Acid-promoted reaction of sulfonyl chlorides with alkenes: New approach to the regioselective synthesis of β-hydroxyl sulfone derivatives

Article abstract of DOI:10.1055/s-2004-829090

Reaction of sulfonyl chlorides with alkenes and water in the presence of catalytic amount of sulfonic acid provided β-hydroxyl sulfone derivatives in high yields.

Full text of DOI:10.1055/s-2004-829090

LETTER
1595
Acid-Promoted Reaction of Sulfonyl Chlorides with Alkenes: New Approach
to the Regioselective Synthesis of b-Hydroxyl Sulfone Derivatives
A
cid-promoted R
h
eaction of Su
a
lfonyl Chl
n
orides
w
ith
A
j
lkenesuan Xi,* Chunbo Lai, Chao Chen, Ruji Wang
Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing
100084, China
Fax +86(10)62618239; E-mail: cjxi@tsinghua.edu.cn
Received 24 March 2004
(0.20 equiv) and water (1.0 equiv). Under these condi-
Abstract: Reaction of sulfonyl chlorides with alkenes and water in
tions, hydroxyl sulfone 1a was formed in excellent yield
and the reaction displayed >10-fold increase in rate
(Scheme 2).
the presence of catalytic amount of sulfonic acid provided b-hy-
droxyl sulfone derivatives in high yields.
Key words: acid-catalyzed, alkene, hydroxyl sulfonylation reac-
tion, sulfone, sulfonyl chloride
sulfonic acid
Ph
20%
+
Ph
TsCl +
H2O
HO
Ts
THF, 50 °C
b-Hydroxyl sulfone derivatives are synthetically useful
intermediates in organic transformations.1 The develop-
ment of methodologies for the synthesis of b-hydroxyl
sulfone derivatives has been an attractive synthetic pur-
suit. Despite the existence of a number of synthetic meth-
ods affording b-hydroxyl sulfones,2 the most attractive
one seems to be the direct hydroxyl sulfonylation of al-
kenes. To the best of our knowledge, the reaction of sul-
fonyl chlorides with alkenes resulting in b-hydroxyl
sulfone derivatives has not been reported thus far. In this
paper, we would like to report a one-pot procedure for the
preparation of b-hydroxyl sulfone derivatives 1 based on
the acid-promoted reaction of sulfonyl chlorides with
alkenes and water (Scheme 1).
1a
Scheme 2
The generality of the reaction is illustrated with the results
reported in Table 1. The yield is high both for using meth-
anesulfonyl chloride (MsCl) or p-toluenesulfonyl chloride
(TsCl) and 1-substituted or 1,1-disubstituted alkenes and
the regioselectivity was always 100% favoring the intro-
duction of the hydroxyl group to the benzylic position.
The structure of hydroxyl sulfonylation compounds was
confirmed by single-crystal X-ray analysis of compound
1d6 (Figure 1).
R1
R2
Acid
Cl SO2R3
+
H2O
R1
R2
+
HO
SO2R3
1
Scheme 1
It is well known that reaction of sulfonyl chlorides with
substituted and unsubstituted alkenes yields b-chloro sul-
fones. These reactions commonly proceed by a radical
mechanism, namely, aryl- and alkylsulfonyl halides un-
dergo bond homolysis and the resulting sulfonyl radicals
subsequently add to alkenes, to yield the corresponding
alkyl halides.3–5 During the course of our study, we found
that the reaction of sulfonyl chlorides with styrene afford-
ed trace b-hydroxyl sulfone derivative based on GC-MS.
When the reaction time was extended to ten days, hydrox-
yl sulfone 1a was observed in 48% yield. Speculating that
adventitious acid might promote hydroxyl sulfonylation
of alkene to form hydroxyl sulfone, we conducted the re-
action in the presence of catalytic amount of sulfonic acid
Figure 1 Structure of 1d
Using a-methyl styrene and p-toluenesulfonyl chloride as
our standard reaction, the scope of the reactive protonic
compounds was investigated to include water and alco-
hols. Surprisingly, addition of MeOH (1.5 equiv) to the re-
action mixture gave the same product as addition of water.
In order to account for this observation, we attempted a re-
action in which benzyl alcohol was used as a protic com-
pound; the same b-hydroxyl sulfone was obtained.
Moreover, benzyl chloride was observed (Scheme 3).
SYNLETT 2004, No. 9, pp 1595–1597
2
2.
0
7.
2
0
0
4
Advanced online publication: 29.06.2004
DOI: 10.1055/s-2004-829090; Art ID: U08404ST
© Georg Thieme Verlag Stuttgart · New York

1596
C. Xi et al.
LETTER
Table 1 Hydroxyl Sulfonylation of Various Olefins with Sulfonyl Chlorides and Water
Entry
1
Olefin
Sulfonyl chloride Time (h)
Product
Yield (%)a
Ph
TsCl
36
75
1a10
1b11
1c12
2
3
4
TsCl
48
72
Cl
Ph
TsCl
TsCl
48
36
70
82
Me Ph
Ph
Me
1d13
1e14
1f15
1g16
5
6
7
8
MsCl
MsCl
MsCl
MsCl
72
72
60
48
51
43
61
71
Ph
Cl
Ph
Me Ph
Ph
Me
1h17
a Yields of isolated pure products after column chromatography on silica gel.
R1
- H+
sulfonic acid
Ph
O
R1
HO
O
S
Ph
OH
R1
20%
O
S
H+
R3
S
OH
PhCH2Cl
R3
Cl
R3
Me
+
+
+
TsCl
O
PhCH2OH
Cl
S
O
Cl
S
Ts
THF, 50 °C
Me
O
R1
HO
R3
4
Cl
O
Cl
R3
Scheme 3
2
3
ROH
R1
HO
R1
O-
S
HO
R1
Although at this point no rigorous mechanistic studies
have been conducted, a working hypothesis has evolved
based on the observed products. The reaction mechanism
is proposed as follows (Scheme 4). Initially, protonation
of the oxygen atom in sulfonyl chloride provides the more
reactive electrophile 2. It is attacked by olefin to generate
the benzylic carbocation 3, which subsequently undergoes
deprotonation to form oxathietane 4. Then, cleavage of
the O-S bond by a protic compound (such as water or an
alcohol) results in intermediate 5, which undergoes H-
transfer and elimination of HCl or RCl in sequence to give
hydroxyl sulfone derivative 1.
H transfer
O
R3
O
R3
S
O
R3
S
- RCl
O
RO
Cl
Cl
HOR
5
1
6
Scheme 4
provides a direct entry to regioselective synthesis of b-hy-
droxyl sulfones. Investigations into the mechanism, ex-
pansion of the reaction scope and enantioselectivities are
now being undertaken in this laboratory.
In summary, we have shown that the acid-promoted reac-
tion of sulfonyl chlorides with alkenes in the presence of
water or alcohol form b-hydroxyl sulfones. This route
Acknowledgment
This work was supported by the National Natural Science Founda-
tion of China (20172032) (20372041).
Synlett 2004, No. 9, 1595–1597 © Thieme Stuttgart · New York

LETTER
Acid-Promoted Reaction of Sulfonyl Chlorides with Alkenes
1597
evaporated and the crude product was purified by column
chromatography on silica gel (EtOAc/petroleum ether = 1:4)
to afford compound 1a7 (207 mg) as white powder in 75%.
1H NMR (CDCl3, SiMe4): d = 2.46 (s, 3 H), 3.32 (d, J = 14.5
Hz, 1 H), 3.47 (dd, J = 10.0, 14.5 Hz, 1 H), 3.76 (br s, 1 H),
5.25 (d, J = 10.0 Hz, 1 H), 7.26–7.31 (m, 5 H), 7.38 (d,
J = 7.8 Hz, 2 H), 7.84 (d, J = 7.8 Hz, 2 H). 13C NMR (CDCl3,
SiMe4): d = 21.7, 64.0, 68.5, 125.7, 128.0, 128.3, 128.8,
130.1, 136.2, 140.7, 145.3. ESI-MS: 283.1 [M + Li+], 299.1
[M + Na+].
References
(1) (a) Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 4833.
(b) Kocienski, P. J.; Lythogoe, B.; Ruston, S. J. J. Chem.
Soc., Perkin Trans. 1 1978, 829. (c) Kocienski, P. J.;
Lythogoe, B.; Waterhouse, I. J. Chem. Soc., Perkin Trans. 1
1980, 1045. (d) Mandai, T.; Yanagi, T.; Araki, K.; Morisaki,
Y.; Kawada, M.; Otera, J. J. Am. Chem. Soc. 1984, 106,
3670. (e) Achmatowicz, B.; Baranowska, E.; Daniewski, A.
R.; Pankowshi, J.; Sansano, J. M. Tetrahedron 1990, 46,
3993.
(2) (a) Tavares, D. F.; Vogt, P. F. Can. J. Chem. 1967, 45, 1519.
(b) Harwood, L. M.; Julia, M.; Thuillier, G. L. Tetrahedron
1980, 36, 2483. (c) Maiti, A. K.; Bhattacharyya, P. Indian J.
Chem., Sect. B 1996, 35, 67. (d) Cho, B.; Kim, D.
Tetrahedron: Asymmetry 2001, 12, 2043. (e) Gotor, V.;
Rebolledo, F.; Liz, R. Tetrahedron: Asymmetry 2001, 12,
513. (f) Zhao, G.; Hu, J.; Qian, Z.; Yin, W. Tetrahedron:
Asymmetry 2002, 13, 2095.
(3) For representative examples of Cu(I)-catalyzed addition of
sulfonyl chlorides to alkenes, see: (a)Asscher, M.;Vofsi, D.
J. Chem. Soc. 1964, 4962. (b) Orochov, A.; Asscher, M.;
Vofsi, D. J. Chem. Soc. B 1969, 255. (c) Sinnreich, J.;
Asscher, M. J. Chem. Soc., Perkin Trans. 1 1972, 1543.
(d) Orochov, A.; Asscher, M.; Vofsi, D. J. Chem. Soc.,
Perkin Trans. 2 1973, 1000. (e) Da Silva Correa, C. M. M.;
Waters, A. J. Chem. Soc. C 1968, 1874. (f) Ameil, Y. J.
Org. Chem. 1974, 39, 3867. (g) Percec, V.; Barboiu, B.;
Kim, H.-J. J. Am. Chem. Soc. 1998, 120, 305.
(11) 1-p-Chlorophenyl-2-(p-toluenesulfonyl)ethanol (1b):2c
white powder (224 mg, 72%). 1H NMR (CDCl3, SiMe4): d =
2.46 (s, 3 H), 3.28 (d, J = 14.5 Hz, 1 H), 3.43 (dd,
J = 10.0, 14.5 Hz, 1 H), 3.88 (br s, 1 H), 5.23 (d, J = 9.5 Hz,
1 H), 7.21–7.28 (m, 4 H), 7.37 (d, J = 7.8 Hz, 2 H,), 7.37 (d,
J = 8.0 Hz, 2 H). 13C NMR (CDCl3, SiMe4): d = 21.7, 63.8,
67.9, 27.1, 128.0, 128.9, 130.1, 134.0, 136.1, 139.3, 145.4.
ESI-MS: 333.1, 335.1 [M + Na+].
(12) 1-Tolyl-2-(p-toluenesulfonyl)ethanol (1c):2c white powder
(206 mg, 70%). 1H NMR (CDCl3, SiMe4): d = 2.30 (s, 3 H),
2.46 (s, 3 H), 3.29 (dd, J = 1.8, 14.3 Hz, 1 H,), 3.47 (dd,
J1 = 10.1 Hz, J2 = 14.3 Hz, 1 H), 3.69 (br s, 1 H), 5.20 (d,
J = 9.84 Hz, 1 H), 7.12–7.18 (m, 4 H), 7.37 (d, J = 8.0 Hz, 2
H), 7.82 (d, J = 8.4 Hz, 2 H). 13C NMR (CDCl3, SiMe4): d =
21.2, 21.8, 64.1, 68.4, 125.7, 128.1, 129.5, 130.2, 136.3,
137.9, 138.2. 145.3. ESI-MS: 297.1 [M + Li+], 313.1 [M +
Na+].
(13) 2-Phenyl-1-(p-toluenesulfonyl)-propan-2-ol (1d):8 white
powder (238 mg, 82%). 1H NMR (CDCl3, SiMe4): d = 1.69
(s, 3 H), 2.37 (s, 3 H), 3.65 (AB, q, J = 14.8 Hz, 2 H), 4.64
(br s, 1 H), 7.14–7.28 (m, 5 H), 7.47 (d, J = 8.2 Hz, 2 H), 7.27
(d, J = 8.4 Hz, 2 H). 13C NMR (CDCl3, SiMe4): d = 21.7,
30.9, 66.8, 73.3, 124.7, 127.2, 127.6, 128.3, 129.8, 137.4,
144.6. ESI-MS: 297.0 [M + Li+], 313.0 [M + Na+].
(14) 2-Methanesulfonyl-1-phenyl-ethanol (1e):2a white powder
(104 mg, 51%). 1H NMR (CDCl3, SiMe4): d = 3.03 (s, 3 H),
3.14 (d, J = 14.8 Hz, 1 H,), 3.44 (dd, J = 10.0, 14.8 Hz, 1 H),
3.21 (br s, 1 H), 5.32 (d, J = 10.3 Hz, 1 H), 7.34–7.38 (m, 5
H). 13C NMR (CDCl3, SiMe4): d = 43.0, 62.5, 69.4, 125.8,
128.7, 129.1, 141.2. ESI-MS: 206.9 [M + Li+], 222.9 [M +
Na+].
(15) 1-(4-Chlorophenyl)-2-methanesulfonylethanol (1f):
white powder (101 mg, 43%). 1H NMR (CDCl3, SiMe4): d =
3.05 (s, 3 H), 3.12 (d, J = 14.8 Hz, 1 H,), 3.41 (dd, J = 10.3,
14.8 Hz, 1 H), 3.26 (br s, 1 H), 5.32 (d, J = 10.0 Hz, 1 H),
7.30–7.35 (m, 4 H). 13C NMR (CDCl3, SiMe4): d = 43.0,
62.3, 68.7, 127.2, 129.3, 134.5, 139.6. ESI-MS: 238.9, 240.9
[M + Na+]. HRMS: anal. calcd for C9H11ClO3S: 234.0117,
236.0088; found: 234.0111, 236.0046.
(4) For peroxide-induced addition of sulfonyl chlorides to
alkenes, see: Kharash, M. S.; Zavist, A. F. J. Am. Chem. Soc.
1951, 73, 964.
(5) For selected examples of Ru(II)-catalyzed addition of
sulfonyl chlorides to alkenes, see: (a) Kamigata, N.;
Sawada, H.; Kobayashi, M. Chem. Lett. 1979, 159.
(b) Kamigata, N.; Sawada, H.; Kobayashi, M. J. Org. Chem.
1983, 48, 3793. (c) Kamigata, N.; Ozaki, J.; Kobayashi, M.
J. Org. Chem. 1985, 50, 5045. (d) Kamigata, N.;
Fukushima, T.; Terakawa, Y.; Yoshida, M.; Sawada, H. J.
Chem. Soc., Perkin Trans. 1 1991, 627. (e) Kameyama, M.;
Kamigata, N.; Kobayashi, M. Chem. Lett. 1986, 527.
(f) Kameyama, M.; Kamigata, N. Bull. Chem. Soc. Jpn.
1989, 62, 648.
(6) Crystallographic data of 1b: colorless plate, orthorhombic,
Space group Pbca (No. 61), a = 10.199 (3), b = 16.367 (6),
c = 17.701 (5) Å, a = 90.00°, b = 90.00°, g = 90.00°, Z = 8,
R1 = 0.1563, wR2 = 0.1519 (all data), GOF = 1.053.
(7) Biswas, G. K.; Bhattacharyya, P. Synth. Commun. 1991, 21,
569.
(8) Bilaya, E. E.; Obushak, N. D.; Ganushchak, N. I. Russ. J.
Org. Chem. 1999, 35, 632.
(9) Young, D. J.; Stirling, C. J. M. J. Chem. Soc., Perkin Trans.
2 1997, 425.
(10) Representative Procedure for the Hydroxyl
Sulfonylation of Alkenes. Preparation of 1-Phenyl-2-(p-
toluenesulfonyl)ethanol (1a).
(16) 1-Tolyl-2-(methanesulfonyl)ethanol (1g): white powder
(130 mg, 61%). 1H NMR (CDCl3, SiMe4): d = 2.34 (s, 3 H),
3.02 (s, 3 H), 3.08–3.13 (m, 2 H), 3.43 (dd, J = 10.1, 14.9
Hz, 1 H), 5.26 (d, J = 10.3 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 2
H), 7.25 (d, J = 7.9 Hz, 2 H). 13C NMR (CDCl3, SiMe4): d =
21.2, 42.9, 62.5, 69.2, 125.7, 129.7, 138.3, 138.6. ESI-MS:
221.0 [M + Li+]. HRMS: anal. calcd for C10H14O3S:
214.0664; found: 214.0665.
p-Toluenesulfonyl chloride (286 mg, 1.5 mmol) and
toluene-4-sulfonic acid (35 mg, 0.20 mmol) were dissolved
in 5 mL THF. To the solution was added styrene (116 mL, 1.0
mmol) and H2O (22 mL, 1.2 mmol) at r.t. The mixture was
warmed up to 50 °C and stirred for 36 h. Then it was
quenched with H2O and the aqueous layers were extracted
with Et2O (20 mL) for 3 times, and the combined organic
layers were dried over Na2SO4. The ether extract was
(17) 1-Methanesulfonyl-2-phenyl-propan-2ol (1h):9 oily liquid
(152 mg, 71%). 1H NMR (CDCl3, SiMe4): d = 1.73 (s, 3 H),
2.42 (s, 3 H), 3.52 (AB q, J = 14.8 Hz, 2 H), 4.36 (br s, 1 H),
7.42–7.49 (m, 5 H). 13C NMR (CDCl3, SiMe4): d = 30.7,
43.2, 65.7, 72.6, 124.9, 127.9, 128.9, 144.65. ESI-MS: 220.9
[M + Li+].
Synlett 2004, No. 9, 1595–1597 © Thieme Stuttgart · New York