A novel and simple procedure for the enantiospecific synthesis of bridgehead norbornane thioethers and thiocyanates

Article abstract of DOI:10.1016/S0957-4166(02)00716-4

An easy three-step route for the enantiospecific synthesis of novel 1-norbornyl thioethers and thiocyanates from readily available natural fenchone and camphor is described. The key step of the synthetic route is the nucleophilic substitution over the sulfenyl sulfur atom of the intermediate thiotriflates by the corresponding C-nucleophiles.

Full text of DOI:10.1016/S0957-4166(02)00716-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2635–2639
A novel and simple procedure for the enantiospecific synthesis of
bridgehead norbornane thioethers and thiocyanates
Antonio Garc´ıa Mart´ınez,a,* Enrique Teso Vilar,b,* Florencio Moreno Jime´nez,a
b
a
´
Ana Mar´ıa Alvarez Garc´ıa and Patricia Pinilla Rodr´ıguez
aDpto. de Qu´ımica Orga´nica I, Fac. de CC. Qu´ımicas, Universidad Complutense de Madrid, Ciudad Universitaria,
28040 Madrid, Spain
bDpto. de Qu´ımica Orga´nica y Biolog´ıa, Fac. de Ciencias, UNED, Senda del Rey 9, 28040 Madrid, Spain
Received 27 July 2002; accepted 30 October 2002
Abstract—An easy three-step route for the enantiospecific synthesis of novel 1-norbornyl thioethers and thiocyanates from readily
available natural fenchone and camphor is described. The key step of the synthetic route is the nucleophilic substitution over the
sulfenyl sulfur atom of the intermediate thiotriflates by the corresponding C-nucleophiles. © 2002 Elsevier Science Ltd. All rights
reserved.
1. Introduction
lar Pauson–Khand reactions.11 On the other hand, thio-
cyanates are very important synthetic intermediates for
the preparation of a wide variety of organosulfur com-
pounds.12 As a result of these applications, the develop-
ment of new chiral camphor– or norbornane–S(II)
derivatives is of particular interest and, in order to
rapidly screen a series of these compounds for their use
in asymmetric synthesis, the development of a method
allowing rapid synthetic entry to these compounds is
desirable.
There is a great deal of current interest in the use of
chiral sulfides in asymmetric synthesis.1,2 This interest is
mainly focused on sulfur ylide-mediated catalytic enan-
tioselective aziridination of imines,1,3 cyclopropanation
of olefins1,3b and epoxidation of aldehydes and
ketones.1,4 These methodologies involve ylide genera-
tion either by deprotonation of the corresponding chi-
ral sulfonium salt (from alkylation of the starting
sulfide),5 or by coupling of the latter with a carbene or
carbenoid generated from a diazomethane derivative.6
Since the pioneering work of Furukawa et al.7 on the
catalytic asymmetric epoxidation of aldehydes, using
10-camphoryl sulfides as ligands, a huge number of
chiral sulfides have been synthesised and tested as chiral
auxiliaries or catalysts for the above mentioned reac-
tions.1–7 Among these, camphor-based sulfides8 (e.g.
camphoroxathianes, mainly developed by Aggarwal et
al.)9 are the most extensively used and have played an
important role in this field. Camphor-derived keto-
sulfides are also key intermediates in syntheses of other
interesting C10–S(II)- and C10–S(IV)-substituted cam-
phor derivatives.10 In addition, homochiral camphor-
based acetylene thioethers have recently found
interesting applications in both intra- and intermolecu-
Over the last decade, we have been interested in the
chemistry of homochiral bridgehead norbornane
derivatives, which have been widely used by us as
starting materials for the preparation of chiral lig-
ands,13
virostatics,14
homochiral
cyclopentane
derivatives15 and other interesting camphor- or fen-
chone-based intermediates.16 In continuation of our
studies in this field, we wish to report herein an easy
and convenient procedure for the enantiospecific syn-
thesis of optically active bridgehead norbornane
thioethers and thiocyanates, which find interesting
applications as chiral controllers in asymmetric
synthesis.
2. Results and discussion
Previously, we have shown17 that the reaction of opti-
cally active thiocamphor and thiofenchone 2 with tri-
* Corresponding authors. Tel.: +34 913987332; fax: +34 913986697;
e-mail: eteso@ccia.uned.es
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00716-4

2636
A. Garc´ıa Mart´ınez et al. / Tetrahedron: Asymmetry 13 (2002) 2635–2639
The reaction of 3 with alkylmagnesium chlorides,
lithium acetylides and tetrabutylammonium cyanide
takes place under very mild conditions, by nucleophilic
attack mainly at the more electrophilic sulfenyl sulfur
atom,19 leading to the corresponding sulfide (or thio-
cyanate) in moderate to good yields. Thus, the treat-
ment of 3 with the in situ-generated acetylide20 afforded
fluoromethanesulfonic anhydride constitutes the key
step for the introduction of a sulfur atom at the bridge-
head position of the norbornane framework, leading to
the corresponding 2-methylene-1-norbornyl thiotriflates
3 (Scheme 1) which, like other thiosulfonates, are good
sulfenylating reagents. Thus, the solvolysis of these
homochiral bridgehead thiotriflates in EtOH and
Et2NH takes place smoothly, by nucleophilic attack at
the sulfenyl sulfur atom, giving the corresponding sulfe-
nates and sulfenamides, which can be oxidised easily to
their sulfonic derivatives.18
the acetylene thioethers 4. Thiocyanates
5 were
obtained in good yield by treatment of 3 with tetra-
butylammonium cyanide in dry dichloromethane.
Finally, the reaction of 3 with the corresponding
organomagnesium reagent leads to a series of bridge-
head norbornane thioethers 6, with different degrees of
steric hindrance around the sulfur atom, in moderate to
good yields.
Taking advantage of the powerful sulfenylating charac-
ter of thiotriflates 3, favoured by the strong nucleo-
fugicity of the triflinate group, we have now assayed
their reactivity with various C-nucleophiles, including
metal acetylides, cyanide ion, organolithium and
organomagnesium reagents (Scheme 2). The results are
summarised in Table 1.
It is noteworthy that the use of alkylmagnesium chlo-
rides leads to the highest yields in the corresponding
sulfide. The reaction of 3 with the more reactive ana-
loguous organometallic reagents, such as alkyllithiums
or alkylmagnesium bromides, under the same condi-
tions, is much less selective, leading to complex reaction
mixtures and lower yield of sulfide. As revealed by
GC/MS monitorisation of the process, a competitive
nucleophilic attack over the sulfonyl sulfur atom take
place in these cases leading to both thiol 817 and
disulfide 9 in variable proportions, depending on the
nature of the organometallic reagent (Scheme 3),
together with the sulfide 6 formed by nucleophilic
attack over the sulfenyl sulfur atom.
Scheme 1.
Scheme 2.
Table 1.
Entry
Product
R1
R2
R3
Yield (%)a
1
2
3
4
5
6
7
8
4a
4b
5a
5b
6a
6b
6c
6d
6e
6f
H
Me
H
Me
H
H
H
H
H
H
Me
H
Me
H
Me
Me
Me
Me
Me
Me
H
CO2Et
CO2Et
71
51
88
92
72
79
76
71
13
45
79
70
Scheme 3.
The formation of disulfide 9 can be explained by com-
petitive nucleophilic attack of the thiolate anion 7 at
the sulfenyl sulfur of thiotriflate 3. A similar mechanism
has been proposed by Langlois et al.21 for the forma-
tion of disulfides in the reaction of thiols with tri-
fluoromethanesulfonic anhydride in the presence of a
base. Low selectivity was also observed in the reaction
of 3 with the bulky tert-butylmagnesium chloride,
probably due to the high steric hindrance for the nucleo-
philic attack over the sulfenyl sulfur atom directly
Me
Et
i-Pr
Bu
t-Bu
Ph
Et
9
10
11
12
6g
6h
Me
Me
H
i-Pr
a The yields are given in isolated product.

A. Garc´ıa Mart´ınez et al. / Tetrahedron: Asymmetry 13 (2002) 2635–2639
2637
attached to the bridgehead position. As a result, only a
13% yield of 6e was obtained, disulfide 9 being the main
product.
drous magnesium sulfate. After filtration and solvent
evaporation, the crude oil was purified by column
chromatography (silica gel/diethyl ether) to yield pure
4.
3. Conclusion
4.2.1. Ethyl 3-{[(1S)-7,7-dimethyl-2-methylenebicyclo-
[2.2.1]hept-1-yl]sulfanyl}-2-propynoate, 4a. Yield 71%.
[h]2D0 −31.4 (c 2.39, CH2Cl2). 1H NMR (CDCl3, 200
MHz): l 5.11 (m, 1H), 4.89 (m, 1H), 4.19 (q, J=7.1 Hz,
2H), 2.51 (dm, J=16.1 Hz, 1H), 2.36–2.20 (m, 1H),
2.10–1.79 (m, 3H), 1.71 (ddd, J=12.1, 9.3, 4.1 Hz, 1H),
1.45–1.27 (m, 1H), 1.28 (t, J=7.1 Hz, 3H), 1.08 (s, 3H),
0.97 (s, 3H) ppm. 13C NMR (CDCl3, 50 MHz) l 153.0,
152.0, 106.0, 87.5, 83.2, 65.9, 61.5, 50.8, 43.6, 36.6, 34.5,
27.9, 19.7, 19.4, 14.1 ppm. FTIR (CCl4): w 3078, 2147,
1705, 1236, 1036 cm−1. MS m/z 264 (M+, 2), 249 (1),
235 (8), 220 (7), 209 (7), 192 (21), 177 (13), 163 (7), 149
(32), 135 (23), 105 (14), 91 (54), 77 (38), 69 (26), 53 (19),
41 (100). HREIMS calcd for C15H20O2S (M+):
264.11840. Found: 264.11835.
In summary, we have developed an easy and short
enantiospecific route to novel bridgehead norbornane
thioethers and thiocyanates. The procedure takes place
in only three steps starting from natural camphor and
fenchone. All these compounds offer interesting appli-
cations as chirality transfer agents in asymmetric syn-
thesis. Acetylene thioethers 4 can be used, for example,
as chiral auxiliaries in stereoselective [2+2] and [4+2]
cycloadditions. Sulfides 6 and its derivatives, find appli-
cations in catalytic enantioselective epoxidation or
aziridination reactions. Thiocyanates 5 can be used as
masked thiols, when required, and starting substrates
for the access to other interesting chiral ligands bearing
a sulfur-containing heterocyclic ring attached to the
bridgehead position of the norbornane skeleton.12 The
presence of the methylene group at C-2 in all these
compounds, in conjunction with all of the possible
different degrees of oxidation of the sulfur atom, opens
a way to other interesting homochiral norbornane
derivatives. Further work in this field is currently in
progress.
4.2.2. Ethyl 3-{[(1R)-3,3-dimethyl-2-methylenebicyclo-
[2.2.1]hept-1-yl]sulfanyl}-2-propynoate, 4b. Yield 51%.
[h]2D0 −74.2 (c 1.46, CH2Cl2). 1H NMR (CDCl3, 200
MHz): l 4.97 (s, 1H), 4.79 (s, 1H), 4.21 (q, J=7.1 Hz,
2H), 2.10–1.48 (m, 7H), 1.29 (t, J=7.1 Hz, 3H), 1.12 (s,
3H), 1.08 (s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l
161.8, 153.0, 101.9, 88.3, 82.6, 61.7, 61.6, 45.9, 44.1,
43.5, 34.6, 29.3, 25.9, 25.6, 14.1 ppm. FTIR (film): w
3072, 2149, 1705, 1236 cm−1. MS m/z 264 (M+, 1) 220
(18), 192 (31), 177 (37), 163 (15), 149 (81), 135 (17), 115
(16), 105 (23), 91 (73), 77 (56), 69 (30), 53 (32), 41 (100).
HREIMS calcd for C15H20O2S (M+): 264.11840. Found:
264.11758.
4. Experimental
4.1. General
NMR spectra were recorded on a Bruker-AC 200 (200
MHz for 1H and 50 MHz for 13C) with TMS as internal
standard; J values are given in hertz. IR spectra were
recorded on a Shimadzu FTIR spectrometer. Reaction
solvents were distilled from an appropriate drying agent
before use. Mass spectra were recorded on a GC–MS
Shimadzu QP5000 (60 eV) mass spectrometer. For gas
chromatography, a Shimadzu 17 AAF chromatograph
equipped with a capillary SGL-1 column was used.
4.3. Typical procedure for synthesis of thiocyanates, 5
To a stirred solution of thiotriflate 3 (3.0 mmol) in dry
CH2Cl2 (25 mL), 3.3 mmol of tetrabutylammonium
cyanide were added. The reaction mixture was stirred
for 20 min at room temperature. After that, the reac-
tion was quenched with water and extracted with
CH2Cl2. The extract was washed with brine and dried
over anhydrous magnesium sulfate. After filtration and
solvent evaporation, the crude oil was purified by
column chromatography (silica gel/hexane) to yield
pure 5.
High-resolution
electron-impact
mass
spectra
(HREIMS) were measured on a VG Auto Spec instru-
ment. Molecular rotation data were recorded on a
Perkin–Elmer 241 polarimeter, concentrations are given
as g/100 mL of solvent.
4.2. Typical procedure for the synthesis of acetylene
thioethers, 4
4.3.1. (1S)-7,7-Dimethyl-2-methylenebicyclo[2.2.1]hept-
1-yl thiocyanate, 5a. Yield 88%. [h]2D0 −43.3 (c 1.59,
CH2Cl2). 1H NMR (CDCl3, 200 MHz): l 5.16 (t, J=2.2
Hz, 1H), 4.96 (t, J=2.1 Hz, 1H), 2.54 (dm, J=16.0 Hz,
1H), 2.31–1.89 (m, 4H), 1.87–1.72 (m, 1H), 1.47–1.32
(m, 1H), 1.12 (s, 3H), 0.96 (s, 3H) ppm. 13C NMR
(CDCl3, 50 MHz): l 151.0, 111.1, 106.5, 66.3, 50.9,
43.3, 36.5, 35.3, 27.9, 19.6, 19.2 ppm. FTIR (CCl4): w
3100, 2154, 1659, 1450 cm−1. MS m/z 193 (M+, 7), 178
(10), 164 (7), 150 (30), 137 (19), 124 (25), 119 (13), 105
(19), 91 (57), 79 (25), 77 (31), 69 (28), 65 (19), 41 (100).
HREIMS calcd for C11H15NS (M+): 193.09252. Found:
193.09254.
A stirred solution of (Me3Si)2NLi (2.0 mmol) in THF
(2.0 mL) cooled at −78°C under an argon atmosphere,
was treated with ethyl propiolate (2.0 mmol). After
stirring for 15 min, the reaction mixture was diluted
with THF (8 mL) and a solution of thiotriflate 3 (1.8
mmol) in THF (5 mL) was added dropwise. The mix-
ture was stirred at −78°C for 24 h (the reaction progress
was monitored by GC). After completion of the reac-
tion, CH2Cl2 (15 mL) was added. The reaction was
quenched with H2O and extracted with CH2Cl2. The
extract was washed with brine and dried over anhy-

2638
A. Garc´ıa Mart´ınez et al. / Tetrahedron: Asymmetry 13 (2002) 2635–2639
4.3.2. (1R)-3,3-Dimethyl-2-methylenebicyclo[2.2.1]hept-
1-yl thiocyanate, 5b. Yield 92%. [h]2D0 −45.6 (c 2.04,
155.6, 105.3, 63.9, 50.1, 43.7, 36.8, 34.2, 33.2, 28.3, 27.1,
25.8, 20.0, 19.5 ppm. FTIR (CCl4): w 3080, 1655, 1450,
1383, 1367 cm−1. MS m/z 210 (M+, 28), 167 (52), 153
(21), 133 (18), 125 (47), 111 (29), 91 (53), 77 (31), 69
(32), 43 (47), 41 (100). HREIMS calcd for C13H22S
(M+): 210.14422. Found: 210.14372.
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.01 (bs, 1H),
4.85 (bs, 1H), 2.12 (dm, J=10.0 Hz, 1H), 2.07–1.54 (m,
6H), 1.13 (s, 3H), 1.10 (s, 3H) ppm. 13C NMR (CDCl3,
50 MHz): l 161.0, 111.3, 102.5, 61.4, 45.9, 44.8, 43.4,
35.1, 29.4, 25.9, 25.6 ppm. FTIR (CCl4): w 3080, 2160,
1660, 1460 cm−1. MS m/z 193 (M+, 9), 178 (6), 164 (6),
150 (42), 124 (28), 119 (16), 105 (15), 91 (80), 79 (24), 77
(28), 69 (44), 65 (25), 41 (100). HREIMS calcd for
C11H15NS (M+): 193.09252. Found: 193.09256.
4.4.4. (1S)-1-(Butylsulfanyl)-7,7-dimethyl-2-methylenebi-
cyclo[2.2.1]heptane, 6d. Yield 71%. [h]2D0 −25.2 (c 1.16,
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.15 (m, 1H),
4.85 (m, 1H), 2.70–2.40 (m, 3H), 2.07–1.75 (m, 4H),
1.67–1.20 (m, 6H), 1.04 (s, 3H), 0.96 (t, J=7.3 Hz, 3H),
0.89 (s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l 154.5,
104.9, 63.0, 50.3, 44.1, 36.8, 35.0, 32.6, 28.4, 28.1, 22.2,
20.7, 19.7, 13.7 ppm. FTIR (film): w 3076, 1657, 1448
cm−1. MS m/z 224 (M+, 30), 181 (16), 169 (34), 168 (33),
167 (34), 153 (5), 135 (14), 125 (30), 105 (30), 91 (59), 77
(28), 69 (24), 55 (25), 41 (100). HREIMS calcd for
C14H24S (M+): 224.15987. Found: 224.16005.
4.4. Typical procedure for the synthesis of thioethers, 6
To a stirred solution, cooled at 0°C, of thiotriflate 3
(2.0 mmol) in hexane (10 mL), a solution of the corre-
sponding alkylmagnesium chloride (10.0 mmol) in THF
was added dropwise. The mixture was stirred at room
temperature until disappearance of starting thiotriflate
(the reaction was monitored by CG). After that, the
reaction was quenched with 10% aqueous hydrochloric
acid and extracted with CH2Cl2. The extract was
washed with brine and dried over anhydrous magne-
sium sulfate. After filtration and solvent evaporation,
the crude oil was purified by column chromatography
(silica gel/hexane) to yield pure 6.
4.4.5. (1S)-1-(tert-Butylsulfanyl)-7,7-dimethyl-2-methyl-
enebicyclo[2.2.1]heptane, 6e. Yield 13%. [h]2D0 +4.8 (c
1
1.43, CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.43 (m,
1H), 4.84 (m, 1H), 2.52–2.27 (m, 2H), 2.09–1.70 (m,
4H), 1.39–1.22 (m, 1H), 1.44 (s, 9H), 1.02 (s, 3H), 0.81
(s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l 156.6,
106.6, 65.6, 51.0, 44.8, 42.6, 36.9, 34.2, 32.9, 28.8, 19.8,
19.5 ppm. FTIR (CCl4): w 3082, 1657, 1471, 1458, 1383,
1363, 1159 cm−1. MS m/z 224 (M+, 4), 168 (21), 167
(11), 153 (7), 135 (8), 113 (23), 112 (20), 91 (25), 77 (15),
57 (56), 41 (100). HREIMS calcd for C14H24S (M+):
224.15987. Found: 224.15936.
4.4.1. (1S)-7,7-Dimethyl-2-methylene-1-(methylsulfanyl)-
bicyclo[2.2.1]heptane, 6a. Yield 72%. [h]2D0 −32.1 (c 5.58,
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.13 (m, 1H),
4.85 (m, 1H), 2.45 (dm, J=16.1 Hz, 1H), 2.09 (s, 3H),
2.11–2.01 (m, 1H), 2.00–1.73 (m, 3H), 1.60–1.43 (m,
1H), 1.39–1.20 (m, 1H) 1.03 (s, 3H), 0.89 (s, 3H) ppm.
13C NMR (CDCl3, 50 MHz): l 153.9, 104.9, 62.2, 50.4,
44.3, 36.8, 34.7, 28.0, 20.8, 19.7, 12.2 ppm. FTIR
(CCl4): w 3078, 1657, 1472, 1448, 1385, 1367, 1298 cm−1.
MS m/z 182 (M+, 35), 167 (41), 140 (33), 127 (54), 119
(30), 105 (40), 91 (91), 69 (38), 41 (100). HREIMS calcd
for C11H18S (M+): 182.11292. Found: 182.11267.
4.4.6. (1S)-7,7-Dimethyl-2-methylene-1-(phenylsulfanyl)-
bicyclo[2.2.1]heptane, 6f. Yield 45%. [h]2D0 +29.7 (c 3.20,
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 7.64–7.54 (m,
2H), 7.27–7.19 (m, 3H), 5.49 (m, 1H), 4.9 (m, 1H), 2.51
(dm, J=16.1 Hz, 1H), 2.04 (dt, J=13.9; 2.1 Hz, 1H),
1.83–1.77 (m, 3H), 1.58–1.20 (m, 2H), 0.99 (s, 3H), 0.91
(s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l 151.4,
135.8, 133.6, 128.2, 127.5, 106.0, 65.8, 50.4, 43.9, 36.8,
34.8, 28.1, 20.0, 19.5 ppm. FTIR (film): w 3084, 1657,
1471, 1458, 1382, 1363 cm−1. MS m/z 244 (M+, 25), 189
(20), 167 (25), 134 (4), 124 (11), 119 (11), 105 (11), 91
(6), 77 (38), 65 (32), 41 (100). HREIMS calcd for
C16H20S (M+): 244.12857. Found: 244.12860.
4.4.2. (1S)-1-(Ethylsulfanyl)-7,7-dimethyl-2-methylenebi-
cyclo[2.2.1]heptane, 6b. Yield 79%. [h]2D0 −22.3 (c 0.40,
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.15 (m, 1H),
4.84 (m, 1H), 2.73–2.53 (m, 2H), 2.49 (dm, J=16.1 Hz,
1H), 2.08–1.74 (m, 4H), 1.54 (m, 1H), 1.36–1.24 (m,
1H), 1.24 (t, J=7.6 Hz, 3H), 1.03 (s, 3H), 0.88 (s, 3H)
ppm. 13C NMR (CDCl3, 50 MHz): l 154.6, 104.9, 63.2,
50.3, 44.1, 36.8, 34.9, 28.1, 22.8, 20.6, 19.7, 15.3 ppm.
FTIR (CCl4): w 3078, 1655, 1558, 1448, 1384, 1367
cm−1. MS m/z 196 (M+, 41), 167 (47), 153 (42), 141 (57),
133 (18), 134 (18), 125 (27), 119 (49), 105 (35), 119 (49),
111 (31), 105 (35), 91 (98), 77 (47), 69 (54), 41 (100).
HREIMS calcd for C12H20S (M+): 196.12857. Found:
196.12820.
4.4.7. (1R)-1-(Ethylsulfanyl)-3,3-dimethyl-2-methylenebi-
cyclo[2.2.1]heptane, 6g. Yield 79%. [h]2D0 −54.6 (c 0.93,
1
CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.02 (s, 1H),
4.73 (s, 1H), 2.50 (q, J=7.5 Hz, 2H), 1.97 (dm, J=9.5
Hz, 1H), 1.89 (m, 1H), 1.87–1.65 (m, 2H), 1.64–1.50 (m,
1H), 1.49–1.30 (m, 2H), 1.23 (t, J=7.5 Hz, 3H), 1.10 (s,
3H), 1.03 (s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l
163.3, 100.8, 59.5, 46.0, 43.6, 42.8, 35.5, 29.3, 26.0, 25.1,
23.5, 14.9 ppm. FTIR (film): w 3070, 1655, 1458 cm−1.
MS m/z 196 (M+, 33), 167 (48), 153 (96), 91 (62), 77
(35), 59 (33), 41 (100). HREIMS calcd for C12H20S
(M+): 196.12857. Found: 196.12850.
4.4.3. (1S)-1-(Isopropylsulfanyl)-7,7-dimethyl-2-methyl-
enebicyclo[2.2.1]heptane, 6c. Yield 76%. [h]2D0 −21.4 (c
1
1.99, CH2Cl2). H NMR (CDCl3, 200 MHz): l 5.23 (m,
1H), 4.82 (m, 1H), 3.05 (sept., J=6.8 Hz, 1H), 2.47
(dm, J=16.1 Hz, 1H), 2.18–1.75 (m, 4H), 1.63 (ddd,
J=11.3, 9.3, 3.5 Hz, 1H), 1.36 (d, J=6.8 Hz, 3H),
1.36–1.34 (m, 1H), 1.32 (d, J=6.8 Hz, 3H), 1.02 (s,
3H), 0.86 (s, 3H) ppm. 13C NMR (CDCl3, 50 MHz): l
4.4.8. (1R)-1-(Isopropylsulfanyl)-3,3-dimethyl-2-methyl-
enebicyclo[2.2.1]heptane, 6h. Yield 70%. [h]2D0 −87.2 (c
2.10, CH2Cl2). 1H NMR (CDCl3, 200 MHz): l

A. Garc´ıa Mart´ınez et al. / Tetrahedron: Asymmetry 13 (2002) 2635–2639
2639
5.06 (s, 1H), 4.71 (s, 1H), 2.86 (sept., J=6.8 Hz, 1H),
5. See for example Refs. 4b, 4d, and 4f–h.
6. See for example Refs. 3, 4a, 4c, and 4e.
7. Furukawa, N.; Sugihara, Y.; Fujihara, H. J. Org. Chem.
1989, 54, 4222–4224.
8. For example, see Refs. 1, 2, 3b, 4a, 4d, 4g, and 7.
9. For some selected examples, see Refs. 1, 3a, and 3c. See
also: (a) Aggarwal, V. K.; Ford, J. G.; Jones, R. V.;
Fieldhouse, R. Tetrahedron: Asymmetry 1998, 9, 1801–
1807; (b) Solladie´-Carvallo, A.; Balaz, M.; Salisova, M.;
Suteu, C.; Nafie, L. A.; Cao, X.; Freedman, T. B. Tetra-
hedron: Asymmetry 2001, 12, 2605–2611.
2.05–1.97 (m, 1H), 1.90 (m, 1H), 1.85–1.69 (m, 2H),
1.65–1.45 (m, 2H), 1.43–1.34 (m, 1H), 1.31 (d, J=6.8
Hz, 3H), 1.26 (d, J=6.8 Hz, 3H), 1.10 (s, 3H), 1.04 (s,
3H) ppm. 13C NMR (CDCl3, 50 MHz): l 164.0, 100.9,
59.9, 46.1, 44.2, 42.8, 36.2, 34.1, 29.4, 26.2, 26.1, 25.1,
24.9 ppm. FTIR (CCl4): w 3070, 1653, 1460, 1388, 1363,
1209, 1149 cm−1. MS m/z 210 (M+, 25), 181 (6), 167
(70), 139 (19), 125 (25), 105 (20), 91 (41), 77 (21), 59
(20), 41 (100). HREIMS calcd for C13H22S (M+):
210.14422. Found: 210.14357.
10. See for example: (a) Montenegro, E.; Echarri, R.; Claver,
C.; Castillo´n, S.; Moyano, A.; Perica´s, M. A.; Riera, A.
Tetrahedron: Asymmetry 1996, 7, 3553–3558; (b) Sewald,
N.; Wendisch, V. Tetrahedron: Asymmetry 1996, 7, 1269–
1272; (c) Takahashi, T. Nakao, N.; Koizumi, T. Tetra-
hedron: Asymmetry 1997, 8, 3293–3308; (d) Verdaguer,
X.; Va´zquez, J.; Fuster, G.; Barnardes-Ge´nisson, V.;
Greene, A. E.; Moyano, A.; Perica´s, M. A.; Riera, A. J.
Org. Chem. 1998, 63, 7037–7052.
Acknowledgements
We would like to thank the Ministerio de Ciencia y
Tecnolog´ıa (MCYT) of Spain (plan nacional I+D+I,
research project BQU2001-1347-C02-02) and UNED
(research project 2001V/PROYT/18) for the financial
support of this work. One of us, A.A.G., wishes to
thank UNED for a post-graduate grant.
11. Montenegro, E.; Poch, M.; Moyano, A.; Perica´s, M. A.;
Riera, A. Tetrahedron 1997, 53, 8651–8664.
12. For a review on the synthetic utility and applications of
thiocyanates, see: Erian, A. W.; Sherif, S. M. Tetrahedron
1999, 55, 7957–8024.
13. Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Garc´ıa Fraile, A.; de
la Moya Cerero, S.; Mart´ınez Ruiz, P.; Chicharro Villas,
P. Tetrahedron: Asymmetry 2002, 13, 1–4.
14. Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Garc´ıa Fraile, A.; de
la Moya Cerero, S.; Rodr´ıguez Herrero, M.; Mart´ınez
Ruiz, P.; Subramanian, L. R. J. Med. Chem. 1995, 38,
4474–4477.
15. Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Garc´ıa Fraile, A.; de
la Moya Cerero, S.; de Oro Osuna, S.; Lora Maroto, B.
Tetrahedron Lett. 2001, 42, 7795–7799.
16. (a) Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Garc´ıa Fraile, A.;
de la Moya Cerero, S.; Lora Maroto, B. Tetrahedron
Lett. 2001, 42, 5017–5019; (b) Garc´ıa Mart´ınez, A.; Teso
Vilar, E.; Garc´ıa Fraile, A.; de la Moya Cerero, S.; Lora
Maroto, B. Tetrahedron: Asymmetry 2001, 12, 3325–3327.
17. Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Moreno Jime´nez, F.;
Mart´ınez Bilbao, C. Tetrahedron: Asymmetry 1997, 8,
3031–3034.
18. Garc´ıa Mart´ınez, A.; Teso Vilar, E.; Moreno Jime´nez, F.;
Garc´ıa Amo, M. Tetrahedron: Asymmetry 2000, 11,
1709–1717.
19. The rate of nucleophilic substitution at the sulfenyl sulfur
is several orders of magnitude faster than the equivalent
reaction at the sulfonyl sulfur. See: Hogg, D. R. Compre-
hensive Organic Chemistry; Pergamon Press: Oxford,
1979; Vol. 3, pp. 300–301 and references cited therein.
20. Jasys, V. J.; Urban, F. J. Tetrahedron: Asymmetry 2001,
12, 361–363.
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