatography
using appropriate eluent to afford the title compound 2.
The bromodifluoromethyl compound 5e was successfully
transformed into gem-difluoromethylene ether 6 by the reaction
with sodium p-nitrophenolate in DMF at room temperature. 5e
also reacted nicely with phenethyl aldehyde under the conditions
using Zn and HgCl2 in THF to provide a-difluoromethylene
alcohol derivative 7 in 63% (Scheme 2).
Conclusions
In summary, a series of unsymmetrical S-(bromodifluoromethyl)-
diarylsulfonium salts were conveniently synthesized in moderate to
good yields by treatment of corresponding bromodifluoromethyl
arylsulfoxides and a variety of substituted benzenes with triflic
anhydride. These sulfonium salts proved to be effective for the
electrophilic bromodifluoromethylation reaction of lithium
acetylides. The resulting bromodifluoromethyl compounds
were successfully used for synthesis of gem-difluoromethylene-
containing compounds. Study of the utility of the S-(bromodi-
fluoromethyl)diarylsulfonium salts for other bromodifluoro-
methylation reactions is currently in progress in our laboratory.
(Bromodifluoromethyl)phenylsulfoxide 2a. Colorless liquid,
89% yield, eluent: hexane/dichloromethane = 4 : 1. The char-
acterization data was consistent with the previous report.13
(Bromodifluoromethyl)(o-bromophenyl)sulfoxide 2c. White
solid, 96% yield, eluent: hexane/dichloromethane = 4 : 1.
1H NMR (CDCl3, 300 MHz) d 8.0 (d, J = 9.0 Hz, 1H),
7.49–7.67 (m, 3H); 19F NMR (CDCl3, 282.3 MHz) d ꢀ50.2
(dd, J = 587.2 Hz, 152.4 Hz, 2F); 13C NMR (CDCl3,
150.9 MHz) d 122.4, 128.5, 129.0, 130.3(dd, J = 683.2 Hz,
663.4 Hz), 133.7, 134.9, 137.9 (d, J = 5.6 Hz); IR (KBr) 2924,
1561,1449, 1428, 1064, 1023, 836, 753 cmꢀ1; mp = 51–53 1C;
HRMS (ESI) calcd. for [C7H4F3OF2SBr2Na]+: 354.8215,
found: 354.8217.
Experimental section
General
All reagents were used as received from commercial sources,
unless specified otherwise, or prepared as described in the
literature. Reactions requiring anhydrous conditions were
Preparation of (bromodifluoromethyl)(p-nitrophenyl)sulfoxide
(2b). Method B
To a solution of p-nitrophenyl bromodifluoromethyl sulfide
(2.13 g, 7.5 mmol) in dichloromethane, m-CPBA (0.62 g,
0.25 equiv.) was added at 0 1C. The mixture was stirred for
2 h at room temperature. The same procedure above was
repeated three times (3 ꢁ 0.25 equiv.). The resulting solution
was quenched with saturated aqueous NaHCO3, and the
aqueous layer was extracted twice again with dichloro-
methane. The combined extracts were washed with water
and brine, and dried over anhydrous Na2SO4. After the drying
agent was filtered off and the solvent was removed in vacuum,
Scheme 2 Synthesis of gem-difluoromethylene-containing compounds 6
and 7.
c
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7.40 (s, 1H), 2.78 (s, 3H), 2.38 (s, 6H),2.33 (s, 3H); 19F NMR
the residue was directly subjected to the silica-gel column
chromatography (hexane/dichloromethane = 2 : 1) to afford
2b (1.3 g, 58%) as light yellow solid. 1H NMR (CDCl3,
300 MHz) d 8.46 (dd, J = 6.6 Hz, 1.8 Hz, 2H), 8.01 (d, J =
8.4 Hz, 2H); 19F NMR (CDCl3, 282.3 MHz) d ꢀ51.9 (dd, J =
677.5 Hz, 169.4 Hz, 2F); 13C NMR (CDCl3, 150.9 MHz)
d 124.4, 127.7, 127.8 (d, J = 362.2 Hz), 143.9 (d, J = 3.0 Hz),
151.0; IR (KBr) 3110, 2853, 1603, 1524, 1366, 1343,
1316, 1149,1112, 1089, 829, 723, 548, 507, 417 cmꢀ1; mp =
106–108 1C; HRMS (EI) calcd. for [C7H4NO3F2SBr]+:
298.9063, found : 298.9072
(CDCl3, 282.3 MHz) d ꢀ33.9 (dd, J = 140.6 Hz, 124.8 Hz,
2F), -78.6 (t, J = 20.9 Hz, 3F); 13C NMR (CDCl3, 150.9 MHz)
d 17.2, 17.4, 18.4, 21.1, 114.1, 115.9 (t, J = 357.6 Hz), 121.7,
122.0 (t, J = 319.9 Hz), 126.0, 129.1, 133.3, 136.0, 138.0,
140.1, 140.3, 140.4,147.6; IR (KBr) 3067, 2978, 1450, 1248,
1168, 1097, 1026, 810, 635 cmꢀ1; mp = 143–147 1C; MS
(ESI, m/z) : 449.2500 [C17H17F2SBr2]+; HRMS calcd. for
[C17H17F2SBr2]+: 448.9386, found : 448.9390.
Bromodifluoromethylation of alkynes using S-
bromodifluoromethyl-S-o-bromophenyl-2,3,4,5-
tetramethylphenylsulfonium triflate 1i0
Preparation of S-(bromodifluoromethyl)diarylsulfonium salts 1
n-BuLi (2.6M in THF, 1.3 equiv.) was added dropwise to a
solution of alkyne (0.1 mmol) in 1 mL anhydrous THF at
ꢀ78 1C under nitrogen atmosphere, the resulting mixture was
maintained for 30 min at the same temperature. Then 1i0 was
added in one portion at ꢀ78 1C, and the reaction mixture was
performed for 1 h at the same temperature , followed warming
to room temperature for additional 1 h. The reaction mixture
(1 equiv. trifluorotoluene was added to reaction mixture as
internal standard to determine the yield of desired product)
was quenched with aqueous NH4Cl and extracted 3 times with
hexane. The combined extracts were washed with water and
brine, and then dried over anhydrous Na2SO4. After filtering
off the drying agent, the solvent was evaporated off carefully in
vacuum, and the residue was subjected to flash silica-gel
column chromatography using hexane as eluent to afford
corresponding title product 5.
To a solution of sulfoxide 2 (0.25 mmol, 1 equiv.) and
substituted benzene 3 (0.375 mmol, 1.5 equiv.) in 1 mL dry
dichloromethane (fluorobenzene was used as solvent for
entry 4 in Table 1) was added dropwise Tf2O (1.5 equiv.,
5.0 equiv. was used for entry 9 in Table 1) at 0 1C under
nitrogen atmosphere. After the resulting reaction was
performed for a appropriate time at 0 1C to room temperature,
the solvent and excess Tf2O were evaporated off under vacuum
and the residue was directly subjected to silica-gel column
chromatography (dichloromethane/CH3CN = 4 : 1) to afford
corresponding S-(bromodifluoromethyl)diarylsulfonium triflate.
The triflate salt was dissolved in 10 mL dichloromethane, and
extracted with NaBF4 solution (1 M, 4 ꢁ 5 mL). After drying
(using anhydrous Na2SO4) and evaporation, the residue was dried
under vacuum to give corresponding tetrafluoroborate salts 1.
S-Bromodifluoromethyl-S-phenyl-2,3,4,5-tetramethylphenyl-
sulfonium tetrafluoroborate (1a). White solid, 62% yield.
1H NMR (CDCl3, 300 MHz) d 8.23 (d, J = 8.1 Hz, 2H),
7.83–7.91 (m, 3H), 7.45 (s, 1H), 2.75 (s, 3H), 2.40 (s, 3H), 2.34
(s, 3H), 2.33 (s, 3H); 19F NMR (CDCl3, 282.3 MHz) d ꢀ35.0
(dd, J = 366.7 Hz, 125.9 Hz, 2F), ꢀ152.6 (s 1F), ꢀ152.7
(s, 3F); 13C NMR (CDCl3, 150.9 MHz) d 17.5, 17.7, 19.0, 21.7,
114.9, 117.2 (t, J = 356.1 Hz), 120.0, 128.9, 132.6, 133.3,
137.0, 139.3, 140.8, 141.3, 147.0; IR (KBr) 3430, 3082, 2930,
1451, 1272, 1255, 1217, 1063, 823, 757, 686, 523 cmꢀ1; mp =
170–172 1C; MS (ESI, m/z): 370.7500 [C17H18F2SBr]+;
HRMS calcd. for [C17H18F2SBr]+: 371.0281, found: 371.0283.
5a–5b, 5d–5g, 5i. The characterization data was consistent
with the previous report.9–12
1-(3-Bromo-3,3-difluoroprop-1-ynyl)-4-pentylbenzene (5c). Color-
less liquid, 69% yield. 1H NMR (CDCl3, 300 MHz) d 7.45 (d, J =
8.1 Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H),
1.56–1.66 (m, 2H), 1.25–1.37 (m, 4H), 0.89 (t, J = 6.9 Hz, 2H);
19F NMR (CDCl3, 282.3 MHz) d ꢀ31.3 (s, 2F); 13C NMR
(CDCl3, 150.9 MHz) d 14.1, 22.6, 30.9, 31.5, 36.1, 80.7 (t, J =
38.0 Hz), 90.6, 102.3, 116.0, 128.9, 132.3, 146.6; IR (NaCl) 2930,
2251, 2221, 1511, 1298, 1136, 1090, 939, 817 cmꢀ1; HRMS (EI)
calcd. for [C14H15F2Br]+: 300.0325, found: 300.0317.
S-Bromodifluoromethyl-S-p-nitrophenyl-2,4,6-trimethoxy-
phenylsulfonium tetrafluoroborate (1h). Brown solids, 49%
yield. 1H NMR (CDCl3, 300 MHz) d 8.53 (d, J = 9.0 Hz,
2H), 8.12 (d, J = 9.0 Hz, 2H), 6.44 (s, 1H), 4.05 (s, 3H), 4.00
(s, 6H),; 19F NMR (CDCl3, 282.3 MHz) d ꢀ26.4 (dd, J =
429.9 Hz, 107.8 Hz, 2F), ꢀ153.0 (s 1F), ꢀ153.1 (s, 3F);
13C NMR (CDCl3, 150.9 MHz) d 58.1, 58.4, 81.7, 94.5,
9-(3-Bromo-3,3-difluoroprop-1-ynyl)phenanthrene (5h). Off-white
solid, 60% isolated yield. 1H NMR (CDCl3, 300 MHz)
d 8.66–8.72 (m, 2H), 8.26–8.29 (m, 1H), 8.14 (s, 1H), 7.89
(d, J = 7.8 Hz, 1H), 7.72–7.77 (m, 3H), 7.64 (t, J = 7.5 Hz,
1H); 19F NMR (CDCl3, 282.3 MHz) d ꢀ31.6 (s, 2F); 13C
NMR (CDCl3, 150.9 MHz) d 85.0 (t, J = 37.7 Hz), 89.1 (t,
J = 6.0 Hz), 102.3 (t, J = 289.7 Hz), 115.4, 123.0, 123.2,
126.4, 127.5, 127.8, 127.9, 129.1, 129.3, 130.2, 130.4
130.6 131.4, 134.8 (t, J = 1.5 Hz); IR (KBr) 2924, 2226,
118.4, 117.2 (dd,
J = 366.7 Hz, 356.1 Hz), 126.7,
128.5, 132.9, 152.4, 165.2, 173.2; IR (KBr) 3110, 1600, 1532,
1422, 1345, 1240, 1086, 1059, 1029, 818, 490 cmꢀ1; mp =
170–172 1C; MS (ESI, m/z) : 449.5000 [C16H15NO5F2SBr]+;
HRMS calcd. for [C16H15NO5F2SBr]+: 449.9822, found:
449.9825.
1451, 1322, 1241, 1181, 1090, 1036, 910, 862, 765, 750 cmꢀ1
;
mp = 83–85 1C; HRMS (EI) calcd. for [C17H9BrF2]+:
329.9856, found: 329.9887.
Synthesis of 2-[3,3-difluoro-3-(4-nitrophenoxy)prop-1-ynyl]-6-
methoxynaphthalene (6)
S-Bromodifluoromethyl-S-o-bromophenyl-2,3,4,5-tetramethyl-
phenylsulfonium triflate (1i0). White solids, 71% yield. 1H NMR
(CDCl3, 300 MHz) d 8.41 (d, J = 8.1 Hz, 1H), 8.07 (t, J =
8.1 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 7.8 Hz, 1H),
To a suspension of sodium hydride (60% suspension in oil,
16 mg, 4 equiv.) in 0.5 mL dry DMF was added p-nitrophenol
c
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(55.6 mg, 4 equiv.) at room temperature under nitrogen
atmosphere, and the resulting mixture was stirred for 1 h at
room temperature. A solution of 5e (31 mg, 1 equiv.) in 0.5 mL
dry DMF was added dropwise at room temperature. After
stirring for 36 h at room temperature, the reaction mixture was
poured into 20 ml water and extracted 3 times (3 ꢁ 10 mL)
with ethyl acetate. The combined extracts were washed with
water and brine, and then dried over anhydrous Na2SO4. After
filtering off the drying agent, the solvent was evaporated off in
vacuum and the crude was purified on silica-gel chromato-
graphy (flash, hexane/ethyl acetate = 8 : 1) to afford desired
product 6 as white solid (22 mg, 60%). 1H NMR (CDCl3,
300 MHz) d 8.26–8.31 (m, 2H), 7.94 (s, 1H), 7.68–7.72
(m, 2H), 7.38–7.45 (m, 3H), 7.17–7.21 (m, 1H), 7.11 (d, J =
2.4 Hz, 1H), 3.93 (s, 3H); 19F NMR (CDCl3, 282.3 MHz)
d ꢀ51.3 (s, 2F); 13C NMR (CDCl3, 150.9 MHz) d 55.6, 88.4
(t, J = 6.0 Hz), 106.0, 113.4, 114.5 (t, J = 247.5 Hz), 120.3,
121.4, 125.6, 127.4, 128.2, 128.4, 129.8, 133.4, 135.6, 145.3,
155.5, 159.5; IR (KBr) 3077, 2237, 1625, 1522, 1348, 1308,
1265, 1205, 1146, 1116, 1046, 853 cmꢀ1; mp = 112–114 1C;
HRMS (ESI) calcd. for [C20H13F2NO4S+Na]+: 392.0710,
found: 392.0716.
Advanced Molecular Transformation by Organocatalysts). We
thank the Asahi Glass Foundation for support in part. We also
thank TOSOH F-TECH INC. and CENTRAL GLASS co., Ltd.
for gifts of some reagents. GL thanks to the Hori Sciences &
Arts Foundation for support.
Notes and references
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1
63%). H NMR (CDCl3, 300 MHz) d 7.97 (s, 1H), 7.68–7.72
(m, 2H), 7.46 (d, J = 8.7 Hz, 1H), 7.16–7.33 (m, 7H), 7.11
(s, 1H), 3.92 (s, 3H), 2.94–3.04 (m, 1H), 2.74–2.87 (m, 1H),
2.30 (s, 1H), 1.95–2.21 (m, 2H); 19F NMR (CDCl3, 282.3 MHz)
d ꢀ95.1 (ddd, J = 282.3 Hz, 260.3 Hz, 7.9 Hz, 2F); 13C NMR
(CDCl3, 150.9 MHz) d 31.5, 32.1, 55.6, 73.6 (t, J = 30.2 Hz),
79.1 (t, J = 39.2 Hz), 89.8 (t, J = 6.0 Hz), 106.0, 114.7, 115.3
(t, J = 236.9 Hz), 120.1, 126.3, 127.2, 128.3, 128.7 (d, J =
4.5 Hz), 129.7, 133.0, 135.2, 141.2, 159.2; IR (KBr) 3427,
2927, 2239, 1627, 1604, 1499, 1390, 1262, 1162, 1073, 1032,
855, 701 cmꢀ1; mp = 78–81 1C; HRMS (ESI) calcd. for
[C23H20F2O2 + Na]+: 389.1329, found: 389.1324.
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Acknowledgements
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12 G. B. Hammond, J. Fluorine Chem., 2006, 127, 476.
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This study was financially supported in part by Grants-in-Aid for
Scientific Research from MEXT (Ministry of Education, Culture,
Sports, Science and Technology) (24105513, Project No. 2304:
c
This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2012
New J. Chem., 2012, 36, 1769–1773 1773