Polystyrene-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene as an efficient and reusable catalyst for the thiolysis of 1,2-epoxides under solvent-free conditions

Article abstract of DOI:10.1002/ejoc.200500791

Polystyrene-supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (PS-TBD) is an effective basic catalyst for the thiolysis of the 1,2-epoxides 1a-e by the aryl- and alkyl-substituted thiols 2A-E under solvent-free conditions while its activity is remarkably redu

Full text of DOI:10.1002/ejoc.200500791

FULL PAPER
DOI: 10.1002/ejoc.200500791
Polystyrene-Supported 1,5,7-Triazabicyclo[4.4.0]dec-5-ene as an Efficient and
Reusable Catalyst for the Thiolysis of 1,2-Epoxides under Solvent-Free
Conditions
Francesco Fringuelli,*[a] Ferdinando Pizzo,[a] Carla Vittoriani,[a] and Luigi Vaccaro*[a]
Keywords: Supported catalysts / Solvent-free reactions / 1,2-Epoxides / Thiolysis / Green chemistry
Polystyrene-supported
1,5,7-triazabicyclo[4.4.0]dec-5-ene
The corresponding hydroxy sulfides have been isolated in
excellent yields and the catalyst has been easily recovered
and reused with no loss in terms of efficiency and selectivity
of the process.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
(PS-TBD) is an effective basic catalyst for the thiolysis of the
1,2-epoxides 1a–e by the aryl- and alkyl-substituted thiols
2A–E under solvent-free conditions while its activity is re-
markably reduced in MeCN. The reactions are totally anti-
diastereoselective and generally highly C-β regioselective.
CH2Cl2, MeOH, and MeCN) by using stoichiometric
amounts of a base to generate a reactive thiolate species.[8]
Under these conditions the reactions generally proceed with
C-β regioselectivity, furnishing the corresponding hydroxy
sulfides in high yields. Alternatively, when thiols are used,
milder reaction conditions are usually required, but an acti-
vating agent is necessary (onium ions,[9] polyethylene
glycols,[10] Lewis acids,[11] solid neutral or acidic cata-
lysts).[12]
We have reported that thiolysis of a variety of 1,2-epox-
ides can be regio- and stereoselectively performed in water
either under acidic[4d] or neutral[4g] conditions by using an
InIII or ZnII salt, respectively. This reaction can be ef-
ficiently performed also under basic aqueous condition at
pH 9.0.[4e] Furthermore, we have demonstrated that a cata-
lytic amount of NaOH is sufficient to promote the regio-
and stereoselective thiolysis of α,β-epoxy ketones in
water.[4i]
According to our interest in the oxirane ring-opening, we
have started a study on the base-catalyzed thiolysis of 1,2-
epoxides 1a–e by the thiols 2A–E under SFC. Triethylamine
(TEA), 4-(dimethylamino)pyridine (DMAP), and 1,5,7-tri-
azabicyclo[4.4.0]dec-5-ene (TBD) as well as their poly-
styrene-supported versions PS-TEA, PS-DMAP, and PS-
TBD were chosen as Brønsted-basic catalysts, while tri-
phenylphosphane (TPP) and polystyrene–diphenylphos-
phane (PS-TPP) were chosen as representative Lewis bases.
All the polystyrene-supported bases chosen in this study are
commercially available.
Introduction
Organic catalysts are a very efficient alternative to metal-
containing promoters for stereoselective transformations.[1]
Their polymer-supported version resolves the problem of
their recovery and reuse and simplifies the isolation of the
reaction products.[2] Environmental issues are pushing an
increasing number of researchers to realize cleaner and
more efficient procedures to improve the sustainability of
organic synthesis. Accordingly, the use of solid organic cat-
alysts is of particular interest and especially in those reac-
tion media that furnish an alternative to classical organic
solvents.[3] Interest is growing rapidly in solvent-free pro-
cesses, in fact solvent-free condition (SFC) can significantly
improve the efficiency of a process while requires simpler
equipments and avoids drying procedures.[4]
Our research is focused on the use of water as reaction
medium and of SFC to define one-pot procedures for the
synthesis of target molecules.[5,6] We have recently found
that the efficiency of a Lewis-acid catalyst is increased un-
der SFC allowing the aminolysis and thiolysis of 1,2-epox-
ides by multidendate nucleophiles and opening the route to
the preparation of new heterocyclic nuclei.[6e,6g]
Thiolysis of 1,2-epoxides is a fundamental organic trans-
formation which is used in nature for metabolic detoxifica-
tion of olefinic xenobiotics.[7] In the laboratory this process
has been performed in anhydrous organic solvents (THF,
Our project is aimed at i) the evaluation of the influence
of the anchorage of a basic catalyst on a polystyrene sup-
port both under SFC and in organic solvent, ii) the selec-
tion of the best polystyrene-supported organic catalyst to
promote the thiolysis of 1,2-epoxides.
[a] CEMIN, Centro di Eccellenza Materiali Innovativi Nanostrut-
turati, Dipartimento di Chimica, Università di Perugia,
Via Elce di Sotto 8, 06123 Perugia, Italy
E-mail: frifra@unipg.it
luigi@unipg.it
Eur. J. Org. Chem. 2006, 1231–1236
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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F. Fringuelli, F. Pizzo, C. Vittoriani, L. Vaccaro
FULL PAPER
Table 2. Thiolysis of 1a with 2A and 2B under SFC and in MeCN
at 30 °C catalyzed by polystyrene-supported organic bases.
Results and Discussion
We have initially studied the reaction of styrene oxide
(1a) with a representative aromatic thiol such as ben-
zenethiol (2A) and an alkane thiol as 1-butanethiol (2B)
under SFC in the presence of 5 mol-% of TEA, DMAP,
TBD, and TPP (Table 1) and 5 mol-% of the commercially
available PS-TEA, PS-DMAP, PS-TBD, and PS-TPP
(Table 2). For comparison, the same transformations were
also performed in MeCN, which is known to be an efficient
organic medium for this process.
Entry Thiol Reaction Base
medium [5 mol-%]
t
[h]
Conversion
[%][a]
1
2
3
4
5
6
7
8
2A
2A
2A
2A
2A
2A
2A
2A
2B
2B
2B
2B
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
PS-TEA
PS-TEA
PS-DMAP
PS-DMAP
PS-TBD
PS-TBD
PS-TPP
5
5
97
traces
Ͼ 99
10
Table 1. Thiolysis of 1a with 2A and 2B under SFC and in MeCN
at 30 °C catalyzed by organic bases.
10
10
1.5
1.5
22
24
21
21
2
Ͼ 99[b]
50
Ͼ 99
traces
Ͼ 99
4
PS-TPP
9
PS-DMAP
PS-DMAP
PS-TBD
PS-TBD
10
11
12
Ͼ 99[c]
15
MeCN
2
Entry Thiol
Reaction
medium
Base
t
[h]
Conversion
[%][a]
[a] Conversion measured by GLC analyses. The same reactions per-
formed in DCM gave no conversion at all. [b] Isolated yield: 95%.
[c] Isolated yield: 94%.
1
2
3
4
5
6
7
8
2A
2A
2A
2A
2A
2A
2A
2A
2B
2B
2B
2B
2B
2B
2B
2B
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
MeCN
SFC
TEA
TEA
DMAP
DMAP
TBD
TBD
TPP
TPP
TEA
TEA
DMAP
DMAP
TBD
TBD
TPP
1
1
1
24
1
Ͼ 99
18
Ͼ 99
13
Ͼ 99[b]
33
were obtained (Table 1, Entries 2, 4, 6, 8, 10, 12, 14, and
16). As expected from our previous experience[6g] the use of
a reaction medium (MeCN) reduced the catalytic efficiency
of the catalyst while the C-α/C-β ratios remained un-
changed (Table 1).
Under SFC and with PS-supported bases, the regioselec-
tivities of the reactions were the same, and the catalysts
showed slightly reduced efficiency (Table 2, Entries 1 and 3)
or almost identical catalytic efficiencies (Table 2, Entries 5,
7, 9, and 11) in comparison to their non-supported counter-
parts.[13] Nevertheless, the slightly reduced catalytic effi-
ciency is fully compensated by the simpler work-up pro-
cedure and by the possibility of recovering the solid catalyst
thus allowing an environmentally-friendly thiolysis process
1
24
24
24
24
20
70
2
2
24
24
Ͼ 99
11
[c]
9
–
10
11
12
13
14
15
16
–
94
traces
Ͼ 99[d]
traces
[e]
–
MeCN
TPP
–
[a] Conversion measured by GLC analyses. [b] 95% Isolation yield.
[c] Complete conversion of 1a to 3aB/4aB was obtained by using
1 equiv. of TEA after 6 h at 65 °C. [d] 94% Isolation yield. [e] The
same result was obtained at 65 °C and by using 1 equiv. of TPP.
The thiolysis of 1a by benzenethiol (2A) under SFC was to be realized.
efficiently catalyzed by TEA, DMAP, and TBD with com-
PS-TBD was shown to be the most efficient supported
plete conversion within 1 h to a 1:2 mixture of the corre- catalyst, and the processes were complete in 1.5 and 2 h,
sponding hydroxy sulfides 3aA and 4aA (Table 1, Entries 1, respectively, affording the hydroxy sulfides in very good
3, and 5), whereas TPP needed 24 h to promote the com- yields (95 and 94%, respectively) (Table 2, Entries 5 and
plete transformation (Table 1, Entry 7).
11).
In the presence of MeCN, the supported catalysts were
In the reaction of 1a with 1-butanethiol (2B) under SFC,
the catalytic activity of TEA, DMAP, and TPP was signifi- not effective at all, always giving disappointing results
cantly reduced (Table 1, Entries 9, 11, and 15). DMAP gave (Table 2, Entries 2, 4, 8, 10, and 12), except in the case of
a 94% conversion of 1a to a mixture of the products 3aB PS-TBD, which showed a modest catalytic activity (Table 2,
and 4aB after 20 h, while 1.0 equiv. of TEA, 65 °C and 6 h Entry 6). According to the results obtained by using TEA
were necessary to obtain the complete conversion of 1a and and TPP in the thiolysis of 1a by 2B (see Table 1, Entries 9
TPP was ineffective at all. Only TBD maintained its high and 15) PS-TEA and PS-TPP were completely inefficient in
catalytic efficiency and promoted the reaction of 1a with promoting this process.
2B to completion in only 2 h (Table 1, Entry 13). In all cases
The use of PS-TBD was then extended to a variety of
the hydroxy sulfides 3aB and 4aB were formed in a 1:3 ra- 1,2-epoxides 1b–e and to functionalized thiols, such as o-
tio. By performing the base-catalyzed thiolysis of 1a in aminobenzenethiol (2C), o-hydroxybenzenethiol (2D), and
MeCN with both thiols 2A and 2B, unsatisfactory results 2-propene-1-thiol (2E). The results are illustrated in Table 3.
1232
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1231–1236

Thiolysis of 1,2-Epoxides
FULL PAPER
Table 3. PS-TBD-catalyzed thiolysis of 1a–e by the thiols 2A–E un- recovered. PS-TBD used in the reaction of 1a with 2A
der SFC at 30 °C.
showed a slight decrease in its efficiency only after five con-
secutive runs (Figure 1). This catalyst could be regenerated
by washing it with an ammonia solution at room tempera-
ture for 1 h. After filtering the aqueous medium and drying
the catalyst, its efficiency was as high as in the first run.
Figure 1. PS-TBD-catalyzed reactions of 1a and 2A. Isolated yield
of the mixture of 3aA and 4aA in the re-use of the catalyst.
Conclusions
In conclusion we have demonstrated that SFC dramati-
cally increased the catalytic efficiency of a polystyrene-sup-
ported base, such as PS-TBD, in the nucleophilic ring-open-
ing of oxiranes by thiols. Swelling problems, related to the
access to reactive sites of the polymer-supported catalysts,
can be overcome under SFC, where, apparently, the reac-
tants are activated as they flow through the polymer net-
work. The polymer-supported catalyst has been recovered
and reused, and the products have been isolated in excellent
yields by simply filtering the reaction mixture. These results
open a new and promising green route to hydroxy sulfides.
[a] Measured by GLC analyses. [b] Overall isolation yield of both
3 and 4. [c] 1.2 Equiv. was used. [d] Only trans-2-[2Ј-(amino)phen-
Experimental Section
ylthio]cyclohexan-1-ol (3eC) was formed. [e] trans-2-(Allylthio)cy-
clohexan-1-ol (3eE) was formed.
All chemicals were purchased and used without any further purifi-
cation. All the polystyrene-supported catalysts are commercially
PS-TBD proved to be a very efficient catalyst, with short
reaction times (0.25–8 h) and high yields (90–98%) in all
cases, also in the reactions of 1a with 2C–E. While the thi-
available. GC-MS analyses were carried out with 70-eV electron
energy. All 1H NMR and 13C NMR spectra were recorded at
200 MHz or 400 MHz, and at 50.3 or 100.6 MHz, respectively,
ols 2C and 2E attacked preferentially the 1,2-epoxide 1a at
the C-β, giving the hydroxy sulfides 3aC, 4aC,and 3aE, 4aE
in 2:3 and 1:4 ratio, respectively (Table 3, Entries 1 and 3),
the 2-hydroxybenzenethiol (2D) displayed reversed regiose-
lectivity (3aD/4aD, 3:1) (Table 3, Entry 2). This unexpected
result can be ascribed to the formation of a hydrogen bond
between the hydroxy group of 2D and the oxirane oxygen
of 1a.
Homostyrene oxide (1b), glycidol (1c), and O-allylglyci-
dol (1d) reacted with complete regioselectivity, in very short
times (0.017–1.5 h), yielding only the corresponding ad-
ducts 4 (Table 3, Entries 4–9). Cyclohexene oxide (1e)
underwent a completely anti stereoselective ring-opening to
give in high yields the corresponding hydroxy sulfide 3eC
and 3eE in 3 h and 8 h, respectively (Table 3, Entries 10 and
11).
using a convenient deuterated solvent (reported in the characteriza-
tion data) and the residual peak as internal standard, or TMS in
the case of CDCl3. All melting points are uncorrected. Thin-layer
chromatography analyses were performed on silica gel on alumi-
num plates and UV and/or KMnO4 were used as revealing systems.
Column chromatography was performed by using silica gel 230–
400 mesh and eluting as reported in the following characterization
data. Hydroxy sulfides 3aA,[11e] 3aB,[14] 4aA,[15] 4aB,[16] are known
compounds; while 3aC,[17] 3aD,[18] 3aE,[5g] 3eC,[19] 4aC,[17,20]
4aD,[19] 4aE,[21] have already been prepared, but spectroscopic data
have not been reported or are not complete to the best of our
knowledge. Compounds 3eE, 4bC, 4bE, 4cC, 4cE, 4dC, 4dE, are
new compounds. Characterization data (1H NMR, 13C NMR, IR,
GC-EIMS, Rf) are listed below.
Typical Procedure of the PS-TBD-Catalyzed Thiolysis: A screw-
capped vial equipped with a magnetic stirrer was charged with PS-
TBD [19 mg, ca. 0.05 mmol (2.6 mmol/g)] and then the thiol
(1.05 equiv.) and the 1,2-epoxide (1.0 mmol) were consecutively
When polystyrene-supported catalysts are employed, an
important issue is the decrease in their activity after being added. The resulting mixture was left at 30 °C whilst stirring until
Eur. J. Org. Chem. 2006, 1231–1236
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1233

F. Fringuelli, F. Pizzo, C. Vittoriani, L. Vaccaro
FULL PAPER
reaction completed (GLC monitoring). EtOAc was then added and
the heterogeneous mixture was left whilst stirring for 30 min. Solid
PS-TBD was recovered by Büchner filtration of the organic layer,
washed with additional EtOAc, dried under vacuum and reused.
The organic layer was evaporated under reduced pressure to furnish
the almost pure hydroxy sulfide product/s. The mixture of the prod-
ucts was separated by silica gel column chromatography (see be-
low).
24.0, 25.7, 32.4, 33.3, 33.6, 51.8, 72.1, 116.6, 134.6 ppm. IR
(CHCl ): ν = 3518 (m), 3018 (m), 2938 (s), 2862 (m), 1636 (w),
˜
3
1448 (m), 1272 (m), 1214 (s), 1067 (m), 924 (m) cm–1. GC-EIMS
(m/z) = 172 (56) [M+], 113 (17), 98 (62), 81 (100), 69 (28), 57 (20).
C9H16OS (172.3): calcd. C 62.74, H 9.36; found C 62.51, H 9.21.
1-[2Ј-(Amino)phenylthio]-2-phenylethan-2-ol
(4aC):
Solid;
chromatography on silica gel, eluent: petroleum ether/EtOAc, 6:4;
TLC-Rf: 0.30 (petroleum ether/EtOAc, 1:1); m.p. 104–105 °C. 1H
NMR (CDCl3, 400 MHz): δ = 2.89 (dd, J = 9.6, 13.7 Hz, 1 H),
3.13 (dd, J = 3.2, 13.7 Hz, 1 H), 4.03 (br. s, 2 H), 4.61 (dd, J = 3.2,
9.6 Hz, 1 H), 6.72–6.77 (m, 2 H), 7.16 (t, J = 7.7 Hz, 1 H), 7.24–
7.36 (m, 5 H), 7.44 (d, J = 7.6 Hz, 1 H) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 44.5, 71.9, 115.4, 117.0, 119.1, 125.8, 127.7, 128.3,
2-[2Ј-(Amino)phenylthio]-2-phenylethan-1-ol (3aC): Oil; chromatog-
raphy on silica gel, eluent: petroleum ether/EtOAc, 6:4; TLC-Rf:
1
0.39 (petroleum ether/EtOAc, 1:1). H NMR (CDCl3, 400 MHz):
δ = 3.74 (br. s, 2 H), 3.88 (d, J = 6.4 Hz, 2 H), 4.12 (t, J = 6.5 Hz,
1 H), 6.65–6.74 (m, 2 H), 7.15 (t, J = 7.7 Hz, 1 H), 7.26–7.34 (m,
6 H) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 55.5, 64.9, 115.3, 130.2, 136.3, 142.2, 148.3 ppm. IR (CHCl ): ν = 3480 (m), 3369
˜
3
116.1, 118.8, 127.6, 127.9, 128.6, 130.6, 137.6, 139.3, 149.0 ppm.
(m), 3015 (w), 1608 (s), 1480 (m), 1306 (m), 1201 (m), 1056 (m),
996 (w) cm–1. GC-EIMS (m/z) = 245 (33) [M+], 139 (100), 124 (62),
107 (19), 94 (27), 79 (33). C14H15NOS (245.3): C, 68.54, H, 6.16,
IR (CHCl ): ν = 3592 (m), 3485 (m), 3370 (m); 3066 (m), 3017 (s),
˜
3
2877 (w), 2351 (m), 1604 (s), 1478 (s), 1304 (m), 1156 (w), 1057
(m), 1021 (w) cm–1. GC-EIMS (m/z) = 245 (27) [M+], 214 (16), 180 N, 5.71; found: C, 67.88, H 5.94, N 5.67.
(5), 125 (100), 103 (35), 91 (20), 80 (21). C14H15NOS (245.3): calcd.
C 68.54, H 6.16, N 5.71; found C 66.27; H 5.80, N 5.60.
1-[2Ј-(Hydroxy)phenylthio]-2-phenylethan-2-ol
chromatography on silica gel, eluent: petroleum ether/EtOAc/
(4aD):
Oil;
2-[2Ј-(Hydroxy)phenylthio]-2-phenylethan-1-ol
(3aD):
Oil; MeOH, 59:40:1; TLC-Rf: 0.34 (petroleum ether/EtOAc, 7:3). 1H
chromatography on silica gel, eluent: petroleum ether/EtOAc/
NMR (CDCl3, 200 MHz): δ = 2.91 (dd, J = 9.3, 13.7 Hz, 1 H),
3.06 (dd, J = 3.8, 13.7 Hz, 1 H), 4.66 (dd, J = 3.8, 9.3 Hz, 1 H),
MeOH, 59:40:1; TLC-Rf: 0.39 (petroleum ether/EtOAc, 6:4). 1H
NMR (CDCl3, 400 MHz): δ = 2.13 (br. s 1 H), 3.88–3.95 (m, 2 H), 7.86–7.01 (m, 2 H), 7.24–7.32 (m, 7 H) ppm. 13C NMR (CDCl3,
4.01 (dd, J = 6.8, 13.6 Hz, 1 H), 6.79–6.95 (m, 3 H), 7.17–7.31 (m,
50.3 MHz): δ = 45.4, 72.2, 115.4, 118.4, 120.8, 125.8, 128.2, 128.6,
6 H) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 56.4, 64.2, 115.2, 131.4, 136.3, 141.9, 157.4 ppm. IR (CHCl ): ν = 3597 (w), 3385
˜
3
116.8, 120.5, 127.7, 127.9, 128.6, 131.6, 137.2, 138.6, 157.6 ppm.
IR (CHCl ): ν = 3597 (m), 3414 (s), 3022 (m), 2938 (w), 1730 (w),
(m), 3069 (w), 2927 (w), 1576 (m), 1472 (s), 1289 (w), 1227 (s), 1212
(s), 1053 (m), 831 (w) cm–1. GC-EIMS (m/z) = 246 (15) [M+], 126
˜
3
1576 (m), 1470 (s), 1289 (m), 1231 (s), 1208 (s), 1054 (m), 832 (w) (35), 121 (100), 107 (54), 88 (32), 77 (19). C14H14O2S (246.3): calcd.
cm–1. GC-EIMS (m/z) = 246 (26) [M+], 215 (19), 126 (73), 121
(100), 103 (68), 91 (41), 77 (27). C14H14O2S (246.3): calcd. C 68.26,
H 5.73; found C 68.35, H 5.91.
C, 68.26, H 5.73; found C 68.10, H 5.57.
1-(Allylthio)-2-phenylethan-2-ol (4aE): Oil; chromatography on sil-
ica gel, eluent: petroleum ether/EtOAc, 8:2; Tlc-Rf: 0.31 (petroleum
ether/EtOAc, 8:2). 1H NMR (CDCl3, 400 MHz): δ = 2.68 (dd, J =
9.3, 13.9 Hz, 1 H), 2.88 (dd, J = 3.7, 14.0 Hz, 1 H), 2.90 (d, J =
2.6 Hz, 1 H), 3.09–3.20 (m, 2 H), 4.74 (td, J = 3.1, 9.3 Hz, 1 H),
5.09–5.15 (m, 2 H), 5.74–5.84 (m, 1 H), 7.27–7.29 (m, 1 H), 7.30–
7.37 (m, 4 H) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 34.5, 40.1,
2-(Allylthio)-2-phenylethan-1-ol (3aE): Oil; chromatography on sil-
ica gel, eluent: petroleum ether/EtOAc, 8:2; TLC-Rf: 0.35 (petro-
leum ether/EtOAc, 7:3). 1H NMR (CDCl3, 400 MHz): δ = 2.99
(dd, J = 7.8, 13.8 Hz, 1 H), 3.12 (dd, J = 6.5, 13.8 Hz, 1 H), 3.83–
3.90 (m, 2 H), 3.95 (t, J = 6.9 Hz, 1 H), 5.05–5.12 (m, 2 H), 5.73–
5.83 (m, 1 H), 7.27–7.30 (m, 1 H), 7.33–7.37 (m, 4 H) ppm. 13C
71.5, 117.7, 125.7, 127.8, 128.4, 133.9, 142.5 ppm. IR (CHCl ): ν
˜
3
NMR (CDCl3, 100.6 MHz): δ = 33.9, 51.3, 65.5, 117.5, 127.6, = 3599 (m), 3508 (s), 3020 (s), 1636 (w), 1409 (m), 1227 (m), 1213
128.2, 128.6, 134.0, 139.4 ppm. IR (CHCl ): ν = 3592 (m), 3020 (s), 1202 (s), 1053 (s), 993 (s), 924 (s) cm–1. GC-EIMS (m/z) = 194
˜
3
(s), 2926 (w), 2632 (w), 1636 (w), 1391 (m), 1220 (m), 1052 (s), 924 (1) [M+], 176 (7), 107 (79), 88 (100), 79 (84), 51 (15). C11H14OS
(m) cm–1. GC-EIMS (m/z) = 194 (11) [M+], 176 (9), 163 (100), 153
(24), 129 (43), 121 (87), 103 (40), 91 (37), 77 (27). C11H14OS
(194.1): calcd. C 68.00, H 7.26; found C 68.10, H 7.35.
(194.1): calcd. C 68.00, H 7.26; found: C 67.89; H 7.12.
1-[2Ј-(Amino)phenylthio]-3-phenylpropan-2-ol (4bC): Solid; purified
1
by recrystallization from Et2O; m.p. 57–59 °C. H NMR (CDCl3,
trans-2-[2Ј-(Amino)phenylthio]cyclohexan-1-ol (3eC): Solid; purified
by recrystallization from EtOAc/petroleum ether, 1:1; m.p. 82–
400 MHz): δ = 2.70–2.89 (m, 4 H), 2.95 (dd, J = 3.6, 13.6 Hz, 1
H), 3.80–3.83 (m, 1 H), 4.36 (br. s, 2 H), 6.69–6.74 (m, 2 H), 7.16–
83 °C. 1H NMR (CDCl3, 400 MHz): δ = 1.21–1.40 (m, 4 H), 1.66– 7.40 (m, 7 H) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 42.0, 42.2,
1.68 (m, 2 H), 2.05–2.12 (m, 2 H), 2.64 (dt, J = 3.9, 10.9 Hz, 1 H), 70.8, 115.3, 118.1, 119.0, 126.4, 128.3, 129.3, 130.0, 136.1, 137.9,
3.28 (dt, J = 4.3, 10.0 Hz, 1 H), 4.13 (m, 2 H), 6.70–6.77 (m, 2 148.2 ppm. IR (CHCl ): ν = 3580 (w), 3477 (m), 3375 (m), 3020
˜
3
H), 7.14–7.18 (m, 1 H), 7.38–7.41 (1 H) ppm. 13C NMR (CDCl3,
100.6 MHz): δ = 24.3, 26.1, 32.9, 34.2, 56.8, 72.5, 115.4, 115.5, 1158 (w), 1033 (m), 857 (w) cm–1. GC-EIMS (m/z) = 259 (67) [M+],
118.9, 130.4, 138.1, 149.1 ppm. IR (CHCl ): ν = 3638 (w), 3491 150 (41), 139 (24), 124 (100), 117 (65), 91 (53), 80 (35). C15H17NOS
(s), 2923 (m), 1730 (w), 1608 (s), 1480 (m), 1448 (m), 1305 (w),
˜
3
(w), 3347 (w), 2939 (s), 2862 (m), 1606 (s), 1479 (m), 1448(w), 1305 (259.1): calcd. C 69.46, H 6.61, N 5.40; found C 69.66, H 6.83, N
(w), 1214 (s), 1066 (m), 960 (w), 852 (w) cm–1. GC-EIMS (m/z) = 5.65.
223 (36) [M+], 162 (20), 125 (100), 93 (12), 80 (18). C12H17NOS
1-(Allylthio)-3-phenylpropan-2-ol (4bE): Oil; chromatography on sil-
(223.3): calcd. C 64.53, H 7.67, N, 6.27; found C 64.44, H 7.58, N
ica gel, eluent: petroleum ether/EtOAc, 8:2. 1H NMR (CDCl3,
6.30.
400 MHz): δ = 2.42 (br. s, 1 H), 2.47 (dd, J = 8.5, 13.7 Hz, 1 H),
trans-2-(Allylthio)cyclohexan-1-ol (3eE): Oil; chromatography on
silica gel, eluent: EtOAc/petroleum ether, 2:8. 1H NMR (CDCl3,
400 MHz): δ = 1.25–1.44 (m, 4), 1.71–1.74 (m, 2 H), 2.05–2.08 (m,
2 H), 2.40 (t, J = 10.8 Hz, 1 H), 3.10–3.35 (m, 3 H), 5.07–5.17 (m,
2 H), 5.80–5.87 (m, 1 H) ppm. 13C NMR (CDCl3, 50.3 MHz): δ =
2.68 (dd, J = 3.8, 13.7 Hz, 1 H), 2.81 (dd, J = 5.7, 13.4 Hz, 1 H),
2.86 (dd, J = 6.7, 13.3 Hz, 1 H), 3.13 (d, J = 7.2 Hz, 2 H), 3.87–
3.89 (m, 1 H), 4.97–5.11 (m, 2 H), 5.69–5.80 (m, 1 H), 7.21–7–23
(m, 3 H), 7.25–7.33 (m, 2 H) ppm. 13C NMR (CDCl3, 100.6 MHz):
δ = 34.8, 37.6, 42.6, 70.5, 117.5, 126.5, 128.5, 129.4, 133.9, 137.9
1234
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Eur. J. Org. Chem. 2006, 1231–1236

Thiolysis of 1,2-Epoxides
FULL PAPER
ppm. IR (CHCl ): ν = 3584 (m), 3083 (w), 3020 (s), 2920 (m), 2362
˜
3
(w), 1730 (w), 1496 (w), 1428 (w), 1223 (s), 1080 (m), 1032 (m), 923
(m) cm–1. GC-EIMS (m/z) = 208 (3) [M+], 190 (39), 148 (36), 117
(97), 103 (45), 91 (100), 73 (25). C11H14OS (208.1): calcd. C 69.19,
H 7.74; found C 69.30, H 7.85.
[1]
[2]
[3]
a) B. List, Tetrahedron 2002, 58, 5573–5590; b) P. I. Dalko, L.
Moisan, Angew. Chem. Int. Ed. 2004, 43, 5138–5175; c) Acc.
Chem. Res. 2004, 37, entire issue 8.
a) C. A. McNamara, M. J. Dixon, M. Bradley, Chem. Rev.
2002, 102, 3275–3300; b) M. Benaglia, A. Puglisi, F. Cozzi,
Chem. Rev. 2003, 103, 3401–3429.
a) P. T. Anastas, Green Chemistry: Theory and Practice, Oxford
University Press, Oxford, 1998; b) P. Tundo, P. T. Anastas,
Green Chemistry: Challenging Perspectives, Oxford University
Press, Oxford, 1999; c) Organic Synthesis in Water (Ed.: P. A.
Grieco), Blackie Academic and Professional: London, 1998; d)
C. J. Li, T. H. Chang, Organic Reactions in Aqueous Media,
Wiley, New York, 1997.
a) J. O. Metzger, Angew. Chem. Int. Ed. 1998, 37, 2975–2978;
b) R. S. Varma, Green Chem. 1999, 1, 43–55; c) K. Tanaka, F.
Toda, Chem. Rev. 2000, 100, 1025–1074; d) R. S. Varma, Pure
Appl. Chem. 2001, 73, 193–198; e) G. W. V. Cave, C. Raston,
J. L. Scott, Chem. Commun. 2001, 2159–2169; f) K. Tanaka, F.
Toda, in: Solvent-free Organic Synthesis, Wiley-VCH, 2003.
As representative papers see: a) F. Fringuelli, F. Pizzo, L. Vac-
caro, Synthesis 2000, 646–650; b) D. Amantini, F. Fringuelli,
O. Piermatti, F. Pizzo, L. Vaccaro, Green Chem. 2001, 3, 229–
232; c) F. Fringuelli, M. Matteucci, O. Piermatti, F. Pizzo,
M. C. Burla, J. Org. Chem. 2001, 66, 4661–4666; d) F. Fring-
uelli, F. Pizzo, S. Tortoioli, L. Vaccaro, Adv. Synth. Catal. 2002,
344, 379–384; e) F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro,
Green Chem. 2003, 5, 436–440; f) F. Fringuelli, F. Pizzo, M.
Rucci, L. Vaccaro, J. Org. Chem. 2003, 68, 7041–7045; g) F.
Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, J. Org. Chem.
2003, 68, 8248–8251; h) D. Amantini, F. Fringuelli, O. Pierm-
atti, F. Pizzo, L. Vaccaro, J. Org. Chem. 2003, 68, 9263–9268;
i) F. Fringuelli, F. Pizzo, L. Vaccaro, J. Org. Chem. 2004, 69,
2315–2321; j) F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro,
Org. Lett. 2005, 7, 4411–4414.
a) D. Amantini, F. Fringuelli, F. Pizzo, L. Vaccaro, J. Org.
Chem. 2001, 66, 6734–6737; b) D. Amantini, F. Fringuelli, F.
Pizzo, J. Org. Chem. 2002, 67, 7238–7243; c) F. Fringuelli, F.
Pizzo, S. Tortoioli, L. Vaccaro, Tetrahedron Lett. 2003, 44,
6785–6787; d) D. Amantini, R. Beleggia, F. Fringuelli, F. Pizzo,
L. Vaccaro, J. Org. Chem. 2004, 69, 2896–2898; e) F. Fringuelli,
F. Pizzo, S. Tortoioli, L. Vaccaro, J. Org. Chem. 2004, 69, 7745–
7747; f) F. Fringuelli, F. Pizzo, S. Tortoioli, L. Vaccaro, J. Org.
Chem. 2004, 69, 8780–8785; g) F. Fringuelli, F. Pizzo, C. Vittor-
iani, L. Vaccaro, Chem. Commun. 2004, 2756–2757.
3-[2Ј-(Amino)phenylthio]propan-1,2-diol (4cC): Oil; chromatography
on silica gel, eluent: EtOAc/petroleum ether, 7:3. 1H NMR (CDCl3,
400 MHz): δ = 2.73 (dd, J = 8.3 Hz, 13.6 Hz, 1 H), 2.84 (dd, J =
4.3, 13.5 Hz, 1 H), 3.46 (dd, J = 6.4, 11.5 Hz, 1 H), 3.56–3.70 (m,
2 H), 4.36 (br. s, 2 H), 6.69–6.72 (m, 2 H), 7.11–7.12 (m, 1 H),
7.37–7.39 (m, 1 H) ppm. 13C NMR (CDCl3, 100.6 MHz): δ = 38.1,
63.3, 70.4, 115.3, 117.3, 118.8, 129.8, 135.8, 148.1 ppm. IR
(CHCl ): ν = 3440 (m), 3379 (s), 3020 (s), 1730 (s), 1608 (s), 1479
˜
3
[4]
[5]
(m), 1305 (w), 1245 (s), 1051 (s), 882 (w) GC-EIMS (m/z) = 199
(49) [M+], 199 (52), 150 (13), 136 (28), 125 (100), 94 (29), 80 (38).
C9H13NO2S (199.3): calcd. C 54.25; H 6.58, N 7.03; found C 54.40,
H 6.72, N 7.15.
3-(Allylthio)propane-1,2-diol (4cE): Oil; chromatography on silica
gel, eluent: EtOAc/petroleum ether, 7:3; TLC-Rf: 0.35 (EtOAc/
1
MeOH, 98:2); 75% yield. H NMR (CDCl3, 400 MHz): δ = 2.53
(dd, J = 8.1, 13.7 Hz, 1 H), 2.62 (dd, J = 4.8, 13.8 Hz, 1 H), 2.80
(br. s, 1 H), 3.14 (d, J = 7.3 Hz, 2 H), 3.50–3.55 (m, 1 H), 3.70–
3.78 (m, 2 H), 5.06–5.12 (m, 2 H), 5.71–5.82 (m, 2 H) ppm. 13C
NMR (CDCl3, 50.3 MHz): δ = 33.5, 34.8, 65.1, 70.4, 117.4, 133.8
ppm. IR (CHCl ): ν = 3586 (s), 3472 (s), 3017 (m), 2923 (m), 1730
˜
3
(m), 1635 (w), 1407 (s), 1226 (s), 1057 (s), 924 (m) cm–1. GC-EIMS
(m/z) = 148 (49) [M+], 117 (11), 99 (42), 87 (37), 74 (100), 61 (42).
C6H12O2S (148.2): calcd. C 48.62, H 8.16; found C 48.80, H 8.23.
1-(Allyloxy)-3-[2Ј-(amino)phenylthio]propan-2-ol (4dC): Oil. 1H
NMR (CDCl3, 200 MHz): δ = 2.79 (dd, J = 7.7, 13.5 Hz, 1 H),
2.93 (dd, J = 4.8, 13.5 Hz, 1 H), 3.13 (br. s, 1 H), 3.38–3.53 (m, 2
H), 3.74–3.84 (m, 1 H), 3.94–3.98 (m, 2), 4.41 (br. s, 2 H), 5.15–
5.30 (m, 2 H), 5.91–5.97 (m, 1 H), 6.68–6.73 (m, 2 H), 7.08–7.16
(m, 1 H), 7.37–7.42 (m, 1 H) ppm. 13C NMR (CDCl3, 100.6 MHz):
δ = 38.3, 68.7, 71.8, 72.3, 114.9, 116.9, 118.3, 129.5, 135.6, 148.0
[6]
ppm. IR (CHCl ): ν = 3573 (m), 3479 (s), 3375 (s), 3019 (s), 2920
˜
3
(m), 2865 (m), 1730 (w), 1608 (s), 1478 (m), 1448 (w), 1306 (m),
1222 (s), 1106 (s), 933 (m) cm–1. GC-EIMS (m/z) = 239 (60) [M+],
164 (14), 150 (24), 136 (28), 124 (100), 97 (27), 80 (39). C12H17NO2S
(188.3): calcd. C 60.22, H 7.16, N 5.85; found C 60.07, H 7.03, N
5.74.
[7]
[8]
a) R. N. Armostrong, Curr. Opin. Chem. Biol. 1998, 2, 618–
623; b) J. Magdalou, S. Fournel-Gigleux, B. Testa, M. Ouzzine,
in: The Practice of Medical Chemistry (Ed.: C. G. Wermuth),
Academic Press: San Diego, CA, 2nd edition, 2004, p. 541.
a) Y. J. Abul-Hajj, J. Med. Chem. 1986, 29, 582–584 [Na, neat];
b) C. H. Behrens, K. B. Sharpless, J. Org. Chem. 1985, 50,
5696–5704 [NaH, THF]; c) O. Yamada, K. Ogasawara, Synlett
1995, 427–428 [NaH, THF]; d) J. C. Justo De Pomar, A. Soder-
quist, Tetrahedron Lett. 1998, 39, 4409–4412 [DBU]; e) H. Ad-
ams, R. Bell, Y.-Y. Cheung, N. D. Jones, N. C. O. Tomkinson,
Tetrahedron: Asymmetry 1999, 10, 4129–4142 [Na].
1-(Allyloxy)-3-(allylthio)propan-2-ol (4dE): Oil; chromatography on
silica gel, eluent: EtOAc/petroleum ether, 3:7; TLC-Rf: 0.33
(EtOAc/MeOH, 98:2). 1H NMR (CDCl3, 400 MHz): δ = 2.53–2.60
(m, 1 H), 2.61–2.77 (m, 2 H), 3.15 (d, J = 7.2 Hz, 2 H), 3.45 (dd,
J = 6.4, 9.6 Hz, 1 H), 3.53 (dd, J = 3.9, 9.6 Hz, 1 H), 3.87–3.88
(m, 1 H), 4.01–4.03 (m, 2 H), 5.07–5.13 (m, 2 H), 5.18–5.29 (m, 2
H), 5.73–5.81 (m, 1 H), 5.85–5.95 (m, 1 H) ppm. 13C NMR
(CDCl3, 50.3 MHz): δ = 34.1, 35.0, 69.0, 72.3, 72.7, 117.3, 117.5,
134.0, 138.9 ppm. IR (CHCl ): ν = 3573 (m), 3018 (m), 2918 (m),
[9]
˜
a) T. Iizawa, A. Goto, T. Nishikubo, Bull. Chem. Soc., Jpn.
1989, 62, 597–598[Bu4NX]; b) D. Albanese, D. Landini, M.
Penso, Synthesis 1994, 34–36 [Bu4NF].
3
2864 (w), 1640 (w), 1424 (w), 1213 (s), 1104 (s), 993 (m), 927 (m)
cm–1. GC-EIMS (m/z) = 188 (1) [M+], 147 (11), 131 (84), 119 (57),
97 (100), 73 (80). C9H16O2S (188.3): calcd. C 57.41, H 8.57; found
C 57.60, H 8.70.
[10]
[11]
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Acknowledgments
The Ministero dell’Istruzione dell’Università
e della Ricerca
(MIUR) and the Università degli studi di Perugia are thanked for
financial support within the funding projects: COFIN, COFIN-
LAB (CEMIN) and FIRB 2001.
Eur. J. Org. Chem. 2006, 1231–1236
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1235

F. Fringuelli, F. Pizzo, C. Vittoriani, L. Vaccaro
FULL PAPER
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Received: October 11, 2005
Published Online: December 22, 2005
1236
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 1231–1236