Cobalt-catalyzed reductive carboxylation on α,β-unsaturated nitriles with carbon dioxide

Article abstract of DOI:10.1246/cl.131163

The reductive carboxylation of α,β-unsaturated carbonyl compounds with carbon dioxide was studied. After the screening of various transition-metal complex catalysts and reducing agents, it was found that the combination of bis(acetylacetonato) cobalt(II)

Full text of DOI:10.1246/cl.131163

Received: December 11, 2013 | Accepted: December 26, 2013 | Web Released: April 5, 2014
CL-131163
Cobalt-catalyzed Reductive Carboxylation on α,β-Unsaturated Nitriles with Carbon Dioxide
Chika Hayashi, Takuo Hayashi, Satoshi Kikuchi, and Tohru Yamada*
Department of Chemistry, Keio University, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522
(E-mail: yamada@chem.keio.ac.jp)
The reductive carboxylation of α,β-unsaturated carbonyl
Ph
OH
E+ : PhCHO
cat. Co(II) complex
compounds with carbon dioxide was studied. After the screening
of various transition-metal complex catalysts and reducing
agents, it was found that the combination of bis(acetylaceto-
nato)cobalt(II) and diethylzinc could effectively afford the
corresponding α-carboxylate in high yield from α,β-unsaturated
nitriles. The product was obtained after esterification by
trimethylsilyldiazomethane. The highly selective carboxylation
was observed at the α-position in the present study.
R
R
EWG
R
Hydride equivalent
EWG
Reductive aldol
Co(II)
E
O
OH
+ : CO2
E+
E
C
R
EWG
EWG
R
EWG
H
H
Reductive carboxylation
Scheme 1. Cobalt-catalyzed C-C bond formations via enolate
equivalents.
Carbon-carbon bond formation is one of the most important
reactions in organic chemistry. Since the report1 by Mukaiyama
in 1973 on the Lewis acid-catalyzed crossed aldol reaction using
silyl enol ether as a metal enolate analogue, this reaction has
been employed as a standard method in organic synthesis. In
principle, the Mukaiyama aldol reaction proceeds in the
presence of a catalytic amount of Lewis acid to exclusively
afford the cross addition product. As no strong base is required,
this reaction has been welcomed by various organic chemists as
a reliable carbon-carbon bond formation reaction, especially in
natural product chemistry.2 In order to improve the catalytic
efficiency or stereoselectivity of this reaction system, various
metal elements have been screened as Lewis acid catalysts.3
Much effort has also been made for designing ligands in
enantioselective catalytic version. As an alternative solution for
the metal-catalyzed crossed aldol reaction, conjugate reductions
have been employed using a catalytic amount of rhodium(III)
chloride and stoichiometric trimethylsilane for α,β-unsaturated
carbonyl compounds, the resulting metal enolate equivalents
were employed for the following aldol reaction.4 Since both the
enolate generation and aldol reaction proceed in one pot, the
reductive aldol reaction has been examined especially for the
catalytic version of carbon-carbon forming reactions. Isayama
and Mukaiyama reported the reductive aldol reaction from α,β-
unsaturated nitriles catalyzed by bis(acetylacetonato)cobalt(II)
and phenylsilane in 1989.5 The reaction mechanism is presumed
to be as follows: phenylsilane could act on the cobalt complex as
a reducing agent to generate “cobalt hydride.” Its 1,4-addition to
an α,β-unsaturated nitrile would afford the corresponding cobalt
enolate equivalent, which would produce the cobalt alkoxide of
the aldol adducts by a nucleophilic attack on the electrophile
such as aldehydes and ketones (Sheme 1). The successive
transmetalation between the cobalt and silane could regenerate
the catalytic cobalt hydride and silyl ether of the aldol adduct.
As the carbon-carbon bond-forming reaction was selectivity
observed at the α-position, the Michael addition-type reaction
should be essential during the first step with cobalt hydride
equivalent. During the course of our continuing studies on
cobalt(II) complex catalysts with the combined use of reducing
agents, various synthetic reactions were reported; the oxidation-
reduction-hydration of various alkenes was proposed in the
presence of 2-propanol and molecular oxygen.6 With the
combined use of sodium borohydride, the catalytic enantiose-
lective reduction of various carbonyl compounds into optically
active secondary alcohols or amines was realized.7 Under similar
conditions, the enantioselective 1,4-reduction of α,β-unsaturated
carboxamides was also reported.8
Carbon dioxide is a safe and abundant C1 resource. Since it
contains a carbonyl group in its structure, the reaction of CO2
with various carbon nucleophiles has been examined for new
carbon-carbon bond formation. Our laboratory has reported the
reactions of carbon dioxide with epoxides catalyzed by cobalt(II)
complexes9a and propargyl alcohols and amines catalyzed by
silver(I) salts,9b,9c respectively. In these reactions, however, an
oxygen or nitrogen nucleophile attacked the carbon dioxide to
afford the corresponding cyclic carbonates or oxazolidinones.
Although these products will release carbon dioxide on
hydrolysis, the corresponding products, formed via a carbon-
carbon bond-forming reaction with carbon dioxide, should be
stable enough to be employed as further synthetic intermediates
for carbon-carbon frameworks. Various methods10,11 have been
reported for the carbon-carbon bond-forming reaction with
carbon dioxide. Our laboratory has proposed the reactions of
enolates with carbon dioxide. In the presence of a silver(I)
catalyst, various ketones containing an alkyne group at the
appropriate position afforded the corresponding γ-lactone
derivatives9d or dihydroisobenzofuran derivatives9e in good to
high yields under mild conditions, respectively. In this commu-
nication, the reductive carboxylation reaction of α,β-unsaturated
nitriles with carbon dioxide in the presence of cobalt(II) catalysts
and reducing agents is reported.
The initially reported standard conditions were used for the
reductive aldol reaction of 5-phenylpent-2-enenitrile (1a) with
benzaldehyde to afford the corresponding aldol adduct in 88%
yield. Under the same reaction conditions, but with the aldehyde
being replaced by carbon dioxide, the desired product 2a was
not obtained at all; the corresponding reduced product was
produced instead. Since the reduced product was obtained, it
was assumed that the 1,4-reduction of the α,β-unsaturated nitrile
would proceed to generate the corresponding enolate equivalent,
which cannot capture carbon dioxide (Table 1, Entry 1). By
Chem. Lett. 2014, 43, 565–567 | doi:10.1246/cl.131163
© 2014 The Chemical Society of Japan | 565

Table 1. Examination of various reductant for reductive
carboxylation
Table 2. Various α,β-unsaturated nitriles for reductive carbox-
ylation
COOH
COOMe
cat.[Co(acac)2]
cat.[Co(acac)2], CO2
TMSCHN2
R
Ph
Ph
CN
R
CN
CN
CO2, Et2Zn
CN
Reductant (2.0 equiv)
1
3
1a
2a
Entrya
Substrate
Product
Yield/%d
Amount of Co(II) CO2 pres.
complex/mol %
Entrya Reductant
Yield/%
COOMe
CN
1
2
3
4
5
6
7
8
Ar = Ph
3a
>99
77
85e
>99
>99
98
/MPa
Ar
CN
Ar
= 4-Me-Ph
3b
3c
3d
3e
3f
1b
2b
3
PhSiH3
PhSiH3
Et3B
5
100
100
100
100
5
1.0
1.0
1.0
1.0
1.3
1.0
0.1
0
10
10
26
62
87c
>99c
= 4-CO2Et-Ph
= 4-Br-Ph
= 4-Cl-Ph
4
5
Et2AlCl
Et2Zn
= 4-OMe-Ph
3g
72
= OBn
6
Et2Zn
3h >99
= 1-Naph
7
Et2Zn
5
CN
COOMe
aReactions were carried out in 0.25 mmol scale with 1.5 mL of
THF at 20 °C. bReaction was carried out in 1.5 mL of 1,2-
dichloroethane at 70 °C. cYield after methylation with
trimethylsilyldiazomethane.
9
3i
3j
78
Ph
Ph
Ph
CN
COOMe
10b
81
38
Ph
CN
Me
CN
CN
COOMe
Me
CN
11b
12b
3k
3l
Ph
Ph
Ph
Ph
COOMe
using a stoichiometric amount of the cobalt complex, the desired
product 2a was obtained in 10% yield (Entry 2). As it was
confirmed that the corresponding reductive carboxylation ac-
tually proceeds in the presence of the cobalt complex, various
reducing agents were examined. Triethylborane, diethylalumi-
num chloride, and diethylzinc were used as a reducing agent
(Entries 3, 4, and 5).12 Based on this screening, it was found that
diethylzinc is the most suitable reducing agent to capture carbon
dioxide. Triethylborane showed a reactivity similar to that of
phenylsilane. Diethylaluminum chloride produced a better yield
than those obtained by silane and borane; however, diethylzinc
gave the best yield. By using diethylzinc and 5 mol % of the
cobalt(II) complex, the desired product 2a was eventually
obtained in quantitative yield under mild conditions with
atmospheric pressure of carbon dioxide.
The optimized conditions were successfully applied to
various α,β-unsaturated nitriles to afford the corresponding
carboxylation products (Table 2). The carboxylation reaction
with carbon dioxide was selectively observed at the α-position
for all substrates in Table 2. 5-Phenylpent-2-enenitrile (1a) and
its derivatives with substituents such as alkyls, ethers, esters, and
halogens exhibited a good reactivity to afford the corresponding
products 3a-3f after methyl esterification in good-to-excellent
yields (Entries 1-6). The substrates with a naphthyl group,
benzyl group, and shortened alkyl chain 1g-1i also afford the
corresponding products in high yields (Entry 7-9). Cinnamo-
nitrile forms the corresponding product 3j in 81% yield
(Entry 10). Similar to the standard Michael additions,13 though
the β-substituted methacryl derivatives were not suitable
substrates for this reaction (Entry 12), the α-substituted
(Entry 11) and γ-methyl-substituted (Entry 13) α,β-unsaturated
nitriles reacted with carbon dioxide to afford the corresponding
carboxylation products in moderate-to-good yield. The α-
phenyl-substituted α,β-unsaturated nitrile was found to react
with carbon dioxide to give the carboxylated product in good
yield (Entry 14). The dihydronaphthalenes with a nitrile at the
α-position 1o and 1p reacted with carbon dioxide to afford the
products in good to high yield (Entries 15 and 16) though no
9f
CN
CN
Me
Me COOMe
Me
Me
13b
14b
3m
3n
67
66
Ph
Ph
CN
CN
CN
CN
COOMe
Ph
CN
Ph
NC COOMe
15b
16c
R′ = H
3o
91
56
R′ = OMe 3p
R′
R′
CN
NC COOMe
Me
Me
17b
3q
0
aReactions were carried out in 0.25 mmol scale with 1.5 mL of
THF at 20 °C under atmospheric pressure of CO2 with 2 equiv
of Et2Zn (ca. 1.0 M in n-hexane) in the presence of 5 mol % of
[Co(acac)2]. b10 mol % of [Co(acac)2] and 4 equiv of Et2Zn
were employed. c15 mol % of [Co(acac)2] and 8 equiv of Et2Zn
were employed. dIsolated yield. e1.0 MPa of CO2. fD.r. =
60:40.
reaction proceeded for the corresponding β-methyl-substituted
nitrile 1q (Entry 17).
The corresponding ethyl-substituted product at the β-
position was detected using GC-MS analysis. For the reaction
of the α,β-unsaturated nitrile 1p, the corresponding ethyl-
substituted product 4p was isolated in 12% yield. The ethyl-
substituted products were exclusively obtained in the absence
of the cobalt complex; however, the desired product was not
detected (Scheme 2, eq 1). Therefore, the combined use of a
cobalt catalyst and diethylzinc is crucial to generate the metal
enolate equivalent hydrated at the β-position (eq 2). It was
reported that the transmetalation of the bis(acetylacetonato)-
nickel(II) complex with alkylaluminum would generate alkyl
nickel species, which would result in nickel hydride after β-
elimination.14 For this reaction, the cobalt hydride generated by
the same process would add the α,β-unsaturated nitrile via a 1,4-
addition to afford the resulting metal enolate equivalent. Though
566 | Chem. Lett. 2014, 43, 565–567 | doi:10.1246/cl.131163
© 2014 The Chemical Society of Japan

CN
NC COOMe
Et
5814.
1) CO2
Co(acac)2
Et2Zn
(1)
4
a) S. Sato, I. Matsuda, Y. Izumi, Chem. Lett. 1985, 1875. b)
A. Revis, T. K. Hilty, Tetrahedron Lett. 1987, 28, 4809.
S. Isayama, T. Mukaiyama, Chem. Lett. 1989, 2005.
a) T. Mukaiyama, S. Isayama, S. Inoki, K. Kato, T. Yamada,
T. Takai, Chem. Lett. 1989, 449. b) K. Kato, T. Yamada, T.
Takai, S. Inoki, S. Isayama, Bull. Chem. Soc. Jpn. 1990, 63,
179.
Et2Zn 2) TMSCHN2
R′
CN
R′
R′
1
4
5
6
EtCo L
NC COOMe
Co
EWG
1) CO2
R′
R
HCo L
(2)
2) TMSCHN2
1o
1p
R′ = H
= OMe
H
3
7
T. Yamada, T. Nagata, K. D. Sugi, K. Yorozu, T. Ikeno, Y.
Ohtsuka, D. Miyazaki, T. Mukaiyama, Chem.®Eur. J. 2003,
9, 4485.
Scheme 2. Cobalt hydride 1,4-addition mechanism.
not yet clear whether the cobalt or zinc enolate captures the
carbon dioxide, the corresponding carboxylated product was
obtained in good-to-high yield for various α,β-unsaturated
nitriles.
It is noted that the combination of bis(acetylacetonato)-
cobalt(II) and diethylzinc could effectively afford the corre-
sponding α-carboxylate in high yield from the α,β-unsaturated
nitriles. Further investigation on the detailed mechanism or
applications is currently underway.15
8
9
T. Yamada, Y. Ohtsuka, T. Ikeno, Chem. Lett. 1998, 1129.
a) H. Tanaka, Y. Kitaichi, M. Sato, T. Ikeno, T. Yamada,
Chem. Lett. 2004, 33, 676. b) W. Yamada, Y. Sugawara,
H. M. Cheng, T. Ikeno, T. Yamada, Eur. J. Org. Chem. 2007,
2604. c) S. Yoshida, K. Fukui, S. Kikuchi, T. Yamada,
Chem. Lett. 2009, 38, 786. d) S. Kikuchi, K. Sekine, T.
Ishida, T. Yamada, Angew. Chem., Int. Ed. 2012, 51, 6989. e)
K. Sekine, A. Takayanagi, S. Kikuchi, T. Yamada, Chem.
Commun. 2013, 49, 11320.
10 a) T. Tsuda, K. Ueda, T. Saegusa, J. Chem. Soc., Chem.
Commun. 1974, 380. b) M. Komatsu, T. Aida, S. Inoue,
J. Am. Chem. Soc. 1991, 113, 8492.
11 H. Maekawa, T. Murakami, T. Miyazaki, I. Nishiguchi,
Chem. Lett. 2011, 40, 368.
This paper is dedicated to Professor Teruaki
Mukaiyama in celebration of the 40th anniversary of the
Mukaiyama aldol reaction.
References and Notes
12 a) H. W. Lam, P. M. Joensuu, G. J. Murray, E. A. F. Fordyce,
O. Prieto, T. Luebbers, Org. Lett. 2006, 8, 3729. b) J.
Montgomery, G. J. Sormunen, in Metal Catalyzed Reductive
C-C Bond Formation in Topics in Current Chemistry, ed. by
M. J. Krische, Springer, Berlin Heidelberg, 2007, Vol. 279,
pp. 1-23. doi:10.1007/128_2007_139.
1
T. Mukaiyama, K. Narasaka, K. Banno, Chem. Lett. 1973,
1011.
2
T. Mukaiyama, in Organic Reactions, ed. by W. G. Dauben,
et al., John Wiley & Sons, 1982, Vol. 28, Chap. 3, pp. 203-
331. doi:10.1002/0471264180.or028.03.
3
a) Y. Ito, M. Sawamura, T. Hayashi, J. Am. Chem. Soc. 1986,
108, 6405. b) G. A. Slough, R. G. Bergman, C. H.
Heathcock, J. Am. Chem. Soc. 1989, 111, 938. c) J.
Nokami, T. Mandai, H. Watanabe, H. Ohyama, J. Tsuji,
J. Am. Chem. Soc. 1989, 111, 4126. d) T. Naota, H. Taki, M.
Mizuno, S.-I. Murahashi, J. Am. Chem. Soc. 1989, 111,
5954. e) E. M. Carreira, R. A. Singer, W. Lee, J. Am. Chem.
Soc. 1994, 116, 8837. f) M. Sodeoka, K. Ohrai, M.
Shibasaki, J. Org. Chem. 1995, 60, 2648. g) D. A. Evans,
J. A. Murry, M. C. Kozlowski, J. Am. Chem. Soc. 1996, 118,
13 N. Krause, A. Hoffmann-Röder, Synthesis 2001, 171.
14 a) M. Kimura, H. Fujimatsu, A. Ezoe, K. Shibata, M.
Shimizu, S. Matsumoto, Y. Tamaru, Angew. Chem., Int. Ed.
1999, 38, 397. b) Y. Sato, M. Takimoto, M. Mori, J. Am.
Chem. Soc. 2000, 122, 1624. c) K. Fischer, K. Jonas, P.
Misbach, R. Stabba, G. Wilke, Angew. Chem., Int. Ed. Engl.
1973, 12, 943.
15 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2014, 43, 565–567 | doi:10.1246/cl.131163
© 2014 The Chemical Society of Japan | 567