BrF3-KHF2: An air-stable fluorinating reagent

Article abstract of DOI:10.1016/j.jfluchem.2014.08.019

BrF₃-KHF₂, an air-stable solid prepared from BrF₃ and KHF₂, was used in the various fluorination reactions, including desulfurizing fluorination reactions of benzylic sulfides, ketone and aldehyde dithioacetals, (phenylthio)glycosides, and trimethyl trithioorthocarboxylates. As the results, one to three fluorine atoms were selectively introduced to the substrates.

Full text of DOI:10.1016/j.jfluchem.2014.08.019

Accepted Manuscript
Title: BrF3-KHF2: An air-stable fluorinating reagent
Author: Toru Shishimi Shoji Hara
PII:
S0022-1139(14)00258-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2014.08.019
FLUOR 8411
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
31-7-2014
25-8-2014
27-8-2014
Please cite this article as: T. Shishimi, S. Hara, BrF3-KHF2: An air-
stable fluorinating reagent, Journal of Fluorine Chemistry (2014),
http://dx.doi.org/10.1016/j.jfluchem.2014.08.019
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

BrF3-KHF2: An air-stable fluorinating reagent
Toru Shishimi, Shoji Hara*
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Keywords: stable fluorinating reagent, KHF2, BrF3, desulfurizing fluorination
Abstract
BrF3-KHF2, an air-stable solid prepared from BrF3 and KHF2, was used in the various
fluorination reactions, including desulfurizing fluorination reactions of benzylic sulfides,
ketone and aldehyde dithioacetals, (phenylthio)glycosides, and trimethyl
trithioorthocarboxylates. As the results, one to three fluorine atoms were selectively
introduced to the substrates.
1. Introduction
Organofluorine compounds are widely used, as medicines, pesticides, functional
materials, and so on [1]. They are generally prepared artificially using fluorinating
reagents because organofluorine compounds are rare in nature. Therefore, the role of the
fluorinating reagent is important for synthesizing desired organofluorine compounds,
and many fluorinating reagents have been produced and used [2]. However, most of
them are sensitive to moisture, and special skills and equipments are required for their
use. Therefore, stable fluorinating reagent is desirable [3]. Recently, we reported the
* Corresponding author.
Tel/Fax: +81(11)7066556
E-mail address: shara@eng.hokudai.ac.jp (S. Hara)
Page 1 of 21

preparation of a new stable fluorinating reagent, IF5-pyridine-HF, and its use in various
fluorination reactions [4]. BrF3 has been also used as a fluorinating reagent, and is more
reactive than IF5 [5]. Therefore, we attempted to synthesize a new stable fluorinating
reagent from BrF3.
2. Results and discussion
BrF3 is known to make a complex of MBF4 where M is Cs, Rb, K [6], or Me4N [7].
However, their ability as a fluorinating reagent has not yet been studied. We attempted
to synthesize a stable complex from BrF3. Addition of BrF3 to KF in CH2Cl2 was
performed at -78 °C, and the cooling bath was removed. When the temperature reached
room temperature, a violent exothermal reaction took place. As BrF3 violently reacts
with CH2Cl2 at room temperature, this result shows that free BrF3 remains in the
mixture and causes the violent reaction. On the other hand, when BrF3 was added to an
excess amount of KHF2 in CH2Cl2, the exothermal reaction did not occur even after
reaching room temperature. A slightly reddish supernatant was removed by decantation
and the remaining solid was washed with CH2Cl2 several times. The remaining solvent
was removed by blowing a nitrogen gas to the solid. The resulting pale yellow solid is
air-stable and can be stored in a Teflon bottle in the refrigerator [8]. We applied this
BrF3-KHF2 complex in various fluorination reactions.
2.1. Desulfurizing difluorination of benzylic sulfide 1 using BrF3-KHF2
Initially, BrF3-KHF2 was used in a desulfurizing difluorination reaction of benzylic
sulfide. When 2-{4-chlorophenyl)thio}-1,2-diphenyletanone (1a) was added to a
2
Page 2 of 21

suspension of BrF3-KHF2 in CH2Cl2 at room temperature, the solution color became
dark red, and 2,2-difluoro-1,2-diphenylethanone (2a) was formed in 88% yield.
Although the yield of 2a was comparable to that obtained by using IF5-pyridine-HF [4a],
the reaction was completed in a shorter time (15 min versus 5 h) (Table 1).
Table 1
Comparison of reactivity of BrF3-KHF2 and IF5-pyridine-HF in desulfurizing
difluorination of 1a a
O
O
fluorinating reagent
CH2Cl2, rt
Ph
Ph
Ph
Ph
F
p-Cl-C6H4S
F
1a
2a
Entry
Fluorinating reagent
IF5-pyridine-HF
BrF3-KHF2
Reaction time
5 h
Yield of 2a(%)b
1
2
88
89
15 min
a 2eq of fluorinating reagent to 1a was used.
bIsolated yield based on 1a used.
In the reaction of BrF3-KHF2 with benzylic sulfides containg an
electron-withdrawing group (1b-d), the corresponding desulfurizing difluorination
products (2a-c) were obtained in high yields as shown in Table 2.
3
Page 3 of 21

Table 2
a
Desulfurizing difluorination of 1 with BrF3-KHF2
Entry
Substrate 1
Reacion
time
Product 2
Yield (%)b
Ph
CO2Bu
Ph
CO2Bu
F
p-Cl-C6H4S
F
1
2
3
3 h
(84)
2b
1b
Ph
PhS
1c
CONEt2
Ph
CONEt2
F
15 min
15 min
76 (85)c
91 (99)c
F
2c
O
O
Ph
Ph
Ph
F
Ph
F
SMe
1d
2a
aIf otherwise not mentioned, the reaction was carried out in CH2Cl2 at room temperature
using 2 eq of BrF3-KHF2 to 1.
bIsloated yield based on 1 used. In parentheses, 19F NMR yield.
c3eq of BrF3-KHF2 to 1 was used.
2.2. Reaction of aldehyde and ketone dithioacetal 3 with BrF3-KHF2
BrF3-KHF2 was also applied to the reaction with the ketone and aldehyde dithioacetals
[3c, 5b, 9]. Reactions with diphenyl dithioacetals of aldehydes (3a-c) and ketones (3d,e)
were completed in 1 h, and the corresponding gem-difluorides (4a-e) were obtained in
4
Page 4 of 21

good yields, as shown in Table 3.
Table 3.
a
The reaction of aldehyde and ketone thioacetals with BrF3-KHF2
F
F
BrF3-KHF2
PhS
R1
SPh
R2
R1
R2
CH2Cl2, rt
4
3
Entry
Substrate 3
Reacion
Product 4
Yield
(%)b
time (min)
PhS
SPh
F
F
1
45
(91)
4a
3a
SPh
SPh
F
F
Ph
Ph
2
3
45
15
81(90)
91(99)
4b
3b
F
SPh
SPh
F
MeO2C
MeO2C
3c
SPh
4c
PhS
F
F
4
45
(84)
4d
3d
5
Page 5 of 21

F
SPh
SPh
F
5
60
(81)c
4e
3e
aIf otherwise not mentioned, the reaction was carried out at room temperature using 2.2
eq of BrF3-KHF2 to 3.
bIsolated yield based on 3. In parentheses, 19F NMR yield.
cThe reaction was carried out at 0 °C.
2.3. Synthesis of glycosyl fluorides 6 by the reaction of (phenylthio)glycosides 5 with
BrF3-KHF2
Glycosyl fluorides have been widely used as glycosyl donors in glycosidation
reactions [10]. They are generally prepared from the corresponding thioglycosides using
a fluorination reagent with or without an oxidizing agent [11]. We applied BrF3-KHF2
for the synthesis of glycosyl fluorides (6) from the corresponding
(phenylthio)glycosides (5). Both pyranosyl fluoride (6a) and furanosyl fluorides (6b-d)
were prepared in good yield by the reaction of the corresponding (phenylthio)glycosides
(5a-d) with BrF3-KHF2 in CH2Cl2 (Table 4). In the reaction with furanosyl derivatives,
only one isomer was selectively formed (Entries 2-4).
Table 4.
a
The reaction of (phenylthio)glycosides with BrF3-KHF2
Entry
Substrate 5
Reacion
Product 6
Yield
6
Page 6 of 21

time
(%)b
83(86)c
( =
63:37)
AcO
AcO
O
O
AcO
AcO
AcO
AcO
1
2
4 h
F
SPh
AcO
AcO
5a
6a
O
O
O
O
15 min
15 min
15 min
89(94)d
O
O
O
O
SPh
O
O
only
F
6b
5b
BzO
BzO
SPh
F
O
O
3
4
87
O
O
O
O
 only
6c
5c
BnO
O
BnO
O
BnO
BnO
SPh
F
(66)
 only
OBn
OBn
5d
6d
aIf otherwise not mentioned, the reaction was carried out at room temperature using 1.1
eq of BrF3-KHF2 to 5.
bIsolated yield based on 5. In parentheses, 19F NMR yield.
c 1.5 eq of BrF3-KHF2 to 5 was used.
d The reaction was carried out at 0 °C.
2.4. Reaction of trimethyl trithioorthocarboxylates 7 with BrF3-KHF2
7
Page 7 of 21

A tris(methylthio)methyl group can be introduced to the electron rich aromatic ring
and -position of the ester group by a reaction with tris(methylthio)methyl cation
species generated from dimethyl trithiocarbonate [12]. The reaction of
N,N-dimethyl-4-(tris(methylthio)methyl)aniline (7a) with BrF3-KHF2 was completed in
15 min at 0 °C, and the tris(methylthio)methyl group was converted to the
trifluoromethyl group. However, bromination at the aromatic ring took place
concurrently and 2-bromo-N,N-dimethyl-4-(trifluoromethyl)aniline (8a) was formed in
moderate yield (Entry
N-methyl-3-tris(methylthio)methylindole
5-bromo-1-methyl-3-(trifluoromethyl)-1H-indole (8b) was obtained selectively (Entry
2). On the other hand, in the reaction of ethyl
1
in Table 5). Similarly, in the reaction of
(7b),
2,2-dimethyl-3,3,3-tris(methylthio)propanoate (7c) with BrF3-KHF2, only two fluorine
atoms were introduced and one methylthio group remained (Entry 3).
Table 5.
a
Reaction of trimethyl trithioorthocarboxylates 7 with BrF3-KHF2
Entry
Substrate 7
Reacion
time
Product 8
Yield (%)b
Br
Me2N
CF3
C(SMe)3
Me2N
1
2
15 min
15 min
52 (62)
76 (83)
7a
C(SMe)3
8a
CF3
Br
N
Me
N
Me
7b
8b
8
Page 8 of 21

O
O
OEt
OEt
3
1 h
81
CF2SMe
C(SMe)3
7c
8c
aThe reaction was carried out in CH2Cl2 at 0 °C using 3.2 eq of BrF3-KHF2 to 7.
bIsolated yield based on 7. In parentheses, 19F NMR yield.
3. Conclusion
A new air-stable fluorinating reagent, BrF3-KHF2, was prepared by the reaction of
BrF3 with KHF2. The reagent was shown to be more reactive than the previously
reported IF5-pyridine-HF in desulfurizing difluorination reaction of the benzylic sulfide.
The reagent was successively applied to desulfurizing fluorination reactions of
dithioacetals, (phenylthio)glycosides, and trimethyl trithioorthocarboxylates.
4. Experimental
4.1. General
The melting points were measured with a Yanagimoto micro melting-point apparatus.
1
The IR spectra were recorded using a JASCO FT/IR-410. The H NMR (400 MHz)
spectra, 19F NMR (376 MHz) spectra, and 13C NMR (100 MHz) were recorded in
CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, δ, is referred to TMS
(1H, 13C) and CFCl3 (19F), respectively. BrF3 in a cylinder was purchased from Galaxy
Chemicals, LLC and used without purification. BrF3 was transferred from cylinder to a
Teflon bottle through a Teflon tube using nitrogen pressure. BrF3 decomposes in air
9
Page 9 of 21

by humidity under emitting HF fume, and should be handled in a bench hood with
rubber-gloved hands under nitrogen atmosphere. BrF3 reacts violently with most of
organic solvents at room temperature and a special care is required for its use.
4.2. Preparation of BrF3-KHF2
To a suspension of KHF2 (3.4 g, 44 mmol) in CH2Cl2 (10 mL) in a Teflon bottle,
BrF3 (3.0g, 22 mmol) was slowly added through a Teflon tube at –78 °C. The
resulting mixture was stirred at –78 °C for 30 min, and the cooling bath was removed
and temperature was allowed to reach room temperature. A slightly reddish supernatant
was removed using a Teflon pipette, and the remaining solid was washed with CH2Cl2
(10 mL) several times, until CH2Cl2 became almost colorless. The remaining solvent
was removed by stirring under nitrogen stream for a few hours. The resulting pale
yellow solid (5.4 g) was stored in a Teflon bottle in the refrigerator. It is slightly
hygroscopic, and therefore, it should be used as quickly as possible to minimize contact
with moisture.
4.2. Desulfurizing difluorination of benzylic sulfides 1 with BrF3-KHF2
4.2.1. 2,2-Difluoro-1,2-diphenylethanone (2a)
To a suspension of BrF3-KHF2 (129 mg) in CH2Cl2 (2.4 mL) in Teflon bottle, 1a
(101 mg, 0.3 mmol) in CH2Cl2 (1.0 mL) was added at room temperature, and the
mixture was stirred at room temperature for 15 min. Then, H2O (5 mL) was added to the
reaction mixture and the resulting product was extracted with CH2Cl2 (5 mL X 3). The
combined organic layer was washed with saturated aqueous NaHCO3 (5 mL) and
10
Page 10 of 21

saturated aqueous Na2S2O3 (5 mL), and dried over MgSO4. After concentration under
reduced pressure, 2a was isolated by column chromatography (silica gel, hexane-ether)
1
in 89% yield. IR (neat) 1703 (C=O), 1450, 1256, 1135 cm-1; H NMR (400MHz,
CDCl3)7.43-7.61 (m, 8H), 8.02-8.04 (m, 2H); 19F NMR (376MHz, CDCl3)–98.12
(s, 2F); 13C NMR (100MHz, CDCl3) 188.9 (t, 2JC-F = 30.7 Hz), 134.2, 133.1 (t, 2JC-F
= 24.9 Hz), 132.1, 130.9, 130.3 (t, 4JC-F = 2.9 Hz, 2C), 128.8 (2C), 128.6 (2C), 125.6 (t,
1
3JC-F = 5.8 Hz, 2C), 116.9 (t, JC-F = 253.9 Hz); HRMS (EI) calcd for C14H10F2O
232.0700, found 232.0683.
4.2.2. Butyl 2,2-difluoro-2-phenylacetate (2b)
1
IR (neat) 2963, 1764 (C=O), 1265, 1105 cm-1; H NMR (400 MHz, CDCl3) 
7.62-7.60 (m, 2H), 7.49-7.45 (m, 3H), 4.24 (t, J = 6.6 Hz, 2H), 1.68-1.60 (m, 2H),
1.37-1.28 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 19F NMR (376 MHz, CDCl3)  –104.65 (s,
2F); 13C NMR (100 MHz) 164.3 (t, 2JC-F = 35.7 Hz), 132.8 (t, 2JC-F = 25.8 Hz), 130.9,
3
1
128.6 (2C), 125.4 (t, JC-F = 6.2 Hz, 2C), 113.4 (t, JC-F =251.9 Hz), 66.8, 30.2, 18.9,
13.5; HRMS (EI) calcd for C12H14F2O2 228.0962, found 228.0956.
4.2.3. N,N-Diethyl-2,2-difluoro-2-phenylacetamide (2c)
1
IR (neat) 2979, 1669 (C=O), 1452, 1364, 1260, 1093 cm-1; H NMR (400MHz,
CDCl3)7.56 (d, J = 7.0 Hz, 2H), 7.44-7.49 (m, 3H), 3.42 (q, J = 7.2 Hz, 2H), 3.25 (q,
J = 7.2 Hz, 2H), 1.17 (t, J = 7.2Hz, 3H), 1.03 (t, J = 7.0 Hz, 3H); 19F NMR (376MHz,
CDCl3) –95.41 (s, 2F); 13C NMR (100MHz, CDCl3)162.7 (t, 2JC-F = 29.7 Hz), 133.9
2
4
3
(t, JC-F = 23.6 Hz), 130.7 (t, JC-F = 1.9 Hz, 2C), 128.7, 125.1 (t, JC-F = 5.8 Hz, 2C),
11
Page 11 of 21

1
4
115.5 (t, JC-F = 251.5 Hz), 42.0 (t, JC-F = 3.8 Hz), 41.4, 13.7, 12.2; HRMS(EI) calcd
for C12H15F2NO 227.1122, found 227.1128.
4.3. The reaction of aldehyde and ketone thioacetals 3 with BrF3-KHF2
4.3.1. 1-(Difluoromethyl)naphthalene (4a)
The reaction was carried out as in the case of 2a using 2.2 eq of BrF3-KHF2 to 3a,
and yield of 4a was determined to be 91 % by 19F NMR using fluorobenzene as an
internal standard. IR (neat) 1514, 1349, 1242 cm-1; 1H NMR  8.19-7.49 (m, 7H), 7.14
(t, J = 55.8 Hz, 1H); 19F NMR  -111.48 (d, J = 56.0 Hz, 2F) (lit.[13] –111.38 (d, J =
2
55.2 Hz)); 13C NMR 133.7, 131.5, 129.7, 129.5 (t, JC-F = 21.1 Hz), 128.7, 127.1,
126.4, 124.8 (t, 3JC-F = 8.6 Hz), 124.6, 123.5, 115.4 (t, 1JC-F = 239.5 Hz).
4.3.2. 4-(Difluoromethyl)-1,1'-biphenyl (4b)
White solid. mp 71-72 °C (lit.[14] 77.0-77.5 °C); IR (KBr) 1414, 1380, 1226, 1077,
1024, 767 cm-1; 1H NMR  7.69-7.39 (m, 9H), 6.70 (t, J = 56.5 Hz, 1H); 19F NMR 
–110.98 (d, J = 57.3 Hz, 2F); 13C NMR 143.7 (t, 5JC-F = 1.9 Hz), 140.2, 133.2 (t, 2JC-F
3
= 22.1 Hz), 128.9 (2C), 127.9, 127.4 (2C), 127.2 (2C), 126.0 (t, JC-F = 6.2 Hz, 2C),
114.7 (t, 1JC-F = 238.5 Hz).
4.3.3. Methyl 4-(difluoromethyl)benzoate (4c)
White solid. mp 38 °C (lit.[15] 36.5-37.0 °C); IR (KBr) 1724 (C=O), 1442, 1281
cm-1; 1H NMR  8.13 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H), 6.70 (t, J = 56.7 Hz,
12
Page 12 of 21

1H), 3.95 (s, 3H); 19F NMR  –112.86 (d, J = 57.9 Hz, 2F); 13C NMR 166.2, 138.4 (t,
2JC-F = 22.5 Hz), 132.3, 129.9 (2C), 125.6 (t, 3JC-F = 6.3 Hz, 2C), 114.0 (t, 1JC-F = 240.9
Hz), 52.3.
4.3.4. 9,9-Difluoro-9H-fluorene (4d)
1
White solid. mp 46-48 °C (lit.[16] 47-48 °C). IR (KBr) 1918, 1454, 1261 cm-1; H
NMR  7.62 (d, J = 7.0 Hz, 2H), 7.56 (d, J = 7.3 Hz, 2H), 7.45 (dd, J = 7.5, 7.5 Hz, 2H),
7.33 (dd, J = 7.6, 7.6 Hz, 2H); 19F NMR  –112.12 (s, 2F); 13C NMR 139.4 (t, 3JC-F
=
5.3 Hz, 2C), 137.9 (t, 2JC-F = 25.1 Hz, 2C), 132.0 (2C), 128.7 (2C), 123.7 (2C), 123.2 (t,
1JC-F = 244.0 Hz), 120.3 (2C).
4.3.5. 2,2-Difluoroadamantane (4e)
White solid. mp 102-103 °C (lit.[17] 104-105 °C); IR (KBr) 2938, 2917, 1389, 1121
cm-1; 1H NMR  2.18 (brs, 2H), 1.97 (brs, 2H), 1.94 (brs, 2H), 1.86 (brs, 2H), 1.78-1.72
(m, 6H); 19F NMR  –100.41 (s, 2F); 13C NMR 125.5 (t, 1JC-F = 248.2 Hz), 36.6 (2C),
35.8 (t, 2JC-F = 4.0 Hz, 2C), 34.0 (t, 3JC-F = 4.0 Hz, 4C), 26.4.
4.4. The reaction of phenylthioglycosides 5with BrF3-KHF2
4.4.1. 2,3,4,5-Tetra-O-acetyl-D-glucopyranosyl fluoride (6a)
The reaction was carried out as in the case of 2a using 1.5 eq of BrF3-KHF2 to 5a,
and 6a was isolated in 83% yield. The ratio of -isomer: -isomer was determined to
1
be 63:37 from H NMR spectra. (6a-) mp 104-106 °C. IR (neat) 2958, 1748 (C=O),
13
Page 13 of 21

1379, 1230, 1038 cm-1. 1H NMR  = 5.76 (dd, J = 53.4, 2.76 Hz, 1H), 5.50 (dd, J = 9.9,
9.9 Hz, 1H), 5.16 (dd, J = 9.9, 9.9 Hz, 1H), 4.96 (ddd, J = 24.6, 10.4, 2.8 Hz, 1H), 4.29
(dd, J = 12.2, 3.8 Hz, 1H), 4.21-4.13 (m, 2H), 2.14 (s, 3H), 2.11 (s, 3H), 2.05 (s, 3H),
2.03 (s, 3H); 19F NMR  –150.34 (dd, J = 52.5, 25.3 Hz, 1F); 13C NMR  = 170.5, 169.9,
1
2
169.8, 169.4, 103.7 (d, JC-F = 228.8 Hz), 70.1 (d, JC-F = 24.8 Hz), 69.7 (d,3JC-F
=
4.1Hz), 69.3, 67.2, 61.1, 20.6, 20.5, 20.4 (2C). (6a-) mp 77-78 °C. IR (neat) 2942,
1
1761, 1439, 1378, 1227, 1109, 1042 cm-1; H NMR  5.37 (dd, J = 52.0, 6.1 Hz, 1H),
5.22-5.20 (m, 2H), 5.18-5.08 (brs, 1H), 4.29-4.20 (m, 2H), 3.93-3.88 (s, 1H), 2.11 (s,
6H), 2.05 (s, 6H); 19F NMR  –137.83 (1F, dd, J = 51.9, 10.4 Hz); 13C NMR  170.5,
170.0, 169.2, 169.1, 106.1 (d, 1JC-F = 219.2 Hz), 72.0 (d, 3JC-F = 4.1 Hz), 71.7 (d, 3JC-F
=
2
8.3 Hz), 71.1 (d, JC-F = 28.9 Hz), 67.4, 61.7, 20.6-20.5 (4C); HRMS (EI) calcd for
C14H20O9F (M++H) 351.1091, found 351.1115.
2,3;5,6-di-O-Isopropylidene--D-mannofuranosyl fluoride (6b-)
IR (neat) 2989, 1374, 1212, 1130, 1070, 972, 849 cm-1; 1H NMR  5.69 (d, J = 59.5
Hz, 1H), 4.77-4.43 (m, 2H), 4.43-4.38 (m, 1H), 4.18-4.05 (m, 3H), 1.46 (s, 6H), 1.39 (s,
3H), 1.35 (s, 3H); 19F NMR  –129.25 (dd, J = 59.5, 6.7 Hz, 1F); 13C NMR  113.6 ( d,
2
1JC-F = 221.6 Hz), 113.2, 109.4, 84.7, (d, JC-F = 42.2 Hz), 82.6, 78.6, 72.7, 66.6, 26.9,
25.8, 25.1, 24.5; HRMS (EI) calcd for C12H19O5F (M++H) 263.1295, found 263.1317.
4.4.4. 2,3-O-Isopropylidene-5-O-benzoyl--D-ribofuranosiyl fluoride (6c)
IR (neat) 2990, 1725, 1273, 1094, 977, 714 cm-1; 1H NMR  8.07 (d, J = 8.2 Hz, 2H),
7.61-7.56 (m, 1H), 7.48-7.42 (m, 2H), 5.83 (d, J = 61.8 Hz, 1H), 4.88-4.85 (m, 2H),
4.71-4.67 (m, 1H), 4.45-4.37 (m, 2H), 1.50 (s, 3H), 1.35 (s, 3H); 19F NMR  –116.44 (d,
14
Page 14 of 21

J = 60.9 Hz, 1F){ lit.[18] –115.85 (dq, J = 61.6, 4.0 Hz, 1F)}; 13C NMR  = 166.1,
1
3
133.4, 129.9 (2C), 129.6, 128.5(2C),115.4 (d, JC-F = 223.1 Hz), 113.3, 86.5 (d, JC-F
=
3.2 Hz), 85.1 (d, 2JC-F = 40.8 Hz), 81.0, 64.7, 26.4, 25.0.
4.4.5. 2,3,5-Tri-O-benzyl-β-D-arabinofuranosyl fluoride (6d)
White solid. mp 78-79 °C (lit.[19] 77-78 °C); IR (KBr) 3062, 3030, 2865, 1454, 1115,
1
1028, 738, 698 cm-1; H NMR δ 7.30-7.17 (m, 15H), 5.79 (d, J = 61.5 Hz, 1H),
4.73-4.45 (m, 7H), 4.17 (dd, J = 9.3, 2.2 Hz, 1H), 3.96 (dd, J = 5.1, 2.0 Hz, 1H),
3.64-3.57 (m, 2H); 19F NMR δ –121.23 (dd, J = 61.6, 9.2 Hz, 1F); 13C NMR δ 137.9,
1
2
137.7, 137.2, 127.7-128.5 (15C), 108.3 (d, JC-F = 229.9 Hz), 84.5 (d, JC-F = 21.5 Hz),
82.4, 81.5, 73.5, 72.6, 72.4, 71.5.
4.5. Reaction of trimethyl trithioorthocarboxylates 7 with BrF3-KHF2
4.5.1. 2-Bromo-N,N-dimethyl-4-(trifluoromethyl)aniline (8a)
The reaction was carried out as in the case of 2a at 0 °C using 3.2 eq of BrF3-KHF2 to
7a, and 8a was isolated in 52% yield. IR (neat) 2952, 2874, 2842, 2791, 1608, 1324,
1
1123 cm-1; H NMR  7.79 (s, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.09 (d, J = 7.5 Hz, 1H),
3
2.87 (s, 6H); 19F NMR  –62.52(s, 3F); 13C NMR  154.9, 131.3, (q, JC-F = 3.8 Hz),
3
1
125.3 (q, JC-F = 3.8 Hz), 125.2 (q, 2JC-F = 34.3 Hz), 123.7 (t, JC-F = 276.0 Hz), 120.3,
117.9, 43.8 (2C); HRMS (EI) calcd for C9H8BrF3N (M+-1) 265.9791, found 265.9792.
4.5.2. 5-Bromo-1-methyl-3-(trifluoromethyl)-1H-indole (8b)
White solid. mp 60 °C (lit.[20] 58-60 °C); IR (KBr) 1558, 1473, 1235, 1095 cm-1; 1H
15
Page 15 of 21

NMR (DMSO-d6)  8.08 (s, 1H), 7.72 (s, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.46 (dd, J =
8.9, 1.9 Hz, 1H), 3.86 (s, 3H); 19F NMR (DMSO-d6)  –54.8 (s, 3F); 13C NMR
(DMSO-d6)  135.4, 131.8 (q, 3JC-F = 4.9 Hz), 125.4, 124.8 (q, 3JC-F = 2.2 Hz), 124.3 (q,
1JC-F = 270.0 Hz), 120.4, 113.9, 113.3, 120.6 (q, 2JC-F = 37.2 Hz), 33.2.
4.5.3. Ethyl 3,3-difluoro-2,2-dimethyl-3-(methylthio)propanoate (8c)
1
IR (neat) 2988, 2938, 1737, 1274, 1175, 1034 cm-1; H NMR  4.20 (q, J = 7.3 Hz,
2H), 2.29 (s, 3H), 1.40 (s, 6H), 1.28 (t, J = 7.3 Hz, 3H); 19F NMR  –84.67 (s, 2F); 13C
NMR  171.7 (t, 3JC-F = 2.8 Hz), 131.5 (t, 1JC-F = 289 Hz), 61.5, 51.6 (t, 3JC-F = 22.0 Hz),
3
2
20.7 (t, JC-F = 3.1 Hz, 2C), 13.9, 9.9 (t, JC-F = 5.3 Hz); HRMS (EI) calcd for
C8H14F2O2S 212.0683, found 262.0682.
Acknowledgment
We are grateful to prof. Hermann-Josef Frohn (University of Duisburg-Essen,
Germany) for his kind advice on the handling of BrF3.
References
[1] (a) P. Kirsh, in Modern Fluoroorganic Chemistry, Wiley-VCH; Weinheim, 2004,
pp. 203-277.
(b) T. Hiyama, in : H. Yamamoto, (Ed.), Organofluorine Compounds, Springer-Verlag
Heidelberg, 2000, pp. 183-233.
(c) R. F. Anderson, J. O. Punderson, in: R. E. Banks, (Ed.), Organofluorine Chemicals
and Their Industrial Applications, Ellis Horwood LTD., Chichester, 1979, pp. 123-247.
[2] Recent reviews and books on fluorination reagent, see: (a) R. P. Singh, J. M.
16
Page 16 of 21

Shreeve, Synthesis (2002) 2561-2578.
(b) K. L. Kirk, Org. Process Res. Dev. 12 ( 2008) 305-321.
(c) K. Uneyama, in Organofluorine Chemistry, Blackwell Publishing, Oxford, 2006.
[3] Recent reviews and books on air stable fluorination reagent, see: (a) R. P. Singh, J.
M. Shreeve, Acc. Chem. Res. 37 (2004) 31-44.
(b) P. T. Nyffeler, S. G. Durón, M. D. Burkart, S. P.Vincent, C.-H. Wong, Angew. Chem.
Int. Ed. 44 (2005) 192-212.
(c) S. Hara, in: K. K. Laali, (Ed.), Advances in Organic Synthesis, Bentham Science
Publishers LTD., Hilversum, 2006; p 49-60.
(d) N. Al-Maharik, D. O’Hagan, Aldrichimica Acta 44 (2011) 65-75.
[4] (a) S. Hara, M. Monoi, R. Umemura, C. Fuse, Tetrahedron 68 (2012) 10145-10150.
(b) M. Kunigami, S. Hara, J. Fluorine Chem. (2014) in press.
[5] As for the reviews of the fluorination using BrF3, see: (a) S. Rozen, Acc. Chem. Res.
38 (2005) 803-812. (b) S. Rozen, Adv. Synth. Catal. 352 (2010) 2691-2707.
[6] (a) S. Siegel, Acta Cryst. 9 (1956) 493-495.
(b) K. O. Christe, C. J. Schack, Inorg. Chem. 9 (1970) 1852-1858.
[7] W. W. Wilson, K. O. Christe, Inorg. Chem. 28 (1989) 4172-4175.
[8] We didn’t have any information about the structure of this solid. But it was
conveniently used as BrF3-2(KHF2) (MW 215) because, two equivalent of KHF2 to
BrF3 was used to make it. This solid is insoluble in most of organic solvents, and a
slightly hygroscopic.
[9] As for the recent review articles of gem-difluoride synthesis from thioacetals, see:
(a) V. Hugenberg, G. Haufe, J. Fluorine Chem. 143 (2012) 238-262.
(b) T. Fuchigami, S. Inagi, Chem. Commun. 47 (2011) 10211-10223.
17
Page 17 of 21

(c) M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 44 (2005) 214-231.
(d) M. Kuroboshi, K. Kanie, T. Hiyama, Adv. Synth. Catal. 343 (2001) 235-250.
(e) V. P. Reddy, G. K. S. Prakash, G. A. Olah, in: K. K. Laali (Ed.), Advances in Organic
Synthesis, Bentham Science Publishers LTD., Hilversum, 2006, pp.183-211.
(f) V. P. Reddy, M. Perambuduru, R. Alleti, in: K. K. Laali (Ed.), Advances in Organic
Synthesis, Bentham Science Publishers LTD., Hilversum, 2006, pp.327-351.
[10] (a) M. Shimizu, H. Togo, M. Yokoyama, Synthesis (1998) 799-822.
(b) K. Toshima, Carbohydr. Res. 327 (2000) 15-26.
(c) T. Mukaiyama, Angew. Chem. Int. Ed. 43 (2004) 5590-5614.
[11] (a) K. C. Nicolau, R. E. Dolle, D. P. Papahatjis, J. L. Randall, J. Am. Chem. Soc.
106 (1984) 4189-4192.
(b) J. C. López, P. B. Albert, C. Uriel, S. Valverde, A. M. Gómez, J. Org. Chem. 72
(2007) 10268-10271.
(c) T. Sawamura, S. Kuribayashi, S. Inagi, T. Fuchigami, Adv. Synth. Catal. 352 (2010)
2757-2760.
(d) S. Tsegay, R. J. Williams, S. J. Williams, Carbohydr. Res. 357 (2012) 16-22.
(e) K. Suzuki, Y. Ito, O. Kanie, Carbohydr. Res. 359 (2012) 81-91.
(f) G. Mugunthan, K. P. R. Kartha, Tetrahedron Lett. 53 (2012) 5631-5634.
[12] M. Barbero, S. Cadamuro, I. Degani, R. Fochi, A. Gatti, V. Regondi, Synthesis
(1988) 22-25.
[13] G. K. S. Prakash, S. K. Ganesh, J.-P. Jones, A. Kulkarni, K. Masood, J. K. Swabeck,
G. A. Olah, Angew. Chem. Int. Ed. 51 (2012) 12090-12094.
[14] K. Fujikawa, Y. Fujioka, A. Kobayashi, H. Amii, Org. Lett. 13 (2011) 5560-5563.
[15] T. Furuya, T. Fukuhara, S. Hara, J. Fluorine Chem. 126 (2005) 721-725.
18
Page 18 of 21

[16] F. E. Ray, C. E. Albertson, J. Am. Chem. Soc. 70 (1948) 1954-1955.
[17] G. A. Olah, M. Nojima, I. Kerekes, J. Am. Chem. Soc. 96 (1974) 925-927.
[18] M. Rapp, X. Cai, W. Xu, W. R. Dolbier Jr., S. F. Wnuk, J. Fluorine Chem. 130
(2009) 321-328.
[19] W. A. Szarek, G. Grynkiewicz, Chem. Lett. (1984) 1751-1754.
[20] M. M. Bastos, L. M. U. Mayer, E. C. S. Figueira, M. Soares, W. B. Kover, N.
Boechat, J. Heterocycl. Chem. 45 (2008) 969-973.
19
Page 19 of 21

An air-stable fluorinating reagent was prepared from BrF3 and KHF2.> BrF3-KHF2 was
used in the various fluorination reactions.> Desulfurizing fluorination reactions of
benzylic sulfides, dithioacetals and trimethyl trithioorthocarboxylates were performed.
20
Page 20 of 21

*Graphical Abstract - Pictogram
Page 21 of 21