Conversion of norbornene derivatives into vicinal-dithioethers via S 8 activation

Article abstract of DOI:10.1016/j.tetlet.2005.07.161

Norbornene reacts with elemental sulfur to give a mixture of trithiolane and pentathiepane. Sulfuration of norbornene derivatives was achieved with elemental sulfur, by using a catalytic amount of a nickel complex, to afford selectively the corresponding trithiolanes. The most effective catalytic system was Ni(NH₃)₆Cl₂ in dimethylformamide. The trithiolanes were reduced with super-hydride into 1,2-dithiolate salts, and quenched in situ to form vicinal-dithioethers.

Full text of DOI:10.1016/j.tetlet.2005.07.161

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 7077–7079
Conversion of norbornene derivatives into vicinal-dithioethers via
S8 activation
a,
a
a,b
*
Sophie Poulain, Sandy Julien and Elisabet Du n˜ ach
a
Laboratoire Ar oˆ mes, Synth e` ses et Interactions, Facult e´ des Sciences de Nice-Sophia Antipolis, Parc Valrose,
6108 Nice cedex 2, France
Laboratoire de Chimie Bioorganique, CNRS, UMR 6001, Facult e´ des Sciences de Nice-Sophia Antipolis, Parc Valrose,
6108 Nice cedex 2, France
0
b
0
Received 23 May 2005; revised 28 July 2005; accepted 29 July 2005
Abstract—Norbornene reacts with elemental sulfur to give a mixture of trithiolane and pentathiepane. Sulfuration of norbornene
derivatives was achieved with elemental sulfur, by using a catalytic amount of a nickel complex, to afford selectively the correspond-
ing trithiolanes. The most effective catalytic system was Ni(NH
super-hydride into 1,2-dithiolate salts, and quenched in situ to form vicinal-dithioethers.
2005 Elsevier Ltd. All rights reserved.
3 6 2
) Cl in dimethylformamide. The trithiolanes were reduced with
ꢀ
The direct functionalisation of non-activated alkenes in
synthesis of some 1,2-disulfides derived from norborn-
ene. The synthesis involves the initial double bond selec-
the presence of thiol derivatives (RSH or H S) has been
2
reported to afford the corresponding thioethers via radi-
cal reactions with an anti Markovnikov-type selectiv-
tive sulfurisation by S , and the further reduction and
alkylation of the isolated trithiolanes to the desired
1,2-dithioethers (Scheme 1).
8
1
ity. In the context of 1,2-functionalisation of alkenes
2
by sulfurde ri vatives, Kondo et al.
have described the
Ru-catalysed addition of organic disulfides with alkenes,
forthe synthesis of vicinal-dithioethe rs . A mild method
foraddition of alkyl disulfides to alkenes and conju-
Particularly strained olefins have been reported to react
with elemental sulfur(S ) to afford mixtures of cyclic
8
4
–8
polysulfides, such as trithiolanes and pentathiepanes.
gated polyenes promoted by ZnCl /montmorillonite
clays has also been reported. We have been interested
in the transformation of C–C double bonds into 1,2-
dithioether derivatives and here we describe the two-step
The chemistry of sulfur allotropes has also been investi-
gated: cyclodecasulfur(S 10) reacted with norbornene to
furnish the trisulfide in good yield and selectivity. With
2
3
9
S8 as sulfur source, the corresponding thiiranes could be
[
Ni(NH ) ]Cl (2 mol%)
S
1
) LiEt BH, THF, 65 C
3
SE
SE
3
6
2
S
+
S8
S
DMF
2) EX
R
R
R
1
1
a R = -H
b R = -CH=CH2
2a-c
3a-c
E = -H, -Me, -CH Ph
2
1
c R = -COCH3
Scheme 1.
Keywords: Norbornene; Elemental sulfur; Trithiolane; Nickel catalysis; Dithioethers.
*
Corresponding author. Tel.: +33 (0) 4 92 07 65 77; fax: +33 (0) 4 92 07 61 25; e-mail: poulain@unice.fr
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.161

7078
S. Poulain et al. / Tetrahedron Letters 46(2005) 7077–7079
obtained only in a few cases.5,10,11 Synthesis of thiiranes
by direct sulfur transfer has been recently reviewed by
Adam and Bargon.
rate. Replacing the NH ligand on Ni(II) by the cyclic
3
tetraamine cyclam (1,4,7,11-tetraazacyclotetradecane)
afforded 2a in 47% yield and 95% selectivity. The use
of nickel acetate as the catalyst did not improve the
results with respect to the use of [Ni(NH ) ]Cl . With
1
2
Upon studying alkene functionalisation by S , we found
8
3 6
2
that Ni(II) complexes were able to catalyse the sulfurisa-
tion of norbornene derivatives to give selectively the cor-
responding 1,2,3-trithiolane heterocycles, 2. Thus, the
reaction of norbornene 1a with elemental sulfurin the
presence of [Ni(NH ) ]Cl as the catalyst (2 mol %),
in DMF at 120 ꢁC, afforded a 75% isolated yield of
exo-1,2,3-trithiolane 2a with 97% selectivity (Table 1,
entry 1).
[Ni(NH ) ]Cl , the sulfuration of 5-vinyl-2-norbornene,
3 6 2
1b and of 2-acetyl-5-norbornene, 1c afforded the corre-
sponding trithiolane derivatives 2b (entry 7) and 2c
(entry 8) in 95% and 96% selectivities and 82% and
1
4
77% yields, respectively. Less strained alkenes such
as cyclohexene were not reactive under the reaction
conditions used.
3
6
2
The reduction of trithiolanes 2 to the corresponding 1,2-
disulfides 3 (Scheme 1) was attempted using different
reducing metals (Ni , Na and Zn/AcOH) orhyd ir des
1
The exo-selectivity of 2a was determined by H NMR
4
0
0
analysis by the W-coupling of J = 1.8 Hz between the
endo proton at C-1 (carbon bearing the sulfur atom)
and the anti proton at the bridge C-3. The W-coupling
is absent in the endo isomer.
(NaH and LiAlH ). All these reducing systems led to
4
the recovery of the starting material 2 orto decomposi-
tion. The formation of vicinal-disulfides 3 from trithio-
lanes 2a–c could be efficiently carried out by reduction
In the absence of Ni(II) catalyst, 1a reacted with elemen-
tal sulfur in DMF to give a 3.5:1 mixture of trisulfide 2a
and pentasulfide (pentathiepane, entry 2), in agreement
with LiEt BH in refluxing THF, followed by the addi-
3
tion of methyl iodide or benzyl bromide as the electro-
philes. The results, summarised in Table 2, indicated
that 3–4 equiv of the hydride were necessary to effi-
ciently transform the trithiolanes into the corresponding
1,2-dithiolate salts before electrophilic quenching.
Yields of 3a and b from 71% to 91% were obtained;
for 3c the yields were lower, due to the partial reduction
of the acetyl group.
4
with previous results. The reaction selectivity was
dependent on the amount of S and was optimised for
8
an alkene: S ratio of 1:3/8. Higher S ratios led to the
8
8
formation of pentathiepane in up to 26% selectivity
entry 3).
(
The effect of the nickel catalyst was examined and the
results on the use of different catalysts are presented in
Table 1 (entries 4–6). Raney-Ni was very selective
towards 2a though the reaction occurred at a very slow
The reduction of trithiolane structures 2a and b was
also studied by using an electrochemical methodology.
No electrochemical trithiolane reduction has been yet
13
8
Table 1. Sulfuration of norbornene derivatives (alkene 5.3 mmol, S 3/8 equiv, catalyst 0.02 equiv, 15 ml DMF)
a
Entry
Substrate
Catalyst, reaction time (h)
Selectivity of 2, % (% of isolated yield of 2)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1c
[Ni(NH
— , 11
[Ni(NH
Ni(OAc)
Raney-Ni, 65
Ni(cyclam)(BF ) , 50
4 2
3
)
6
]Cl
2
, 11
97 (75)
76 (48)
74 (54)
90 (48)
100 (26)
95 (47)
95 (82)
96 (77)
b
3
)
6
]Cl
2
, 1
2 2
Æ4H O, 39
[Ni(NH
[Ni(NH
3
)
)
6
6
]Cl
]Cl
2
, 7
, 11
3
2
a
1
Selectivity calculated according to H NMR spectra of the crude reaction mixture.
5
b
/4 equiv of elemental sulfurwe re employed.
15
Table 2. Reduction of trithiolane derivatives 2a–c
Entry
Substrate
Reagent (nb equiv), time (h)
Electrophile
Yield of 3 (%)
b
1
2
3
4
5
6
8
9
2a
2a
2a
2a
2b
2c
2a
2b
LiEt
LiEt
LiEt
LiEt
LiEt
LiEt
3
3
3
3
3
3
BH (2), 4
BH (3), 2
BH (4), 1
BH (4), 1.5
BH (4), 1
—
19
90
91
b
—
CH
PhCH
CH
CH
CH
CH
3
I
2
Br98
3
3
3
3
I
I
I
I
71
21
84
50
BH (4), 1
a
Electrolysis, 7
Electrolysis, 7
a
a
The reaction was carried out at constant current intensity, at room temperature, in DMF containing LiClO
followed by GC, consumed 8 F/mol of substrate for a complete conversion.
The reaction was quenched with H O and the vicinal-dithiol was isolated.
2
4
as supporting electrolyte. The reaction,
b

S. Poulain et al. / Tetrahedron Letters 46(2005) 7077–7079
7079
4
reported. Efficient reactions were obtained in a single-
compartment cell, with a consumable magnesium
anode. In DMF, at room temperature, and after
quenching with MeI, the 1,2-dimethylthio derivatives
d · 2, CHS · 2, J = 1.8 Hz), 2.63 (1H, m, CH), 2.46 (2H,
m, CHCO and CH), 2.16 (3H, s, CH ), 2.05 (1H, m,
CHH CHCO), 1.82 (1H, dt, CHHanti, J = 10.9 Hz,
J = 1.7 Hz), 1.44 (1H, ddd, CHH
J = 8.9 Hz, J = 2.4 Hz), 1.06 (1H, dt, CHHsyn,
3
2
1
6
a
4
3
2
2
b
CHCO, J = 11.8 Hz,
3
3
a and b were obtained in 84% and 50% yields, respec-
4
13
J = 10.9 Hz, J = 1.7 Hz). C NMR (CDCl
CO), 70.1 and 70.0 (CHS · 2), 53.5 (CHCO), 44.1 and
CHCO), 30.8 (CH ), 29.5 (CH ).
3
) d: 207.3
tively (Table 2, entries 8 and 9).
(
4
1.1 (CH · 2), 31.1 (CH
2
2
3
+
Å
In conclusion, a Ni(II)-catalysed selective functionalisa-
tion of norbornene derivatives to trithiolanes was devel-
oped by using elemental sulfuras the sulf ua rt ing
reagent. The further transformation of the trithiolanes
to the corresponding 1,2-disulfides was achieved by a
MS (EI, 70 eV): m/z (%) 232 (M , 38.9), 198 (5.2), 168
(19.5), 125 (26.9), 98 (53.3), 91 (30.9), 71 (37.2), 66 (54.7),
43 (100), 39 (26.6).
15. To a stirred solution of trithiolane 2 (200 mg, 1.05 mmol)
in THF (2 ml) was added LiEt
.2 mmol) dropwise, at room temperature. The mixture
was heated to 65 ꢁC. After 1 h, the reaction mixture was
quenched with CH I (0.65 ml, 10.5 mmol). The mixture
was cooled and poured into 10 ml of H O. It was extracted
3
BH (1 M in THF, 4.2 ml,
4
chemical reduction with LiEt BH orby an elect ro chem-
3
ical reduction procedure.
3
2
References and notes
with Et O (3 · 10 ml) and washed with 10 ml of H O. The
2
2
organic layer was dried over MgSO
4
and concentrated
1
2
3
4
5
6
. Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273–
87.
. Kondo, T.; Uenoyama, S.; Fujita, K.; Mitsudo, T. J. Am.
Chem. Soc. 1999, 121, 482–483.
under reduced pressure. The resulting oil was purified by
column chromatography (eluant: petroleum ether) to give
the dithioether 3 as a colourless oil. Following the same
procedure, the reduction of 2a–c gave the corresponding
vicinal-dithioethers 3a–c, as colourless oils.
2
. Clark, P.; Mesher, S.; Parvez, M. Catal. Lett. 1997, 47, 73–
7
5.
. Bartlett, P. D.; Ghosh, T. J. Org. Chem. 1987, 52, 4937–
943.
. Nakayama, J.; Ito, Y.; Mizumura, A. Sulfur Lett. 1992,
4, 247–250.
. Sugihara, Y.; Takeda, H.; Nakayama, J. Tetrahedron Lett.
998, 39, 2605–2608.
Forexample, spect ar l data forcompounds
3b and c. 5-
Ethenyl-2,3-bis(methylthio)bicyclo[2.2.1]heptane 3b: col-
1
4
3
ourless oil, yield = 71%. H NMR (CDCl ) d: 5.77 (1H,
3 3 3
ddd, CH@CH
Hz), 5.03 (1H, ddd, CH@CHH , Jcis = 10.8 Hz, J = 1.6
a
3
2
, Jtrans = 16.9 Hz, Jcis = 10.8 Hz, J = 5.5
3 2
1
4
b trans
Hz, J = 1.6 Hz), 4.99 (1H, ddd, CH@CHH , J =
2
4
1
16.9 Hz, J = 1.6 Hz, J = 1.6 Hz), 3.12 (1H, dd, CHS,
3
4
3
4
3
7
8
. Weller, K.; Hwang, L. U.S. Patent 6211345, 2001, 7 pp.
. Emsley, J.; Griffiths, D.; Jayne, G. J. Chem. Soc. Perkin
Trans. 1 1979, 228–232.
J = 7.8 Hz, J = 1.8 Hz), 2.81 (1H, dd, CHS, J = 7.8 Hz,
3
J = 1.8 Hz), 2.55 (1H, dddd, CHCH@CH
, J = 6.8 Hz,
J = 5.5 Hz, J = 1.8 Hz, J = 1.8 Hz), 2.2 (2H, m,
· 2), 1.82 (2H, m, CHH
and CHHanti), 1.28 (1H, m, CHHsyn),
2
4
4
9
. Lest e´ -Lasserre, P.; Harpp, D. Tetrahedron Lett. 1999, 40,
CH · 2), 2.1 (6H, s, CH
CHCH@CH
1.02 (1H, ddd, CHH
3
a
-
7
961–7964.
0. Ashitani, T.; Nagahama, S. Nat. Prod. Lett. 1999, 13, 163–
67.
1. Sugihara, Y.; Noda, K.; Nakayama, J. Tetrahedron Lett.
000, 41, 8913–8916.
2. Adam, W.; Bargon, R. Chem. Rev. 2004, 104, 251–261.
3. Elemental sulfurS (510 mg, 2 mmol) and the catalyst
Ni(NH ]Cl (25 mg, 0.1 mmol) were added to a solution
2
2
3
1
1
b
CHCH@CH
2
,
J = 11.0 Hz, J =
NMR (CDCl d: 140.1
), 57.4 (CHS), 50.4 (CHS),
), 44.8 and 43.5 (CH · 2), 35.9 and 34.0
3
13
1
6.8 Hz, J = 2.2 Hz).
(CH@CH ), 115.8 (CH@CH
49.3 (CHCH@CH
(CH · 2), 17.9 and 18.0 (CH · 2). MS (EI, 70 eV): m/z
C
3
)
2
2
2
2
1
1
2
3
+
Å
(%) 214 (M , 100), 167 (45.7), 113 (97.1), 91 (64.5), 66
(63.6).
8
[
3
)
6
2
of alkene 1 (500 mg, 5.3 mmol) in 15 ml of DMF, at room
temperature. The reaction mixture was stirred at 120 ꢁC
during 11 h. The reaction was followed by GC. After
cooling down to room temperature, the mixture was
filtered on silica gel and eluted with petroleum ether. The
filtrate was washed with water (3 · 10 ml). The organic
layer was concentrated under reduced pressure to afford
the norbornane trithiolane 2 as a colourless oil. The
trisulfides 2a–c were obtained following the same
procedure.
5-Acetyl-2,3-bis(methylthio)bicyclo[2.2.1]- heptane 3c: col-
1
ourless oil, yield = 21%. H NMR (CDCl
3
) d: 2.68 and
4
2.62 (2H, d · 2, CHS · 2, J = 2.0 Hz), 2.38 (1H, m,
CHCO), 2.23 (2H, m, CH · 2), 2.17 (3H, s, CH CO), 2.04
(6H, s, CH S · 2), 1.55 (1H, m, CHHanti), 1.25–1.08 (3H,
m, CH and CHHsyn). C NMR (CDCl
(CHCO), 48.3 (CHS · 2), 44.6 and 42.9 (CH · 2), 38.6
and 35.6 (CH CO), 19.0 (CH
3
3
1
3
2
3
) d: 64.9
· 2), 22.4 (CH
S · 2). MS
2
3
3
+
Å
(EI, 70 eV): m/z (%) 230 (M , 44.1), 215 (20.6), 167 (47.1),
135 (11.8), 127 (15.7), 107 (54.9), 91 (57.4), 75 (47.1), 55
(37.3), 45 (100).
1
4. Forexample, spect ar l data forcompound, 5-acetylhexa-
hydro-4,7-methanobenzotrithiole 2c: colourless oil,
16. Chaussard, J.; Folest, J. C.; Nedelec, J. Y.; Perichon, J.;
Sibille, S.; Troupel, M. Synthesis 1990, 5, 369–381.
1
yield = 77%. H NMR (CDCl ) d: 3.69 and 3.67 (2H,
3