Cobalt-catalyzed heck-type reaction of alkyl halides with styrenes

Article abstract of DOI:10.1021/ja026296l

(Chemical Equqtion Presentation) A cobalt complex, CoCl₂[1,6-bis(diphenylphosphino)hexane], catalyzes an alkylation reaction of styrenes in the presence of Me₃SiCH₂MgCl in ether to yield β-alkylstyrenes. A variety of alkyl halides including alkyl chlorides can be employed as an alkyl source. A radical mechanism is strongly suggested for this alkylation reaction. Copyright

Full text of DOI:10.1021/ja026296l

Published on Web 05/15/2002
Cobalt-Catalyzed Heck-Type Reaction of Alkyl Halides with Styrenes
Yousuke Ikeda, Tomoaki Nakamura, Hideki Yorimitsu, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received March 23, 2002
1
The Heck reaction is a powerful tool in organic synthesis. The
scope and limitations have therefore been well investigated. The
major limitation is that one cannot use alkyl halides having
hydrogen at the â-position to the halide atom, because such
Scheme 1
2
substrates suffer from the â-hydride elimination problem. Although
there are some examples of the palladium-catalyzed Heck reaction
of alkyl halides, the reactions employ only bridgehead halides such
as 1-adamantyl bromide.3 A nickel-catalyzed reaction of alkyl
Table 1. Cobalt-Catalyzed Alkylation of Styrene
4
bromides with styrenes was also reported. However, few alkyl
bromides were examined, and the yields were moderate. A similar
5
catalytic transformation with a cobaloxime was known, although
photolysis was required for the successful reaction. Very recently,
Kambe et al. have reported a titanocene-catalyzed alkylation
reaction of styrenes, using butylmagnesium bromide as a base.6
This protocol enables the employment of a variety of alkyl bromides
and some alkyl chlorides as precursors, although yields are still
not satisfactory. Functional group compatibility of this titanocene-
based method remained uninvestigated.
entry
R−X
time/h
temp/°C
yield/%
1
2
3
4
5
6
7
8
9
n-C6H13CH(Br)CH3
n-C H Br
8
8
3
8
8
3
3
3
3
3
3
20
20
35
20
20
35
35
35
35
35
35
2b
2c
2c
2d
2e
2e
2c
2c
2d
2a
2f
73
76
71
87
11
67
57
74
90
84
1
2
25
n-C12H25Br
Ad-Bra
We have been interested in radical reactions mediated by a cobalt
7
t-C4H9Br
t-C4H9Br
n-C12H25I
n-C12H25Cl
Ad-Cla
complex. Here we wish to report a complementary method to the
palladium-catalyzed reaction. A cobalt-phosphine complex cata-
lyzes a Heck-type reaction of alkyl halides with styrenes in the
presence of Me SiCH MgCl.
3 2
1
1
0
1
c-C6H11Cl
CH3I
Trimethylsilylmethylmagnesium chloride (1.0 M ether solution,
.5 mmol) was added to a mixture of styrene (1.0 mmol) and
b
55
2
2
bromocyclohexane (1.5 mmol) in ether in the presence of CoCl -
a
Ad ) 1-adamantyl. b p-Chlorostyrene was used instead of styrene.
8
(dpph) (0.05 mmol) at 0 °C. The reaction mixture was stirred for
8
h at 20 °C. After aqueous workup, silica gel column purification
Table 2. Reaction with Styrene Derivatives
provided â-cyclohexylstyrene (2a) in 86% yield. Heating the
reaction mixture at reflux improved the yield of 2a up to 91%.
The reaction proceeded similarly in dark conditions. Cobalt bromide,
instead of cobalt chloride, worked equally well. PhMe
also effected the alkylation reaction (78% yield of 2a, at 35 °C)
2 2
SiCH MgCl
9
(
Scheme 1).
entry
1
Ar
C6H4-p-Me
C6H4-p-Cl
C6H4-m-Cl
C6H4-o-Cl
C6H4-p-OMe
C6H4-p-CON(CH2Ph)2
C6H4-m-CON(CH2Ph)2
C6H4-m-COO-t-C4H9
4
yield/%
A variety of alkyl halides were examined as shown in Table 1.
1
2
3
4
5
6
7
8
1b
1c
1d
1e
1f
1g
1h
1i
4b
4c
4d
4e
4f
4g
4h
4i
87
85
82
85
82
29
95
66
Not only secondary alkyl bromides but also primary and tertiary
ones participated in the alkylation reaction (entries 1-6). The
reaction of lauryl bromide with styrene at 20 °C yielded â-lauryl-
styrene in 76% yield (entry 2). tert-Butyl bromide was less reactive
and required heating to attain a satisfactory result (entries 5 and
6
). Use of lauryl iodide resulted in a low yield of 2c (entry 7). It
is particularly noteworthy that alkyl chlorides, which are usually
less reactive in transition metal-catalyzed reactions, proved to be
good alkyl sources in this reaction (entries 8-10). For instance,
The reaction tolerates various functionalities (Table 2). Methoxy-
and chlorostyrenes were alkylated efficiently under the standard
heated conditions (entries 2-5). Disappointingly, the presence of
a carbamoyl group at the para position decreased the yield of the
product (entry 6). In contrast, the meta isomer 1h underwent
efficient alkylation (entry 7). A tert-butoxycarbonyl group survived
under the reaction conditions (entry 8).
treatment of a mixture of lauryl chloride and styrene with Me
SiCH MgCl in ether at reflux furnished 2c in 74% yield under
CoCl (dpph) catalysis. The reaction with iodomethane afforded
â-methylstyrene 2f in moderate yield (entry 11).
3
-
2
2
*
To whom correspondence should be addressed. E-mail: oshima@
fm1.kuic.kyoto-u.ac.jp.
6
514 J. AM. CHEM. SOC. 2002, 124, 6514-6515
9
10.1021/ja026296l CCC: $22.00 © 2002 American Chemical Society

C O MMU N I C A T I O N S
Scheme 2
in the presence of Me
SiCH
MgCl. The procedure is simple, and
3
2
the reaction tolerates a variety of functionalities because of the low
reactivity of Me SiCH MgCl. The mechanism of the cobalt-
3
2
catalyzed reaction is quite different from the palladium-catalyzed
one. The former proceeds via a radical pathway and would consist
of the following sequence: generation of an alkyl radical from an
alkyl halide by single-electron transfer from a cobalt complex, an
addition of the alkyl radical to styrene, formation of a benzylic
carbon-cobalt bond, and â-hydride elimination.
Acknowledgment. This work was supported by Grants-in-Aids
for Scientific Research (Nos. 12305058 and 10208208) from the
Ministry of Education, Culture, Sports, Science and Technology,
Government of Japan. H.Y. and T.N. acknowledge JSPS for
financial support.
Scheme 3
Supporting Information Available: Experimental details and
characterization data for new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(
1) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44,
5
81. (b) Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem. 1972, 37, 2320-
2322.
(
2) (a) Br a¨ se, S.; de Meijere, A. In Metal-catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter
3
. (b) Link, J. T.; Overman, L. E. In Metal-catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim,
1998; Chapter 6. (c) Heck, R. F. Org. React. 1982, 27, 345-390. (d)
Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009-3066.
3) (a) Hori, K.; Ando, M.; Takaishi, N.; Inamoto, Y. Tetrahedron Lett. 1987,
(
2
8, 5883-5886. (b) Br a¨ se, S.; Waegell, B.; de Meijere, A. Synthesis 1998,
148-152.
(
4) Lebedev. S. A.; Lopatina, V. S.; Petrov, E. S.; Beletskaya, I. P. J.
Organomet. Chem. 1988, 344, 253-259.
The reaction with cyclopropylmethyl bromide provided a ring-
opening product, â-(3-butenyl)styrene (5), in 50% yield (Scheme
). In addition, tetrahydrofuran derivative 7 was obtained when iodo
acetal 6 was employed. Ring-opening of a cyclopropylmethyl
radical and ring-closure of a 5-hexenyl radical are well-known
processes.10 Generation of an alkyl radical from an alkyl halide is
consequently suggested. It is notable that bis-styrylation of 1,2-
dibromoethane proceeded, albeit the yield was low. A mechanism
via carbometalation of styrene is unlikely, because a 2-bromoeth-
ylmetal reagent undergoes rapid â-bromine elimination.
(
5) Branchaud, B. P.; Detlefsen, W. D. Tetrahedron Lett. 1991, 32, 6273-
6
276.
2
(6) Terao, J.; Kambe, N. J. Synth. Org. Chem., Jpn. 2001, 59, 1044-1051.
(
7) Wakabayashi, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2001,
23, 5374-5375.
(
1
8) dpph ) 1,6-bis(diphenylphosphino)hexane. The choice of the bidentate
ligand was crucial. When dppb, dppp, dppe, dppm, and triphenylphosphine
were employed, (2-cyclohexylethyl)benzene and its dimer 3 were obtained
significantly in addition to 2a.
On the basis of these observations, we propose a draft mechanism
for the catalytic reaction as shown in Scheme 3 in analogy with
(
9) Trialkylsilylmethyl Grignard reagents were essential to obtain the desired
product. The reaction of 1-bromododecane with styrene in the presence
of methyl or ethyl Grignard reagents provided a trace of â-laurylstyrene.
Dodecenes were obtained mainly instead.
7
the previous report. The reaction of CoCl
2
(dpph) with Me
3 2
SiCH -
MgCl gives complex 8, which is electron-rich due to coordination
of the Grignard reagent.11 Complex 8 effects single-electron transfer
to an alkyl halide to yield an anion radical of the halide and cobalt
complex 9. Immediate loss of halide from the anion radical affords
an alkyl radical intermediate, which adds to styrene to yield a
benzylic radical. Cobalt species 9 would then recombine with the
carbon-centered radical to form cobalt species 10. Finally, â-hydride
elimination provides the product and complex 11, which affords 8
(10) (a) Newcomb, M. In Radicals in Organic Synthesis; Renaud, P., Sibi,
M., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, Chapter 3.1. (b)
Newcomb, M.; Choi, S. Y.; Horner, J. H. J. Org. Chem. 1999, 64, 1225-
1
231. (c) Beckwith, A. L. J.; Glover, S. A. Aust. J. Chem. 1987, 40, 157-
1
73.
(
3 2
11) The abbreviation Ln in Scheme 3 represents Me SiCH groups, and the
X represents valence of cobalt. The active cobalt species is unclear at
this stage. A preliminary result can help understanding a mechanistic
aspect: treatment of CoCl
mmol) afforded a trace of Me
that (Me SiCH Co species is stable and that reductive elimination
2
(dpph) (1.0 mmol) with Me
3 2
SiCH MgCl (2.0
3
SiCH CH SiMe . This experiment suggests
2
2
3
by the action of remaining Me
In summary, CoCl (dpph) efficiently catalyzes a Heck-type
reaction of alkyl halides, including alkyl chlorides, with styrenes
3
2
SiCH MgCl.
3
2 2
)
providing a low-valent cobalt complex did not take place.
2
JA026296L
J. AM. CHEM. SOC.
9
VOL. 124, NO. 23, 2002 6515