Exploratory study of the reaction of bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor reagent) with diaryl sulfoxides: Novel routes to Ar2SF2 and Ar2SF(OTf) via sulfoxide activation

Article abstract of DOI:10.1016/S0022-1139(02)00058-1

Neither bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor reagent) nor HF/pyridine alone can fluorinate diaryl sulfoxides. S-fluorination can be effected by activating the sulfoxide via protonation with HF/pyridine (70:30) to form sulfoxonium ions in

Full text of DOI:10.1016/S0022-1139(02)00058-1

Journal of Fluorine Chemistry 115 (2002) 169±173
Exploratory study of the reaction of bis(2-methoxyethyl)aminosulfur
tri¯uoride (Deoxo¯uorTM reagent) with diaryl sulfoxides: novel
routes to Ar2SF2 and Ar2SF(OTf) via sulfoxide activation
Kenneth K. Laali*, Gennady I. Borodkin1
Department of Chemistry, Kent State University, Kent, OH 44242, USA
Received 25 January 2002; received in revised form 25 January 2002; accepted 7 March 2002
Abstract
Neither bis(2-methoxyethyl)aminosulfur tri¯uoride (Deoxo¯uorTM reagent) nor HF/pyridine alone can ¯uorinate diaryl sulfoxides. S-
¯uorination can be effected by activating the sulfoxide via protonation with HF/pyridine (70:30) to form sulfoxonium ions in equilibrium
which are then S-¯uorinated in situ with Deoxo¯uorTM to give Ar2SF2 compounds. Conversions depend strongly on steric factors and the
reactions require the use of excess Deoxo¯uorTM and HF/pyridine. NMR data for the resulting diarylsulfur di¯uorides are gathered and
discussed. Sulfoxide activation via diaryl (tri¯oxy) sulfonium tri¯ate generated in situ from Ar2SO with tri¯ic anhydride at low temperature
represents another strategy for S-¯uorination with Deoxo¯uorTM to generate Ar2S(OTf)F. # 2002 Elsevier Science B.V. All rights reserved.
Keywords: Bis(2-methoxyethyl)aminosulfur tri¯uoride; Diaryl sulfoxides; HF/pyridine
1. Introduction
Ph2SF2, whereas with Me2S the outcome was a-¯uorination
(as with DAST and its analogues). a-Fluorosul®des are also
formed from sul®des by ¯uorination with various NF reagents
[6]. Formation of a-¯uorosulfoxides and a-¯uorosulfones
from sulfoxides and sulfones have also been documented
in some cases [6]. Ruppert synthesized Ph2SF2 from Ph2S by
direct ¯uorination or by reaction with AgF2 [9].
The recent discovery of bis(2-methoxyethyl)aminosulfur
tri¯uoride (Deoxo¯uorTM reagent), (MeO±CH2CH2)2NSF3
1 by Lal et al. [1,2] as a more selective and thermally stable
analogue of DAST (Et2NSF3) has opened up a new chapter
in selective ¯uorination.
By and large the area of greatest focus in ¯uorination with
1 (as with DAST itself and its analogues) has been in
carbonyl and thiocarbonyl compounds, and in comparison
studies dealing with ¯uorination of sulfoxides and sul®des
have been rather limited [2±6].
When at least one a-hydrogen is present, the outcome of
¯uorination with DAST is the formation of a-¯uorosul®des
with both ArS(=O)R and ArSR. Reagent 1 reacts in a similar
fashion and the reactions are catalyzed by SbCl3 or ZnI2. It has
been suggested that this transformation occurs via a ¯uoro-
Pummerer type rearrangement [2,7]. However, there are no
reported studies which examined the interaction of 1 or DAST
with diaryl sulfoxides under Lewis or protic acid catalysis.
Janzen and co-workers [8] had earlier reported on the
oxidative ¯uorination of Ph2S 2 with XeF2 leading to
Over a decade ago, we reported a one-pot synthesis of
symmetrical and non-symmetrical (mixed) diaryl sulfoxides
by reacting simple arenes with FSO3HÁSbF5 (1:1)/SO2,
‡
proceeding via in situ generation of ArSO and its arylation
[10a]. Diaryl sulfoxide formation was accompanied by
minor formation of the sul®de whose origin was traced to
‡
the O-protonated sulfoxonium ions (Ar2SOH ) and the
‡
dimeric mono- and disulfonium ions (Ar2S ±O±S(OH)Ar2
‡
‡
and Ar2S ±O±S Ar2) as key intermediates [10].
Independent protonation of diaryl sulfoxides with
FSO3HÁSbF5 (1:1)/SO2 and quenching furnished the sul-
®des. Low temperature reaction of authentic ditolyl sulf-
oxide 3 with HFÁSbF5 (1:1)/SO2 followed by quenching
gave Ar2S (90%) and a by-product proposed to be Ar2SF2.
Independent reaction of Ar2SO with SbF5 in Freon-113
solvent did not give Ar2S but gave the same by-product
in increased amounts (19%).
* Corresponding author. Tel.: ‡1-330-6722988; fax: ‡1-330-6723816.
E-mail address: klaali@kent.edu (K.K. Laali).
1 Visiting Scientist on leave from Novosibirsk Institute of Organic
In an effort to broaden the scope of S-¯uorination in
Ar2SO, we report here an exploratory study on the reactions
of various diaryl sulfoxides with Deoxo¯uorTM and show
Chemistry, Russia.
0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 0 5 8 - 1

170
K.K. Laali, G.I. Borodkin / Journal of Fluorine Chemistry 115 (2002) 169±173
that HF/pyridine and tri¯ic anhydride can be used to activate
the sulfoxide towards S-¯uorination.
In another experiment, p-chlorophenyl sulfoxide 4 was
allowed to react with 1 in benzene solvent initially at RT for
several hours and subsequently under re¯ux for 30 min.
NMR analysis (in CDCl3 following the removal of benzene)
indicated ꢀ1% conversion to the diaryl sulfur di¯uoride
(d 19F À13.9, see further for additional examples). The
reported ¯uorine chemical shift for Ph2SF2 is d À5.43 (in
CD2Cl2 with added ¯uoride scavenger (TMS)2NH) [8] (in
[9], the 19F chemical shift for Ph2SF2 was reported at d 6.8).
In addition, the 19F NMR spectrum exhibited a major broad
peak at d À133.7 (plus those d À152.5 and d 56.2). See also
further for comparative and tabulated data (Tables 1 and 2).
2. Results and discussion
2.1. Reaction of Ar2SO with DeoxofluorTM
1
2.1.1. Preliminary studies
Sample of 1 received from Air Products had a purity of ca.
95% (estimated from 1H NMR). Its 19F NMR spectrum
(using internal CFCl3 as reference and CDCl3 as solvent)
exhibited a major broad peak centered at d 33.4 for the
(MeOCH2CH2)2N±SF3 (lit.1a: d 40) and small sharp peaks at
À152.5 (in correct range for BF4À!), 56.2 and 75.0 ppm (HF
is a reasonable candidate).
2.1.2. Protic activation
Looking back at our previous studies of diaryl sulfoxides
in superacids [10], protic activation to generate sulfoxonium
ions and subsequent S-¯uorination with 1 appeared a more
reasonable approach. For this purpose, commercially avail-
able HF/pyridine (70:30 (w/w)) seemed most convenient.
At the onset, in a control experiment, when p-ditolyl
sulfoxide 3 was allowed to react with HF/pyridine (four-
fold excess) for 40 h in CH2Cl2 at RT in the absence of 1, the
NMR spectrum of the reaction mixture (after venting off the
HF) was essentially that of unreacted sulfoxide.
Reaction of 3 with 1 in CH2Cl2 at room temperature (RT)
was extremely sluggish. After 45 h stirring at RT, >98% of
the sulfoxide was still unreacted (1H and 19F NMR).
In subsequent experiments, the catalytic effects of Lewis
acids B(C6F5)3 and SbCl3 were explored in RT reactions in
CH2Cl2 solvent using sulfoxide to Deoxo¯uorTM to Lewis
acid molar ratios of 1:2:0.1, respectively. With B(C6F5)3
1
after 18 h, tiny new resonances appeared in the H NMR
spectrum and the ¯uorine NMR spectrum showed small
resonances which matched closely the reported values for
[B(C6F5)3F]À [11] in addition to a peak at d À129.6 and the
usual impurities (at d À151.4 and 56.3). With SbCl3 after 2
days a mixture of products were formed but the total
conversion did not increase beyond 10%.
Several experiments were then performed using reagent 1
in which the ratio of the Deoxo¯uorTM and HF/pyridine was
varied. The reactions were analyzed directly by NMR after
venting off the HF under a fast stream of dry nitrogen. These
studies illustrated that maximum conversions to Ph2SF2
could be achieved when both Deoxo¯uorTM and the HF/
Table 1
Fluorine resonances observed in different reactions
Entry
Ar2SO
Ar2SO:DeoxofluorTM:HF/pyridine
19F NMR resonances
1
2
3
4
2
2
1:1.1:0
À133.7 (major); À152.5; À13.9 (Ar2SF2); 56.2
À130.0 (major, ex); À128 (ex); À153.2; À146.3; À78.7
À165.8 (major); À129.6; À152.1 (trace); À78.7 (trace); À14.2
(Ar2SF2) (trace); 37.7 (trace)
1:1.4:2.8
1: 1.3:1.4
4
5
2
2
3
4
5
6
7
1:2.2:1.2
1:3.2:3.4
1:3.2:3.3
1:3.3:3.4
1:3.4:5.1
1:3.8:3. 8
1:2:2.7
À152.0; À145.0; À129.4 (major); À128.5
À166.2 (major); À152.6 (trace); À14.0 (Ar2SF2); 37.7 (trace)
À168.6 (major); À151.7; À14.0 (Ar2SF2); 73.7 (trace)
À166 (major, ex); À151.6; À129.5 (ex); À14.4 (Ar2SF2); 37.7 (trace)
À155.0; À14.1 (Ar2SF2); 37.4; 56.4; 60.4; 75.0
À153.3 (br); À129.5; À78.9
6
7
8
9
10
À160.5 (br); À151.8; À129.2 (major)
Table 2
Multinuclear NMR Data for Ar2SF2 compounds
Compound
1H
19F
13C
Ph2SF2
7.56 (m); 7.51 (m); 7.34 (m)
À14.2
À14.1
À14.4
À14.2
142.8 (br, C-1); 130.6; 129.4 (br); 128.7 (br, C-2/C-6)
144.9 (br, C-1); 142.0 (br); 131.1; 129.5 (C-2/C-6); 21.2 (Me)
147.7 (br, C-1); 129.5; 129.2; 125.0 (C-2/C-6)
146.9 (br, C-1); 138.8; 133.7; 130.1; 127.3 (C-2/C-6) 21.5
and 20.1 (Me)
(4-MeC6H4)2SF2
(4-ClC6H4)2SF2
(2,4-Me2C6H3)2SF2
7.60 (d, J ˆ 8.5 Hz); 7.52 (d, J ˆ 8.5 Hz); 2.49 (s)
7.88 (d, J ˆ 9 Hz); 7.51 (d, J ˆ 9 Hz)
7.89 (d, J ˆ 8.5 Hz); 7.26 (br, s); 7.22
(d, J ˆ 8.5 Hz) 2.44 and ca. 2.46 (Me)

K.K. Laali, G.I. Borodkin / Journal of Fluorine Chemistry 115 (2002) 169±173
171
Fig. 1. Substrates examined.
pyridine were used in excess (three molar equivalents),
whereas employing slight excess of either one resulted in
little or no conversion. Thus, optimal conversions were
achieved with Ar2SO:1:HF/pyridine ˆ 1:3.2:3.4, respec-
tively.
by multinuclear NMR. Under these conditions, conversion to
Ar2SF2 was ꢀ90% for 2 and 93% for 3. Introduction of p-Cl
groups (4) reduced the conversion to 27%. Introduction of
ortho methyl groups (5) reduced the yield of Ar2SF2 to
ꢀ10%.2
The 19F resonance for the polyhydrogen ¯uoride species
in HF/pyridine (70:30) has been reported at 188 ppm (a
quintet at À60 8C; each ¯uorine is surrounded by four
hydrogens) [12]. A peak in this range is no longer observed
in the 19F NMR spectrum of mixtures of Ar2SO, Deoxo-
Based on AM1 minimizations the dihedral angle between
‡
‡
the two aryl rings in Ph2SOH (1H ) is 46.68 and does not
change to any noticeable extent when para substituents are
‡
‡
‡
introduced (as in 3H and 4H ). Steric crowding in 5H and
‡
6H causes one aryl ring to twist out of plane leading to
¯uorTM and HF/pyridine. Table 1 sketches a summary of 19
F
dihedral angles of À40.4 and À71.08, respectively. The
observed reactivity pattern re¯ects both the stability of the
sulfoxonium ion and steric problems associated with nucleo-
philic attack by Deoxo¯uorTM on the sulfoxonium ion. The
followingmechanisticscenarioseemsreasonable(Scheme1).
The NMR data for the resulting Ar2SF2 compounds are
summarized in Table 2. Notable features are minimal
sensitivity of the ¯uorine chemical shifts to substituent
effects, observation of small long-range C/F couplings in
the 13C spectra, and the deshielding of the proton reso-
nances relative to the starting sulfoxides. The 2J C/F and 3J
C/F couplings for Ph2SF2 were reported as 4.5 and 6.7 Hz,
respectively [8] (in [9], they are 4.5 and 4.5 Hz). In
Deoxo¯uorTM/HF/pyridine system dynamic ¯uorine
exchange averages these small couplings leading to broad-
ening of the ipso and ortho ring carbons. Minimal sensi-
tivity of the ¯uorine chemical shifts to substituent effects
was previously noted by Furin et al. [13] in XC6H4SF3
resonances observed at RT in different reactions. In entry 2,
the major resonance from Deoxo¯uorTM/HF/pyridine sys-
tem appears around À130 ppm and dynamic exchange is
apparent between this signal and a nearby smaller peak at d
À128. In other entries, the major signal is dramatically
up®eld shifted and appears in the À166 to À169 ppm range
depending on the reaction. It is conceivable that thesÀe
resonances are due to Deoxo¯uorTM±sulfeniminium/HF2
equilibrium, analogous to equilibrium ¯uoride removal from
DAST by ZnI2 proposed by McCarthy et al. [7a].
2.1.3. Survey of diaryl sulfoxides
Availability of several diaryl sulfoxides synthesized via
the previously developed one-pot procedure [10a] provided
the opportunity to examine structural effects on the course of
Ar2SO ¯uorination using 1/HF/pyridine. Substrates exam-
ined were diphenyl sulfoxide 2, p-tolyl sulfoxide 3, p-
chlorophenyl sulfoxide 4, 2,4-dimethylphenyl sulfoxide 5,
2,4,6-trimethylphenyl sulfoxide 6 and pentamethylphenyl
tolyl sulfoxide 7 (Fig. 1).
2 The following experimental observations are noteworthy:
(i) yields depend critically on the structure of the diaryl sulfoxide;
For these reactions, excess 1 (3±3.8 molar equivalent)
and excess HF/pyridine were employed (3.4±5.1 molar
equivalent). Whereas parent Ph2SF2 is reasonably stable
and was previously isolated [8,9], substituted Ar2SF2 appear
to be considerably less stable. In our hands, attempted
isolation of (4-MeC6H4)2SF2 by crystallization or small-
scale column chromatography led to decomposition. It was,
therefore, decided to analyze the reaction mixtures directly
(ii) the experiments were performed under very similar reaction
conditions;
(iii) in selected cases NMR monitoring of the progress of the reactions
clearly showed that the resonances for Ar2SO decrease and new
peaks for the product appear and increase in the mixture (for
confirmation, in some cases, authentic Ar2SO was added into the
NMR tube);
(iv) in the absence of HF/pyridine the fluorine resonance assigned to
Ar2SF2 was not observed.

172
K.K. Laali, G.I. Borodkin / Journal of Fluorine Chemistry 115 (2002) 169±173
3. Experimental
Phenyl sulfoxide 2, p-chlorophenyl sulfoxide 4 and HF/
pyridine were high purity commercial samples (Aldrich)
which were used as received. Methylene chloride (Aldrich)
was distilled from P2O5 and benzene was distilled over
sodium.
Diaryl sulfoxides 3, 5, 6 and 7 were high purity samples
synthesized as part of our previous study [10a]. Deoxo-
¯uorTM (Air Products) was used as received. Reactions
involving HF/pyridine were carried out in Nalgene bottles
under argon whereas others were performed in Schlenk
tubes (under argon). NMR spectra were recorded in CDCl3
at RTon a Varian INOVA 500 MHz instrument using a 5 mm
broad-band probe. Proton and carbon chemical shifts are
relative to internal TMS or CDCl3 (d 77.23) and ¯uorine
shifts are relative to internal CFCl3. AM1 minimizations
were carried out using Hyperchem Pro. Release 6 program.
Scheme 1.
(X ˆ H, F, CF3). With 6 and 7, a combination of steric
crowding to S-¯uorination by Deoxo¯uorTM and increased
stability of the derived benzenium ions (ipso attack com-
peting with sulfoxonium ion formation), favored dearyla-
tion. Thus, for the reaction of 6 with 1 and HF/pyridine
major ¯uorine resonances are seen at d À153.3 (br) and d
À129.5 (¯uoromesitylene) and for 7 at d À164.2 and d
À129.2 (¯uoropentamethylbenzene) with corroboratory
evidence from the proton spectra.
3.1. Reaction of Ar2SO with deoxofluor in HF/pyridine
(typical run)
2.1.4. Sulfoxide activation by triflic anhydride (Tf2O)
Tri¯oxysulfonium tri¯ate is formed in situ when DMSO
or Ph2SO are reacted with Tf2O at low temperature, and
subsequently undergo nucleophilic attack at sulfur by a
variety of nucleophiles [14]. In the context of present study,
To solution of phenyl sulfoxide (102 mg, 0.5 mmol) in dry
CH2Cl2 (charged into Nalgene bottle) was added under an
argon atmosphere the Deoxo¯uorTM reagent (331 mg,
1.49 mmol) followed by HF/pyridine (258 mg), and the
mixture was stirred at RT for 40 h. Then a stream of dry
nitrogen was bubbled through the reaction mixture to vent
off the HF and to remove most of the solvent. The residue
was dissolved in CDCl3 and analyzed directly by multi-
nuclear NMR.
‡
we have found that tri¯oxysulfonium tri¯ate Ph2S ±OTf
OTfÀ formed at low temperature in dry methylene chloride
reacts with Deoxo¯uorTM 1 to form Ph2SF(OTf) which
appears as a white solid when the solvent and most of the
unreacted Tf2O are removed. The 19F NMR spectrum of the
residue dissolved in CDCl3 exhibits one resonance at d 11.5
together with a peak at d À78.9 for the residual Tf2O
(possibly there is intermolecular OTf exchange between
Ph2SF(OTf) and residual Tf2O which is fast at RT). Based
on the 1H NMR spectrum the conversion is about 90% based
on the sulfoxide. The ring protons for Ph2SF(OTf) (d 8.06
(d), 7.97 (t) and 7.83 (d)) are more deshielded relative to
Ph2SF2.
3.2. Reaction of Ar2SO with DeoxofluorTM in benzene
solvent without HF/pyridine
Sulfoxide 3 (99 mg, 0.37 mmol) was charged into small
Schlenk tube and dry benzene (ꢀ10 ml) was added (sulf-
oxide is only partly soluble), followed by Deoxo¯uorTM
(92 mg, 0.42 mmol) under argon. The resulting mixture was
stirred at RT for 3 h (white solution) and then re¯uxed for
30 min (yellow solution). The solvent was removed under
vacuum and the residue was taken up in CDCl3 and analyzed
directly by multinuclear NMR (Table 2).
In summary, we have shown that S-¯uorination of diaryl
sulfoxides to form Ar2SF2 can be effected with reagent 1,
following sulfoxide activation with HF/pyridine. It is essen-
tial that both Deoxo¯uorTM and HF/pyridine are used in
excess. The conversions are strongly in¯uenced by the
structure of the diaryl sulfoxide substrates and the yields
decrease as steric crowding around the sulfoxonium moiety
increases. The resulting Ar2SF2 compounds were not stable
enough for isolation and could only be analyzed in the
mixture by multinuclear NMR. The 19F NMR spectra for
the mixtures of Ar2SO/Deoxo¯uorTM/HF/pyridine give evi-
dence for equilibrium ¯uoride ion exchange and depend
strongly on the ratios of these reagents. It has also been
shown that Deoxo¯uorTM reagent reacts with diphenyl(tri-
¯oxy)sulfonium tri¯ate generated in situ from Ph2SO and
Tf2O to generate Ph2S(OTf)F.
3.3. Reaction of Ph2SO with DeoxofluorTM and triflic
anhydride Tf2O
The sulfoxide (111.7 mg, 0.55 mmol) was charged into a
small Schlenk tube and dissolved in dry methylene chloride.
The tube was cooled to dry ice/acetone temperature and Tf2O
(1.154 g, 4.09 mmol) was added followed by Deoxo¯uorTM
(240.3 mg, 1.08 mmol) to form a yellow solution. The tem-
perature was then slowly raised while stirring. At À30 8C a
white solid was formed which subsequently disappeared over-
time upon raising temperature under stirring, to eventually
produce a yellow solution at RT. The solvent and excess Tf2O

K.K. Laali, G.I. Borodkin / Journal of Fluorine Chemistry 115 (2002) 169±173
173
[4] R.P. Singh, U. Majumder, J.M. Shreeve, J. Org. Chem. 66 (2001)
6263.
were removed under vacuum, the residue (white solid) was
taken up in CDCl3 and analyzed directly by NMR.
[5] W. Dmowski, in: B. Baasner, H. Hagemann, J.C. Tatlow (Eds.),
Methods of Organic Chemistry (Houben-Weyl), Vol. E-10a, Georg
Thime, New York (Chapter 8).
Acknowledgements
[6] S.C. Taylor, C.C. Kotoris, G. Hum, Tetrahedron 55 (1999) 12431.
[7] (a) J.R. McCarthy, N.P. Peet, M.E. LeTourneau, M. Inbasekaran, J.
Am. Chem. Soc. 107 (1985) 735;
We are grateful to Dr. Robert Syvret, Fluorine Technology
Center, Air Products and Chemical Inc. for a sample of
Deoxo¯uorTM. This work was supported in part by the NCI
of NIH (1R15 CA 78235-01A1) in the context of selective
¯uorination of arenes.
(b) S.F. Wnuk, M.J. Robins, J. Org. Chem. 55 (1990) 4757;
(c) M.J. Robins, S.F. Wnuk, J. Org. Chem. 58 (1993) 3800.
[8] R.K. Marat, A.F. Janzen, Can. J. Chem. 55 (1977) 3031;
X. Ou, A.F. Janzen, J. Fluorine Chem. 101 (2000) 279.
[9] I. Ruppert, Chem. Ber. 112 (1979) 3023.
[10] (a) K.K. Laali, D.S. Nagvekar, J. Org. Chem. 56 (1991) 1867;
(b) K.K. Laali, J.J. Houser, J. Phys. Org. Chem. 5 (1992) 244.
[11] D. Naumann, W. Tyrra, Chem. Commun. (1989) 47.
[12] G.A. Olah, J.T. Welch, Y.D. Vankar, M. Nojima, I. Kerekes, J.A.
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