Nickel-catalyzed cross-coupling reactions of alkyl aryl sulfides and alkenyl alkyl sulfides with alkyl grignard reagents using (Z)-3,3-dimethyl-1,2- bis(diphenylphosphino)but-1-ene as ligand

Article abstract of DOI:10.1055/s-2008-1067193

A combination of nickel(II) acetylacetonate and (Z)-3,3-dimethyl-1,2- bis(diphenylphosphino)but-1-ene catalyzes cross-coupling reactions of alkyl aryl sulfides and alkenyl alkyl sulfides with alkyl Grignard reagents. Not only primary but also secondary alkyl Grignard reagents can be employed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067193

SPECIAL TOPIC
2659
Nickel-Catalyzed Cross-Coupling Reactions of Alkyl Aryl Sulfides and
Alkenyl Alkyl Sulfides with Alkyl Grignard Reagents Using (Z)-3,3-Dimethyl-
1,2-bis(diphenylphosphino)but-1-ene as Ligand
C
ross-Couplin
h
g of Sulfide
s
i
w
ith A
g
lkyl Grigna
r
e
d
R
eagentsnari Kanemura, Azusa Kondoh, Hideki Yorimitsu,* Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Fax +81(75)3832438; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received 21 April 2008
With ligand 3a in hand, various combinations of aryl
Abstract: A combination of nickel(II) acetylacetonate and (Z)-3,3-
dodecyl sulfides and alkyl Grignard reagents were sub-
jected to the nickel-catalyzed reaction (Table 2). The re-
dimethyl-1,2-bis(diphenylphosphino)but-1-ene catalyzes cross-
coupling reactions of alkyl aryl sulfides and alkenyl alkyl sulfides
actions with butylmagnesium bromide proceeded
smoothly (entries 1–6). In the reactions of aryl sulfides
having an electron-donating group (entries 4–6), the more
bulky and less volatile ethereal solvents, diisopropyl ether
(bp 69 °C) or cyclopentyl methyl ether (bp 106 °C), en-
hanced the efficiency of the reaction. It is worth noting
that cyclohexylmagnesium bromide, a secondary alkyl
Grignard reagent, participated in the cross-coupling reac-
tion (entries 8–14); cyclopentyl methyl ether was the sol-
vent of choice in this case. A substituent at the ortho
position (1b and 1f) retarded the cyclohexylation reaction
(entries 9 and 13). The reactions of aryl sulfides 1h, 1e and
1g with isopropylmagnesium bromide under nickel catal-
ysis provided the desired products 2p–r, along with small
amounts of the corresponding n-propylated products 2p¢–r¢
(entries 15–17). The formation of 2p¢–r¢ would result
from isomerization of isopropylmetal to n-propylmetal
with alkyl Grignard reagents. Not only primary but also secondary
alkyl Grignard reagents can be employed.
Key words: cross-coupling, nickel, sulfur, ligands, magnesium
Transition-metal-catalyzed cross-coupling reactions are
extremely useful in organic synthesis. Among them, the
reactions of organosulfur compounds with organometallic
reagents are promising because of the ready availability of
organosulfur compounds. However, such reactions are
not as well established1 as those of organic halides. The
strong carbon–sulfur and metal–sulfur bonds retard the
oxidative addition and transmetalation, respectively. Or-
ganosulfur compounds can thus deteriorate transition-
metal catalysts. Hence, development of new procedures
for the cross-coupling reactions of organosulfur com-
pounds with organometallic reagents has been awaited.
Table 1 Ligand Screening
Although there are several reports on the cross-coupling
reactions of sulfides with Grignard reagents,1a,2 the use of
secondary alkyl Grignard reagents always resulted in very
low yields1a because of the possible b-hydride elimination
from sec-alkylmetal intermediates. Here we report a new
catalyst that realizes the cross-coupling reaction with sec-
ondary as well as primary alkyl Grignard reagents.
Ni(acac)2 (5 mol%)
ligand (5 mol%)
Ph SnC12H25
nBuMgBr
Ph nBu
+
Et2O, reflux, 5 h
1a (0.50 mmol)
(1.5 equiv)
2a
Entry
Ligand
Yield (%)
Recovery of 1a (%)
1
2
PPh3 (10 mol%)
DPPE
24
79
6
0
We chose the nickel-catalyzed cross-coupling reaction of
dodecyl phenyl sulfide (1a) with butylmagnesium bro-
mide as a model reaction. As reported previously,1a mon-
odentate triphenylphosphine was not a good ligand
(Table 1, entry 1). Bidentate ligands such as 1,2-
bis(diphenylphosphino)ethane and 1,2-bis(diphenylphos-
phino)benzene improved the yield (entries 2 and 3). Inter-
estingly, tert-butyl-substituted (Z)-1,2-bis(diphenylphos-
phino)ethene (3a),3 which we recently developed, proved
to be the best ligand among those we tested (entry 4). Cy-
clohexyl- and phenyl-substituted analogues 3b and 3c
were inferior to 3a (entries 5 and 6).
3
4
75
88
9
0
Ph2P
tBu
PPh2
H
Ph2P
PPh2
3a
cC6H11
H
5
6
82
51
0
Ph2P
PPh2
3b
Ph
H
SYNTHESIS 2008, No. 16, pp 2659–2664
x
x.
x
x
.
2
0
0
8
28
Ph2P
PPh2
Advanced online publication: 24.07.2008
DOI: 10.1055/s-2008-1067193; Art ID: C02708SS
© Georg Thieme Verlag Stuttgart · New York
3c

2660
S. Kanemura et al.
SPECIAL TOPIC
Table 2 Nickel-Catalyzed Reactions of Aryl Dodecyl Sulfides with Alkyl Grignard Reagents Using 3a as Ligand
Ni(acac)2 (5 mol%)
3a (5 mol%)
Ar SnC12H25
+
RMgBr
Ar
R
solvent, reflux
1 (0.50 mmol)
(1.5 equiv)
2
Entry
Ar
1
R
Solvent
Time (h)
2
Yield (%)
95
1
2
2-MeC6H4
3-CF3C6H4
2-pyridyl
1b
1c
1d
1e
1f
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
Et2O
5
5
2b
2c
2d
2e
2f
Et2O
70
3
Et2O
5
70
4
4-MeOC6H4
2-MeOC6H4
4-(Me2N)C6H4
Ph
i-Pr2O
5
93
5
i-Pr2O
5
90
6
1g
1a
1a
1b
1c
1d
1e
1f
c-C5H9OMe
Et2O
12
5
2g
2h
2i
82
7
Ph(CH2)3
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
c-C6H11
i-Pr
95
8
Ph
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
c-C5H9OMe
Et2O
5
97
9
2-MeC6H4
3-CF3C6H4
2-pyridyl
5
2j
65
10
11
12
13
14
15
16
17
18
5
2k
2l
86
5
95
4-MeOC6H4
2-MeOC6H4
4-(Me2N)C6H4
4-(i-Pr)C6H4
4-MeOC6H4
4-(Me2N)C6H4
Ph
12
12
5
2m
2n
2o
2p
2q
2r
2s
87 (93a)
29
1g
1h
1e
1g
1a
60
13
12
13
5
89b
80c
90d
0
i-Pr
i-Pr
t-Bu
a Performed on a 5 mmol scale.
b An 88:12 mixture of isopropylated 2p and 1-propyl-4-isopropylbenzene (2p¢) was obtained.
c A 77:23 mixture of isopropylated 2q and 4-propylanisole (2q¢) was obtained.
d A 77:23 mixture of isopropylated 2r and N,N-dimethyl-4-propylaniline (2r¢) was obtained.
through b-hydride elimination from isopropylnickel fol- sulfide (1a¢) also reacted under the reaction conditions
lowed by anti-Markovnikov hydronickelation to propene. (Scheme 1).
Unfortunately, tert-butylbenzene (2s) was not obtained in
the reaction with tert-butylmagnesium bromide (entry
18).
The reactions of 1-alkenyl dodecyl sulfides also proceed-
ed smoothly (Table 3). In most cases, the reaction pro-
ceeded with retention of configuration. In the reactions of
We chose the dodecylthio group as the leaving group be- (Z)-4b (entries 3, 7, and 11), significant amounts of the
cause 1-dodecanethiol is odorless.4,5 In addition, 1-dode- corresponding E products were formed. The loss of ste-
canethiol is involatile enough to recover quantitatively reospecificity was confirmed as being due to isomeriza-
after the cross-coupling reaction (see experimental sec- tion of the initially formed Z products into the E products
tion). Cheap and commercially available methyl phenyl under the reaction conditions. In contrast to the reactions
of aryl sulfides with isopropylmagnesium bromide
5 mol% Ni(acac)2/3a
(Table 2, entries 15–17), formation of n-propyl-substitut-
nBuMgBr
Ph nBu
(1)
+
Ph SMe
1a' (0.50 mmol) (1.5 equiv)
Et2O, reflux, 5 h
ed alkenes was not observed (Table 3, entries 9–12). Un-
fortunately, the yield of (Z)-5f was low, with 1-octene
being the main product (entry 11). The reactions of a-
dodecylthiostyrene (6) were inefficient, providing the cor-
responding coupling products 7 in only moderate yields
(Scheme 2).
2a 91%
5 mol% Ni(acac)2/3a
cC6H11MgBr
(1.5 equiv)
SMe
Ph cC6H11
+
Ph
(2)
cC5H9OMe, reflux, 5 h
1a' (0.50 mmol)
2i 95%
Scheme 1
Synthesis 2008, No. 16, 2659–2664 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cross-Coupling of Sulfides with Alkyl Grignard Reagents
2661
Table 3 Nickel-Catalyzed Reactions of 1-Alkenyl Dodecyl Sulfides with Alkyl Grignard Reagents Using 3a as Ligand
Ni(acac)2 (5 mol%)
3a (5 mol%)
R1
SnC12H25
R1
R2
R2MgBr
(1.5 equiv)
+
conditions A or B
4 (0.50 mmol)
5
Entry
R1
Ph
Ph
4
R2
Conditionsa
5
Yield (%)
1
2
(Z)-4a (E/Z = 4:96)
(E)-4a (E/Z = 90:10)
(Z)-4b (E/Z = 9:91)
(E)-4b (E/Z > 99:1)
(Z)-4a (E/Z = 4:96)
(E)-4a (E/Z = 90:10)
(Z)-4b (E/Z = 9:91)
(E)-4b (E/Z > 99:1)
(Z)-4a (E/Z = 4:96)
(E)-4a (E/Z = 90:10)
(Z)-4b (E/Z = 9:91)
(E)-4b (E/Z > 99:1)
n-Bu
n-Bu
n-Bu
n-Bu
c-C6H11
c-C6H11
c-C6H11
c-C6H11
i-Pr
A
A
Bb
A
B
B
B
B
B
B
B
B
(Z)-5a (E/Z = 8:92)
(E)-5a (E/Z = 91:9)
(Z)-5b (E/Z = 27:73)
(E)-5b (E/Z > 99:1)
(Z)-5c (E/Z = 8:92)
(E)-5c (E/Z > 99:1)
(Z)-5d (E/Z = 11:89)
(E)-5d (E/Z = 94:6)
(Z)-5e (E/Z = 8:92)
(E)-5e (E/Z > 99:1)
(Z)-5f (E/Z = 36:64)
(E)-5f (E/Z = 95:5)
75
70
78
74
93
70
84
95
72
72
37
80
3
n-C6H13
n-C6H13
Ph
4
5
6
Ph
7
n-C6H13
n-C6H13
Ph
8
9
10
11
12
Ph
i-Pr
n-C6H13
n-C6H13
i-Pr
i-Pr
a Reaction conditions (A) Et2O, reflux, 5 h. (B) cyclopentyl methyl ether, reflux, 12 h.
b Reaction performed for 13 h.
Materials obtained from commercial suppliers were used without
further purification. Et2O was purchased from Kanto Chemical and
stored under argon. Cyclopentyl methyl ether was obtained from
ZEON or purchased from Wako Pure Chemical. Nickel(II) acetyl-
acetonate was purchased from Wako Pure Chemical. Ligand 3 was
prepared according to the literature.3 Sulfides 1 and 4 were prepared
according to the procedures shown below, except for (Z)-4a.5b
Ph
Ph
Ni(acac)2 (5 mol%)/ 3a
nBuMgBr
(1.5 equiv)
(3)
(4)
+
+
cC5H9OMe, reflux, 13 h
SnC12H25
nBu
7a 46%
6 (0.50 mmol)
Ph
Ph
Ni(acac)2 (5 mol%)/ 3a
cC6H11MgBr
(1.5 equiv)
cC5H9OMe, reflux, 13 h
cC6H11
7b 44%
SnC12H25
6 (0.50 mmol)
Characterization Data
Compounds 1a,6 1e,7 1g,8 2a,9 2b,10 2d,11 2e,10 2f,12 2g,10 2i,13 2j,14
2k,15 2l,16 2m,17 2o,18 2q,19 (Z)-4a,5b (Z)-5a,20 (E)-5a,21 (Z)-5b,22
(E)-5b,23 (Z)-5c,24 (E)-5c,22 (E)-5d,25 (Z)-5e,26 (E)-5e,27 (E)-5f,28
7a29 and 7b30 gave spectra identical to those reported in the litera-
ture. Products 2h and 2p were identical to commercially available
reagents.
Scheme 2
In summary, we have developed a new protocol for the
nickel-catalyzed cross-coupling reaction of organic sul-
fides with Grignard reagents. The protocol allows for the
use of secondary alkyl Grignard reagents as well as prima-
ry ones as efficient alkylating agents. Ligand 3a serves as
a useful ligand under the present reactions.
Preparation of Didodecyl Disulfide
THF (15 mL), 1-dodecanethiol (2.0 g, 10 mmol), and Et3N (1.1 g,
11 mmol) were placed in a 50 mL reaction flask under argon. Iodine
(2.8 g, 11 mmol) was then added to the solution at 0 °C. After being
stirred at 25 °C for 6 h, the mixture was poured into a sodium thio-
sulfate solution (1 M, 20 mL). The product was extracted with
EtOAc (3 × 20 mL) and the combined organic layers were dried
over Na2SO4 and concentrated in vacuo. The residue was purified
by silica gel column chromatography (hexane) to afford didodecyl
disulfide (2.0 g, 100%).
1H NMR (500 MHz) and 13C NMR (125.7 MHz) spectra were taken
on a Varian Unity Inova 500 spectrometer and were obtained in
CDCl3 with TMS as an internal standard. IR spectra were taken on
a Shimadzu FTIR-8200PC spectrometer. Mass spectra were deter-
mined on a JEOL MStation 700 spectrometer. TLC analyses were
performed on commercial glass plates bearing a 0.25 mm layer of
Merck Silica gel 60F254. Silica gel (Wakogel 200 mesh) was used
for column chromatography unless otherwise noted. Gel perme-
ation chromatography was performed using LC-908 (Japan Analyt-
ical Industry Ltd., two in-line JAIGEL-2H, toluene, 3.8 mL/min,
UV and RI detectors). Elemental analyses were carried out at the El-
emental Analysis Center of Kyoto University. Silica gel column
chromatography was performed with a mixture of hexane and
EtOAc as eluent.
Preparation of Aryl Dodecyl Sulfide; Typical Procedure
The preparation of 1e is representative. Didodecyl disulfide (2.0 g,
5.0 mmol) and THF (10 mL) were placed in a 50 mL reaction flask
under argon. 4-Methoxyphenylmagnesium bromide (1.1 M in THF,
6.8 mL, 7.5 mmol) was then added to the reaction mixture at 25 °C.
After stirring at 25 °C for 10 h, the mixture was poured into H2O (10
mL) and the product was extracted with EtOAc (3 × 10 mL). The
combined organic layers were dried over Na2SO4 and concentrated
Synthesis 2008, No. 16, 2659–2664 © Thieme Stuttgart · New York

2662
S. Kanemura et al.
SPECIAL TOPIC
in vacuo and the resulting residue was purified on silica gel (hex-
ane–EtOAc) to afford 1e (1.5 g, 100%). 1-Dodecanethiol (1.0 g,
100%) was also recovered and used for the synthesis of didodecyl
disulfide.
J = 7.5 Hz, 2 H), 7.36–7.41 (m, 2 H), 7.43–7.47 (m, 1 H), 7.50–
7.54 (m, 1 H).
13C NMR (CDCl3): d = 14.10, 22.69, 28.79, 28.82, 29.12, 29.35,
29.47, 29.56, 29.62, 29.64, 31.91, 33.10, 122.04 (q, J = 3.9 Hz),
123.87 (q, J = 271.0 Hz), 124.61 (q, J = 3.9 Hz), 129.06, 131.21 (q,
J = 32.5 Hz), 131.23, 138.91.
Preparation of 1-Alkenyl Dodecyl Sulfide; Typical Procedure
The preparation of (E)-4a is representative. b-Bromostyrene (0.55
g, 3.0 mmol, E:Z > 99:1) and Et2O (6.0 mL) were placed in a 30 mL
reaction flask under argon. t-BuLi (1.6 M in pentane, 3.8 mL, 6.0
mmol) was then added to the reaction mixture at –78 °C. After stir-
ring at –78 °C for 30 min, didodecyl disulfide (1.1 g, 2.7 mmol) was
added and the mixture was stirred for 5 h. The dry ice–acetone bath
was removed and the reaction was stirred for 1 h at r.t., then the mix-
ture was poured into H2O (10 mL). The product was extracted with
EtOAc (3 × 10 mL) and the combined organic layers were dried
over Na2SO4. After evaporation, the resulting residue was purified
by silica gel column chromatography (hexane) and gel permeation
chromatography, to afford (E)-4a (0.82 g, 100%, E/Z = 90:10).
Anal. Calcd for C19H29F3S: C, 65.86; H, 8.44. Found: C, 66.08; H,
8.67.
Dodecyl 2-Pyridyl Sulfide (1d)
Colorless oil.
IR (neat): 3045, 2924, 2854, 2360, 1580, 1557, 1456, 1125, 756
cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.36 (m,
16 H), 1.41–1.47 (m, 2 H), 1.70 (tt, J = 7.5, 7.5 Hz, 2 H), 3.15 (t,
J = 7.5 Hz, 2 H), 6.95 (dd, J = 5.0, 8.0 Hz, 1 H), 7.16 (d, J = 8.0 Hz,
1 H), 7.43 (dd, J = 5.0, 5.0 Hz, 1 H), 8.42 (d, J = 5.0 Hz, 1 H).
13C NMR (CDCl3): d = 14.11, 22.68, 28.96, 29.20, 29.30, 29.33,
29.51, 29.59, 29.62, 29.64, 30.12, 31.90, 119.12, 122.10, 135.75,
149.41, 159.63.
Cross-Coupling Reaction; Typical Procedure
The reaction of 1b with butylmagnesium bromide is representative.
Nickel(II) acetylacetonate (6.4 mg, 0.025 mmol) and ligand 3a
(0.011 g, 0.025 mmol) were placed in a 20 mL reaction flask. An-
hydrous Et2O (3.0 mL) and substrate 1b (0.15 g, 0.50 mmol) were
added under argon. Butylmagnesium bromide (1.0 M in Et2O, 0.75
mL, 0.75 mmol) was then added to the reaction mixture at ambient
temperature. After being stirred at reflux for 5 h, the mixture was
poured into sat. NH4Cl (10 mL) and extracted with EtOAc (3 × 10
mL). The combined organic layers were dried over Na2SO4. Con-
centration followed by silica gel column purification (hexane–
EtOAc) afforded 2b (0.070 g, 95%).
Anal. Calcd for C17H29NS: C, 73.06; H, 10.46. Found: C, 73.31; H,
10.44.
Dodecyl 2-Methoxyphenyl Sulfide (1f)
White solid; mp 30.5–31.0 °C.
IR (neat): 2853, 1734, 1700, 1569, 1429, 1242, 1072, 1022, 712
cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.34 (m,
16 H), 1.40–1.48 (m, 2 H), 1.66 (tt, J = 7.5, 7.5 Hz, 2 H), 2.88 (t,
J = 7.5 Hz, 2 H), 3.89 (s, 3 H), 6.84 (d, J = 8.5 Hz, 1 H), 6.93 (dd,
J = 8.5, 8.5 Hz, 1 H), 7.17 (dd, J = 8.5, 8.5 Hz, 1 H), 7.24 (d, J = 8.5
Hz, 1 H).
13C NMR (CDCl3): d = 14.11, 22.68, 28.88, 28.96, 29.20, 29.33,
29.49, 29.57, 29.61, 29.63, 31.83, 31.90, 55.73, 110.27, 120.99,
125.26, 126.53, 128.54, 156.97.
Cross-Coupling Reaction of 1e with Cyclohexylmagnesium
Bromide Performed on a 5 mmol Scale (Table 2, entry 12)
Nickel(II) acetylacetonate (0.064 g, 0.25 mmol), ligand 3a (0.11 g,
0.25 mmol) and substrate 1e (1.5 g, 5.0 mmol) were dissolved in cy-
clopentyl methyl ether (30 mL) in a 100 mL reaction flask under ar-
gon. Cyclohexylmagnesium bromide (1.0 M in Et2O, 7.5 mL, 7.5
mmol) was then added and the reaction was stirred at reflux for 5 h.
The mixture was poured into sat. NH4Cl (20 mL) and the product
was extracted with EtOAc (3 × 20 mL). The combined organic lay-
ers were dried over Na2SO4 and the solvent was removed to give a
residue that was purified by silica gel column chromatography (hex-
ane–EtOAc) to afford 2m (0.88 g, 93%). 1-Dodecanethiol (0.93 g,
92%) was also recovered.
Anal. Calcd for C19H32OS: C, 73.97; H, 10.45. Found: C, 73.85; H,
10.59.
Dodecyl 4-Isopropylphenyl Sulfide (1h)
Colorless oil.
IR (neat): 2959, 2925, 2854, 1497, 1460, 1093, 817 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.32 (m,
22 H), 1.36–1.44 (m, 2 H), 1.63 (tt, J = 7.5, 7.5 Hz, 2 H), 2.87 (sept,
J = 7.0 Hz, 1 H), 2.88 (t, J = 7.5 Hz, 2 H), 7.14 (d, J = 8.5 Hz, 2 H),
7.27 (d, J = 8.5 Hz, 2 H).
13C NMR (CDCl3): d = 14.10, 22.68, 28.92, 28.82, 29.16, 29.27,
29.33, 29.51, 29.57, 29.62, 29.64, 31.91, 33.66, 34.19, 126.95,
129.54, 133.62, 146.74.
Dodecyl 2-Methylphenyl Sulfide (1b)
Colorless oil.
IR (neat): 2924, 2854, 1590, 1456, 1379, 1066, 1048, 741 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.34 (m,
16 H), 1.40–1.46 (m, 2 H), 1.66 (tt, J = 7.0, 7.0 Hz, 2 H), 2.36 (s,
3 H), 2.89 (t, J = 7.0 Hz, 2 H), 7.07 (dd, J = 7.0, 7.0 Hz, 1 H), 7.13–
7.17 (m, 2 H), 7.25 (d, J = 7.0 Hz, 1 H).
13C NMR (CDCl3): d = 14.11, 20.31, 22.68, 28.96, 28.98, 29.19,
29.34, 29.50, 29.57, 29.62, 29.64, 31.91, 32.76, 125.19, 126.28,
127.21, 129.96, 136.41, 137.12.
HRMS (EI): m/z [M+] calcd for C21H36S: 320.2537; found:
320.2538.
3-Butyl-1-trifluoromethylbenzene (2c)
Colorless oil.
Anal. Calcd for C19H32S: C, 78.01; H, 11.03. Found: C, 78.26; H,
10.78.
IR (neat): 2933, 2862, 2360, 1448, 1326, 1164, 1127, 1074, 799
cm–1.
1H NMR (CDCl3): d = 0.95 (t, J = 7.5 Hz, 3 H), 1.37 (qt, J = 7.5, 7.5
Hz, 2 H), 1.62 (tt, J = 7.5, 8.0 Hz, 2 H), 2.67 (t, J = 8.0 Hz, 2 H),
7.34–7.41 (m, 2 H), 7.42–7.46 (m, 2 H).
13C NMR (CDCl3): d = 13.88, 22.29, 33.43, 35.47, 122.47 (q,
J = 3.8 Hz), 124.32 (q, J = 270.6 Hz), 125.06 (q, J = 3.8 Hz),
128.59, 130.51 (q, J = 31.9 Hz), 131.80, 143.72.
Dodecyl 3-Trifluoromethylphenyl Sulfide (1c)
Brown oil.
IR (neat): 2928, 2855, 1583, 1468, 1423, 1323, 1168, 1130, 1074,
791, 696 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.20–1.34 (m,
16 H), 1.39–1.46 (m, 2 H), 1.66 (tt, J = 7.5, 7.5 Hz, 2 H), 2.95 (t,
Synthesis 2008, No. 16, 2659–2664 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cross-Coupling of Sulfides with Alkyl Grignard Reagents
2663
HRMS (EI): m/z [M+] calcd for C11H13F3: 202.0969; found:
202.0964.
1H NMR (CDCl3): d = 0.89 (t, J = 7.0 Hz, 3 H), 1.00–1.10 (m, 2 H),
1.14–1.38 (m, 11 H), 1.57–1.74 (m, 5 H), 2.03 (dt, J = 7.0, 7.0 Hz,
2 H), 2.21–2.29 (m, 1 H), 5.16–5.28 (m, 2 H).
N,N-Dimethyl-4-isopropylaniline (2r)
Brown oil.
13C NMR (CDCl3): d = 14.10, 22.67, 26.02, 26.10, 27.44, 28.99,
29.98, 31.79, 33.41, 36.30, 128.05, 135.98.
IR (neat): 2958, 2870, 2799, 1616, 1521, 1340, 1219, 1166, 948,
816 cm–1.
1H NMR (CDCl3): d = 1.24 (d, J = 7.0 Hz, 6 H), 2.84 (sept, J = 6.5
Hz, 1 H), 2.92 (s, 6 H), 6.73 (d, J = 8.5 Hz, 2 H), 7.13 (d, J = 8.5 Hz,
2 H).
Anal. Calcd for C14H26: C, 86.52; H, 13.48. Found: C, 86.82; H,
13.70.
Dodecyl 1-Phenylethenyl Sulfide (6)
Brown oil.
13C NMR (CDCl3): d = 24.21, 33.02, 40.94, 112.98, 126.91, 128.99,
137.20.
IR (neat): 3059, 2925, 2360, 1675, 1599, 1456, 1276, 1069, 843,
699 cm–1.
HRMS (EI): m/z [M+] calcd for C11H17N: 163.1361; found:
163.1360.
1H NMR (CDCl3): d = 0.90 (t, J = 7.0 Hz, 3 H), 1.20–1.34 (m,
16 H), 1.36–1.44 (m, 2 H), 1.64 (tt, J = 7.5, 7.5 Hz, 2 H), 2.69 (t,
J = 7.5 Hz, 2 H), 5.16 (s, 1 H), 5.46 (s, 1 H), 7.30–7.37 (m, 3 H),
7.54–7.57 (m, 2 H).
Dodecyl (E)-2-Phenylethenyl Sulfide [(E)-4a]
Colorless oil.
13C NMR (CDCl3): d = 14.11, 22.68, 28.46, 28.91, 29.16, 29.34,
29.47, 29.57, 29.62, 29.63, 31.90, 32.13, 110.16, 127.08, 128.26,
128.29, 139.82, 145.28.
IR (neat): 2923, 2853, 2360, 1599, 1468, 1315, 1125, 933, 734, 691
cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 5.0 Hz, 3 H), 1.20–1.36 (m,
16 H), 1.38–1.46 (m, 2 H), 1.69 (tt, J = 7.5, 7.5 Hz, 2 H), 2.80 (t,
J = 7.5 Hz, 2 H), 6.46 (d, J = 15.5 Hz, 1 H), 6.73 (d, J = 15.5 Hz,
1 H), 7.16–7.22 (m, 1 H), 7.27–7.31 (m, 4 H).
13C NMR (CDCl3): d = 14.11, 22.68, 28.81, 29.18, 29.33, 29.43,
29.50, 29.58, 29.62, 29.64, 31.90, 32.61, 125.35, 125.42, 126.61,
126.73, 128.60, 137.16.
Anal. Calcd for C20H32S: C, 78.88; H, 10.59. Found: C, 79.16; H,
10.47.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research
and COE and GCOE Research Programs from JSPS. A.K. acknowl-
edges JSPS for financial support. Cyclopentyl methyl ether was a
gift from ZEON Corp.
Anal. Calcd for C20H32S: C, 78.88; H, 10.59. Found: C, 78.69; H,
10.53.
Dodecyl (Z)-1-Octenyl Sulfide [(Z)-4b]
Brown oil.
References
IR (neat): 2925, 2854, 2360, 1609, 1467, 1267, 938, 721, 690 cm–1.
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1H NMR (CDCl3): d = 0.88 (t, J = 6.0 Hz, 6 H), 1.20–1.42 (m,
26 H), 1.61 (tt, J = 7.5, 7.5 Hz, 2 H), 2.11 (dt, J = 7.5, 7.5 Hz, 2 H),
2.64 (t, J = 7.5 Hz, 2 H), 5.54 (dt, J = 9.5, 7.0 Hz, 1 H), 5.89 (d,
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13C NMR (CDCl3): d = 14.08, 14.10, 22.62, 22.68, 28.61, 28.93,
28.96, 29.15, 29.20, 29.34, 29.51, 29.59, 29.62, 29.64, 30.33, 31.71,
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13.08.
Dodecyl (E)-1-Octenyl Sulfide [(E)-4b]
Brown oil.
IR (neat): 2925, 2854, 1734, 1653, 1558, 1457, 938 cm–1.
1H NMR (CDCl3): d = 0.88 (t, J = 7.0 Hz, 6 H), 1.20–1.42 (m,
26 H), 1.61 (tt, J = 7.5, 7.5 Hz, 2 H), 2.06 (dt, J = 7.5, 7.5 Hz, 2 H),
2.62 (t, J = 7.5 Hz, 2 H), 5.61 (dt, J = 15.0, 7.0 Hz, 1 H), 5.90 (d,
J = 15.0 Hz, 1 H).
13C NMR (CDCl3): d = 14.08, 14.11, 22.61, 22.68, 28.73, 28.79,
29.21, 29.32, 29.35, 29.48, 28.51, 29.59, 29.63, 29.65, 31.67, 31.91,
32.74, 33.21, 122.63, 130.81.
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Anal. Calcd for C20H40S: C, 76.85; H, 12.90. Found: C, 76.91; H,
12.79.
(Z)-1-Cyclohexyl-1-octene [(Z)-5d]
Colorless oil.
IR (neat): 2999, 2925, 2853, 1653, 1558, 1448, 966, 890, 735 cm–1.
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Synthesis 2008, No. 16, 2659–2664 © Thieme Stuttgart · New York

2664
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Synthesis 2008, No. 16, 2659–2664 © Thieme Stuttgart · New York