Silver(I) oxide-mediated facile and practical sulfonylation of alcohols

Article abstract of DOI:10.1016/S0040-4039(01)01913-X

Primary and secondary alcohols were efficiently sulfonylated in the presence of silver(I) oxide and potassium iodide in dichloromethane. The sulfonylation occurs under mild, neutral reaction conditions. The ease of isolation of the final product presents a marked advantage over the known methodologies.

Full text of DOI:10.1016/S0040-4039(01)01913-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8781–8783
Silver(I) oxide-mediated facile and practical sulfonylation
of alcohols
Abderrahim Bouzide,*,† Nicolas LeBerre and Gilles Sauve´*
INRS-Institut Armand Frappier, 531, Boulevard des prairies, Laval, QC, Canada H7V 1B7
Received 15 August 2001; revised 8 October 2001; accepted 9 October 2001
Abstract—Primary and secondary alcohols were efficiently sulfonylated in the presence of silver(I) oxide and potassium iodide in
dichloromethane. The sulfonylation occurs under mild, neutral reaction conditions. The ease of isolation of the final product
presents a marked advantage over the known methodologies. © 2001 Elsevier Science Ltd. All rights reserved.
The sulfonates are very important intermediates in
organic synthesis. They are usually prepared by con-
densing the corresponding alcohols with sulfonating
agents using pyridine or triethylamine1 as a base.
Recently, tetramethylalkyldiamine was reported to be
an efficient base for sulfonylation reactions.2 Other
sulfonylations were achieved in aqueous sodium
hydroxide3 when the alcohols are sufficiently
hydrophilic. Ring opening of dibutylstannylene acetal
with sulfonyl chloride is another method for the mono-
sulfonylation of diols.4
fonates are often isolated pure after a simple filtration;
if purification is required, a short column suffices to
yield a clean product.
General method for the sulfonylation of alcohols with
Ag2O: To a stirred solution of alcohol (1 mmol) in
CH2Cl2 (4 mL) was added freshly prepared Ag2O6
(1.5–2.0 mmol), TsCl (1.1–2.0 mmol) and KI (0.2–2
mmol). The mixture was then stirred at room tempera-
ture or at 40°C until complete consumption of the
alcohol (Table 1, conditions A, B and C). The reaction
was filtered and the solvent evaporated. The product
was further purified by flash chromatography. The
results are summarized in Table 1.
Silver(I) oxide (Ag2O) is a well known reagent for the
alkylation of alcohols in the presence of alkyl halide.5,6
However, sulfonylation of alcohols with Ag2O was yet
to be reported in the literature. Herein, we would like
to report that Ag2O is an excellent reagent to promote
sulfonylation of alcohols and diols in the presence of
sulfonyl chloride and a catalytic amount of potassium
iodide (KI) (Scheme 1).
In the absence of KI, the alcohols react very slowly
with the sulfonating agent and the yields are generally
low. For example, the methoxyethanol, when treated
with tosyl chloride (TsCl) and Ag2O in dichloro-
methane, the corresponding tosylate was isolated,
after 36 h, in only 42% yield.‡ However, when a
catalytic amount of KI was added to the reaction
medium, the yield increased to 60% within 5 h (entry 1,
condition A). The KI accelerates the reaction rate by
converting in situ the tosyl chloride into the much more
reactive tosyl iodide.§ The yield was significantly
improved when the reactions were heated at 40°C (con-
The Ag2O promoted sulfonylation described herein pre-
sents several advantages over the known methods. For
instance, the reaction proceeds in neutral media and
necessitates no work-up. Moreover, the reaction does
not produce any chloride by-product2 and the sul-
O
RO S R1
O
O
R1 S Cl
O
Ag2O, KI
CH2Cl2
ROH
‡ No reaction took place in the absence of Ag2O.
Scheme 1.
§ In addition to its role as an insoluble base and as a halide acceptor,
Ag2O probably facilitated the Finklestein-like reaction with KI;
only starting material was recovered from the reaction of TsCl with
KI in CH2Cl2 after 2 days. However, addition of Ag2O to a mixture
of TsCl and KI resulted in the disappearance of starting material
* Corresponding authors. E-mail: abouzide@invenux.com
† Present address: Invenux Inc., 6840, N. Broadway, Suite F, Denver,
CO 80221, USA.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01913-X

8782
A. Bouzide et al. / Tetrahedron Letters 42 (2001) 8781–8783
Table 1. Ag2O-mediated sulfonylation of alcohols
Entry
Alcohol
Conditionsa
Sulfonate
Yield
A
B
60%
94%
95%
MeO
1
2
MeO
BnO
OTs
OTs
OH
OH
BnO
BnO
C
3
12%
56%
96%
BnO
BnO
BnO
OH
OTs
A
B
C
BnO
BnO
4
5
90%
C
OH
OTs
94%
A
O
O
OH
O
O
O
OTs
O
6
7
99%
92%
A
BnO
TsO
OTs
OTs
BnO
HO
OH
Cb
OTs
OH
8
91%
98%
91%
HO
HO
O
OH
Ab
Ab
C
TsO
TsO
O
O
OTs
O
9
O
O
OH
10
OH
OH
OTs
O
O
88%
89%
C
C
11
OTs
OH
OTs
12
13
O
O
O
O
TsO
HO
93%
B
C
OEt
OEt
14
66%
92%
OH
OTs
ONs
O
O
OH
OMe
OMe
Ac
Ac
MeO
BnO
15
16
MeO
BnO
O
O
91%
O
OMs
O
OH
a Conditions: A: Ag2O (1.5 equiv.), TsCl (1.1 equiv.), KI (0.2 equiv.), 20°C, B: Ag2O (1.5 equiv.), TsCl (1.1 equiv.), KI (0.2 equiv.), 40°C, C: Ag2O
(2.0 equiv.), TsCl (2.0 equiv.), KI (2.0 equiv.), 40°C. b Reagent quantities of condition A were doubled. c NsCl and MsCl were used as
sulfonating agent.
dition B). In some case as in entry 3, the use of 2 equiv.
of reagent afforded high yields of the sulfonate (condi-
tions C). On the other hand, condition A was enough
to convert oligoethylene glycols to their corresponding
tosylates in excellent yields (entries 5–9). Secondary
tosylates (entries 12–14) were also obtained in high
yields. Other sulfonating agents such as para-nitroben-
zenesulfonyl chloride (NsCl) and methanesulfonyl chlo-
ride (MsCl) gave excellent yield of the corresponding
sulfonate (entries 15 and 16).
Since the reaction does not require any aqueous work-
up, the transformation of hydroxyl groups into other
functionalities can be achieved straightforward without
isolating the intermediates. For example, treatment of
triethylene glycol under the present conditions followed
1) TsCl (2.2 eq), Ag2O (3 eq)
KI (0.2 eq), CH2Cl2
N3
O
O
N3
HO
O
O
OH
2) NaN3, DMF, 80oC
Scheme 2.

A. Bouzide et al. / Tetrahedron Letters 42 (2001) 8781–8783
8783
by an SN2 displacement of the ditosylate with sodium
azide afforded the corresponding diazide in 85% over-
all yield (Scheme 2).
Coll. Vol. 3, p. 366; (b) Fieser, L. F.; Fieser, M.
Reagents for Organic Synthesis; Wiley: New York, 1967;
Vol. 1, p. 1179; (c) Sandler, S. R.; Karo, W. Organic,
Functional Group Preparations; Academic: New York,
1983; Vol. 1, p. 633.
In conclusion, silver(I) oxide combined with potas-
sium iodide is an efficient reagent system to mediate
sulfonylation of alcohols in high yield under mild
reaction conditions. A key merit of the present
method is its applicability in neutral conditions. Thus,
base- or acid-sensitive substrates are sulfonylated
without detecting any side-products during the course
of the reaction. All compounds were characterized by
NMR, IR and MS and are consistent with the
assigned structures.7
2. Yoshida, Y.; Shimonishi, K.; Sakakura, Y.; Okada, S.;
Aso, N.; Tanabe, Y. Synthesis 1999, 9, 1633.
3. (a) Ouchi, M.; Inoue, Y.; Liu, Y.; Nagamune, S.; Naka-
mura, S. Bull. Chem. Soc. Jpn. 1990, 63, 1260; (b) Fen-
ton, D. E.; Parkin, D. J. Chem. Soc., Perkin Trans. 1
1981, 449; (c) Cornforth, J. W.; Morgan, E. D.; Potts,
K. T.; Rees, R. J. W. Tetrahedron 1973, 29, 1659.
4. (a) Boons, G.-J.; Castle, G. H.; Clase, J. A.; Grice, P.;
Ley, S. V.; Pinel, C. Synlett 1993, 913; (b) Purdie, T.;
Mar-tinelli, M. J.; Nayyar, K. N.; Moher, E. D.; Dhokt,
U. P.; Pawlak, J. M.; Vaidyanathan, R. Org. Lett. 1999,
1, 447.
Acknowledgements
5. (a) Irvine, J. C. J. Chem. Soc. 1903, 83, 1021; (b) Pur-
die, T.; Bridgett, R. C. J. Chem. Soc. 1903, 83, 1037; (c)
Mislow, K. J. Am. Chem. Soc. 1951, 73, 4043.
6. Tanabe, M.; Peters, R. H. Org. Synth. Coll. Vol. VII
1990, 386.
The authors gratefully acknowledge the financial sup-
port of the foundation Armand-Frappier and the
Natural Sciences and Engineering Research Council
(NSERC) of Canada. We would like to thank Dr.
Gervais Berube´ and Ming Chou for comments on the
manuscript.
7. Selected spectral data for the product of entry 13: 1H
NMR (500 MHz, CDCl3): l 1.21 (t, J=7.5 Hz, 3H),
1.51 (d, J=6.0 Hz, 3H), 2.44 (s, 3H), 4.11 (q, J=7.7
Hz, 2H), 4.30 (q, J=6.0 Hz, 1H), 7.34 (d, J=7.5 Hz,
2H), 7.82 (d, 7.5 Hz, 2H); 13C NMR (65 MHz, CDCl3):
l 13.9, 18.4, 21.65, 61.8, 74.1, 128.0, 129.8, 133.4, 145.1,
169.0.
References
1. (a) Wagner, R. B.; Zook, H. D. Synthetic Organic
Chemistry; Horning, E.C., Ed.; Wiley: New York, 1955;