From difluoromethyl 2-pyridyl sulfone to difluorinated sulfonates: A protocol for nucleophilic difluoro(sulfonato)methylation

Article abstract of DOI:10.1002/anie.201007594

An efficient method for the synthesis of alkyl α,α- difluorosulfonates has been developed. The selection of the 2-pyridyl group as the aryl substitute on the sulfone is critically important for the success of this transformation (see scheme). The synthetic application of fluorinated sulfones is extended and a unique solution is provided for a long-standing challenge in nucleophilic difluoro(sulfonato)methylation reactions. Copyright

Full text of DOI:10.1002/anie.201007594

DOI: 10.1002/anie.201007594
Fluorinated Sulfonates
From Difluoromethyl 2-Pyridyl Sulfone to Difluorinated Sulfonates:
A Protocol for Nucleophilic Difluoro(sulfonato)methylation**
G. K. Surya Prakash,* Chuanfa Ni, Fang Wang, Jinbo Hu, and George A. Olah*
Fluorine, characterized by its small size and high electro-
negativity, often furnishes organic molecules with unequalled
chemical and biological properties including stability, lip-
ophilicity, and bioavailability.[1] The sulfonic acid functional
group has not only found its use in modern materials such as
proton-exchange membranes and surfactants,[2] but also in
synthetic molecules with important biological and pharmaco-
logical activities such as antiulcer, antibacterial, antipseudo-
monal, and squalene synthase inhibition activities.[3] Based on
this scenario, a,a-difluorinated sulfonate derivatives, as an
important subclass of lightly fluorinated compounds, are of
great interest in life and materials sciences. Furthermore,
owing to the isopolar and isosteric characters of the difluoro-
methylene group to an oxygen atom, difluorinated sulfonates
can be exploited to replace the labile sulfate esters.[1d]
Although a,a-difluorinated phosphonic acids have been
used to inhibit and probe enzymes and proteins that bind or
hydrolyze phosphate for many years, only in recent years,
attention has been paid on a,a-difluorinated sulfonates to
design effective sulfatase inhibitors.[4,6] Moreover, in relation
with the perfluorinated sulfonic acids and their derivatives,
the performance of these difluorinated counterparts are also
of great interest in materials science owing to their acidity and
facile biodegradability.[5] Thus, many a,a-difluorinated sulfo-
nates have been synthesised using different protocols, includ-
ing the electrophilic fluorination of the sulfonates,[4c,6] dehalo-
sulfination or -sulfonation of a,a-difluoroalkyl halides,[7a–c]
sulfonation of 1,1-difluoroalkenes,[7d] sulfination of a,a-
difluorosilanes,[7e] and fluorinated sultone rearrangements.[7f]
Apparently, one of the disadvantages of these protocols is that
the fluorine atoms and sulfonato group have to be incorpo-
rated sequentially.
Based on nucleophilic fluoroalkylation,[8] one can envi-
sion a nucleophilc difluoro(sulfonato)methylation pathway
for the direct introduction of difluoro(sulfonato)methyl group
into organic frameworks. Indeed, Li and Liu had reported a
nucleophilic introduction of a difluoromethylene sulfonamide
group (-CF2SO2NR2) into aromatic aldehydes.[9] However,
these synthons are not ideal for the introduction of the
sulfonic acid functional group owing to the sluggish hydrolysis
rates of the sulfonamides. Our initial attempts towards this
goal involved treating difluoromethanesulfonates (as pronu-
cleophiles) and alkyl iodides (as electrophiles) under basic
conditions. These attempts failed as a result of the instability
and low reactivity of difluoromethanesulfonates anions
(Scheme 1, for details, see the Supporting Information), thus
implying that there are some challenges in the nucleophilic
difluoro(sulfonato)methylation reaction.
Scheme 1. Attempted nucleophilic difluoro(sulfonato)methylation reac-
tion of alkyl iodides with difluoromethanesulfonates.
It is well known that alkyl sulfonyl-substituted heteroar-
omatic compounds can readily undergo ipso-substitution
reaction with nucleophiles, thus giving the corresponding
heteroaromatics and alkyl sulfinates.[10] However, to the best
of our knowledge, there has been no report on the synthetic
utility of heteroaryl sulfones as sulfinate or sulfonate equiv-
alents in the nucleophilic (sulfonato)methylation reactions.[11]
Herein, we disclose a new synthetic application of difluor-
omethyl sulfones as a difluoro(sulfonato)methyl equivalent
(-CF2SO3À), which enables a unique synthesis of a,a-difluor-
oalkyl sulfonates from primary alkyl halides and primary
alcohol triflates (Scheme 2).
To realize this nucleophilic substitution, the reaction
between difluoromethyl heteroaryl or electron-deficient aryl
sulfones and alkyl halides or sulfonates were examined with
extensive screening of the reaction conditions (Table 1).
Surprisingly, by applying the reported optimal reaction
conditions for the nucleophilic substitution of difluoromethyl
phenyl sulfone with alkyl iodides,[12] only difluoromethyl 2-
pyridyl sulfone 1b gave a detectable amount of substituted
product (Table 1, entries 1–4). In all cases, the decomposition
of the difluoromethyl sulfones was observed as the predom-
inant outcome. The preliminary results showed that these aryl
substituents were less effective for the stabilization of
difluoromethyl anions in comparison with the phenyl group.
To suppress the decomposition of the anion species, the
[*] Prof. Dr. G. K. S. Prakash, Dr. C. Ni, F. Wang, Prof. Dr. G. A. Olah
Loker Hydrocarbon Research Institute and
Department of Chemistry, University of Southern California
University Park, Los Angeles, CA 90089-1661 (USA)
Fax: (+1)213-740-6679
E-mail: gprakash@usc.edu
olah@usc.edu
Prof. Dr. J. Hu
Key Laboratory of Organofluorine Chemistry
Shanghai Institute of Organic Chemistry, CAS
345 Ling-ling Road, Shanghai 200032 (China)
[**] Support of our work by the Loker Hydrocarbon Research Institute is
gratefully acknowledged. J.H. also thanks the National Natural
Science Foundation of China (20825209, 20832008) for financial
support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201007594.
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Communications
alents of sulfone 1b and 1.5 equivalents of LiHMDS in THF/
HMPA (10:1, v/v) at À988C for 5 minutes (Table 1, entry 10).
The additional investigation on the influence of metal cations
(Na+ and K+; Table 1, entries 11 and 12) revealed that
LiHMDS was the most suitable base. Other than alkyl
iodides, alkyl bromides and triflates were also found to be
reactive, and the latter exhibited the highest reactivity
(Table 1, entries 16–19). A secondary alkyl iodide, however,
did not give the anticipated product, thus indicating that the
reaction is very sensitive to steric hindrance (Table 1,
entry 20). Noticeably, although other difluoromethyl hetero-
aryl sulfones such as 1a could also
Scheme 2. Nucleophilic difluoro(sulfonato)methylation reaction with
difluoromethyl sulfones.
Table 1: Screening of reagents and optimization of reaction conditions.
react with triflate, the yield was only
moderate
(Table 1,
entry 21).
Taking availability, stability, as well
as high reactivity into account, the
combination of alkyl halides and 1b
explicitly turns out to be advanta-
geous in terms of the general applic-
ability of the protocol.
Having established the reaction
conditions, we further examined the
scope of the current protocol
(Table 2). The nucleophilic substi-
tution was found to be very efficient
with primary alkyl iodides, which
afforded a,a-difluoroalkyl 2-pyridyl
sulfones 3a–3i in good yields
(Table 2, entries 1–9). Notably,
despite benzyl and allyl halides
displaying fairly high reactivity
(Table 2, entries 10-14), the corre-
sponding products 3j–3n were
much more sensitive to the base
than 3a–3i, and readily underwent
b elimination in the presence of
excess base. In the case of 4-bro-
Entry Sulfone (equiv) Base (equiv)
Halide (equiv)
Solvent[a]
T [oC] Yield [%][b]
1
2
3
4
5
6
7
8
1a (1.0)
1b (1.0)
1c (1.0)
1d (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (1.0)
1b (2.0)
1b (1.3)
1b (1.3)
1b (1.3)
1a (1.0)
1c (1.0)
1d (1.0)
1d (1.0)
1b (1.3)
1b (1.3)
1b (1.3)
1b (1.0)
1a (1.0)
tBuOK (2.0)
tBuOK (2.0)
tBuOK (2.0)
tBuOK (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (1.5)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (4.0)
n-C7H15I (1.0)
n-C7H15I (1.0)
DMF
DMF
DMF
DMF
THF
THF/HMPA
THF/HMPA
Et2O/HMPA À98
À45
À45
À45
À45
À78
À78
À98
0
10
0
0
0
45
88
57
80
79
0
9
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
THF/HMPA
À98
À98
À98
À98
À98
À98
À98
À98
À98
À98
À98
À98
À98
10
11
12
13
14
15
16
17
18
19
20
21
NaHMDS (1.5) n-C7H15I (1.0)
KHMDS (1.5)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (2.0)
LiHMDS (1.5)
LiHMDS (1.5)
LiHMDS (1.5)
LiHMDS (2.0)
LiHMDS (1.5)
n-C7H15I (1.0)
n-C7H15I (1.0)
n-C7H15I (1.0)
n-C7H15I (1.0)
n-C5H11Br (4.0)
n-C4H9OTs (1.0)
n-C4H9OMs (1.0)
CH3CH2OTf (1.0)
iPrI (4.0)
0
0
0
0
37
0
0
mobenzyl
bromide
(Table 2,
entry 11), the by-product 1,1-
difluoroalkene could further react
with the anion of 1b, thus compli-
cating the reaction.
Considering the ready availabil-
ity of alcohols compared with alkyl
halides, as an alternative route, the
one-pot synthesis of substituted
97
0
53
Ph(CH2)3OTf (1.0) THF/HMPA
[a] THF/HMPA and Et2O/HMPA were used in 10:1 (v/v) ratio. [b] Yield was determined by 19F NMR
spectroscopy with PhCF3 as the internal standard. DMF=N,N-dimethylformamide, HMDS=
1,1,1,3,3,3-hexamethyldisilazane, Ms=mesyl, Py=pyridyl, THF=tetrahydrofuran, Tf=trifluorometh-
anesulfonyl, Ts=tosyl.
reaction temperature was further lowered to À788C with
THF as the solvent. The addition of hexamethylphosphor-
amide (HMPA) was found to be necessary, which improved
the yield to 45% when lithium hexamethyldisilazide
(LiHMDS) was used as the base (Table 1, entries 5 and 6).
Further lowering the temperature to À988C gave a consid-
erably higher yield (Table 1, entry 7). Diethyl ether was also
examined as the solvent, in which, a decreased yield was
observed (Table 1, entry 8). Under similar conditions, other
sulfones (1a, 1c, and 1d) were not significantly reactive
(Table 1, entries 13–15). With exhaustive optimization of the
proportion of the substrates, the best reaction conditions were
established as 1.0 equivalent of iodide reacting with 1.3 equiv-
difluoromethyl sulfones 3 from alcohols was investigated
(Table 3). By adopting triflates as intermediates, the primary
alcohols 4 could be transformed into sulfones 3 in good yields
(Table 3, entries 1–4). Owing to the lability of THF towards
triflic anhydride,[13] Et2O was chosen as the solvent in the first
step. Intriguingly, 2-pyridyl sulfone 1b itself could serve both
as a base and as a pronucleophile during the course of the
transformation. In the triflation step, 1b was protonated to
give a pyridinium salt and in the subsequent nucleophilic
reaction step, it was recovered by an excess amount of base.
Although triflates are essentially more reactive than alkyl
halides, isopropyl triflate remained inert under the current
chemical scenario (Table 3, entry 5).
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Table 2: Preparation of substituted aifluoromethyl sulfones from hal-
Table 4: Screening of conditions for aromatic substitution.
ides.[a]
Entry Nucleophile (equiv) Solvent
t [h] Conv. Yield
[%][a]
[%][a]
Entry Halide
Product
Yield
[%][b]
1
2
3
4
5
6
7
8
EtONa (1.6)
EtSNa (2.0)
PhSNa (2.0)
tBuSNa (2.0)
NaBH4 (2.0)
NaCN (4.0)
NaCH(CN)2 (4.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
EtSNa (2.0)
CH3CN
CH3CN
CH3CN
CH3CN
MeOH
DMF
3
3
quant.
0
50
0
0
0
0
0
0
0
88
10
33
7
0
0
quant.
0
86
5
quant.
79
30
63
10
1
CH3CH2I
3a, CH3CH2CF2SO2(2-Py)
74
24
20
24
20
20
24
12
12
12
12
12
12
2
2
3
4
5
6
7
8
9
CH3CH2CH2I
CH3(CH2)2CH2I
CH3(CH2)3CH2I
CH3(CH2)5CH2I
Ph(CH2)2CH2I
Ph(CH2)3CH2I
PhO(CH2)2CH2I
PhO(CH2)3CH2I
PhCH2Br
3b, CH3 CH2CH2CF2SO2(2-Py)
3c, CH3(CH2)2CH2CF2SO2(2-Py)
3d, CH3(CH2)3CH2CF2SO2(2-Py)
3e, CH3(CH2)5CH2CF2SO2(2-Py)
3 f, Ph(CH2)2CH2CF2SO2(2-Py)
3g, Ph(CH2)3CH2CF2SO2(2-Py)
3h, PhO(CH2)2CH2CF2SO2(2-Py)
3i, PhO(CH2)3CH2CF2SO2(2-Py)
3j, PhCH2CF2SO2(2-Py)
73
78
75
69
88
73
71
73
DMF
EtOH
CH2Cl2
THF
PhCH3
DMF
acetone
Et2O
tBuOH
EtSH
9
10
11
12
13
14
15
16
17
18[b]
71
0
10
11
88
60
45
15
15
10
4-BrC6H4CH2Br
3k, 4-BrC6H4CH2CF2SO2(2-Py)
35[c]
(82)
99
12
13
14
2,5-Me2C6H3CH2I 3l, 2,5-Me2C6H3CH2CF2SO2(2-Py)
4-vinyl-C6H4CH2I
3m, 4-vinyl-C6H4CH2CF2SO2(2-Py) 78
20
=
=
CH2 CHCH2I
3n, CH2 CHCH2CF2SO2(2-Py)
76
EtSH/THF (1:2) 12
EtSH/THF (1:2) 12
quant. quant.
0
[a] All reactions were performed under the optimized conditions.
[b] Yield of isolated product after flash column chromatography. The
yield in parentheses was determined by 19F NMR spectroscopy. [c] Yield
after recrystallization, which was carried out twice. HMPA=hexamethyl
phosphoramide.
0
[a] Determined by 19F NMR spectroscopy. [b] PhSO2CF2CH2CH3 (6) was
used.
(Table 4, entry 16). Encouragingly, using ethanethiol/THF
(1:2, v/v) as a buffered solvent system, the reaction proceeded
smoothly to provide the sulfinate 5 in quantitive yield with
excellent selectivity (Table 4, entry 17). However, phenyl
sulfone 6 failed to be converted under these reaction
conditions (Table 4, entry 18), thus indicating the necessity
of the 2-pyridyl group in this transformation.
Table 3: One-pot synthesis of substituted difluoromethyl sulfones from
alcohols.
Entry[a]
R1
R2
Product
Yield [%][b]
The optimized reaction conditions developed for the
transformation of sulfone 3j were applied to other difluori-
nated sulfones. With the combined dearylation–oxidation
procedure, the a,a-difluoroalkyl sulfonates 7 could be pre-
pared from 3 in one pot in excellent yield and high purity
(Table 5). In addition to the simple sulfonates, the current
protocol was applied for the conversion of a variety of
substrates bearing bromine, phenoxy, and vinyl groups—such
products are rarely available. Notably, the vinyl group is
amenable to the oxidation with hydrogen peroxide to afford
the vinyl-containing sulfonates 7m and 7n that are highly
useful for further polymerization (Table 5, entries 13 and 14).
To further demonstrate the synthetic utility of this
protocol, an efficient synthesis of an a,a-difluorosulfonate
analogue of sulfated carbohydrate was performed
(Scheme 3). Compound 11 (with Li+ as the cation), which
has been previously prepared by electrophilic fluorination of
a protected sulfonate precursor, was obtained in only
moderate yield owing to its rapid decomposition to 1,1-
difluoro-1-alkene under the basic reaction conditions.[6d] By
the means of novel nucleophilic difluoro(sulfonato)methyla-
tion reaction, starting from the triflate 8, the benzyl-protected
b-pyranoside sulfonate 10 was obtained in 85% overall yield,
and can further afford fluorinated carbohydrate sulfonate 11
through the removal of the benzyl groups.
1
2
3
4
5
CH3
H
H
H
H
3a
3e
3 f
3g
3o
82
62
87
79
0
CH3(CH2)5
Ph(CH2)2
Ph(CH2)3
CH3
CH3
[a] Reaction conditions: 1. Tf2O, Et2O, 08C, 30 min; 2. LiHMDS, THF/
HMPA (10:1), À988C, 5 min. [b] Yield of isolated product.
With a series of substituted difluoromethyl 2-pyridyl
sulfones 3 on hand, we continued our investigation on the
preparation of difluoroalkylsulfonates. Considering the base-
lability of the benzyl-substituted compounds, the sulfone 3j
was selected as a model substrate for the establishment of
appropriate dearylation conditions (Table 4). Among a series
of nucleophiles that were examined (Table 4, entries 1–7), the
less basic sodium ethanethiolate (EtSNa) was identified as the
most promising reagent owing to the highest yield of sulfinate
5 in comparison with others (Table 4, entry 2). Subsequently,
using EtSNa as the optimal nucleophile (Table 4, entries 8–
16), a screening of solvents showed that the highest yield of
sulfinate 5 could be obtained in THF (Table 4, entry 10). In
particular, although only low conversion was achieved in
ethanethiol, the selectivity of the reaction (yield/conversion)
was found to be remarkably higher under buffered conditions
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2561

Communications
Table 5: Synthesis of various difluorinated sulfonates.
the absence of resonance. These
results explicitly rationalize the
superior stability of 12a over 12b–
12 f, which readily degrade into
difluorocarbene and the corre-
sponding sulfinates under the reac-
tion conditions (see above). More-
over, according to the computa-
tional studies, the Mulliken charges
on the anionic carbon atoms was
found to increase from 12b to 12 f,
thus revealing a gradual decrease in
nucleophilicity of the fluorinated
carbanions.
Apart from the electronic pro-
files of the intermediates, the ther-
modynamic aspects of the reactions
were further investigated. As
depicted in Table 6, all the nucleo-
philic substitution reactions are
shown to be thermodynamically
favorable at the B3LYP/6-311 + G
level.[14] Moreover, the reactions of
Entry
Sulfone
Sulfonate
Yield
(purity) [%][a]
1
CH3CH2CF2SO2(2-Py)
7a, CH3CH2CF2SO3Na
99 (95)
96 (98)
94 (98)
99 (95)
99 (97)
96 (98)
98 (95)
97 (95)
97 (95)
90 (99)
92 (95)
96 (97)
96 (95)
90 (99)
2
3
4
5
6
7
8
9
10
11
12
13
14
CH3 CH2CH2CF2SO2(2-Py)
CH3(CH2)2CH2CF2SO2(2-Py)
CH3(CH2)3CH2CF2SO2(2-Py)
CH3(CH2)5CH2CF2SO2(2-Py)
Ph(CH2)2CH2CF2SO2(2-Py)
Ph(CH2)3CH2CF2SO2(2-Py)
PhO(CH2)2CH2CF2SO2(2-Py)
PhO(CH2)3CH2CF2SO2(2-Py)
PhCH2CF2SO2(2-Py)
7b, CH3CH2CH2CF2SO3Na
7c, CH3(CH2)2CH2CF2SO3Na
7d, CH3(CH2)3CH2CF2SO3Na
7e, CH3(CH2)5CH2CF2SO3Na
7 f, Ph(CH2)2CH2CF2SO3Na
7g, Ph(CH2)3CH2CF2SO3Na
7h, PhO(CH2)2CH2CF2SO3Na
7i, PhO(CH2)3CH2CF2SO3Na
7j, PhCH2CF2SO3Na
4-BrC6H4CH2CF2SO2(2-Py)
2,5-Me2C6H3CH2CF2SO2(2-Py)
4-vinyl-C6H4CH2CF2SO2(2-Py)
7k, 4-BrC6H4CH2CF2SO3Na
7l, 2,5-Me2C6H3CH2CF2SO3Na
7m, 4-vinyl-C6H4CH2CF2SO3Na
=
=
CH2 CHCH2CF2SO2(2-Py)
7n, CH2 CHCH2CF2SO3Na
[a] Yield of isolated product. Purity was determined by 1H NMR spectroscopy.
CH3Br with 12b and 12c are of substantial energetic
preference over those involving 12d–12 f, and is in good
agreement with the experimental outcomes. The cleavage of
À
the S CX2 bond was also found to be thermodynamically
allowed in light of the dimerization of the carbenes; however,
in comparison with 12d–12 f, the decomposition of 12b,c is
less likely to occur due to the formation of thermodynami-
cally less stable sulfinates. Notably, even though the decom-
position of 12a into the corresponding sulfinate and ethylene
is energetically rather favorable than that of 12b and 12c, the
carbene intermediate (DCH2) exhibits much less stability than
the difluorocarbene (DCF2). Therefore, the facile nucleophilic
substitution of 12b and 12c towards alkyl halides can be
rationalized as consequences of both energetically favored
formation of the products and relatively difficult decompo-
sition regimen. Particularly, the lower reactivity of 12c in
Scheme 3. Synthesis of fluorinated b-pyranoside sulfonate 11.
Bn=benzyl.
Finally, to manifest the struc-
ture–reactivity relationship ob-
Table 6: Structural parameters associated with arylsulfonylmethide anions.
served for various aryl sulfones,
computational studies based on the
density functional theory (DFT)
were performed at the B3LYP/6-
311 + G(2d,p) level.[14] As shown in
Table 6, significantly lower bond
orders were found to be associated
with difluoromethides (12b–12 f),
Bond order[a] Bond length [ꢀ] Mulliken charge
DG [kcalmolÀ1
DG1 DG2 DG3
]
À
thus indicating weaker S CX2
À
S CX2
À
S CX2
(Qanionic C
)
bonds compared with the non-fluo-
rinated analogue (12a). In contrast
PhSO2CH2À (12a)
PhSO2CF2À (12b)
1.028
0.733
0.753
1.664
1.873
1.868
1.846
1.851
1.859
À0.432
+0.010
+0.053
+0.085
+0.092
+0.145
À51.0 +75.3 À25.2
À51.3 +18.0 À18.9
À51.4 +16.2 À20.7
À39.5 +14.7 À22.2
À43.9 +11.1 À25.8
À
with the S CH2 bond in 12a that
À
possesses partial double bond char-
2-PySO2CF2 À(12c)
À
4-NPSO2CÀF2 (12d) 0.761
acter, the S CF2 bond lengths are
BTSO2CF2À (12e)
0.786
0.753
calculated to be much longer than
PTSO2CF2 (12 f)
À37.7 +5.2
À31.7
À
that of the typical Csp3 SO2 bonds
(1.764–1.790 ꢀ),[15] thus suggesting [a] Atom–atom overlap-weighted NAO (natural atomic orbital) bond order.
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Experimental Section
Typical procedure for the reaction between difluoromethyl sulfone
and halides: Under an atmosphere of N2, into a 100 mL Schlenk flask
containing 1-iodoheptane (678 mg, 3.0 mmol) and 2-PySO2CF2H (1b;
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(3 mL) at the same temperature. After removal of the cold bath,
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(3 ꢁ 50 mL), and the combined organic phase was dried over MgSO4.
After the removal of solvents under reduced pressure, the crude
residue was purified by flash column chromatography on silica gel
(hexanes/EtOAc, from 3:1 to 2:1) to give 3e (612 mg, 69% yield).
Received: December 3, 2010
Published online: February 18, 2011
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Keywords: fluorine · ipso-substitution ·
nucleophilic fluoroalkylation · sulfonates · sulfones
.
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