Isolation and Stereochemical Studies of a Cyclic Alkoxysulfonium Salt, an Important Intermediate in the Nucleophilic Reaction of Chlorooxasulfuranes

Full text of DOI:10.1021/jo980314t

J . Org. Chem. 1998, 63, 5265-5267
5265
Sch em e 1
Isola tion a n d Ster eoch em ica l Stu d ies of a
Cyclic Alk oxysu lfon iu m Sa lt, a n Im p or ta n t
In ter m ed ia te in th e Nu cleop h ilic Rea ction
of Ch lor ooxa su lfu r a n es
J ian Zhang, Shinichi Saito,*,† and Toru Koizumi*,†
Faculty of Pharmaceutical Sciences,
Toyama Medical & Pharmaceutical University,
2630 Sugitani, Toyama 930-01, J apan
Received February 19, 1998
The stereochemical research on the nucleophilic reac-
tion of compounds at a tetracoordinated atom, such as
carbon, has been widely carried out, and the SN1 or SN2
pathway has been accepted as the general concept of
organic reactions. In contrast, the study of the stereo-
chemical process of the nucleophilic reaction of the hy-
pervalent compounds has been carried out to a much
lesser extent. Chalcogenurane, a pentacoordinated hy-
pervalent compound, usually adopts a trigonal-bipyra-
midal geometry. The stereochemical study on the reac-
tion of chalcogenurane would lead to the understanding
of the general mechanism of the reactions occurring at a
multicoordinated heteroatom. However, since the lack
of optically pure chalcogenurane, few studies have been
reported in this field. Twenty years ago, Martin et al.
studied the mechanism of the basic hydrolysis of chiral
chlorosulfurane 1 to give sulfoxide 2 and proposed an
associative mechanism involving a hexacoordinated sul-
fur species 3 with a negative charge on sulfur (Scheme
1).1 They also reported the isolation and hydrolysis of
chiral sulfonium salt 3′ (X ) BF4-) during their research.
However, the absolute configuration of the sulfonium salt
3′ and the chlorosulfurane 1 was indirectly confirmed,
and the stereochemical relationship between the sulfo-
nium salt and chlorosulfurane as well as the mechanism
of the reaction remains to be clearly established.
Sch em e 2
atmosphere gave chlorooxasulfurane 6 as a white solid
after evaporation of the solvent and excess reagents.3 The
stereochemistry of 6 was determined by comparing the
spectroscopic data of 6 with those of a selenium analogue.2e
Reaction of chlorosulfurane 6 with AgF at 0 °C for 30
min afforded fluorosulfurane 7 as the sole product via
halogen-exchange reaction. It is likely that the reaction
proceeds via an SN1 pathway which involves a sulfonium
cation as an intermediate (Scheme 3).2f
To isolate the cationic intermediate, chlorosulfurane
6 was treated with silver tetrafluoroborate (1.1 equiv) to
give optically pure alkoxysulfonium salt 8 in 96% yield
and as a single diastereomer (Scheme 3).5 Other epimeric
compounds were not detected. The salt 8 was character-
We have carried out the synthesis, reaction, and
stereochemical research on the chiral hypervalent chal-
cogenium compounds and assumed that the chiral chal-
cogenonium cations 4 would be an intermediate in some
reactions (Scheme 2).2 In this paper we report the
isolation, stereochemistry, and hydrolysis of a chiral
alkoxysulfonium salt which has been proposed as an
intermediate in the hydrolysis of chlorosulfuranes.3
Reaction of sulfide 5 with t-BuOCl (1.1 equiv) at 0 °C
for 20 min in anhydrous dichloromethane under nitrogen
† Address for correspondence: Institute for Chemical Reaction
Science, Tohoku University, Sendai 980-8578, J apan.
‡ Deceased, J an 12, 1998.
(1) (a) Balthazor, T. M.; Martin, J . C. J . Am. Chem. Soc. 1975, 97,
5634-5635. (b) Martin, J . C.; Balthazor, T. M. J . Am. Chem. Soc. 1977,
99, 152-162.
1
ized by spectroscopic means. In the H NMR spectrum,
the signals of methylene protons (Ha, Hb) of 8 appeared
(2) (a) Takahashi, T.; Kurose, N.; Kawanami, S.; Arai, Y.; Koizumi,
T.; Shiro, M. J . Org. Chem. 1994, 59, 3262-3264. (b) Takahashi, T.;
Kurose, N.; Kawanami, S.; Nojiro, A.; Arai, Y.; Koizumi, T.; Shiro, M.
Chem. Lett. 1995, 379-380. (c) Kurose, N.; Takahashi, T.; Koizumi,
T. J . Org. Chem. 1996, 61, 2932-2933. (d) Takahashi, T.; Zhang, J .;
Kurose, N.; Takahashi, S.; Koizumi, T.; Shiro, M. Tetrahedron:
Asymmetry 1996, 7, 2797-2800. (e) Kurose, N.; Takahashi, T.; Koi-
zumi, T. Tetrahedron 1997, 53, 12115-12129. (f) Takahashi, S.; Zhang,
J .; Saito, S.; Koizumi, T. Heterocycles 1997, 46, 373-384. (g) Zhang,
J .; Saito, S.; Koizumi, T. Tetrahedron: Asymmetry 1997, 8, 3357-3361.
(3) Zhang, J .; Takahashi, T.; Koizumi, T. Heterocycles 1997, 44, 325-
339.
(4) For the reactions involving sulfonium salts, see: (a) Mancuso,
A. J .; Swern, D. Synthesis 1981, 164-185. (b) Oae, S. Organic
Chemistry of Sulfur; Kagakudoujin: Kyoto, 1982. (c) Glass, R. S.;
Petsom, A.; Hojjatie, M.; Coleman, B. R.; Duchek, J . R.; Klug, J .;
Wilson, G. S. J . Am. Chem. Soc. 1988, 110, 4772-4778. (d) Tidwell, T.
T. Synthesis 1990, 857-870. (e) Pickersgill, I. F.; Marchington, A. P.;
Rayner, C. J . Chem. Soc., Chem. Commun. 1994, 2597-2598. (f)
Vederas, J . C.; Liu, Y.-Q. J . Org. Chem. 1996, 61, 7856-7859. (g)
Nakajima, N.; Ubukata, M. Tetrahedron Lett. 1997, 38, 2099-2102.
(h) Majetich, G.; Hicks, R.; Reister, S. J . Org. Chem. 1997, 62, 4321-
4326. (i) Kobayashi, K.; Obinata, T.; Furukawa, N. Chem. Lett. 1997,
1175-1176.
S0022-3263(98)00314-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/03/1998

5266 J . Org. Chem., Vol. 63, No. 15, 1998
Notes
Sch em e 3a
F igu r e 1. X-ray structures of 8 and 9.
length of 1.598(8) Å is longer than the 1.49 ( 0.2 Å found
for that in sulfoxides but significantly shorter than the
S-O bond length of a spirosulfurane [1.686(6) Å].6 This
result could be interpreted in terms of the increased
double-bond character of the S-O bond in 8.7 In addi-
tion, the C(3)-S-O, C(2)-S-O, and C(2)-S-C(3) bond
angles of 107.2(5)°, 98.6(5)°, and 105.2(5)° in salt 8 are
comparable to those found in the cyclic alkoxysulfonium
salts reported by Glass et al.,8 while the S-O-C(1) bond
angle of 109.0(7)° of salt 8 is quite smaller than that of
their six-membered salts [121.2(9)°]. Thus, the geometry
about tetrahedral sulfur has a pyramidal geometric
structure with S absolute configuration at the sulfur
center as depicted in Figure 1.9
a
Reagents and conditions: (a) t-BuOCl, CH2Cl2, 0 °C; (b) AgF,
CH2Cl2, 0 °C; (c) AgBF4, CH2Cl2, 0 °C; (d) satd NaHCO3(aq).
Ta ble 1. 1H a n d 13C NMR Ch em ica l Sh ifts (p p m ) of 5, 6,
8, a n d 9
The hydrolysis of salt 8 was performed under the same
condition employed for the hydrolysis of chlorosulfuranes.
Stirring a solution of 8 in CH2Cl2 with saturated NaHCO3-
(aq)10 at room temperature for 10 min gave sulfide 9 in
quantitative yield as the sole product. The spectroscopic
data of 9 are identical with that of the product obtained
via the hydrolysis of chlorooxasulfurane, and the stere-
ochemistry of the sulfoxide was unambiguously deter-
mined by an X-ray crystallographic analysis as shown
in Figure 1, which indicated that the absolute configu-
ration at the sulfur center is R.9 Therefore, the reaction
proceeded via the same stereochemical process as that
of the chlorooxasulfurane.
Although the results we obtained do not exclude the
possibility that the hydrolysis of chlorosulfuranes pro-
ceeds via an associative pathway, we now have support-
ing evidence that the reaction may proceed through a
dissociative mechanism involving an alkoxysulfonium
salt as an intermediate. We assume that an associative
mechanism is operating in the presence of a strong
nucleophile such as R- (R ) alkyl group), while a
dissociative mechanism is operating in the presence of a
weak nucleophile such as X- (X ) halogen) or H2O.11
In summary, we have succeeded in the isolation of a
chiral cyclic alkoxysulfonium salt which was prepared
compd
Ha, Hb
Hc
C1
5
6
8
9
2.96, 3.23
4.57, 4.69
4.21, 4.69
2.38, 3.35
3.94
4.34
5.05
4.20
77.0
100.4
105.0
77.2
at very low field compared to those of the corresponding
sulfide 5 and sulfoxide 9 (Table 1). The chemical shift
of the proton (Hc) in salt 8 appeared at ever lower field
(5.05 ppm) as compared with that of the chlorophenyl-
sulfurane 6 (4.34 ppm). In the 13C NMR spectrum, the
signal of C1 appeared at 105.0 ppm while the signals of
the corresponding carbon of sulfide 5 and sulfurane 6
appeared at 77.0 and 100.4 ppm, respectively. These
results indicate that the sulfur atom is positively charged
and the positive charge is delocalized onto the oxygen
atom. The mass spectrum of 8 did not show a molecular
peak except for m/z ) 261 (M+ - BF4). These spectral
features are consistent with the five-membered cyclic
alkoxysulfonium salt 8.
(6) Zhang, J .; Saito, S.; Koizumi, T. J . Am. Chem. Soc. 1998, 120,
1631-1632.
The structure of 8 was confirmed by a single-crystal
X-ray crystallographic analysis (Figure 1). The X-ray
data indicated that there is no covalent interaction
between the anion and cation. The C-C and C-S bond
lengths are within the expected values. The S-O bond
(7) A referee has pointed out that this shortening may indicate a
decrease in electronic repulsion between the two atoms.
(8) (a) Glass, R. S.; Setzer, W. N.; Prabhuu, D. G.; Wilson, G. S.
Tetrahedron Lett. 1982, 23, 2335-2338. (b) Glass, R. S.; Hojjatie, M.;
Setzer, W. N.; Wilson, G. S. J . Org. Chem. 1986, 51, 1815-1820. (c)
Glass, R. S.; Petsom, A.; Wilson, G. S. J . Org. Chem. 1987, 52, 3537-
3541.
(5) For recent examples on the isolation of optically active sulfonium
salts, see: (a) Kimura, T.; Nakayama, H.; Furukawa, N. Chem. Lett.
1994, 27-28. (b) Matsugi, M.; Hashimoto, K.; Inai, M.; Fukuda, N.;
Furuta, T.; Minamikawa, J .; Otsuka, S. Tetrahedron: Asymmetry 1995,
6, 2991-3000.
(9) The assignment of the absolute configuration of the sulfur atom
was based on the known absolute configuration of the borneol residue.
(10) This weak base was used to trap the acid formed by hydrolysis
and shift the equilibrium. It is less possible that this weak base
functions as a nucleophile.

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5267
(52 mg) in 93% yield. The product was further purified by
from a chiral chlorooxasulfurane. Hydrolysis of the
alkoxysulfonium salt afforded a sulfoxide with the same
stereochemistry which was observed in the hydrolysis of
a chlorooxasulfurane. This result is helpful on the un-
derstanding of the mechanism concerning the nucleo-
philic reactions of a pentacoordinated halooxachalco-
genurane. Isolation and reaction of other chiral chalco-
genonium salts are ongoing in our group.
crystallization from hexane and CH2Cl2: mp 124-125 °C; [R]27
D
+133.0 (c 1.00, CHCl3); IR (KBr) 3375, 2956, 1446, 1032, 995
cm-1; 1H NMR δ 0.80 (s, 3H), 1.06 (s, 3H), 1.2-2.0 (m, 7H), 2.38
(d, J ) 13.2, 1H), 3.35 (d, J ) 13.7, 1H), 4.14 (br d, J ) 3.3, 1H),
4.20 (ddd, J ) 1.9, 3.8, 5.8, 1H), 7.5-7.6 (m, 3H), 7.6-7.75 (m,
2H); 13C NMR δ 20.1, 20.7, 27.4, 31.2, 38.7, 45.3, 48.5, 52.2, 60.0,
77.2, 123.9, 129.5, 131.3, 144.3; MS m/z 278 (M+), 262, 260, 244,
229, 217, 201, 181, 153, 138, 135, 126, 110, 93, 78, 57. Anal.
Calcd for C16H22O2S: C, 69.02; H, 7.96. Found: C, 69.06; H,
7.92.
Recrystallization of the product from hexane and CH2Cl2 gave
a crystal which was suitable for X-ray analysis. Crystallographic
data for 9: orthorhombic, space group P212121 (No. 19) with a
) 11.508(3) Å, b ) 13.437(3) Å, c ) 9.798(3) Å, V ) 1515.1(6)
Å3, and Z ) 4 (dcalcd ) 1.220 g cm-3); µ(Mo KR) ) 2.10 cm-1
absorption corrected by ω scans; 2013 total reflections, 1159 with
I > 3.00σ(I) were used in refinement; R ) 4.2%, Rw ) 4.2%.
Further details of the crystal structure investigation are avail-
able on request from the Director of the Cambridge Crystal-
lographic Data Centre, 12 Union Road, GB-Cambridge, CB2 1EZ
(U.K.), on quoting the full journal citation.
Exp er im en ta l Section
Gen er a l. Common experimental procedures and instrumen-
tation have been described previously.1f J values are given in
hertz (Hz).
(1S)-10-(P h en ylth io)-2-exo-bor n eol (5):3 colorless oil; [R]24
D
-35.05 (c 2.44, CHCl3); IR (neat) 3463, 2952, 1480, 1438, 1071,
1026, 737, 690 cm-1; 1H NMR δ 0.88 (s, 3H), 1.09 (s, 3H), 1.05-
1.9 (m, 7H), 2.19 (br, 1H), 2.96 (d, J ) 11.0, 1H), 3.23 (d, J )
11.0, 1H), 3.94 (dd, J ) 3.9, 7.7, 1H), 7.15-7.4 (m, 5H); 13C NMR
δ 20.2, 21.0, 27.4, 31.3, 34.1, 39.5, 45.4, 48.2, 52.5, 77.0, 111.5,
126.1, 129.0, 129.1, 137.3; MS m/z 263 (M+ + 1), 262 (M+), 245,
153, 135, 123; HRMS calcd for C16H22OS 262.1390, found
262.1353.
Alk oxysu lfon iu m Sa lt 8. To a solution of chlorooxasul-
furane (101 mg, 0.34 mmol) in anhydrous CH2Cl2 (10 mL) was
added silver tetrafluoroborate (66.3 mg, 0.34 mmol) at 0 °C under
nitrogen atmosphere. The reaction mixture was stirred at 0 °C
for 20 min, while the precipitate of AgCl deposited. Then
filtration of AgCl and evaporation of the solvent gave optically
pure alkoxysulfonium salt 8 as crystals (114 mg) in 96% yield.
The product was further purified by crystallization from hexane
(1S ,R S )-5-Ch lor o-10,10-d im e t h yl-5-p h e n yl-5λ4-t h ia -4-
oxa tr icyclo[5.2.1.03,7]d eca n e (6). To a solution of sulfide 5
(89 mg, 0.34 mmol) in anhydrous CH2Cl2 (4 mL) was added
t-BuOCl dropwise at 0 °C under nitrogen atmosphere. The
reaction mixture was stirred at 0 °C for 20 min; then evaporation
of the solvent and excess reagents afforded chlorooxasulfurane
6 (101 mg) as a white solid in quantitative yield: 1H NMR δ
0.99 (s, 3H), 1.17 (s, 3H), 0.8-2.35 (m, 7H), 4.34 (dd, J ) 3.3,
7.7, 1H), 4.57 (d, J ) 15.4, 1H), 4.69 (d, J ) 14.8, 1H), 7.50-
7.71 (m, 3H), 7.90-8.05 (m, 2H); 13C NMR δ 20.0, 20.1, 26.4,
27.5, 37.1, 46.1, 47.2, 56.6, 56.9, 100.4, 123.8, 127.8, 129.4, 129.8,
132.7, 136.0; MS m/z 298 (M+, 37Cl), 296 (M+, 35Cl), 279, 277,
262, 260, 171, 253, 135, 126, 109, 93, 78, 67, 55; HRMS Calcd
for C16H21OSCl 298.0972 (M+, 37Cl), 296.1002 (M+, 35Cl), found:
298.0941, 296.1027.
and CH2Cl2. 8: mp 150-151 °C; [R]26 +68.56 (c 1.08, CHCl3);
D
IR (KBr) 2953, 1443, 1395, 1084, 1034, 996, 752 cm-1; 1H NMR
δ 0.90 (s, 3H), 1.13 (s, 3H), 1.31-1.39 (m, 1H), 1.63-1.69 (m,
1H), 1.82-1.99 (m, 2H), 2.02-2.11 (m, 1H), 2.15-2.30 (m, 1H),
2.38-2.44 (m, 1H), 4.21 (d, J ) 14.3, 1H), 4.69 (d, J ) 14.3, 1H),
5.05 (dd, J ) 2.8, 7.7, 1H), 7.63-7.81 (m, 3H), 7.88-7.98 (m,
2H); 13C NMR δ 19.7, 19.8, 26.3, 26.6, 37.4, 46.7, 47.4, 53.3, 59.8,
105.0, 128.9, 131.0, 131.1, 135.7; MS m/z 262, 261 (M+ - BF4),
260, 244, 229, 201, 153, 126, 110, 93, 79. Anal. Calcd for C16H21
BF4OS: C, 55.19; H, 6.08. Found: C, 55.05; H, 5.91.
-
(1S,RS)-10,10-Dim et h yl-5-flu or o-5-p h en yl-5λ4-t h ia -4-ox-
a tr icyclo[5.2.1.03,7] d eca n e (7). To a solution of a chlorophe-
nylsulfurane (prepared from 52.5 mg of sulfide, 0.20 mmol) in
dry CH2Cl2 (4 mL) was added AgF (80 mg, 0.63 mmol) at 0 °C
under a N2 atmosphere. The whole mixture was stirred at 0 °C
for 30 min, and the precipitates were filtered. The filtrate was
evaporated to give the product in 94% yield (53 mg) as a white
solid. This highly hygroscopic compound could not be fully
characterized: 1H NMR δ 0.96 (s, 3H), 1.13 (s, 3H), 1.2-1.38
(m, 2H), 1.61-1.91 (m, 3H), 1.95-2.01 (m, 1H), 2.08-2.29 (m,
2H), 4.32 (dd, J ) 3.3, 7.7, 1H), 4.53 (d, J ) 15.4, 1H), 4.63 (d,
J ) 15.4, 1H), 7.54-7.61 (m, 3H), 7.93-7.96 (m, 2H); 13C NMR
δ 20.0, 20.1, 26.5, 27.5, 37.2, 46.3, 47.4, 56.1, 57.3, 101.1, 128.1,
130.0, 131.5, 133.1.
Recrystallization of the product from hexane and CH2Cl2 gave
a crystal which was suitable for X-ray analysis. Crystallographic
data for 8: orthorhombic, space group P212121 (No. 19) with a
) 13.653(3) Å, b ) 15.915(4) Å, c ) 7.544(2) Å, V ) 1639.3(6)
Å3, and Z ) 4 (dcalcd ) 1.411 g cm-3); µ(MoKR) ) 2.38 cm-1
absorption corrected by ω scans; 1745 unique reflections, 1086
with I > 3.00σ(I) were used in refinement; R ) 8.2%, Rw ) 8.0%.
Further details of the crystal structure investigation are avail-
able on request from the Director of the Cambridge Crystal-
lographic Data Centre, 12 Union Road, GB-Cambridge, CB2 1EZ
(U.K.), on quoting the full journal citation.
Hyd r olysis of Alk oxysu lfon iu m Sa lt 8. To a solution of
alkoxysulfonium salt 8 (19 mg, 0.055 mmol) in CH2Cl2 (30 mL)
was added saturated NaHCO3 (ca. 1 mL) at room temperature
in a separatory funnel. The two-phase solution was shaken
vigorously and separated. The organic layer was washed with
water (2 mL × 1) and brine (2 mL × 1) and dried over MgSO4.
Evaporation of solvent under reduced pressure gave product 9
as crystals (16 mg) in quantitative yield.
Hyd r olysis of Ch lor osu lfu r a n e 6. To a solution of chlo-
rooxasulfurane 6 (60 mg, 0.2 mmol) in CH2Cl2 (50 mL) was added
saturated NaHCO3 (ca. 2 mL) at room temperature in
a
separatory funnel. The two-phase solution was shaken vigor-
ously and separated. The organic layer was washed with water
(2 mL × 1) and brine (2 mL × 1) and dried over MgSO4.
Evaporation of solvent under reduced pressure gave the product
(1S,RS)-10-(phenylsulfinyl)-2-exo-borneol (9) as colorless crystals
Ack n ow led gm en t. This work was supported by
Grants-in-Aid for Scientific Research from the Ministry
of Education, Science, Sports and Culture, J apan.
(11) (a) Kaplan, L. K.; Martin, J . C. J . Am. Chem. Soc. 1973, 95,
793-798. (b) Martin, J . C.; Perozzi, E. F. J . Am. Chem. Soc. 1974, 96,
3155-3168.
J O980314T