Synthesis of C2-symmetric tris-thioethers via optically active mustards

Article abstract of DOI:10.1016/S0040-4020(01)00006-0

Chiral dihydroxy thioethers derived from L-mandelic and L-lactic acid are activated with SOCl₂, SOBr₂ and by bis-trifluoroacetate formation to give optically active mustard gas analogues. These compounds serve as substrates for stereospecific nucleophilic substitution reactions with NaSEt and NaSPh to furnish C₂-symmetric tris-thioethers with overall inversion of configuration.

Full text of DOI:10.1016/S0040-4020(01)00006-0

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 1779±1783
Synthesis of C2-symmetric tris-thioethers via optically
active mustards
a,p
Jens Christoffers and Ulrich Roûler
b
È
a
È
È
Institut fur Organische Chemie der Universitat Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
È È
Institut fur Organische Chemie der Technischen Universitat Berlin, Sekretariat C 3, Straûe des 17. Juni 135, D-10623 Berlin, Germany
b
Received 20 November 2000; accepted 20 December 2000
AbstractÐChiral dihydroxy thioethers derived from l-mandelic and l-lactic acid are activated with SOCl2, SOBr2 and by bis-tri¯uoro-
acetate formation to give optically active mustard gas analogues. These compounds serve as substrates for stereospeci®c nucleophilic
substitution reactions with NaSEt and NaSPh to furnish C2-symmetric tris-thioethers with overall inversion of con®guration. q 2001
Elsevier Science Ltd. All rights reserved.
1. Introduction
the reaction mixture nor to isolate any unique compound.
Obviously, there is a signi®cant neighboring group effect of
the adjacent thioether function preventing the formation of
unique materials. Having in mind that mustard gasÐbis(2-
In the course of our combinatorial catalysis project on asym-
metric Michael reactions1±3 we prepared a number of new
chiral bi- and tridentate ligands being phosphines,4
amines,5±6 imines,7 and oxazolines8 having a thioether
moiety as an additional donor function. In continuation of
this work, we herein wish to report on novel C2-symmetric
tris-thioethers 1a±d (Scheme 1) being accessible from
chiral dihydroxy thioethers 2a,b by a sequence of alcohol
activation and stereospeci®c nucleophilic substitution. The
starting materials 2a,b are readily available on a multigram
scale from optically active ethyl lactate and mandelate in
75±76% yield over ®ve steps.9±10
chlororethyl)sul®deÐis
a
very reactive but stable
compound we considered alcohol activation by formation
of the corresponding halides with SOCl2 and SOBr2
(Scheme 2). Compounds 3a11,12 and 3c13 have been reported
before as racemic materials. Conversion of 2a,b with the
two thionyl halides proceeded with almost quantitative
conversion in all four cases (Table 1). For 2a elevated
temperatures were required in both cases. As detectable
by NMR spectroscopy all four products were obtained as
single diastereoisomers and moreover as optically active
materials. Partial racemization would have caused at least
some formation of the meso-diastereoisomer.
Only compound 3b showed long-term stability at ambient
temperature and was obtained as an analytically pure
material without particular puri®cation (on SiO2 decompo-
sition is observed). Congeners 3a and 3c,d always contained
Scheme 1. Retrosynthesis of tris-thioethers 1a±d from dihydroxy
thioethers 2a,b.
2. Results and discussion
In initial attempts to activate alcohols 2a,b as sulfonates we
tried to synthesize the corresponding tosylates, mesylates,
or tri¯ates according to standard protocols. However, in
every case we were neither able to detect the product in
Keywords: alcohols; diols; substitution; sulfur compounds; thioethers.
Corresponding author. Fax: 149-711-685-4269;
e-mail: jchr@po.uni-stuttgart.de
Scheme 2. Activation of dihydroxy thioethers 2a,b and synthesis of tris-
thioethers 1a±d. Reagents, conditions, and yields: (a) see Table 1, (b) see
Table 2. For de®nition of 2a,b and 1a±d see Scheme 1. Tfaˆtri¯uoroacetyl.
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00006-0

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J. Christoffers, U. Roûler / Tetrahedron 57 (2001) 1779±1783
1780
Table 1. Activation of dihydroxy thioethers 2a,b
bis-tri¯uoroacetate 3f for the synthesis of 1c,d at elevated
temperature resultedÐsimilar to 3eÐin lower yields.
Starting material Reagent Solvent Conditions Product Yield (%)
All products 1a±d were formed stereospeci®cally with
inversion of con®guration independently from the nature
of the starting material (bis-chloride or bis-tri¯uoroacetate).
Meso-diastereoisomers were not detectable by NMR spec-
troscopy in any case. Moreover, all products were of course
optically active. The values of optical rotations were inde-
pendent from the starting material (bis-chloride or bis-
tri¯uoroacetate) or the reaction temperature applied. We
have included compounds 1a±d in our library of chiral
ligands and investigations on the asymmetric catalysis of
Michael reactions, as mentioned in the introduction, are
presently in process.
2a
2b
2a
2b
2a
2b
SOCl2
SOCl2
SOBr2
SOBr2
Tfa2Oc
Tfa2O
None
None
1.5 h, 508C 3a
2 h, 238C 3b
CH2Cl2 2 h, re¯ux 3c
94a
94b
100a
100a
97b
CH2Cl2 4 h, 238C
CH2Cl2 3 h, 238C
CH2Cl2 2 h, 238C
3d
3e
3f
97b
a
Crude materials, decomposition even at 2208C within days.
Analytically pure without puri®cation, no decomposition at 2208C over
b
weeks.
TfaˆTri¯uoroacetyl.
c
Table 2. Synthesis of tris-thioethers 1a±d, solvent: DMF
Starting material Nucleophile Temperature (8C) Product Yield (%)
3a
3e
3a
3e
3b
3b
3f
3b
3b
3f
NaSEt
NaSEt
NaSPh
NaSPh
NaSEt
NaSEt
NaSEt
NaSPh
NaSPh
NaSPh
23
60
23
70
23
70
60
23
70
70
1a
1a
1b
1b
1c
4
1c
1d
1d
1d
61a
8b
3. Experimental
60a
24b
50b
78b
21b
33b
39b
17b
3.1. General procedure
Column chromatography was accomplished with Merck
silica gel (Type 60, 0.063±0.200 mm) using tert-butyl
methyl ether (MTB) and hexanes (PE) as solvents. Prepara-
tive TLC was performed on ICN silica gel plates (type 60A,
F254, 20 cm£20 cm). Absolute CH2Cl2 was freshly distilled
from CaH2, DMF (HPLC grade quality) was used as
purchased. 1H NMR: Bruker AM 400 (400 MHz). 13C
NMR: Bruker AC 200 (50 MHz), assignments were made
using DEPT experiments. MS: Varian MAT 711 and MAT
955Q (high resolution). IR: Nicolet Magna IR 750. Elemen-
tal analyses: Analytik Jena Vario EL. Optical rotations:
Perkin±Elmer polarimeter 341.
a
Contains impurities even after repeated chromatography.
Analytically pure after chromatography.
b
impurities resulting from continuous decomposition.
Attempts to purify them by chromatography or distillation
lead to complete decomposition. As expected for a mustard
gas analogue, 3a showed a strong biological activity in a
primary anticancer assay. Since the instability of 3a and
3c,d turned out to be problematic in terms of clean conver-
sion of these compounds we additionally decided to activate
alcohols 2a,b as the bis-tri¯uoroacetate 3e,f, which were
readily available in quantitative yields and as analytically
pure products without chromatography (Table 1).
Dihydroxy thioethers were prepared as reported
previously,10 all other starting materials were commercially
available.
3.1.1. (S,S)-(1)-Bis(2-chloropropyl)sul®de (3a). Under an
atmosphere of nitrogen SOCl2 (2.00 ml, 27.5 mmol) was
added to diol 2a (375 mg, 2.50 mmol). After being stirred
for 90 min at 508C water was added (15 ml), and the mixture
extracted with CH2Cl2 (3£25 ml). Drying of the combined
organic layers (MgSO4) and ®ltration was followed by
evaporation of all volatile materials to yield the dichloride
3a (440 mg, 2.35 mmol, 94%) as a brown liquid, which
decomposes upon chromatography as well as on storage at
Compounds 3a±f were converted with sodium thioethano-
late and thiophenolate in order to prepare tris-thioethers
1a±d (Scheme 2, Table 2). The bis-bromides 3c,d turned
out to be too unstable to give products in satisfying purity.
Bis-chloride 3a gave acceptable yields of 1a,b at ambient
temperature, however, since decomposition of 3a occurred
along with the substitution reaction, impurities resulted
which could not be removed from the products 1a,b, not
even by repeated chromatography. Conversion of the bis-
tri¯uoroacetate 3e at elevated temperature furnished 1a,b in
analytically pure form after chromatography, but in low
yields. Reaction of the more stable bis-chloride 3b yielded
analytically pure products 1c,d after chromatography,
however, the yields were moderate at ambient temperature.
Attempts to raise the yields by elevation of the reaction
temperature did not signi®cantly improve the formation of
1d. In the case of conversion of 3b with NaSEt at 708C no
product 1c was isolable after workup. Instead the bis-
thioether 414 was formed in good yield as a racemic
material. A number of pathways can be considered for the
formation of 4 under the reaction conditions all involving
thiiranium species as intermediates. Application of the
20
1
ambient temperature. [a]D ˆ19.61 (c 3.85, CHCl3). H
NMR (400 MHz, CDCl3): dˆ1.60 (d, Jˆ6.6 Hz, 3H), 2.83
(dd, Jˆ13.7, 7.9 Hz, 1H), 3.01 (dd, Jˆ13.7, 5.8 Hz, 1H),
4.06±4.16 (m, 1H) ppm. 13C{1H} NMR (50 MHz, CDCl3):
dˆ23.89 (CH3), 42.58 (CH2), 56.68 (CH) ppm. IR (ATR):
nˆ2976 (m), 2928 (m), 1713 (vs), 1450 (m), 1419 (m),
1377 (m), 1362 (s), 1221 (s), 1107 (m) cm21. MS (EI,
70 eV), m/z (%): 186 (31) [M1], 137 (35), 123 (100), 110
(21), 87 (43), 77 (43), 61 (17). C6H12Cl2S (187.13): Mol.
mass calcd 186.0037; found 186.0039 (HRMS).
3.1.2. (S,S)-(1)-Bis(2-phenyl-2-chloroethyl)sul®de (3b).
According to the previous procedure for 3a SOCl2
(2.00 ml, 27.5 mmol) and diol 3b (640 mg, 2.33 mmol)
were converted for 2 h at 238C to yield the dichloride 2b
(685 mg, 2.20 mmol, 94%) as an analytically pure brown

È
J. Christoffers, U. Roûler / Tetrahedron 57 (2001) 1779±1783
1781
oil, which is stable below 08C over weeks, but decomposes
added. After extraction with CH2Cl2 (3£30 ml), drying
(MgSO4), and ®ltration, all volatile materials were removed
yielding the bisacetate 3e (479 mg, 1.40 mmol, 97%) as a
20
upon chromatography on SiO2. [a]D ˆ1125 (c 2.9,
CHCl3). 1H NMR (400 MHz, CDCl3): dˆ2.98 (dd,
Jˆ13.9, 8.5 Hz, 1H), 3.06 (dd, Jˆ13.9, 6.4 Hz, 1H), 4.79
(dd, Jˆ8.5, 6.4 Hz, 1H) 7.28±7.48 (m, 5H) ppm. 13C{1H}
NMR (50 MHz, CDCl3): dˆ41.70 (CH2), 62.04 (CH),
127.27 (CH), 128.63 (CH), 128.78 (CH), 139.57 (C) ppm.
IR (ATR): nˆ1493 (m), 1454 (s), 768 (m), 723 (m), 696
(vs) cm21. MS (EI, 70 eV), m/z (%): 310 (10) [M1], 149
(100), 135 (20), 125 (26), 115 (16), 104 (60), 103 (47), 91
(25), 77 (22), 51 (12). C16H16Cl2S (311.27): Anal. calcd C
61.74, H 5.18; found C 61.84, H 5.31. Mol. mass calcd
310.0350; found 310.0349 (HRMS).
20
yellowish, analytically pure oil. [a]D ˆ213.1 (c 11.3,
CHCl3). 1H NMR (400 MHz, CDCl3): dˆ1.45 (d,
Jˆ6.2 Hz, 3H), 2.81 (d, Jˆ6.2 Hz, 2H), 5.21 (sextet,
Jˆ6.2 Hz, 1H) ppm. 13C{1H} NMR (50 MHz, CDCl3):
dˆ18.48 (CH3), 37.18 (CH2), 74.71 (CH), 114.30 (q,
Jˆ286 Hz, CF3), 156.74 (q, Jˆ42 Hz, CO) ppm. IR
(ATR): nˆ1781 (vs), 1380 (m), 1331 (m), 1218 (s), 1154
(vs), 1122 (vs), 1031 (m), 862 (m), 776 (m), 728 (m) cm21
.
MS (EI, 70 eV), m/z (%): 342 (4) [M1], 228 (38), 155 (16),
114 (100) [CF3CO2H1], 99 (15), 87 (58), 73 (15), 69 (83),
59 (13). C10H12F6O4S (342.25): Anal. calcd C 35.09, H 3.53;
found C 35.14, H 3.82. Mol. mass calcd 342.0360; found
342.0361 (HRMS).
3.1.3. (S,S)-(1)-Bis(2-bromopropyl)sul®de (3c). Under an
atmosphere of nitrogen SOBr2 (1.65 g, 7.92 mmol) was
added to a solution of diol 2a (297 mg, 1.98 mmol) in
CH2Cl2 (10 ml). After being heated to re¯ux for 2 h water
was added (30 ml) and the mixture extracted with CH2Cl2
(3£30 ml). Drying of the combined organic layers (MgSO4)
and ®ltration was followed by evaporation of all volatile
materials to yield the dibromide 3c (547 mg, 1.98 mmol,
100%) as a brown liquid, which decomposes upon chroma-
3.1.6. (S,S)-(1)-Bis(2-phenyl-2-tri¯uoroacetoxyethyl)-
sul®de (3f). According to the previous procedure for 3e
Tfa2O (527 mg, 2.51 mmol), diol 2b (172 mg,
0.627 mmol), and CH2Cl2 (4 ml) were converted to yield
bisacetate 3f (284 mg, 0.609 mmol, 97%) as a yellowish,
20
1
analytically pure oil. [a]D ˆ192.6 (c 10.4, CHCl3). H
NMR (400 MHz, CDCl3): dˆ2.89 (dd, Jˆ14.4, 5.6 Hz,
1H), 3.03 (dd, Jˆ14.4, 8.1 Hz, 1H), 5.92 (dd, Jˆ8.1,
5.6 Hz, 1H), 7.24±7.46 (m, 5H) ppm. 13C{1H} NMR
(50 MHz, CDCl3): dˆ37.46 (CH2), 79.27 (CH), 114.45 (q,
Jˆ284 Hz, CF3), 126.49 (CH), 128.88 (CH), 129.37 (CH),
136.34 (C), 156.49 (q, Jˆ42 Hz, CO) ppm. IR (ATR):
nˆ1785 (s), 1224 (s), 1149 (vs), 697 (m) cm21. MS (EI,
70 eV), m/z (%): 466 (10) [M1], 352 (55), 203 (29), 149
(100), 135 (20), 115 (20), 104 (31), 91 (29), 77 (14), 69 (17).
C20H16F6O4S (466.40): Anal. calcd C 51.51, H 3.46; found
C 51.60, H 3.65. Mol. mass calcd 466.0673; found 466.0678
(HRMS).
20
tography as well as on storage below 08C. [a]D ˆ123 (c
0.8, CHCl3). 1H NMR (400 MHz, CDCl3): dˆ1.78 (d,
Jˆ6.6 Hz, 3H), 2.91 (dd, Jˆ13.7, 8.9 Hz, 1H), 3.15 (dd,
Jˆ13.7, 5.3 Hz, 1H), 4.06±4.32 (m, 1H) ppm. 13C{1H}
NMR (50 MHz, CDCl3): dˆ24.66 (CH3), 42.93 (CH2),
47.68 (CH) ppm. IR (ATR): nˆ2970 (s), 2923 (s), 1727
(m), 1447 (s), 1416 (m), 1375 (vs), 1243 (m), 1220 (m),
1163 (vs), 1099 (m), 1045 (m), 996 (s) cm21. MS (EI,
70 eV), m/z (%): 274 (19) [M1], 195 (100) [M1±Br], 153
(38), 125 (20), 121 (64), 75 (30). C6H12Br2S (276.03): Mol.
mass calcd 273.9027; found 273.9022 (HRMS).
3.1.4. (S,S)-(1)-Bis(2-phenyl-2-bromoethyl)sul®de (3d).
Under an atmosphere of nitrogen SOBr2 (208 mg,
1.00 mmol) was added to a solution of diol 2b (94.1 mg,
0.343 mmol) in CH2Cl2 (2 ml). After being stirred for 4 h at
238C water was added (10 ml), and the mixture extracted
with CH2Cl2 (2£20 ml). Drying of the combined organic
layers (MgSO4) and ®ltration was followed by evaporation
of all volatile materials to yield the dibromide 3d (137 mg,
0.343 mmol, 100%) as a green liquid, which decomposes
upon chromatography as well as on storage below 08C.
3.1.7. (R,R)-(1)-Bis[2-(ethylsulfanyl)propyl]sul®de (1a).
A solution of bisacetate 3e (916 mg, 2.68 mmol) in DMF
(6 ml) was added to NaSEt (757 mg, 9.00 mmol), and the
resulting mixture was stirred overnight at 608C in a tightly
closed reaction vial. After dilution with MTB (75 ml) the
solution was washed with water (3£30 ml), dried (MgSO4),
®ltered and the solvent evaporated. Column chromato-
graphy (SiO2, MTB/PE 1:50, Rfˆ0.13) of the residue
followed by removal of small amounts of higher volatile
impurities in high vacuum furnished tris-thioether 1a
(52.2 mg, 0.219 mmol, 8%) as an analytically pure, color-
less oil.
[a]D ˆ112 (c 0.95, CHCl3). 1H NMR (400 MHz,
20
CDCl3): dˆ4.03 (dd, Jˆ10.6, 10.3 Hz, 1H), 4.09 (dd,
Jˆ10.3, 5.5 Hz, 1H), 5.15 (dd, Jˆ10.6, 5.5 Hz, 1H),
7.28±7.50 (m, 5H) ppm. 13C{1H} NMR (50 MHz,
CDCl3): dˆ34.99 (CH2), 50.83 (CH), 127.59 (CH),
128.79 (CH), 128.89 (CH), 139.52 (C) ppm. IR (ATR):
nˆ1496 (m), 1454 (s), 1155 (m), 1137 (m), 767 (s), 694
(vs) cm21. MS (EI, 70 eV), m/z (%): 398 (1) [M1], 319 (12),
183 (46), 104 (100), 103 (31), 91 (15), 78 (17), 77 (17), 51
(14). C16H16Br2S (400.17): Mol. mass calcd 397.9340;
found 397.9337 (HRMS).
Analogous conversion of dichloride 3a (468 mg,
2.50 mmol) with NaSEt in DMF at ambient temperature
yielded the title compound 1a (364 mg, 1.53 mmol, 61%)
containing impurities, which could not be removed by
20
1
chromatography. [a]D ˆ186 (c 3.1, CHCl3). H NMR
(400 MHz, CDCl3): dˆ1.26 (t, Jˆ7.4 Hz, 3H), 1.36 (d,
Jˆ6.8 Hz, 3H), 2.52±2.64 (m, 1H), 2.59 (q, Jˆ7.4 Hz,
2H), 2.82±2.98 (m, 2H) ppm. 13C{1H} NMR (50 MHz,
CDCl3): dˆ14.79 (CH3), 20.23 (CH3), 24.65 (CH2), 39.42
(CH), 40.28 (CH2) ppm. IR (ATR): nˆ2962 (vs), 2925 (vs),
2869 (m), 1451 (s), 1373 (s), 1261 (s), 1225 (w) cm21. MS
(EI, 70 eV), m/z (%): 238 (2) [M1], 176 (7), 135 (12), 103
(100) [C5H11S1], 102 (47), 93 (8), 89 (54), 75 (25), 61 (38).
C10H22S3 (238.46): Anal. calcd C 50.37, H 9.30; found C
3.1.5. (S,S)-(2)-Bis(2-tri¯uoroacetoxypropyl)sul®de (3e).
Under an atmosphere of nitrogen Tfa2O (1.21 g, 5.76 mmol)
was added at 08C to a solution of diol 2a (217 mg,
1.44 mmol) in CH2Cl2 (10 ml). The mixture was stirred
for 3 h while warming up to ambient temperature, then
water (5 ml) and saturated Na2CO3 solution (30 ml) were

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J. Christoffers, U. Roûler / Tetrahedron 57 (2001) 1779±1783
1782
50.39, H 9.16. Mol. mass calcd 238.0884; found 238.0883
(HRMS).
Jˆ7.4 Hz, 3H), 1.19 (t, Jˆ7.4 Hz, 3H), 2.30±2.41 (m,
2H), 2.44 (q, Jˆ7.4 Hz, 2H), 2.99 (dd, Jˆ8.6, 13.0 Hz,
1H), 3.04 (dd, Jˆ6.5, 13.0 Hz, 1H), 3.99 (dd, Jˆ6.5,
8.6 Hz, 1H), 7.24±7.38 (m, 5H) ppm. 13C{1H} NMR
(50 MHz, CDCl3): dˆ14.34 (CH3), 14.62 (CH3), 25.42
(CH2), 26.71 (CH2), 37.96 (CH2), 49.68 (CH), 127.38
(CH), 127.79 (CH), 128.41 (CH), 141.28 (C) ppm. IR
(ATR): nˆ2966 (s), 2926 (s), 2870 (m), 1491 (m), 1452
MS (EI, 70 eV), m/z (%): 226 (21) [M1], 165 (26), 151 (100)
[C9H11S1], 135 (50), 123 (24), 121 (13), 103 (47), 91 (27),
77 (27). C12H18S2 (226.39): Anal. calcd C 63.66, H 8.01;
found C 63.43, H 7.85. Mol. mass calcd 226.0850; found
226.0843 (HRMS).
3.1.8. (R,R)-(1)-Bis[2-(phenylsulfanyl)propyl]sul®de (1b).
According to the previous procedure for 1a bisacetate 3e
(758 mg, 2.21 mmol) in DMF (3 ml) was converted with
NaSPh (1.17 g, 8.84 mmol) at 708C. After workup twofold
column chromatography on SiO2 (1. MTB/PE 1:30, Rfˆ0.37;
2. MTB/PE 1:50, Rfˆ0.23) yielded a material, which was
submitted to preparative TLC on SiO2 (MTB/PE 1:50) to
yield the analytically pure title compound 1b (180 mg,
0.539 mmol, 24%) as a colorless oil.
(s), 1265 (m), 765 (m), 733 (m), 713 (s), 698 (vs) cm21
.
Analogous conversion of dichloride 3a (374 mg,
2.00 mmol) with NaSPh in DMF at ambient temperature
yielded the title compound 1b (398 mg, 1.19 mmol, 60%)
containing impurities, which could not be removed by chro-
3.1.11. (R,R)-(2)-Bis[2-phenyl-2-(phenylsulfanyl)ethyl]-
sul®de (1d). According to the procedure given above for
1c NaSPh (137 mg, 1.04 mmol) was converted with dichlor-
ide 3b (81.0 mg, 0.260 mmol) in DMF (2 ml) at 708C to
give a crude material, which was puri®ed ®rst by column
chromatography (SiO2, MTB/PE 1:30, Rfˆ0.27) and subse-
quently by preparative TLC (SiO2, MTB/PE 1:30) to furnish
the analytically pure compound 1d (46.0 mg, 0.100 mmol,
20
matography. [a]D ˆ169.5 (c 5.50, CHCl3). 1H NMR
(400 MHz, CDCl3): dˆ1.35 (d, Jˆ6.7 Hz, 3H), 2.49 (dd,
Jˆ13.2, 9.5 Hz, 1H), 2.79 (dd, Jˆ13.2, 4.3 Hz, 1H), 3.18±
3.30 (m, 1H), 7.16±7.42 (m, 5H) ppm. 13C{1H} NMR
(50 MHz, CDCl3): dˆ19.60 (CH3), 39.53 (CH2), 42.93
(CH), 127.29 (CH), 128.94 (CH), 132.47 (CH), 134.08 (C)
ppm. IR (ATR): nˆ2960 (m), 2922 (m), 1583 (m), 1480
(m), 1473 (m), 1540 (m), 1438 (s), 1371 (m), 1025 (m),
738 (vs), 701 (m), 690 (vs) cm21. MS (EI, 70 eV), m/z
(%): 334 (36) [M1], 224 (7), 184 (26), 183 (44), 151
(100) [C9H11S1], 150 (30), 141 (47), 137 (31), 123 (16),
109 (28). C18H22S3 (334.55): Anal. calcd C 64.62, H 6.63;
found C 64.59, H 6.66. Mol. mass calcd 334.0884; found
334.0885 (HRMS).
20
1
39%) as a yellowish oil. [a]D ˆ2150 (c 1.8, CHCl3). H
NMR (400 MHz, CDCl3): dˆ2.85 (dd, Jˆ13.3, 9.3 Hz,
1H), 2.91 (dd, Jˆ13.3, 5.8 Hz, 1H), 4.12 (dd, Jˆ9.3,
5.8 Hz, 1H), 7.08±7.40 (m, 10H) ppm. 13C{1H} NMR
(50 MHz, CDCl3): dˆ38.50 (CH2), 53.47 (CH), 127.56
(CH), 127.67 (CH), 127.94 (CH), 128.44 (CH), 128.85
(CH), 132.84 (CH), 134.11 (C), 139.89 (C) ppm. IR
(ATR): nˆ1581 (m), 1491 (m), 1479 (m), 1452 (m), 1437
(m), 1024 (m), 738 (s), 689 (vs), 658 (m) cm21. MS (EI,
70 eV), m/z (%): 458 (1) [M1], 349 (18), 245 (43), 213 (16),
199 (29), 141 (94), 135 (100), 109 (39), 104 (30), 91 (17), 77
(10). C28H26S3 (458.71): Anal. calcd C 73.32, H 5.71; found
C 73.17, H 5.84. Mol. mass calcd 458.1197; found 458.1199
(HRMS).
3.1.9. (R,R)-(2)-Bis[2-phenyl-2-(ethylsulfanyl)ethyl]sul-
®de (1c). NaSEt (312 mg, 3.71 mmol) was added to a solu-
tion of dichloride 3b (289 mg, 0.928 mmol) in DMF (7 ml).
The mixture was stirred overnight at ambient temperature.
After dilution with MTB (50 ml) and extraction with water
(3£30 ml) the organic layer was dried (MgSO4), ®ltered and
the solvent evaporated. The residue was twice column chro-
matographed on SiO2 (MTB/PE 1:50, Rfˆ0.11) to give tris-
thioether 1c (168 mg, 0.463 mmol, 50%) as an analytically
Acknowledgements
pure, colorless oil. [a]D ˆ2151 (c 6.95, CHCl3). 1H NMR
20
We are grateful to the Fonds der Chemischen Industrie and
the Deutsche Forschungsgemeinschaft for generous support.
(400 MHz, CDCl3): dˆ1.14 (t, Jˆ7.4 Hz, 3H), 2.30 (q,
Jˆ7.4 Hz, 1H), 2.31 (q, Jˆ7.4 Hz, 1H), 2.84 (dd, Jˆ8.9,
13.3 Hz, 1H), 2.89 (dd, Jˆ6.3, 13.3 Hz, 1H), 3.86 (dd,
Jˆ6.3, 8.9 Hz, 1H), 7.20±7.38 (m, 5H) ppm. 13C{1H}
NMR (50 MHz, CDCl3): dˆ14.39 (CH3), 25.45 (CH2),
39.13 (CH2), 49.68 (CH), 127.46 (CH), 127.87 (CH),
128.47 (CH), 141.05 (C) ppm. IR (ATR): nˆ1490 (m),
1451 (m), 696 (vs) cm21. MS (EI, 70 eV), m/z (%): 362
(1) [M1], 226 (8), 165 (20), 164 (18), 151 (100)
[C9H11S1], 135 (14), 123 (6), 104 (20), 103 (12), 91 (11),
77 (8). C20H26S3 (362.61): Anal. calcd C 66.25, H 7.23;
found C 66.36, H 7.28. Mol. mass calcd 362.1197; found
362.1199 (HRMS).
References
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20
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