Cobalt-mediated Mizoroki-Heck-type reaction of epoxide with styrene

Article abstract of DOI:10.1002/adsc.200404074

Treatment of a mixture of epoxide and styrene with trimethylsilylmethylmagnesium bromide in the presence of a cobalt-phosphine complex afforded homocinnamyl alcohol in good yield. The reaction should begin with ring opening of the epoxide by the action of magnesium bromide which leads to the formation of a magnesium 2-bromoethoxide derivative and not with a direct single electron transfer from a cobalt complex to the epoxide.

Full text of DOI:10.1002/adsc.200404074

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Cobalt-Mediated Mizoroki–Heck-Type Reaction of Epoxide with
Styrene
Yousuke Ikeda, Hideki Yorimitsu, Hiroshi Shinokubo, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Fax: (þ81)-75-383-2438, e-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received: March 10, 2004; Accepted: July 2, 2004
Abstract: Treatment of a mixture of epoxide and
styrene with trimethylsilylmethylmagnesium bro-
mide in the presence of a cobalt-phosphine complex
afforded homocinnamyl alcohol in good yield. The
reaction should begin with ring opening of the epox-
ide by the action of magnesium bromide which leads
to the formation of a magnesium 2-bromoethoxide
derivative and not with a direct single electron trans-
fer from a cobalt complex to the epoxide.
synthesizing an authentic sample by the copper-mediat-
ed ring opening of 1a with (E)-2-phenylethenyl
Grignard reagent.[6] The use of cobalt(II) bromide and
trimethylsilylmethylmagnesium bromide slightly in-
creased the yield of 2a (entry 2). In addition, the reac-
tion with 7 mol % of the cobalt catalyst resulted in the
formation of 2a in 81% yield (entry 3). However, neither
a higher catalyst loading (10 mol %) nor higher reaction
temperature (in refluxing ether) was effective (entries 4
and 5). The ligand DPPH was essential to obtain 2a in
satisfactory yields. Use of Ph2P(CH2)nPPh2 (n¼1–5)
as a ligand decreased the yields of 2a (12, 7, 20, 1,
60%, respectively), along with formation of significant
amounts of 2-bromocyclopentanol.
Keywords: cobalt; epoxide ring opening; 2-hydroxy-
ethylation; Mizoroki-Heck reaction; radical reaction
Table 1. Reaction of cyclopentene oxide with styrene.[a]
The Mizoroki–Heck arylation and vinylation reaction of
alkenes is a powerful tool in organic synthesis.[1,2] Aryl or
vinyl halides (or pseudohalides) are usually the precur-
sors. On the other hand, there are only scattered exam-
ples of the palladium-catalyzed Mizoroki–Heck alkyla-
tion reaction of alkenes.[3] Recently, Mizoroki–Heck
type reactions of alkyl halide with alkene mediated by
transition metal catalysts other than palladium have at-
tracted increasing attention.[4] We have also reported a
cobalt-mediated alkylation reaction of styrene with al-
kyl halide.[5] Here we report the use of epoxide as a pre-
cursor of the alkylation reaction instead of alkyl halide.
The established reaction is equivalent to the 2-hydroxy-
ethylation of styrene, for which no successful palladium
catalysts is known.
Entry
X
Co catalyst [mol %] Temp [ 8C] Yield [%]
1
2
3
4
5
Cl
Br
Br
Br 10
Br
5
5
7
20
20
20
20
35
62
71
81
78
75
7
[a]
Styrene (1.0 mmol), 1a (1.5 mmol), (CH3)3SiCH2MgX
(2.5 mmol, 1.0 M ethereal solution), and ether (1.0 mL)
were used.
We first examined the reaction of cyclopentene oxide
(1a) with styrene (Table 1). A mixture of 1a (1.5 mmol)
The reaction of cyclohexene oxide (1b) with styrene un-
and styrene (1.0 mmol) was treated with trimethylsilyl- der the same reaction conditions furnished the corre-
methylmagnesium chloride (2.5 mmol) in ether in the sponding alkenol 2b in 65% yield as a mixture of the trans
presence of cobalt(II) chloride combined with 1,6-bis- and cis isomers in a ratio of 77/23 (Table 2, entry 1). To im-
(diphenylphosphino)hexane (DPPH) at 208C for 20 h. prove the yield of 2b, we further examined several reac-
Usual work-up followed by silica gel column purifica- tion conditions. Gratifyingly, we found that cobalt(III)
tion afforded 2-(2-phenylethenyl)-1-cyclopentanol acetylacetonate [Co(acac)3] was a good precursor of the
(2a) in 62% yield (entry 1). The styrene moiety of 2a active catalyst (entry5). Co(acac)3 isfarlessmoisture-sen-
had the E configuration according to 1H NMR analysis. sitive than CoCl2 or CoBr2 and hence much easier to han-
It is worth noting that the trans isomer was exclusively dle. Moreover, toluene was the solvent of choice for this
formed with respect to the hydroxy and 2-phenylethenyl reaction. All the reactions shown in Table 2 yielded a mix-
groups. The trans stereochemistry of 2a was verified by ture of the stereoisomers in essentially the same ratio.
Adv. Synth. Catal. 2004, 346, 1631–1634
DOI: 10.1002/adsc.200404074
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Yousuke Ikeda et al.
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Table 2. Cobalt-mediated reaction of cyclohexene oxide with
Table 3. Reaction of 1-alkene oxides with styrene.
styrene.[a]
trans/cis[b]
Entry
R
3
Conditions[a] Yield [%] 4/5
Entry
Co salt
Solvent
Yield [%]
1
2
3
4
5
6
CH3
3a
3b
3c
3d
3e
A
A
A
B
A
A
57
58
46
48
26
50
79/21
57/43
46/54
63/37
>99/1
>99/1
1
2
3
4
5
CoBr2
CoBr2
CoBr2
Co(acac)2
Co(acac)3
ether
65
53
70
72
74
77/23
77/23
76/24
74/26
74/26
n-C4H9
n-C12H25
c-C6H11
t-C4H9
hexane
toluene
toluene
toluene
CH3OCH2 3f
[a]
Styrene (1.0 mmol), 1b (1.5 mmol), (CH3)3SiCH2MgBr
(2.5 mmol, 1.0 M ethereal solution), cobalt salt
(7 mol %), DPPH (8.5 mol %), and solvent (1.0 mL)
were used.
[a]
Conditions A: the conditions of entry 5 in Table 1. Condi-
tions B: the conditions of entry 5 in Table 2.
[b]
With respect to the hydroxy and 2-phenylethenyl groups.
Cycloheptene oxide (1c) was less reactive. Homocin-
namyl alcohol 2c was obtained in 42% yield by using
15 mol % of CoBr2(dpph) and 3.0 molar equivalents of
(CH3)3SiCH2MgBr in ether [Eq. (1)]. 1,2-trans-Alcohol
2c was obtained as the sole isomer and no 1,2-cis-isomer
was observed. Unfortunately, use of cyclooctene oxide
(1d) and cyclododecene oxide (1e) resulted in recovery
of the starting epoxides under the various reaction con-
ditions we tested.
Scheme 1.
ð1Þ
ð3Þ
We next examined the reaction of epoxides prepared
from acyclic 1-alkenes (Table 3). The yields were fair
and the products were obtained as a mixture of re-
gioisomers 4 and 5, except for the reactions of 3e and
3f. The reaction of epoxides with 1-octene failed to af-
ford the corresponding products.
The 2-aminoethylation of styrene was also successful
[Eqs. (2) and (3)]. Treatment of aziridines 6a and 6b
with (CH3)3SiCH2MgBr in the presence of styrene and
the cobalt catalyst afforded the corresponding homocin-
namylamines.
The generation of radicals from epoxides by metal re-
ductants is well known[7] and that by titanocene chloride
Cp2TiCl has been extensively studied.[8] Direct electron
transfer to an epoxide is quite likely to generate the
more substituted radical 8 and finally 4 predominantly
(Scheme 1). The results in Table 3 and Eq. (3) are highly
suggestive of a stepwise single electron transfer path-
way. Namely, 2-bromoethoxide formation followed by
single electron transfer to the bromide 9 and 10 would
form 8 and 11, respectively. Magnesium bromide formed
via the Schlenk equilibrium would effect ring opening.
The equilibria between epoxides and the correspond-
ing 2-bromoethoxides under the reaction conditions are
the key for the present reaction. We thus tried to obtain
further information on the equilibria. Three-membered
rings 3a, 3c, and 6b were subjected to the trimethylsilyl-
methylmagnesium bromide-mediated ring opening re-
ð2Þ
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Adv. Synth. Catal. 2004, 346, 1631–1634

Cobalt-Mediated Mizoroki–Heck-Type Reaction
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Experimental Section
Synthesis of trans-2-[(E)-2-
Phenylethenyl]cyclopentanol (2a)
Anhydrous cobalt(II) bromide (15.3 mg, 0.070 mmol) was
placed in a 20-mL two-necked flask and was heated with a
hair dryer under vacuum for 3 min. 1,6-Bis(diphenylphosphi-
no)hexane (38.6 mg, 0.085 mmol) and anhydrous ether
(1 mL) were sequentially added under argon. After the mix-
ture was stirred for 30 min to obtain a blue suspension, cyclo-
pentene oxide (1a, 0.13 g, 1.5 mmol), styrene (0.10 g,
1.0 mmol), and trimethylsilylmethylmagnesium bromide (1.0
M ethereal solution, 2.5 mL, 2.5 mmol) were successively add-
ed dropwise to the reaction mixture at 08C. After being stirred
for 20 h at 208C, the reaction mixture was poured into saturat-
ed ammonium chloride solution. The products were extracted
with ethyl acetate (20 mL ꢀ 3). The combined organic layer
was dried over sodium sulfate and concentrated. Purification
on a silica gel column (hexane/ethyl acetate¼5/1) of the crude
product provided trans-2-[(E)-2-Phenylethenyl]cyclopentanol
(2a) as a colorless oil; yield: 0.15 g (0.81 mmol, 81%); IR (neat):
n¼3358, 3026, 2957, 1649, 1599, 1497, 1448, 1072, 964, 908, 841,
746, 692 cmꢁ1; 1H NMR (CDCl3, 300 MHz): d¼1.47–1.81 (m,
5H), 1.95–2.11 (m, 2H), 2.44–2.55 (m, 1H), 3.97 (dt, J¼6.9,
6.9 Hz, 1H), 6.14 (dd, J¼15.9, 8.4 Hz, 1H), 6.48 (d, J¼
15.9 Hz, 1H), 7.18–7.39 (m, 5H); 13C NMR (CDCl3,
75 MHz): d¼21.31, 30.09, 33.60, 52.26, 78.54, 125.90, 126.95,
128.35, 130.23, 132.13, 137.19; anal. found: C 82.92, H 8.71%;
calcd. for C13H16O: C 82.94, H 8.57%.
Scheme 2.
Scheme 3.
action (Scheme 2). For example, treatment of 3c with
the Grignard reagent in ether for 2 h followed by hydrol-
ysis afforded 1-bromo-2-tetradecanol and 2-bromo-1-
tetradecanol in a ratio of 56/43. This fact suggests that
two magnesium 2-bromoethoxide derivatives exist in
the reaction mixture. Treatment of 1-bromo-2-tetrade-
canol and 2-bromo-1-tetradecanol with the Grignard re-
agent also resulted in formation of the two alkoxides in
the same ratio. The ratio of 4c/5c was ca. 1/1 as shown in
Table 3 and reflects the equilibrium distribution.
Synthesis of 2-(2-Phenylethenyl)cyclohexanol (2b)
Anhydrous
cobalt(III)
acetylacetonate
(24.9 mg,
0.070 mmol) and DPPH (38.6 mg, 0.085 mmol) were placed
in a 20-mL reaction flask. Anhydrous toluene was then added
under argon. The mixture was stirred for 15 min. A dark green
solution was obtained. Cyclohexene oxide (1b, 0.15 g,
1.5 mmol), styrene (0.10 g, 1.0 mmol), and trimethylsilylme-
thylmagnesium bromide (1.0 M ethereal solution, 2.5 mL,
2.5 mmol) were successively added to the reaction mixture
The equilibria between 1 and their open forms are re-
lated to the reactivity of 1 toward the present reaction
and the yield of 2 (Scheme 3). The equilibrium was shift-
ed toward the open form in the case of 1a, and hence 2a at 08C. After stirring for 20 h at 208C, work-up and purifica-
tion on silica gel by the aforementioned procedure provided
2b as a mixture of stereoisomers (trans/cis¼74/26); yield:
0.15 g (0.74 mmol, 74%).
was obtained in good yield. The poor conversion of 1e
would stem from the equilibrium where 1e predomi-
nates over its open form.
In conclusion, we have developed a cobalt-mediated
synthesis of homocinnamyl alcohols from epoxides
and styrene. The reaction is equivalent to the 2-hydroxy-
ethylation of styrene. The reaction proceeds via ring
opening of epoxides by means of magnesium bromide
to yield 2-bromoethoxides and generation of radicals
by single electron transfer from an electron-rich cobalt
complex to the 2-bromoethoxides. The mechanism is
completely different from the reductive addition of ep-
oxide with alkene reported in the literature although
these reactions produce similar radical intermediates.[7,8]
The reaction is applicabletothe synthesis ofhomocinna-
mylamines starting from aziridines.
Ring Opening of 3c with
Trimethylsilylmethylmagnesium Bromide
1-Tetradecene oxide (0.11 g, 0.50 mmol) and ether (1 mL)
were placed in a 20-mL flask. Trimethylsilylmethylmagnesi-
um bromide (1.0 M ethereal solution, 1.0 mL, 1.0 mmol)
was added dropwise at 08C. After being stirred for 2 h at
208C, the reaction mixture was quenched with ammonium
chloride solution. Silica gel column purification provided
the corresponding bromohydrins (primary alcohol/secondary
alcohol¼43/56).
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Yousuke Ikeda et al.
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Acknowledgements
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This work was supported by a Grant-in-Aid for Scientific Re-
search and COE Research from the Ministry of Education, Cul-
ture, Sports, Science, and Technology, Japan.
[5] Y. Ikeda, T. Nakamura, H. Yorimitsu, K. Oshima, J. Am.
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