Cobalt-catalyzed coupling of alkenyl triflates with aryl and alkenyl grignard reagents

Article abstract of DOI:10.1246/cl.2008.654

Co(acac)₃-PPh₃ was found to effectively catalyze the C(sp²)-C(sp²) coupling of Grignard reagents to give alkenyl-arenes and conjugated dienes, utilizing close affinity towards alkenyl triflates. Copyright

Full text of DOI:10.1246/cl.2008.654

654
Chemistry Letters Vol.37, No.6 (2008)
Cobalt-catalyzed Coupling of Alkenyl Triflates with Aryl and Alkenyl Grignard Reagents
Eiji Shirakawa,Ã Yusuke Imazaki, and Tamio HayashiÃ
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received April 14, 2008; CL-080382; E-mail: shirakawa@kuchem.kyoto-u.ac.jp, thayashi@kuchem.kyoto-u.ac.jp)
Co(acac)3–PPh3 was found to effectively catalyze the
the yield to 88% (Entry 2). Higher conversion with PPh3 possi-
bly shows that the main role of the ligand is stabilization of the
cobalt catalyst. High activity of the cobalt catalyst was disclosed
by higher conversion (83%) in a short reaction period (30 min)
than that with the corresponding palladium catalyst (Entry 3
vs. 4), which though scored a high yield in a long reaction period
(Entry 5). A close affinity of the cobalt catalyst towards triflates
was shown in comparison with the reaction of 1-octen-2-yl
bromide, which coupled with 1a only in 60% yield (Entry 6).
The cobalt catalyst was applied to the coupling of alkenyl
triflates not only with arylmagnesium bromides (Table 2) but
also with alkenylmagnesium bromides (Table 3).8,9 In addition
to nonsubstituted phenyl Grignard reagent 1a, those having an
electron-donating methoxy group at p, m, or o position under-
went the coupling with triflate 2a in high yields (Entries 1–4
of Table 2). Introduction of an electron-withdrawing group is
C(sp2)–C(sp2) coupling of Grignard reagents to give alkenyl-
arenes and conjugated dienes, utilizing close affinity towards
alkenyl triflates.
The cobalt-catalyzed cross-coupling reaction of Grignard
reagents has recently attracted considerable attention because
the catalysts and the organometallic reagents are fairly inexpen-
sive and easily available.1 However the cobalt-catalyzed cou-
pling shows a much limited scope compared with the palladi-
um-catalyzed reaction, which covers a variety of cross-coupling
reactions between carbon atoms in diverse hybridized states.2 A
marked difference is observed for C(sp2)–C(sp2) coupling,3,4 in
particular for alkenyl–alkenyl coupling, which has only one ex-
ample with cobalt catalysis.5 In this context, we have reported
that alkenyl triflates, which are easily prepared from ketones,
as alkenyl electrophiles have a close affinity towards cobalt cat-
alysts to undergo the coupling with alkynyl Grignard reagents.6,7
In this first cobalt-catalyzed C(sp)–C(sp2) coupling, we used
a simple catalyst system consisting merely of Co(acac)3 and
THF respectively as a catalyst and a solvent. Here, we report that
addition of triphenylphosphine to the system makes alkenyl
triflates effectively react also with aryl and alkenyl Grignard
reagents to give C(sp2)–C(sp2) coupling products in good to high
yields.
Table 2. Cobalt-catalyzed coupling of aryl Grignard reagents
with alkenyl triflatesa
Co(acac)3 (3 mol %)
Ar
TfO
PPh3 (12 mol %)
THF, 3 h
R2
R2
+
Ar MgBr
R1
R1
2
1
3
Entry
Temp Prod Yield
1
2
/%b
/°C
TfO
1
2
0
87
3aa
3ba
2a
TfO
2a
Hex
Hex
MgBr
1a
MeO
0
80
We chose phenylmagnesium bromide (1a) and 1-octen-2-yl
triflate (2a) as a substrate combination to evaluate the catalyst
system for C(sp2)–C(sp2) coupling. The reaction of 1a
(1.8 equiv) with 2a (1.0 equiv) using the same catalyst system
[3 mol % of Co(acac)3 with no ligands in THF] as the coupling
of alkynyl Grignard reagents with alkenyl triflates6 at 0 ꢀC for
3 h gave 2-phenyl-1-octene (3aa) only in 67% yield (Entry 1
of Table 1). Addition of PPh3 (12 mol %) as a ligand increased
MgBr
1b
TfO
2a
3
0
87
3ca
Hex
MeO
MgBr
1c
OMe
MgBr
TfO
2a
4
5
6
7
20
0
72
79
67
77
3da
3ea
3fa
3ga
Hex
Hex
Hex
Hex
1d
F3C
TfO
2a
MgBr
1e
Cl
TfO
2a
0
MgBr
1f
Table 1. Comparison of catalysts in the coupling of phenyl-
magnesium bromide with 1-octen-2-yl triflatea
TfO
2a
40
MgBr
1g
Catalyst (3 mol %)
TfO
2a
TfO
2b
+
Ph
3aa
TfO
(Br)
2a
Ph MgBr
8
9
40
71
78
3ha
3ab
THF, 0 °C
Hex
Hex
S
MgBr
MgBr
MgBr
MgBr
MgBr
MgBr
1h
1a
1a
1a
1a
1a
Hex
1a
Pent
–20
Entry
Catalyst
Co(acac)3
Co(acac)3/PPh3 (1/4)
Co(acac)3/PPh3 (1/4)
Pd(acac)2/PPh3 (1/4)
Pd(acac)2/PPh3 (1/4)
Time/h Conv./%b Yield/%b
40 (71)c
11 (20)c
93
TfO
2c
TfO
10
11
12
13
0
20
20
20
3ac
3ad
3ae
3af
1
2
3
4
5
3
3
0.5
0.5
24
3
91
>99
83
30
96
67
88 (87)c
69
27
2d
TfO
93
60
2e
TfO
6d Co(acac)3/PPh3 (1/4)
98
93
2f
aThe reaction was carried out in THF (1.0 mL) at 0 ꢀC using 1a
(0.45 mmol) and 2a (0.25 mmol) in the presence of Co(acac)3
(7.5 mmol) and PPh3 (30 mmol). bDetermined by 1H NMR of
the crude product. cIsolated yield based on 2a. dThe correspond-
ing bromide was used instead of 2a.
aThe reaction was carried out in THF (1.0 mL) for 3 h using 1
(0.45 mmol) and 2 (0.25 mmol) in the presence of Co(acac)3
(7.5 mmol) and PPh3 (30 mmol). bIsolated yield based on 2.
cTris(4-methoxyphenyl)phosphine was used instead of PPh3.
Copyright ꢀ 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.6 (2008)
655
Table 3. Cobalt-catalyzed coupling of alkenyl Grignard re-
agents with alkenyl triflatesa
Co(acac)3
MgBr
1 or 4
R2
R = aryl, alkenyl
5
R
R
TfO
2
R1
MgBrOTf
–
R3
R2
R3
Co(acac)3 (3 mol %)
PPh3 (12 mol %)
[R2Co]2–·2 (MgBr)+
R2Co
(MgBr)+
R4
R4
TfO
R2
R2
R3
6
+
MgBr
R5
R1
5
7
THF, 0 °C, 3 h
R1
R5
MgBr
1 or 4
4
2
R2
R
Entry
Prod
Yield
/%b
87
4
2
[RCo]–·(MgBr)+
R3
8
3 or 5
1c
2
TfO
OMe
OMe
MgCl
5ag
5bg
4a
Scheme 1.
2g
TfO
93
flates with aryl and alkenyl Grignard reagents, where C(sp2)–
C(sp2) coupling products are obtained in good to high yields.
MgBr
MgBr
MgBr
2g
TfO
2f
TfO
4b
4b
4b
3
4
73
5bf
5be
References and Notes
84d
1
2
3
For early examples, see: a) M. S. Kharasch, C. F. Fuchs, J. Am.
Chem. Soc. 1943, 65, 504. b) G. Cahiez, H. Avedissian, Tetra-
hedron Lett. 1998, 39, 6159.
2e
TfO
OMe
OMe
MgBr
5
6
69
88
5cg
5dg
4c
2g
TfO
For a review on the palladium-catalyzed coupling of Grignard
reagents, see: Metal-catalyzed Cross-coupling Reactions, 2nd ed.,
ed. by A. de Meijere, F. Diederich, Wiley-VCH, Weinheim, 2004.
To the best of our knowledge, the reports on the cobalt-catalyzed
C(sp2)–C(sp2) coupling using Grignard reagents are limited to
the followings except for ref 1. a) T. J. Korn, G. Cahiez, P. Knochel,
Synlett 2003, 1892. b) T. J. Korn, M. A. Schade, M. N. Cheemals,
S. Wirth, S. A. Guevara, G. Cahiez, P. Knochel, Synthesis 2006,
3547. c) T. Hatakeyama, M. Nakamura, J. Am. Chem. Soc. 2007,
129, 9844.
Many reports, predominantly by Oshima and co-workers, are avail-
able for the cobalt-catalyzed coupling of Grignard reagents with
C(sp3) electrophiles. For alkyl halides: a) T. Tsuji, H. Yorimitsu,
K. Oshima, Angew. Chem., Int. Ed. 2002, 41, 4137. b) H. Ohmiya,
T. Tsuji, H. Yorimitsu, K. Oshima, Chem.—Eur. J. 2004, 10, 5640.
c) H. Ohmiya, H. Yorimitsu, K. Oshima, J. Am. Chem. Soc. 2006,
128, 1886. d) H. Ohmiya, K. Wakabayashi, H. Yorimitsu, K.
Oshima, Tetrahedron 2006, 62, 2207. e) A. Kuno, N. Saino, T.
Kamachi, S. Okamoto, Tetrahedron Lett. 2006, 47, 2591. f) H.
Ohmiya, H. Yorimitsu, K. Oshima, Org. Lett. 2006, 8, 3093. For
the coupling of alkyl halides accompanied by insertion of a
carbon–carbon unsaturated bond, see: g) K. Wakabayashi, H.
Yorimitsu, K. Oshima, J. Am. Chem. Soc. 2001, 123, 5374. h) K.
Mizutani, H. Shinokubo, K. Oshima, Org. Lett. 2003, 5, 3959.
i) H. Someya, H. Ohmiya, H. Yorimitsu, K. Oshima, Org. Lett.
2007, 9, 1565. j) H. Someya, H. Ohmiya, H. Yorimitsu, K. Oshima,
Tetrahedron 2007, 63, 8609. For allyl methoxides: k) K. Mizutani,
H. Yorimitsu, K. Oshima, Chem. Lett. 2004, 33, 832. l) H. Yasui, K.
Mizutani, H. Yorimitsu, K. Oshima, Tetrahedron 2006, 62, 1410.
The coupling of 2-methyl-1-propenylmagnesium bromide with
styryl bromide in the presence of 5 mol % of Co(acac)2 at
60–65 ꢀC for 15 min gave 60% yield of the coupling product. See
ref 1b.
MgBr
2g
TfO
2g
4d
OMe
7
79
5eg
MgBr
4e
aThe reaction was carried out in THF (1.0 mL) at 0 ꢀC for 3 h
using 4 (0.45 mmol) and 2 (0.25 mmol) in the presence of
Co(acac)3 (7.5 mmol) and PPh3 (30 mmol). bIsolated yield based
on 2. cReaction temperature = 40 ꢀC. dDetermined by 1H NMR
of the crude product.
4
compatible with the reaction (Entry 5). The chloroarene moiety
of Grignard reagent 1f did not participate in the cross-coupling
(Entry 6). Bulky aryl Grignard reagent 1g and 2-thienylmagne-
sium bromide (1h) coupled with triflate 2a (Entries 7 and 8).
The reaction is applicable also to linear and cyclic alkenyl tri-
flates 2b–2f to give the corresponding coupling products with
1a, though a large drop of the yield was observed in the reaction
of cyclopentenyl and -hexenyl triflates (Entries 9–13).10 For the
reaction of these cyclic triflates, use of tris(4-methoxyphenyl)-
phosphine instead of PPh3 gave better results. On the other hand,
conjugated dienes are obtained by the coupling of alkenyl
Grignard reagents. Nonsubstituted vinyl Grignard reagent 4a re-
acts with 1-alken-2-yl triflate 2g having a methoxyphenyl moiety
to give 2-substituted 1,3-butadiene 5ag (Entry 1 of Table 3). The
scope of alkenyl triflates was examined with monosubstituted
vinyl Grignard reagent 4b, which coupled with cyclic triflates
2f and 2e in addition to acyclic 2g (Entries 2–4). Disubstituted
vinyl Grignard reagents 4c–4e also underwent the coupling reac-
tion with triflate 2g (Entries 5–7). During the coupling reaction,
the stereochemistry of 2-buten-2-yl Grignard reagents 4d and 4e
was retained to give (Z)- and (E)-dienes, respectively.
A plausible mechanism based on those proposed in the re-
ports by Oshima et al.4d,4g and us6 is shown in Scheme 1, though
we do not have any evidence for the present C(sp2)–C(sp2)
coupling. The catalytic cycle includes three distinct steps: 1)
oxidative addition of alkenyl triflate 2 to R2Co0 di-ate complex
6, generated through reduction of Co(acac)3 by Grignard reagent
1 or 4, giving cobalt(II) complex 7, 2) reductive elimination of
coupling product 3 or 5 to give RCo0 ate complex 8, 3) regener-
ation of di-ate complex 6 through the reaction of 8 with a
Grignard reagent.
5
6
7
E. Shirakawa, T. Sato, Y. Imazaki, T. Kimura, T. Hayashi, Chem.
Commun. 2007, 4513.
For the examples of the cobalt-catalyzed coupling of alkenyl
halides, see ref 1. See also: a) T. Kamachi, A. Kuno, C. Matsuno,
S. Okamoto, Tetrahedron Lett. 2004, 45, 4677. b) W. Affo, H.
Ohmiya, T. Fujioka, Y. Ikeda, T. Nakamura, H. Yorimitsu, K.
Oshima, Y. Imamura, T. Mizuta, K. Miyoshi, J. Am. Chem. Soc.
2006, 128, 8068.
Supporting Information, which contains experimental details
including characterization data, is also available electronically on
the CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
8
9
Under several similar conditions, p-tolyl triflate coupled with
phenylmagnesium bromide in yields less than 15%.
10 In the reaction of the 5- and 6-membered cyclic triflates, low
conversions were observed even in a longer reaction period. Cyclo-
hexenyl triflate is a rather poor electrophile also in the cobalt-
catalyzed coupling with alkynyl Grignard reagents. See ref 6.
In conclusion, we have disclosed an effective catalyst
consisting of Co(acac)3 and PPh3 for the coupling of alkenyl tri-
Published on the web (Advance View) May 24, 2008; doi:10.1246/cl.2008.654