Nickel-catalyzed alkenylative cross-coupling reaction of alkyl sulfides

Article abstract of DOI:10.1021/ja104155f

A novel cross-coupling reaction of alkyl aryl sulfides with aryl Grignard reagents has been achieved to produce the alkenyl-aryl coupling products in high yields by using catalytic Ni(cod)₂ and a bulky N-heterocyclic carbene ligand, SIPr.

Full text of DOI:10.1021/ja104155f

Published on Web 09/03/2010
Nickel-Catalyzed Alkenylative Cross-Coupling Reaction of Alkyl Sulfides
Kentaro Ishizuka,†,‡ Hirofumi Seike,† Takuji Hatakeyama,† and Masaharu Nakamura*,†
International Research Center for Elements Science, Institute for Chemical Research, and Institute of Sustainability
Science, Kyoto UniVersity, Uji, Kyoto, 611-0011, Japan
Received May 14, 2010; E-mail: masaharu@scl.kyoto-u.ac.jp
Table 1. Nickel Catalyst and Additive Screening on the
Abstract: A novel cross-coupling reaction of alkyl aryl sulfides
with aryl Grignard reagents has been achieved to produce the
alkenyl-aryl coupling products in high yields by using catalytic
Ni(cod)2 and a bulky N-heterocyclic carbene ligand, SIPr.
Cross-Coupling of Dodecyl Phenyl Sulfide with p-TolMgBr
yield (%)
2 (E/Z)b
RSM (%)d
1c
entrya
nickel cat.
additive
3c
1
2
3
Ni(cod)2
Ni(cod)2
Ni(cod)2
Ni(cod)2
Ni(acac)2
NiCl2
SIPr·HCl
SIPr
92 (94/6)
84 (95/5)
76 (95/5)
19 (92/8)
70 (95/5)
75 (95/5)
0
0
0
0
0
3
4
4
59
8
5
67
57
75
19
0
0
<1
0
IPr·HCl
SIMes·HCl
SIPr·HCl
SIPr·HCl
PtBu3
none
none
none
SIPr ·HCl
Transition-metal-catalyzed cross-coupling reactions are powerful
tools in organic synthesis. While various electrophilic substrates
have been utilized in the cross-coupling reactions, organosulfur
compounds1 have received far less attention among them in spite
of the long history since the independent publications by Wenkert2
and Takei3 in 1979. The current status of underutilization of
organosulfur compounds is partly due to their malodorous smell4
and also due to our perception of them as a mere substitute for the
other electrophiles. In fact, it has been shown that their reactivity
is virtually the same as those of the widely used organic halides
and pseudohalides,5 and thus, there does not seem to be a significant
advantage in pursuing their utility in modern cross-coupling
technology. In light of the ample supply of sulfur sources,6
especially as byproducts of refinery, in industrial chemistry, we
have explored the reactivity of organosulfur compounds in the cross-
coupling reaction and found that alkyl aryl sulfides act as alkenyl
electrophiles to give the arylation products with the simultaneous
installation of an olefinic part in the products (Scheme 1).7 Herein,
we report a novel Ni-catalyzed “alkenylative” cross-coupling
reaction of alkyl sulfides with aryl Grignard reagents, which
provides a new access to olefinic compounds of various substitution
patterns.
4
10
0
0
19
23
17
64
>95
5e
6e
7
NiCl2
8
9
10
11
NiCl2(dppe)
NiCl2(PPh3)2
NiCl2
none
a Reactions were carried out on a 0.5 mmol scale. b The yield and E/
1
Z selectivity were determined by H NMR analysis using pyrazine as an
internal standard. c The yield was determined by GC analysis using
undecane as an internal standard. d Recovery of the starting material 1.
e Reactions were carried out at 80 °C.
desired alkenylative coupling product 2 was not obtained (entries
7-10). In the absence of a nickel catalyst, the coupling reactions
did not proceed at all (entry 11).
Scope of the present nickel-catalyzed alkenylative cross-coupling
reaction is shown in Table 2. The reactions of dodecyl sulfides
possessing an electron-rich, electron-poor, or bulky aryl group all
gave the alkenylative coupling products in high yields with excellent
E/Z selectivities, and the parent dodecyl phenyl sulfide was found
to give the optimum yield (entries 1-5). Secondary alkyl aryl
sulfides also participate in the alkenlylative coupling reaction:
cyclohexyl (or cycloheptyl) phenyl sulfide reacted with a variety
of aryl Grignard reagents bearing dimethylamino, methoxy, methyl,
and fluoro substituents to give the corresponding arylated cycloalk-
enes in good to excellent yields (entries 6-9, 13). The reaction
was found to be rather sensitive to the steric demands of the aryl
nucleophile, and thus, the coupling products with o-tolyl and mesityl
Grignard reagents were obtained in poor yields (entries 10 and 11).
A 2-naphthyl Grignard reagent took part in the reaction (entry 12).
Excellent E/Z selectivity was achieved in the formation of
disubstituted acyclic olefin, exemplified by the stereoselective
synthesis of the E-stilbene derivative (entry 14). In contrast, low
selectivity was observed in the formation of trisubstituted olefin
(entry 15). This may be accounted for by nonstereoselective
formation of enthiolate intermediates (see the mechanistic discussion
below). When a nonsymmetrical secondary alkyl sulfide was
subjected to the reaction conditions, the corresponding internal olefin
4 and terminal olefin 5 were obtained in a ratio of 46:54. Note that
the stereoselectivity of this trisubstituted olefin 4 is acceptably high
(entry 16). The olefin moiety in the sulfide substrate did not interfere
with the coupling reaction (entry 17). As in entry 18, 8-phenylthio-
1,4-dioxaspiro[4,5]decane gave a double arylation product, 8,8-
diphenyl-1,4-dioxaspiro-[4,5]decane, in 37% yield along with the
Scheme 1. Alkenylative Cross-Coupling of Alkyl Aryl Sulfide
Table 1 summarizes the results of catalyst screening. In the
presence of Ni(cod)2, the highest yield (92%) of the desired
alkenylative coupling product 2 was obtained after 6 h at 60 °C
when a saturated-type N-heterocyclic carbene (NHC) ligand precur-
sor, 1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride (SIPr ·HCl),
was used (entry 1). The reaction with the NHC ligand itself (SIPr)
showed similar selectivity but gave a slightly lower yield (entry
2). Other NHC ligand precursors, IPr ·HCl and SIMes ·HCl, gave
lower yields (entries 3 and 4). Ni(acac)2 and NiCl2 showed lower
catalytic activity and required a higher reaction temperature, 80
°C, for complete conversion (entries 5 and 6). While phosphine
ligands improved the yield of the biaryl coupling product 3, the
† International Research Center for Elements Science (IRCELS), Institute for
Chemical Research.
‡ Institute of Sustainability Science.
9
10.1021/ja104155f  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 13117–13119 13117

C O M M U N I C A T I O N S
Table 2. Substrate Scope of Alkenylative Cross-Coupling
Scheme 2. A Plausible Mechanism
gives a diorganonickel G with production of byproducts MgBr2 and
MgS.14 Reductive elimination gives the alkenylative coupling product,
such as 2, with regeneration of the active species A. The diarylation
could take place via addition of an aryl Grignard reagent to a
thiocarbonyl intermediate C,15 followed by a nickel-catalyzed arylation
of the resulting benzylthiolate.16
DFT calculations provide deeper insights into the alkenylative
coupling reaction as shown in Figure 1: An unprecedented transition
structure model was obtained for the transformation from B to C.
The phenylnickel(II) B (R ) H, L ) none in Scheme 2) isomerizes
to B′, in which an agostic Ni-H interaction is present. A concerted
ꢀ-hydride-reductive elimination of benzene takes place via a five-
centered transition structure TSB-C to form a Ni(0)-thioaldehyde
complex C. On the other hand, the transmetalation from B to D
takes place via a transition structure resembling σ-bond methathesis,
TSB-D. Relative Gibbs free energy of TSB-D is 3.0 kcal/mol higher
than that of TSB-C probably owing to the steric demand of a bulky
SIPr at TSB-D. These results are in good accordance with the
experimental results, the selective formation of alkenylative cou-
pling products in the presence of SIPr.
In summary, we have developed a nickel-catalyzed alkenylative
cross-coupling reaction of alkyl aryl sulfides with aryl Grignard
reagents. The key to success is the use of a bulky NHC ligand,
SIPr, which suppresses the conventional biaryl coupling reaction.
The theoretical calculation suggests a concerted mechanism for the
ꢀ-hydride elimination and reductive elimination process from
nickel(II) thiolate species, which accounts for the new reactivity
of the organosulfur electrophile in the present alkenylative cross-
coupling.
a Reactions were carried out on a 0.5-1.0 mmol scale following the
procedure in entry 1 in Table 1 unless otherwise noted. b Ni(cod)2 (5
mol %) and SIPr ·HCl (10 mol %) were used in the case of secondary
alkyl sulfides. c NMR yields using pyrazine as an internal standard.
d The reaction was carried out on a 10 mmol scale. e GC yield.
formation of the expected alkenylative coupling product (43%
yield). The geminal diarylation products were also found as a minor
byproduct (1-3% yields) in all the other entries, and the mechanism
of the formation is discussed below.
Scheme 2 shows a plausible mechanism based on the experimental
results,8,9 computational studies10 (Figure 1), and related literature.10-13
The catalytic cycle starts with the oxidative addition of an alkyl phenyl
sulfide to a Ni(0) species A to afford a phenylnickel(II) intermediate
B. ꢀ-Hydride elimination and subsequent reductive elimination of
benzene give a Ni(0)-thioaldehyde complex C. A bulky NHC ligand
would suppress the conventional biaryl coupling pathway (A-B-D).
The thioaldehyde undergoes deprotonation by ArMgBr to give a Ni(0)-
enethiolate complex E,11,12 and the following C-S bond cleavage gave
an alkenyl nickel(II) F.13 Transmetalation between F and ArMgBr
Figure 1. Reaction pathways for the reductive ꢀ-hydride elimination
process (B to C) and the transmetalation process (B to D). Relative Gibbs
free energies (∆G, calculated at the B3LYP/6-311+G(d,p)-SDD//B3LYP/
6-31G(d)-LANL2DZ level) relative to B are given in kcal/mol.
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C O M M U N I C A T I O N S
Guillaumet, G. Org. Lett. 2003, 5, 803. (f) Liebeskind, L. S.; Srogl, J. Org.
Lett. 2002, 4, 979. (g) Srogl, J.; Liu, W.; Marshall, D.; Liebeskind, L. S.
J. Am. Chem. Soc. 1999, 121, 9449. (h) Tiecco, M.; Testaffrri, L.; Tingoli,
M. Tetrahedron 1983, 39, 2289.
Acknowledgment. We thank the Ministry of Education, Culture,
Sports, Science and Technology Japan (MEXT) and Japan Society
for the Promotion of Science (JSPS) for financial support, Grant-
in-Aids for Young Scientists (S, M.N., 20675003; B, T.H.,
21750098). Financial support from Tosoh Finechem and Tosoh
Corporations as well as the Noguchi Institute is gratefully acknowl-
edged. We also thank Prof. S. Ogoshi (Osaka University) for his
valuable comments. We truly appreciate the insightful suggestions
provided by the reviewers during the reviewing process.
(6) For the industrial supply of sulfur, see: Ober, J. A. U.S. Geol. SurV., Mineral
Commodity Summaries 1998, 166–167. For archives at USGS, see: http://
minerals.usgs.gov/minerals/pubs/commodity/sulfur/.
(7) For reactions of dithioacetals with Grignard reagents giving olefins, see:
(a) Luh, T.-Y. J. Organomet. Chem. 2002, 653, 209. (b) Luh, T.-Y. Acc.
Chem. Res. 1991, 24, 257.
(8) The use of dodecanethiol instead of dodecyl phenyl sulfide did not give
the alkenylative coupling product 2 but the conventional coupling product,
1-dodecyl-4-methylbenzene (7%), dodecane (24%), and 1-dodecene (27%),
respectively.
(9) The reaction of 2,2,4,4,6,6-hexamethyl-1,3,5-trithiane, a trimer form of
propane-2-thione, with 4-(N,N-dimethylamino)phenyl Grignard reagent gave
the corresponding alkenylative coupling product, N,N-dimethyl-4-(prop-
1-en-2-yl)aniline (17%) with recovery of the trithiane (51%), which indicates
an intermediacy of thioketone in the present alkenylative coupling reaction.
(10) See the Supporting Information for details.
Supporting Information Available: For details of the experimental
procedure, computational studies, characterization, and physical data
of the products. This material is available free of charge via the Internet
at http://pubs.acs.org.
(11) For the deprotonation of thiocarbonyl compounds, see: (a) Nocher, A.-
M. L.; Metzner, P. Tetrahedron Lett. 1992, 33, 6151. (b) Murase, M.;
Yoshida, S.; Hosaka, T.; Tobinaga, S. Chem. Pharm. Bull. 1991, 39, 489.
(12) For the tautomerization of thiocarbonyl compounds, see: Zhang, X.-M.;
Malick, D.; Petersson, G. A. J. Org. Chem. 1998, 63, 5314.
(13) For cross-couplings of aryl thiolates, see: (a) Cho, Y.-H.; Kina, A.; Shimada,
T.; Hayashi, T. J. Org. Chem. 2004, 69, 3811. (b) Swindell, C. S.; Blase´,
F. R. Tetrahedron Lett. 1990, 31, 5405.
(14) For generation of MgS, see: Nieto, J. T.; Are´valo, A.; Gutie´rrez, P. G.;
Ram´ırez, A. A.; Garc´ıa, J. J. Organometallics 2004, 23, 4534.
(15) For addition of Grignard reagents to thioketone, see: Lin, C.-E.; Richardson,
S. K.; Wang, W.; Wang, T.; Garvey, D. S. Tetrahedron 2006, 62, 8410.
(16) The reaction of naphthalene-2-ylmethanethiol with 3 equiv of p-tolyl
Grignard reagent under the present reaction conditions gave the coupling
product, 2-(4-methylbenzyl)naphthalene (35%), and the reduced product,
2-methyl naphthalene (27%). For geminal dimethylation of dithioacetals,
see: Yang, P.-F.; Ni, Z.-J.; Luh, T.-Y. J. Org. Chem. 2002, 653, 209.
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