Ni(0)-catalyzed conjugate addition of Me3SiCN to Ynones: α-bromo-β-cyano tetrasubstituted enones

Article abstract of DOI:10.1021/ol802508q

(Chemical Equation Presented) Conjugate addition of Me₃SiCN to ynones is smoothly catalyzed by Ni(cod)₂ to give the β-cyanosilyloxyallene quantitatively. Further reaction of the silyloxyallenes with NBS provides the tetrasubstituted

Full text of DOI:10.1021/ol802508q

ORGANIC
LETTERS
2009
Vol. 11, No. 2
333-335
Ni(0)-Catalyzed Conjugate Addition of
Me3SiCN to Ynones: r-Bromo-ꢀ-cyano
Tetrasubstituted Enones
Takayoshi Arai,* Yuuki Suemitsu, and Yui Ikematsu
Department of Chemistry, Graduate School of Science, Chiba UniVersity, Inage 1-33,
Chiba 263-8522, Japan
tarai@faculty.chiba-u.jp
Received October 30, 2008
ABSTRACT
Conjugate addition of Me3SiCN to ynones is smoothly catalyzed by Ni(cod)2 to give the ꢀ-cyanosilyloxyallene quantitatively. Further reaction
of the silyloxyallenes with NBS provides the tetrasubstituted r-bromo-ꢀ-cyano enones in high yields (up to 95%) with excellent Z-selectivity
(E/Z ) up to >1/99). X-ray crystallographic analysis showed a bent structure of the r-bromo-ꢀ-cyano enone due to a deconjugation of the
π-bond and carbonyl group.
Due to the great importance of conjugate addition reactions (i.e.,
1,4-addition) in organic synthesis, R,ꢀ-unsaturated carbonyl
compounds have been extensively utilized.1 Horner-Emmons
reactions, Claisen-Schmidt condensations, and eliminations of
phenylselenium groups via oxidation have been employed
widely for preparing such R,ꢀ-unsaturated carbonyl com-
pounds.2 While these conventional methods are quite useful, a
general method for the synthesis of highly functionalized
tetrasubstituted R,ꢀ-unsaturated carbonyl compounds is still
needed.3 Because tetrasubstituted olefins are also of interest for
the development of light- and/or electron-responsive materials
such as liquid crystals and molecular devices including sensors,
switches, and motors,4 the efficient regio- and stereoselective
synthesis of the tetrasubstituted olefins having four different
functional groups becomes an important task in organic
synthesis. We report herein the nickel(0)-catalyzed conjugate
addition of trimethylsilyl cyanide (Me3SiCN) to ynones to
provide silyloxyallenes, and further transformation to the
R-bromo-ꢀ-cyano tetrasubstituted enones.5,6
Regarding the Ni(0)-catalyzed conjugate addition of
Me3SiCN, Shibasaki et al. reported one elegant example in
the synthesis of Tamiflu, in which the reaction proceeded
on the cyclohexenone derivative.7 This Ni(0)-catalyzed
conjugate addition is quite efficient for cyclic enones;
however, the simple application of the Ni(0)-catalyst to
acyclic substrates were unsuccessful (Scheme 1).8
One possibility for the obstacle in the reaction using
acyclic enones might be explained by the formation of a
stable Ni-enone complex (A). These examinations led us
to experiment further on ynones, which would avoid forma-
tion of a tight Ni-substrate complex such as A.9
To our delight, the reaction of diphenyl ynone10 with
Me3SiCN was smoothly catalyzed by Ni(cod)2 in THF, and
the corresponding ꢀ-cyano enone was obtained in 90% yield
(2) Takeda, T., Ed. Modern Carbonyl Olefination; Wiley-VCH: Wein-
heim, Germany, 2004.
(3) Flynn, A. B.; Ogilvie, W. W. A Review for the synthesis of
tetrasubstituted olefins. Chem. ReV. 2007, 107, 4698.
(4) (a) Balzani, V.; Venturi, M.; Credi, A. Molecular DeVices and
Machines - A Journey into the Nanoworld; Wiley-VCH: Weinheim, 2003.
(b) Molecular Switches; Feringa, B. L., Ed.; Wiley-VCH: Weinheim, 2001.
(c) Irie, M., Ed. Photochromism: Memories and Switches, Special Issue.
Chem. ReV. 2000, 100, 1683.
(1) (a) Jung, M. E. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, UK, 1999; Vol. 4, pp 1-67. (b)
Perlmutter, P. In Conjugate Addition Reactions in Organic Synthesis;
Baldwin, J. E., Magnus, P. D., Eds.; Pergamon: Oxford, UK, 1992.
10.1021/ol802508q CCC: $40.75
Published on Web 12/10/2008
2009 American Chemical Society

Actually, in the Ni(0)-catalyzed reaction of diphenyl ynone and
t-BuMe2SiCN, the corresponding silyloxyallene was isolated
in 64% yield (rt, 3 h). The mild reaction conditions would be
an alternative way for the synthesis of silyloxyallenes without
use of the 1,2-Brook rearrangement.12
Scheme 1. Ni(cod)2-Catalyzed Conjugate Addition of Enones
Next, we tried to trap the silyloxyallene with a halogen
ion to obtain R-halo-ꢀ-cyano enones.13 After completion of
the Ni-catalyzed conjugate addition, 1.0 mol equiv of
N-bromosuccinimide (NBS) was added to the reaction
mixture. Bromination at the R-position occurred smoothly
at -78 °C to give R-bromo-ꢀ-cyano enones with high
isolated yields (Table 3).
after treatment with 1 N HCl (Table 1, entry 1).11 Though
the E/Z selectivities of the obtained ꢀ-cyano enones are low
when the reactions were quenched by strong acids, quenching
with AcOH improved the Z-selectivity in the ratio of 11:89
(Table 1, entry 2).
Table 3. Catalytic Synthesis of R-Bromo-ꢀ-cyano
Tetrasubstituted Enones
Table 1. Ni(cod)2-Catalyzed Conjugate Addition of Me3SiCN to
Ynones
entry
R
R′
yield (%)
E/Z
1
Ph
Ph
t-Bu
Ph
Ph
Ph
Me
Ph
4-MeOC6H4
4-BrC6H4
Ph
94
44
90
89
84
95
>1/99
>1/99
>1/99
>1/99
>1/99
>1/99
2
3a
4
entry
H+ source
yield (%)
E/Z
5
6
1
2
3
4
5
1 N HCl (aq)
AcOH
TFA
PhCO2H
PhOH
90
94
92
85
88
58/42
11/89
25/75
30/70
59/41
4-MeOC6H4
a Conjugate addition was carried out at rt.
The bromination proceeded in a highly (Z)-selective
manner, which was confirmed by NOE experiments after
The current procedure is useful not only for aromatic
ynones, but aliphatic ynones as well, which give ꢀ-cyano
trisubstituted enones efficiently (Table 2). The introduction
of electron donating or withdrawing group on the aromatic
substrates couldn’t improve the E/Z selectivities of the
products.
Scheme 2
.
Reduction of R-Bromo-ꢀ-cyano Tetrasubstituted
Enones and NOE Experiments
Table 2. Catalytic Synthesis of ꢀ-Cyano Trisubstituted Enones
conversion to the allylic alcohols by reduction of the enones.
In the R-bromination, the substituent on the aromatic ring
did not reduce the high (Z)-selectivity of the products.
entry
R
R′
yield (%)
E/Z
1
2
Ph
Ph
n-Bu
t-Bu
Ph
Ph
Me
Ph
Ph
94
68
92
84
84
71
94
11/89
24/76
24/76
31/69
27/73
46/54
35/65
3
4a
5
(5) Selected catalytic conjugate additions of cyanide (non asymmetric):
(a) Evans, D. A.; Hoffman, J. M.; Truesdale, L. K. J. Am. Chem. Soc. 1973,
95, 5822. (b) Utimoto, K.; Obayashi, M.; Shishiyama, Y.; Inoue, M.; Nozaki,
H. Tetrahedron Lett. 1980, 21, 3389. (c) Higuchi, K.; Onaka, M.; Izumi,
Y. J. Chem. Soc., Chem. Commun. 1991, 1035.
4-MeOC6H4
4-BrC6H4
Ph
6
7
Ph
4-MeOC6H4
(6) Selected catalytic conjugate additions of cyanide (asymmetric): (a)
Sammis, G. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2003, 125, 4442. (b)
Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126,
9928. (c) Mita, T.; Sasaki, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
2005, 127, 514. (d) Fujimori, I.; Mita, T.; Maki, K.; Shiro, M.; Sato, A.;
Furusho, S.; Kanai, M.; Shibasaki, M. Tetrahedron 2007, 63, 5820. (e)
Tanaka, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2008, 130, 6072.
a Conjugate addition was carried out at rt.
The predominant formation of the silyloxyallene (B) was
1
confirmed by H NMR analysis of the reaction mixture.
334
Org. Lett., Vol. 11, No. 2, 2009

Furthermore, the structures of the compounds obtained in
entry 3 of Table 3 were confirmed by X-ray crystallographic
analysis as shown in Figure 1.
Scheme 3. Plausible Reaction Mechanism of Ni(0)-Catalyzed
Conjugate Addition of Me3SiCN to Ynones
Figure 1. ORTEP diagram of R-bromo-ꢀ-cyano tetrasubstituted
enones (Table 3, entry 3).
reductive elimination from the nickel enolate intermediate would
provide the silyloxyallene (B), and the Me3Si-Ni-CN catalyst
would be regenerated by the reaction with Me3SiCN.
In conclusion, a facile conjugate addition of Me3SiCN to
ynones is presented using the simple Ni(cod)2 catalyst. The
reaction of the silyloxyallenes with NBS provides tetrasub-
stituted R-bromo-ꢀ-cyano enones in a Z-selective manner.
Further applications of silyloxyallenes and R-bromo-ꢀ-cyano
enones are in progress, including a mechanistic study on the
Ni(0) catalysis.
Interestingly, the X-ray structure depicted in Figure 1
suggests an extremely bent enone structure caused by a
deconjugation of the π-bond and carbonyl group due to
significant steric repulsion between the carbonyl group and
the t-Bu substituent (θ OdC-CdC ) 81.1°).
Typically, when R,ꢀ-unsaturated carbonyl compounds are
mixed with Ni(cod)2 in THF, the solution has a dark brown
color. We originally thought the dark brown color suggested
the formation of a Ni-π-bond complex, and the coordination
resulted in activation of the π-bond to promote the subsequent
conjugate addition of cyanide ion.14,15 The addition of
Me3SiCN into the mixture of Ni(cod)2 and ynone, however,
caused the dark brown color to disappear spontaneously. In
the infrared (IR) spectrum, the mixture of the Ni(cod)2 and
Me3SiCN showed a CN absorption at 2146 cm-1, though
the Me3SiCN itself has a CN absorption at 2188 cm-1. The
DFT simulation of the IR spectrum using the Gaussian
program for Me3Si-Ni-CN, which is generated by an
oxidative addition of Ni(0) to Me3SiCN, suggested a CN
absorption at 2137 cm-1.16
Based on these experimental observations and the theoretical
study, the possible mechanism for the current Ni(0)-catalyzed
conjugate addition of Me3SiCN to ynones is proposed as shown
in Scheme 3. Ni(cod)2 would smoothly cause oxidative addition
to Me3SiCN to give the Me3Si-Ni-CN complex. The more
Lewis acidic Ni(II) intermediate would form a π-complex with
the ynones to promote the conjugate addition of cyanide. Further
Acknowledgment. This work was supported by a founda-
tion of the venture business laboratory, Chiba University,
and a Grant-in Aid for Scientific Research from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan. We thank Prof. Akira Yanagisawa at Chiba University
for helpful discussions.
Supporting Information Available: Detailed descriptions
of experimental procedures. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL802508Q
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