Efficient synthesis of α-(fluoro/chloro/methoxy)disulfonylmethane derivatives as tunable substituted methyl synthons via a new C-S bond forming strategy

Article abstract of DOI:10.1016/j.jfluchem.2010.07.006

A new synthetic protocol for the preparation of α-fluoro(disulfonyl) methane and its chloro as well as methoxy analogues has been developed. Due to the synthetic utility of α-fluoro(bisphenylsulfonyl)methane (FBSM) as a versatile synthon in the preparatio

Full text of DOI:10.1016/j.jfluchem.2010.07.006

Journal of Fluorine Chemistry 131 (2010) 1007–1012
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Efficient synthesis of
a
-(fluoro/chloro/methoxy)disulfonylmethane derivatives as
tunable substituted methyl synthons via a new C–S bond forming strategy
a
a
G.K. Surya Prakash a, , Fang Wang , Chuanfa Ni , Tito Joe Thomas a,b, George A. Olah a
*
a Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, 837 Bloom Walk, Los Angeles, CA 90089-1661, USA
b Siemens Competition Regional Finalist and Intel Science Talent Search Semifinalist, Troy High School, 2200 E. Dorothy Lane, Fullerton, CA 92831, USA
A R T I C L E I N F O
A B S T R A C T
Article history:
A new synthetic protocol for the preparation of
a-fluoro(disulfonyl)methane and its chloro as well as
Received 15 May 2010
Received in revised form 7 July 2010
Accepted 8 July 2010
methoxy analogues has been developed. Due to the synthetic utility of
a
-fluoro(bisphenylsulfonyl)-
methane (FBSM) as a versatile synthon in the preparation of various useful fluoromethylated organic
molecules, search for an easy and economic for its preparation route has been essential. The C–S bond
forming strategy is utilized in this new synthetic approach, which can be applied to a variety of
substrates with high efficiency and selectivity.
Available online 16 July 2010
Keywords:
ß 2010 Elsevier B.V. All rights reserved.
Fluorination
Monofluoromethylation
KF
Disulfonylmethane synthons
C–S bond forming strategy
1. Introduction
these fluoromethylation reagents can essentially suppress the a-
elimination of fluoride from the corresponding carbanions and
increase the thermodynamic stability of these species by
delocalizing the negative charge [7]. Among these elegant
Sulfone-based organic compounds are widely used for the
introduction of synthetically useful building blocks as well as
bioactive functionalities [1]. In particular, arylsulfonylmethane
derivatives have been extensively utilized in modern organic
chemistry as methyl synthons [2]. Sulfonyl, a strong electron-
withdrawing group, is capable of activating sp3-hybridized C–H
bond by significantly increasing the acidity of the proton.
Successive substitution of protons with methyl sulfonyl groups
in a methane molecule leads to pKa values of the corresponding
derivatives in water to 29, 12 and 0, respectively [3]. The resulting
carbon-acids can be readily used as tunable pronucleophiles in
many organic reactions [2]. On the other hand, further transforma-
tions of sulfonyl group can be achieved via a variety of methods
compatible with different functional groups [4].
Incorporation of fluoromethyl groups into organic molecules
has significant attention in pharmaceutical arena due to their
profound influence on physical and biological properties of the
molecules [5]. In recent years, phenylsulfonyl functionalized
fluoromethylation reagents and related methodologies have been
developed by Prakash, Hu, Shibata, and many others as highly
selective and efficient fluoromethylation protocols in organo-
fluorine chemistry [6]. The presence of phenylsulfonyl group in
reagents,
a-fluorobis(phenylsulfonyl)methane (FBSM) and its
analogues have been used as efficient monofluoromethyl equiva-
lents in various transformations [6d–l]. Although FBSM has been
successfully applied in numerous reactions, it is still not an easily
available reagent due to the practical difficulties of its preparation.
Our continuing efforts on using FBSM and its derivatives as
fluoromethyl synthons have lead to a convenient synthesis of
fluoro(disulfonyl)methanes as well as the chlorinated and
methoxylated analogues.
Fluoro(disulfonyl)methanes were first synthesized in 1998 by
Wickiser et al. as anthelmintic and insecticidal active compounds
via C–F bond forming reaction between Selectfluor1 and
disulfonylmethide anions [8]. Realizing the potential applications
of fluoro(disulfonyl)methanes in organic synthesis, FBSM was
utilized by Shibata, Hu and Prakash as an efficient nucleophilic
fluoromethylation reagent [6d–l]. Recently, Nagura and Fuchi-
gami described the electrochemical reaction between NEt4F-4HF
and phenyl phenylsulfonylmethyl sulfide (PhSO2CH2SPh) to
afford FBSM in 52% yield [9]. However, the major problems of
the synthetic routes involving the C–F bond formation are: (a) the
fluorine sources are expensive or highly hazardous; (b) the
reactions can only afford the products in moderate yield (50–
70%); (c) the selectivity of the reactions is unsatisfactory due to
the formation of mixtures of compounds; (d) the separation,
* Corresponding author. Tel.: +1 213 7405984; fax: +1 213 7405087.
E-mail address: gprakash@usc.edu (G.K. Surya Prakash).
0022-1139/$ – see front matter ß 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2010.07.006

[
G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1007–1012
Scheme 1. Synthesis of fluorobis(phenylsulfonyl)methane (FBSM) by (a) C–F bond forming strategy and (b) C–S bond forming strategy.
including chromatographic process, limits the application of
these reactions.
Lately, Hu et al. disclosed the synthesis of FBSM by the
treatment of PhSO2CH2F with methyl benzenesulfinate followed
by the oxidation using m-chloroperoxybenzoic acid (mCPBA)
(Scheme 1) [10]. The synthetic route is a practical method for the
To our dismay, FBSM was not formed under these conditions,
however, chlorofluoromethyl phenyl sulfone (PhSO2CHClF) was
found as the major product (Table 1, entries 3–6). In comparison
with NaHMDS and LiHMDS, KHMDS was the base affording higher
yields which presumably diminishes the defluorination of
PhSO2CHFÀ because of the weaker coordination between fluoride
and potassium ions (Table 1, entries 1–6). It appears that the
formation of PhSO2CHClF is due to the lower electrophilicity of the
PhSO2 group compared to that of the Cl toward the PhSO2CHFÀ
anion, in accordance with a previous report [12].
The results indicate that the sulfur atom on the phenylsulfonyl
halides PhSO2X needed to be more electrophilic toward PhSO2CHFÀ
anion. Among various sulfonating reagents, we decided to utilize
PhSO2F, which has been shown as a superior precursor due to the
strong electronegativity of F [13]. As anticipated, the halogenation
process was suppressed, and FBSM was obtained in almost
quantitative yield with high NMR purity (>95%) by the treatment
of PhSO2CH2F and PhSO2F with 2 equiv. of KHMDS (Table 1, entry 8).
The extra amount of the base was required, as it was consumed
during the facile deprotonation of the (disulfonyl)methanes.
Furthermore, the product can be easily isolated in high purity by
extraction technique since all the by-products are water-soluble or
volatile. The newly developed synthetic strategy successfully avoids
tedious separation processes or utilization of any expensive or low
efficient reagents. RSO2CH2F is readily synthesized on a large scale
from fairly inexpensive substrate, chloromethyl phenyl sulfide and
KF followed by oxidation with Oxone1 [14]. Phenylsulfonyl fluoride
can be prepared from the corresponding chlorine-containing
counterpart (phenylsulfonyl chloride) by chlorine–fluorine ex-
change using KF. It is important to note that KF is the only fluorine
source used in the new protocol, which increases the atom
efficiency and remarkably reduces the cost of the reaction.
Compared to the utilization of Selectfluor1 as electrophilic
fluorinating agent, the application of KF as the fluorine source is
preparation of a-fluoro(disulfonyl)methane derivatives via a ‘‘C–S
bond forming strategy’’ instead of the conventional C–F bond
forming processes. By this methodology the problems mentioned
above were successfully eliminated, and the products can be
obtained in high selectivity and excellent yield. However, the
employed sulfinates are less available, which also introduces an
additional step in the preparation. Shank et al., on the other hand,
have reported the synthesis of methoxy(disulfonyl)methanes by
the C–S bond forming strategy using methoxymethyl phenyl
sulfone and phenylsulfonyl chloride (PhSO2Cl) which significantly
reduces the expense and shortens the synthetic route.
2. Results and discussion
Inspired by the earlier work of Shank et al. [11], we first
performed the reaction between fluoro(phenylsulfonyl)methide
anion (PhSO2CHFÀ) and PhSO2Cl expecting the formation of FBSM.
Table 1
Formation of fluorophenylsulfonylmethide anion under different bases and its
reaction with phenyl sulfonyl halides.
[TD$INLE]
.
Entry
X
Base
Molar ratio 1/2/base
Yield (%) 3/4aa
e[S(cheme_)2FITD]$G conomic, efficient and advantageous (Scheme 2).
1b
2b
3b
4c
5b
6c
7c
8c
Cl
Cl
Cl
Cl
Cl
Cl
F
LHMDS
LHMDS
NaHMDS
NaHMDS
KHMDS
KHMDS
KHMDS
KHMDS
1.01/1.0/1.0
1.0/1.0/2.0
1.0/1.2/2.0
1.0/1.2/2.0
1.0/1.2/2.0
1.0/1.2/2.0
1.0/1.0/1.0
1.0/1.0/2.0
–
–
66/0
42/0
77/0
85/0
0/48
0/99
F
a
19F NMR yield.
b
Base was added to 1 at À78 8C and stirred for 30 min followed by dropwise
addition of 2a at the same temperature and stirred for another 30 min before
quenching by dil. HCl.
c
Base was added dropwise at À78 8C to a solution of 1 and 2a and the mixture
Scheme 2. The new C–S bond forming strategy for the preparation of
was stirred at À78 8C for 30 min followed by quenching with HCl.
fluorobis(phenylsulfonyl)methane (FBSM) and its derivatives.

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1007–1012
1009
Table 2
Synthesis of 1-fluorobis(phenylsulfonyl)methane derivatives by the new C–S bond forming strategya.
[TD$INLE]
.
Entry
1
Substrate
Product
Yield (%)b
[
[
95
2
E
E
93
3
E
E
90
4
E
E
97
5
E
E
73
6
E
E
86
a
Conversion was 100% in all cases.
b
Isolated yields.
To examine the scope of the methodology, we carried out the
alkoxybenzo-1,3-disulfone was prepared by the oxidation of the
corresponding sulfide with MoO5ÁHMPAÁH2O [15]. However,
attempts to oxidize methoxybis(phenylthio)methane under the
similar conditions lead to the decomposition of the starting
material. As mentioned above, methoxydisulfonylmethanes can
also be obtained by the treatment of methoxyphenylsulfonyl-
methide with the corresponding sulfonyl chlorides in moderate
yield (50–70%) [11]. Encouraged by the successful preparation of
fluoro(disulfonyl)methanes by the new C–S bond forming strategy,
we explored the synthesis of methoxy(disulfonyl)methanes using
similar strategy. The desired products were obtained in higher
yields by the sulfonylation of methoxyphenylsulfonylmethide
using sulfonyl fluorides instead of sulfonyl chlorides (Table 3,
entries 5a–d, 5f).
reaction between PhSO2CH2F and other sulfonyl fluorides. It has
been shown that the method can be successfully applied to a
variety of sulfonyl fluorides including perfluoroalkylsulfonyl
fluorides, the arylsulfonyl fluorides bearing both electron-with-
drawing and electron-donating groups, and even the hindered
sulfonyl fluoride. The reaction generally affords the products in
good to excellent yield with high NMR purity (>95%, Table 2).
It has been demonstrated that alkoxymethyl sulfonylmethanes
can be readily applied as a carbonyl 1,1-dipole synthon [15] and
methoxymethyl synthon [16]. Diekmann, in 1965, reported the
synthesis of alkoxybis(phenylsulfonyl)methanes by photolysis of
bis(phenylsulfonyl)diazomethane in alcohols [17]. The drawbacks
of this method appear to be: (a) the availability of bis(phenylsul-
fonyl)diazomethane is limited; (b) the alcoholysis has to be
performed under UV irradiation, a setup which may be not
generally available in many organic chemistry laboratories. The 2-
On the other hand, Gibson reported the synthesis of
chloro(disulfonyl)methanes from the reaction between disulfo-
nylmethide salts and PhSO2Cl [18]. Symmetric chloro(disulfo-

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G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1007–1012
Table 3
Synthesis of
a-methoxy and
a-chloro derivatives of bis(phenylsulfonyl)methane by the new sulfonylation protocol.
[TD$INLE]
.
Entry
1
Substrate
Product
Yield (%)a,b
[
[
(5a) 78
(6a) 78
2
E
E
(5b) 82
(6b) 75
3
E
E
(5c) 62
(6c) 83
4
E
E
(5d) 77
(6d) 74
5
E
E
(5f) 79
(6f) 52
a
Conversion was 100% in all cases.
Isolated yields.
b
nyl)methanes can be also achieved by treatment of disulfonyl-
methanes in aqueous NaOH solution with NaOCl [19]. Our
attempts to obtain chloro(disulfonyl)methanes via the oxidation
of the corresponding disulfides failed due to the high instability of
the chloro(disulfonyl)methanes. Since the disulfonylmethanes
are much less acidic than the monochlorinated intermediates,
chlorination of disulfonylmethide with stoichiometric amount of
N-chlorosuccinimide (NCS) always leads to a mixture of mono-
and dichlorinated products along with unreacted starting
material. However, when we followed the new C–S bond forming
protocol using PhSO2CH2Cl and RSO2F, the corresponding
chloro(disulfonyl)methanes were feasibly formed in good yields
and purity (Table 3, 6a–d, 6f).
sis of the substituted disulfonylmethanes as useful methyl
synthons for various reactions. Particularly, the practical synthesis
of FBSM and its analogues based on the nucleophilic nature of
fluorine (the starting materials are derived only from KF)
successfully diminishes the problems encountered in the conven-
tional synthetic approaches, employing electrophilic fluorine-
based reagents.
4. Experimental
Unless otherwise mentioned, all chemicals were purchased
from commercial sources. 1H, 13C and 19F NMR spectra were
recorded on a 400 MHz superconducting NMR spectrometer. All
the unknown compounds have been fully characterized by NMR
spectroscopy and MS analysis, whereas structures of all known
products were confirmed by comparison of their NMR spectra with
3. Conclusions
A practical and highly efficient ‘‘C–S bond forming strategy’’ for
the reported data. 1H NMR chemical shifts (
relative to internal tetramethylsilane at 0.0 ppm or to the signal
of a residual solvent in CDCl3 (
7.26 ppm). 13C NMR chemical shifts
d) were determined
the synthesis of
a
-substituted disulfonylmethane derivatives was
d
developed. The novel methodology achieves the one-step synthe-
d

G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1007–1012
1011
were determined relative to internal tetramethylsilane at
0.0 ppm or to the 13C signal of CDCl3 at
77.16 ppm.
d
J = 274.5 Hz), 105.1–121.6 (m, 4C), 130.0, 130.7, 134.3, 136.9. 19F
NMR (CDCl3)
2F), À126.3 (m, 2F), À166.5 (m, 1F). MS (ESI, m/z): 932.5 (2M + Na-
2HÀ), 455.0 (MÀHÀ), 282.8. HRMS: calcd for C11H5F10O4S2
454.9475 (MÀHÀ) found: m/z 454.9469.
d
d
À81.2 (t, J = 9.7 Hz, 3F), À109.9 (m, 2F), À121.5 (m,
4.1. Typical procedure for the preparation of
a-
fluorobis(phenylsulfonyl)methane (4a)
PhSO2CH2F (1, 348 mg, 2 mmol) and phenyl sulfonyl fluoride
(2a, 320 mg, 2 mmol) were dissolved in anhydrous THF (10 mL) in
a Schlenk flask under inert atmosphere. The solution was cooled to
À78 8C. KHMDS (499 mg, 5 mmol) was dissolved in anhydrous THF
(5 mL) and added to the Schlenk flask dropwise. The reaction
mixture was stirred for 30 min at the same temperature before
poured into 4 M HCl aqueous solution (20 mL). The resultant
mixture was washed with water and was extracted with CH2Cl2
(15 mL Â 3). The combined organic layer was dried over MgSO4,
and the solvent was evaporated to afford an oil which crystallized
after standing for a while as the product (4a, 598 mg, 95%). 1H NMR
and 19F NMR spectroscopy showed the high purity (>95%) of the
product.
4.2. Typical procedure for the preparation of
methoxy(disulfonyl)methanes (5a–d, 5f)
Methoxy(disulfonyl)methanes (5a–d, 5f) were prepared by the
same procedure for fluoro(disulfonyl)methane synthesis. The
products were obtained with a small amount of PhSO2CH2OCH3
which can be removed by chromatography with hexanes–CH2Cl2
as the eluent.
4.2.1.
As white solid in 78% yield isolated. 1H NMR (CDCl3)
3H), 5.03 (s, 1H), 7.55–7.59 (m, 4H), 7.68–7.73 (m, 2H), 7.94–8.96
a-Methoxybis(phenylsulfonyl)methane (5a)
d
3.61 (s,
(m, 4H), 13C NMR (CDCl3)
d 64.6, 106.1, 129.2, 130.3, 135.1, 136.3.
MS (ESI, m/z): 349.0 (M+Na+). HRMS: calcd for C14H14NaO5S2
349.0175 (M+Na+) found: m/z 349.0173.
4.1.1.
As white solid 1H NMR (CDCl3)
7.66 (t, J = 7.6 Hz, 4H), 7.74–7.83 (t, J = 7.6 Hz, 2H), 7.95–8.03 (m,
4H). 19F NMR (CDCl3)
À168.2 (d, J = 45.6 Hz, 1F). The data are
consistent with Ref. [6d].
a
-Fluorobis(phenylsulfonyl)methane (4a)
d
5.70 (d, J = 45.8 Hz, 1H), 7.60–
4.2.2. 1-Chloro-4-(methoxy(phenylsulfonyl)methylsulfonyl)benzene
d
(5b)
As white solid in 82% yield isolated. 1H NMR (CDCl3)
d
2.46 (s,
3H), 3.60 (s, 3H), 5.00 (s, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.55–7.58 (m,
2H), 7.67–7.73 (m, 1H), 7.82–7.84 (m, 2H), 7.94–7.96 (m, 2H). 13
4.1.2. 1-(Fluoro(phenylsulfonyl)methylsulfonyl)-4-methylbenzene
C
(4b)
NMR (CDCl3) d 21.9, 64.5, 106.1, 129.1, 129.9, 130.2, 133.3, 135.0,
As white solid in 93% yield isolated. 1H NMR (CDCl3)
d
2.48 (s,
136.4, 146.4. MS (ESI, m/z): 702.7 (2M+Na+), 363.0 (M+Na+). HRMS:
calcd for C15H16NaO5S2 363.0331 (M+Na+) found: m/z 363.0334.
3H), 5.70 (d, J = 45.6 Hz, 1H), 7.39–7.41 (m, 2H), 7.59–7.63 (m, 2H),
7.74–7.78 (m, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.97–8.00 (m, 2H). 19F
NMR (CDCl3)
with Ref. [9].
d
À168.87 (d, J = 45.5 Hz, 1F). The data are consistent
4.2.3. 1-(Methoxy(phenylsulfonyl)methylsulfonyl)-4-nitrobenzene
(5c)
As white solid in 62% yield isolated. 1H NMR (CDCl3)
d
3.66 (s,
3H), 5.08 (s, 1H), 7.59 (t, J = 7.6 Hz, 2H), 7.74 (m, 1H), 7.93 (m, 2H),
8.18 (d, J = 8.8 Hz, 2H), 8.40 (d, J = 8.8 Hz, 2H). 13C NMR (CDCl3)
4.1.3. 1-(Fluoro(phenylsulfonyl)methylsulfonyl)-4-nitrobenzene (4c)
As white solid in 90% yield isolated. 1H NMR (CDCl3)
5.83 (d,
J = 45.6 Hz, 1H), 7.61–7.65 (m, 2H), 7.77–7.81 (m, 1H), 7.94–7.96
(m, 2H), 8.22–8.24 (m, 2H), 8.43–8.46 (m, 2H). 13C NMR (CDCl3)
105.8 (d, J = 265.4 Hz), 124.7, 130.0, 130.2, 132.2, 135.2, 136.3,
d
d
64.8, 106.2, 124.1, 129.5, 130.1, 132.2, 135.4, 136.2, 141.5, 151.6.
d
MS (ESI, m/z): 370.0 (MÀHÀ), 153.6, 145.8. HRMS: calcd for
C
14H12NO7S2 370.0061 (MÀHÀ) found: m/z 370.0066.
140.7, 152.1. 19F NMR (CDCl3)
d
À168.47 (d, J = 45.8 Hz, 1F). MS
(ESI, m/z): 357.9 (MÀHÀ), 202.1, 157.0, 137.9. HRMS: calcd for
4.2.4. 1-Chloro-4-(methoxy(phenylsulfonyl)methylsulfonyl)benzene
C
13H9FNO6S2 357.9861 (MÀHÀ) found: m/z 357.9859.
(5d)
As white solid in 74% yield isolated. 1H NMR (CDCl3)
d
3.62 (s,
3H), 5.07 (s, 1H), 7.51–7.59 (m, 4H), 7.72 (m, 1H), 7.86–7.94 (m,
4H) 13C NMR (CDCl3)
64.6, 106.1, 129.3, 129.5, 130.2, 131.8,
134.5, 135.1, 136.3, 142.1. MS (ESI, m/z): 382.9 (M+Na+). HRMS:
calcd for
382.9784.
4.1.4. 1-Chloro-4-(fluoro(phenylsulfonyl)methylsulfonyl)benzene
(4d)
d
As white solid in 97% yield isolated. 1H NMR (CDCl3)
d
5.72 (d,
J = 46.0 Hz, 1H), 7.58–7.64 (m, 4H), 7.76–7.80 (m, 1H), 7.92–7.98
(m, 4H). 13C NMR (CDCl3)
105.8 (d, J = 265.0 Hz), 129.7, 130.0,
130.2, 131.9, 133.6, 135.4, 136.0, 143.1. 19F NMR (CDCl3)
À168.61
(d, J = 45.8 Hz, 1F). MS (ESI, m/z): 371.0 (M+Na+). HRMS: calcd for
13H10ClFO4S2Na 370.9591 (M+Na+) found: m/z 370.9590.
C
14H13ClNaO5S2 382.9785 (M + Na+) found: m/z
d
d
4.2.5. (Methoxy(perfluorobutylsulfonyl)methylsulfonyl)benzene (5f)
As white waxy solid in 74% yield isolated. 1H NMR (CDCl3)
3.91
(s, 3H), 5.55 (s, 1H), 7.63 (t, J = 7.6 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H),
8.03 (d, J = 8.0 Hz, 2H), 13C NMR (CDCl3)
64.4, 105.3–121.8 (m,
4C), 104.6, 129.5, 130.7, 135.1, 136.0. 19F NMR (CDCl3)
À81.2 (t,
C
d
4.1.5. 2-(Fluoro(phenylsulfonyl)methylsulfonyl)-1,3,5-
trimethylbenzene (4e)
d
d
As pale powder in 73% yield isolated. 1H NMR (CDCl3)
d
2.32 (s,
J = 9.0 Hz, 3F), À110.5 to À108.5 (m, 2F), À122.6 to À120.5 (m, 2F),
À127.3 to À125.4 (m, 2F). MS (ESI, m/z): 620.9 (2M + Na-2HÀ),
299.2 (C4F9SO3À). HRMS: calcd for C12H8F9O5S2 466.9675 (MÀHÀ)
found: m/z 466.9670.
3H), 2.61 (s, 6H), 5.68 (d, J = 46.4 Hz, 1H), 6.99 (s, 2H), 7.62 (t,
J = 7.8 Hz, 2H), 7.77 (t, J = 7.7 Hz, 1H), 8.04 (d, J = 7.8 Hz, 2H). 13C
NMR (CDCl3)
d 21.4, 23.2, 106.4 (d, J = 265.9 Hz), 129.4, 130.4,
130.5, 132.8, 135.4, 135.7, 142.4, 145.9. 19F NMR (CDCl3)
d
À168.02
(d, J = 46.4 Hz, 1F). MS (ESI, m/z): 379.1 (M+Na+), 338.3. HRMS:
calcd for C16H18FO4S2 357.0631 (M+H+) found: m/z 357.0625.
4.3. Typical procedure for the preparation of
chloro(disulfonyl)methanes (6a–d, 6f)
4.1.6. (Fluoro(perfluorobutylsulfonyl)methylsulfonyl)benzene (4f)
Chloro(disulfonyl)methanes were obtained according to the
same procedure for fluoro(disulfonyl)methane synthesis. The
reactions afforded the products in high purity (>95%) by a simple
extraction technique.
As white waxy solid in 86% yield isolated. 1H NMR (CDCl3)
d
6.15
(d, J = 46.5 Hz, 1H), 7.67–7.71 (m, 2H), 7.85 (tq, 1J = 7.7 Hz,
2J = 1.2 Hz, 1H), 8.05–8.08 (m, 2H). 13C NMR (CDCl3)
103.4 (d,
d

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G.K.S. Prakash et al. / Journal of Fluorine Chemistry 131 (2010) 1007–1012
References
4.3.1.
a-Chlorobis(phenylsulfonyl)methane (6a)
As white solid in 78% yield isolated. 1H NMR (CDCl3)
d
5.56 (s,
1H), 7.61–7.65 (m, 4H), 7.75–7.80 (m, 2H), 8.03–8.05 (m, 4H). 13
NMR (CDCl3) 84.0, 129.4, 130.7, 135.6, 135.7. The data are
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d
(b) M. Nielsen, C.B. Jacobsen, N. Holub, M.W. Paixao, K.A. Jørgensen, Angew.
Chem. Int. Ed. 49 (2010) 2668–2679;
consistent with Ref. [20].
(c) J. Hu, W. Zhang, F. Wang, Chem. Commun. 48 (2009) 7465–7478;
4.3.2. 1-(Chloro(phenylsulfonyl)methylsulfonyl)-4-methylbenzene
´
(d) A.-N.R. Alba, X. Companyo, R. Rios, Chem. Soc. Rev. (2010), doi: 10.1039/
b911852g.
(6b)
[3] D.J. Cram, Fundamentals of Carbanion Chemistry, Academic Press, New York,
1965.
As white solid in 82% yield isolated. 1H NMR (CDCl3)
d 2.48 (s,
3H), 5.56 (s, 1H), 7.40 (d, J = 8.0 Hz 2H), 7.59–7.63 (m, 2H), 7.73–
7.78 (m, 1H), 7.90 (d, J = 8.0 Hz, 2H), 8.01–8.04 (m, 2H). 13C NMR
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(c) F. Schoenebeck, J.A. Murphy, S. Zhou, Y. Uenoyama, Y. Miclo, T. Tuttle, J. Am.
Chem. Soc. 129 (2007) 13368–13369;
(CDCl3) d 22.0, 84.0, 129.3, 130.0, 130.7, 130.8, 132.5, 135.6, 135.7,
147.2. MS (ESI, m/z): 710.5 (2M + Na+), 367.0 (m + Na+). HRMS:
calcd for C14H13ClO4S2Na 366.9836 (M + Na+) found: m/z 366.9831
(d) C. Ni, J. Hu, Tetrahedron Lett. 46 (2005) 8273–8277;
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(b) Y. Li, J. Hu, Angew. Chem. Int. Ed. 44 (2005) 5882–5886;
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4.3.3. 1-(Chloro(phenylsulfonyl)methylsulfonyl)-4-nitrobenzene (6c)
As white solid in 77% yield isolated. 1H NMR (CDCl3)
d
5.63 (s,
1H), 7.62–7.66 (m, 2H), 7.77–7.81 (m, 1H), 7.99–8.02 (m, 2H),
8.27–8.30 (m, 2H), 8.45–8.47 (m, 2H). 13C NMR (CDCl3)
83.9,
d
124.3, 129.6, 130.6, 132.6, 135.3, 136.0, 140.8, 151.9. MS (ESI, m/z):
374.0 (MÀHÀ). HRMS: calcd for C13H9ClNO6S2 373.9565 (MÀH)
found: m/z 373.9561.
(f) G.K.S. Prakash, S. Chacko, S. Alconcel, T. Stewart, T. Mathew, G.A. Olah, Angew.
Chem. Int. Ed. 46 (2007) 4933–4936;
(g) T. Furukawa, N. Shibata, S. Mizuta, S. Nakamura, T. Toru, M. Shiro, Angew.
Chem. Int. Ed. 47 (2008) 8051–8054;
(h) G.K.S. Prakash, S. Chacko, Curr. Opin. Drug Discov. Dev. 11 (2008) 793–
802;
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U.S.A. 106 (2009) 4090–4094;
(j) A.N. Alba, X. Companyo´, A. Moyano, R. Rios, Chem. Eur. J. 15 (2009) 7035–
7038;
4.3.4. 1-Chloro-4-(chloro(phenylsulfonyl)methylsulfonyl)benzene
(6d)
As white solid in 74% yield isolated. 1H NMR (CDCl3)
d
5.58 (s,
1H), 7.58–7.64 (m, 4H), 7.75–7.79 (m, 1H), 7.96–8.03 (m, 4H), 13
NMR (CDCl3) 83.9, 129.5, 129.7, 130.6, 132.3, 133.8, 135.5, 135.8,
142.8. MS (ESI, m/z): 386.9 (M + Na+). HRMS: calcd for
13H11Cl2O4S2 364.9470 (M + H+) found: m/z 364.9476.
C
d
(k) F. Ullah, G.L. Zhao, L. Deiana, M. Zhu, P. Dziedzic, I. Ibrahem, P. Hammar, J. Sun,
A. Co´rdova, Chem. Eur. J. 15 (2009) 10013–10017;
C
(l) C. Ni, J. Hu, Tetrahedron Lett. 50 (2009) 7252–7255.
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Olah, Angew. Chem. Int. Ed. 48 (2009) 5358–5362.
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Med. Chem. 41 (1998) 1092–1098.
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46 (1990) 4925–4950;
4.3.5. (Chloro(perfluorobutylsulfonyl)methylsulfonyl)benzene (6f)
As white waxy solid in 52% yield isolated. 1H NMR (CDCl3)
5.93
(s, 1H), 7.66 (t, J = 7.8 Hz, 2H), 7.83 (t, J = 7.7 Hz, 1H), 8.08 (d,
J = 7.7 Hz, 2H). 13C NMR (CDCl3)
81.0, 106.6–119.8 (m, 4C), 129.7,
131.2, 134.5, 136.6. 19F NMR (CDCl3)
2F), À122.2 (m, 2F), À126.2 (m, 2F). MS (ESI, m/z): 964.5 (2M + Na+-
2HÀ), 471.1 (MÀHÀ). HRMS: calcd for C11H5ClF9O4S2 470.9180
(MÀHÀ) found: m/z 470.9183.
d
d
d
À81.1 (m, 3F), À106.1 (m,
Acknowledgement
(b) S.V. Ley, M.N. Tackett, M.L. Maddess, J.C. Anderson, P.E. Brennan, M.W. Cappi,
J.P. Heer, C. Helgen, M. Kori, C. Kouklovsky, S.P. Marsden, J. Norman, D.P. Osborn,
M.A. Palomero, J.B.J. Pavey, C. Pinel, L.A. Robinson, J. Schnaubelt, J.S. Scott, C.D.
Spilling, H. Watanabe, K.E. Wesson, M.C. Willis, Chem. Eur. J. 15 (2009) 2874–
2914.
Support of work by the Loker Hydrocarbon Research Institute is
gratefully acknowledged.
Appendix A. Supplementary data
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[20] H. Boehme, M. Junga, Liebigs Ann. Chem. 758 (1972) 132–142.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jfluchem.2010.07.006.