S-(4-methoxyphenyl) benzenethiosulfinate (MPBT)/ trifluoromethanesulfonic anhydride: A convenient system for the generation of glycosyl triflates from thioglycosides

Article abstract of DOI:10.1021/ol006715o

(Matrix presented) The combination of S-(4-methoxyphenyl) benzenethiosulfinate (MPBT, 1) and trifluoromethanesulfonic anhydride forms a powerful, metal-free, thiophile which readily activates thioglycosides, via glycosyl triflates, at -60°C in dichloromet

Full text of DOI:10.1021/ol006715o

ORGANIC
LETTERS
2000
Vol. 2, No. 25
4067-4069
S-(4-Methoxyphenyl)
Benzenethiosulfinate (MPBT)/
Trifluoromethanesulfonic Anhydride: A
Convenient System for the Generation
of Glycosyl Triflates from
Thioglycosides
David Crich* and Mark Smith
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received October 10, 2000
ABSTRACT
The combination of S-(4-methoxyphenyl) benzenethiosulfinate (MPBT, 1) and trifluoromethanesulfonic anhydride forms a powerful, metal-free,
thiophile which readily activates thioglycosides, via glycosyl triflates, at −60 °C in dichloromethane, in the presence of 2,6-di-tert-butyl-4-
methylpyridine. The glycosyl triflates are rapidly and cleanly converted to glycosides, upon treatment with alcohols, in good yield and selectivity.
Benzenesulfenyl triflate (PhOTf) is a superior reagent for
the activation of thioglycosides, converting them to highly
reactive glycosyl triflates in a matter of minutes at -78 °C.1,2
It has also proven to be the reagent of choice in the activation
of glycosyl xanthates in coupling reactions, activating them
rapidly at -40 °C.3 In terms of reactivity, therefore, benzene-
sulfenyl triflate is clearly preferable to other common metal-
free systems for the activation of thioglycosides such as
dimethyl(methylthio)sulfonium triflate (DMTST),4 methyl-
sulfenyl triflate (MeSOTf),5 benzeneselenyl triflate (Ph-
SeOTf),6 and iodonium dicollidine perchlorate (IDCP)7 which
are typically used at significantly higher temperatures and
require much longer reaction times. Nevertheless, this potent
electrophile has not been widely adopted in glycosylation
chemistry. Most likely, the need to prepare benzenesulfenyl
triflate in situ from benzenesulfenyl chloride and silver
triflate, neither of which are ideal reagents, is in large part
responsible for its lack of appreciation in all but a few
laboratories. Indeed, benzenesulfenyl chloride itself is not
commercially available owing to its limited shelf life and
obnoxious odor, whereas silver triflate is light- and water-
sensitive as well as expensive. Consequently we have been
searching for a more convenient preparation of benzene-
sulfenyl triflate (or its equivalent) with a view to making
this reagent more readily available and to facilitating ongoing
projects in our own laboratory.
We report here that the combination of S-(4-methoxy-
phenyl) benzenethiosulfinate (MPBT, 1) and trifluoromethane-
(1) Crich, D.; Sun, S. J. Am. Chem. Soc. 1998, 120, 435-436.
(2) Crich, D.; Sun, S. Tetrahedron. 1998, 54, 8321-8348.
(3) Martichonok, V.; Whitesides, G. M. J. Org. Chem. 1996, 61, 1702-
1706.
(4) Fugedi, P.; Garegg, P. J. Carbohydrate Res. 1986, 149, C9-C12.
(5) Dasgupta, F.; Garegg, P. J. Carbohydrate Res. 1988, 177, C13-
C17.
(6) Ito, Y.; Ogawa, T. Tetrahedron Lett. 1988, 29, 1061-1064.
(7) Veeneman, G. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31, 275-
278.
10.1021/ol006715o CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/11/2000

sulfonic anhydride fulfills most of our criteria. MPBT (1) is
readily prepared, crystalline, and stable, while trifluoro-
methanesulfonic anhydride is a common commercial reagent.
The system is metal-free and converts thioglycosides to
glycosyl triflates very conveniently in a matter of minutes
at -60 °C.
(-78 °C) probe of the spectrometer and the 1H and 19F NMR
spectra were recorded. To our surprise, the 19F spectrum
displayed only two peaks, corresponding to Tf2O and the
formation of a species indistinguishable from TfO- (at δ 4.26
1
and δ -3.07, respectively). The low-temperature H NMR
spectrum of the same reaction mixture showed that not all
the thiosulfinate 2 had been consumed. Nevertheless, in a
further low-temperature NMR experiment, the thioglycoside
7 was shown to be converted to the corresponding glycosyl
triflate 8 (Scheme 2).11
Scheme 2
Our investigation of the thiosulfinates was based on earlier
work from the Oae group in which it was established that
thiosulfinate 2 reacts with trifluoroacetic anhydride at -20
°C to give a complex mixture of products. The mixture was
thought to contain the sulfenyl carboxylate 3 and sulfinyl
carboxylate 4 and resulted, ultimately, in the formation of
diphenyl disulfide 5 (Scheme 1).8
This series of observations led us to the conclusion that
the reaction of the thiosulfinate 2 with Tf2O at low temper-
ature is an equilibrium (Scheme 3) and perhaps stops after
Scheme 1
Scheme 3
We reasoned that the more reactive Tf2O would react
rapidly with 2 at lower temperatures and provide two mole-
cules of benzenesulfenyl triflate cleanly. To investigate this
proposal, we prepared the thiosulfinates 1, 2, and 6 according
to a standard literature procedure involving reaction of the
sulfinyl chloride with the appropriate thiol, followed by
recrystallization.9,10 It is noteworthy that 1, 2, and 6 are all
crystalline, odorless, and stable on the laboratory bench at
room temperature when stored in standard amber bottles.
In an exploratory NMR tube experiment, a solution of the
thiosulfinate 2 in CD2Cl2, cooled to -78 °C, was treated
with Tf2O. The tube was rapidly inserted into the precooled
the initial sulfonylation. This equilibrium may then be
displaced in the forward direction by the addition of a trap
for the thiophile, i.e., a thioglycoside.
Attempts to shift this equilibrium by substituting this
reagent led to the realization that optimum results were
obtained with 1, with 6 having comparable reactivity. At the
present time it is not clear whether the actual electrophile
generated is benzenesulfenyl triflate or a species such as 9.
What is clear, however, is that a readily available, metal-
free, preparation of a potent thiophile from two stable
reagents is at hand.
To demonstrate the synthetic potential of these systems,
a series of couplings were carried out with the most reactive
system, namely, 1 and Tf2O. The results of these experiments
are presented in Table 1. As can be seen the â:R ratio
observed was comparable to those obtained by both the
sulfoxide and the thioglycoside methods.1,2,12 The greater
reactivity of MPBT (1) over the thiosulfinate 2 can clearly
be seen from the reaction of the thiomannoside 7 with the
acceptor 14, whereby only 30% of the starting thiomannoside
7 was converted to the desired â-mannoside when the
(8) Morishita, T.; Furukawa, N.; Oae, S. Tetrahedron. 1981, 37, 3115-
3120.
(9) Backer, H. J.; Kloosterziel, H. Recl. TraV. Chim. Pays Bas. 1954,
73, 129-139.
(10) Preparation of S-(4-Methoxyphenyl) benzenethiosulfinate (MPBT,
1): Sulfuryl chloride (2.75 mL, 34.35 mmol) was slowly added to a mixture
of diphenyl disulfide (2.50 g, 11.45 mmol) and acetic anhydride (2.16 mL,
22.9 mmol) cooled to 0 °C. After 20 min of stirring, the orange solution
was concentrated under reduced pressure. The residue (PhSOCl) was diluted
with Et2O (25 mL) and slowly added to a solution containing 4-methoxy-
benzenethiol (2.80 mL, 22.9 mmol) and pyridine (2.04 mL, 25.2 mmol) in
Et2O (25 mL) at room temperature under an argon atmosphere. After 20
min of stirring, the mixture was quenched by the addition of 1 M H2SO4
(40 mL). The organics were separated, washed with brine, dried (MgSO4),
and concentrated under reduced pressure. Crystallisation from ether-
petroleum ether (bp 40-60 °C) gave the title product (4.36 g, 72%) as a
pale yellow solid: mp 76-77 °C, lit.9 mp 77-78 °C; 1H NMR (300 MHz,
CDCl3) δ 3.82 (3 H, s, OMe), 6.87 (2 H, d, J ) 9 Hz, 2 × ArH), 7.40 (2
H, d, J ) 9 Hz, 2 × ArH), 7.45-7.48 (3 H, m, 3 × ArH), and 7.60-7.63
(2 H, m, 2 × ArH); 13C NMR (75 MHz, CDCl3) δ 55.6, 114.9, 119.6,
124.4, 129.0, 131.5 144.2, and 161.9.
(11) The R-mannosyl triflate 7 can be readily identified by the appearance
of a broad singlet at δ 6.20 attributed to the anomeric proton in the 1H
NMR spectrum and from a signal at δ 0.01 in the 19F NMR spectrum.2
(12) Crich, D.; Cai, W. J. Org. Chem. 1999, 64, 4926-4930.
4068
Org. Lett., Vol. 2, No. 25, 2000

Table 1. Coupling Reactions of Thioglycosides
1
1
a Isolated yield. b Ratio determined from the integrals in the crude H NMR spectra. c Determined from the integrals in the crude H NMR spectrum.
reaction was performed in the presence of the thiosulfinate
2 (entries 5 and 6).13
In summary, treatment of MPBT (1) with Tf2O furnishes
an electrophile comparable in activity to PhSOTf, though
attempts to identify the electrophile have so far proved
unsuccessful. The combination of MPBT (1) with Tf2O is a
new and powerful method for the in situ formation of
glycosyl triflates from thioglycosides. Moreover, this method
has allowed access to â-mannosides and R-glucosides in
good yield and selectivity. MPBT (1) is crystalline and stable
and can be readily prepared in good yield from inexpensive
starting materials.
(13) General experimental protocol for the preparation of glycosides:
To a stirred solution containing the thioglycoside (0.185 mmol), MPBT (1,
0.231 mmol), DTBMP (0.462 mmol), and activated 3 Å powdered sieves
in dichloromethane (5 mL) at -60 °C under argon is added Tf2O (0.370
mmol). After 5 min, a solution of the glycosyl acceptor (0.370 mmol) in
dichloromethane (2 mL) is added. The reaction mixture is stirred for 2 min
at -60 °C and then quenched with methanol, warmed to room temperature,
filtered, washed with saturated aqueous NaHCO3, followed by brine, dried
(MgSO4), and concentrated under reduced pressure. The glycosides are
isolated by chromatography on silica gel.
Acknowledgment. We thank NIGMS for support of this
work (GM-57335).
OL006715O
Org. Lett., Vol. 2, No. 25, 2000
4069