Rhodium-catalyzed alkenylation of nitriles via silicon-assisted C-CN bond cleavage

Article abstract of DOI:10.1021/ol100481h

Rhodium-catalyzed Mizoroki-Heck type reaction of nitriles via the cleavage of C-C bonds is described. Orthogonal and iterative functionalizations of arenes were also demonstrated by combining the present and conventional halide-based cross-coupling reacti

Full text of DOI:10.1021/ol100481h

ORGANIC
LETTERS
2010
Vol. 12, No. 8
1864-1867
Rhodium-Catalyzed Alkenylation of Nitriles
via Silicon-Assisted C-CN Bond Cleavage
Yusuke Kita,† Mamoru Tobisu,*,‡ and Naoto Chatani*,†
Frontier Research Base for Global Young Researchers, Graduate School of Engineering,
Osaka UniVersity, Suita, Osaka 565-0871, Japan, and Department of Applied Chemistry,
Faculty of Engineering, Osaka UniVersity, Suita, Osaka 565-0871, Japan
tobisu@chem.eng.osaka-u.ac.jp; chatani@chem.eng.osaka-u.ac.jp
Received February 25, 2010
ABSTRACT
Rhodium-catalyzed Mizoroki-Heck type reaction of nitriles via the cleavage of C-C bonds is described. Orthogonal and iterative functionalizations
of arenes were also demonstrated by combining the present and conventional halide-based cross-coupling reactions.
The Mizoroki-Heck reaction has been recognized as a
powerful tool for the arylation of alkenes.1 In addition to
Scheme 1. Catalytic Arylation of Alkenes
the standard Mizoroki-Heck reaction using aryl halides or
their equivalents2 (Scheme 1a), several variants have been
developed. They can be classified based on the method used
to generate the key aryl-metal species: transmetalation from
organometallic reagents (oxidative Mizoroki-Heck reaction,
Scheme 1b),3 electrophilic subsitution of arenes (Fujiwara-
† Department of Applied Chemistry, Faculty of Engineering.
‡ Frontier Research Base for Global Young Researchers, Graduate School
of Engineering.
(1) For reviews of the Mizoroki-Heck reaction, see: (a) Beletskaya,
I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009. (b) Whitcombe, N. J.;
Hii, K. K. M.; Gibson, S. E. Tetrahedron 2001, 57, 7449. (c) Knowles,
J. P.; Whiting, A. Org. Biomol. Chem. 2007, 5, 31. (d) The Mizoroki-Heck
Reactione; Oestreich, M., Ed.; Wiley-VCH: Weinheim, 2009.
(2) Selected recent examples; aroyl chloride: (a) Sugihara, T.; Satoh,
T.; Miura, M. Tetrahedron Lett. 2005, 46, 8269. Diazonium salt: (b)
Kikukawa, K.; Ikenaga, K.; Kono, K.; Toritani, K.; Wada, F.; Matsuda, T.
J. Organomet. Chem. 1984, 270, 277. Arylsulfonyl chloride: (c) Dubbaka,
S. R.; Vogel, P. Chem.sEur. J. 2005, 11, 2633. N-nitroso-N-arylacetamide:
(d) Kikukawa, K.; Naritomi, M.; He, G. X.; Wada, F.; Matsuda, T. J. Org.
Chem. 1985, 50, 299. Aryl phoshonium salt: (e) Hwang, L. K.; Na, Y.;
Lee, J.; Do, Y.; Chang, S. Angew. Chem., Int. Ed. 2005, 44, 6166.
Hypervalent iodo compound: (f) Aydin, J.; Larsson, J. M.; Selander, N.;
Szabo, K. J. Org. Lett. 2009, 11, 2852–2854.
(3) Selected recent examples; M ) B: (a) Xiong, D.-C.; Zhang, L.-H.; Ye,
X.-S. Org. Lett. 2009, 11, 170. M ) Sn: (b) Parrish, J. P.; Jung, Y. C.;
Shin, S. I.; Jung, K. W. J. Org. Chem. 2002, 67, 7127. M ) Si: (c) Koike,
T.; Du, X.; Sanada, T.; Danda, Y.; Mori, A. Angew. Chem., Int. Ed. 2003,
42, 89. M ) P(O)(OH)2: (d) Inoue, A.; Shinokubo, H.; Oshima, K. J. Am.
Chem. Soc. 2003, 125, 1484. M ) Bi: (e) Asano, R.; Moritani, I.; Fujiwara,
Y.; Teranishi, S. Bull. Chem. Soc. Jpn. 1973, 46, 2910. M ) Sb: (f) Matoba,
K.; Motofusa, S.-i.; Sik Cho, C.; Ohe, K.; Uemura, S. J. Organomet. Chem.
1999, 574, 3.
Moritani reaction, Scheme 1c),4 and decarboxylation of aryl
carboxylic acids (Scheme 1d).5 Herein, we report a new
variant of the Mizoroki-Heck process, in which an aryl-metal
(4) A review: (a) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res.
2001, 34, 633. A recent report: (b) Zhang, Y.-H.; Shi, B.-F.; Yu, J.-Q. J. Am.
Chem. Soc. 2009, 131, 5072.
10.1021/ol100481h  2010 American Chemical Society
Published on Web 03/25/2010

species is generated from aryl cyanides via the cleavage of
a carbon-carbon bond. Synthetic applications of this decy-
anative Mizoroki-Heck reaction, including orthogonal and
iterative functionalization of arenes, are also demonstrated.
Previously, we reported rhodium-catalyzed silylation6a,b
and decyanation6c reactions of aryl cyanides via the cleavage
of C-CN bonds. In these reactions, an arylrhodium species
generated from aryl cyanides and organosilicon reagents is
postulated to be a key intermediate. Indeed, we also reported
that tethered electrophiles can intercept the arylrhodium
intermediate to afford cyclized products.6b On the basis of
these results, we envisioned that an arylrhodium complex
generated in our catalytic system should react with external
alkenes to furnish an alkenylated product, especially in
consideration of the number of catalytic reactions involving
the addition of arylrhodium intermediates to alkenes.7 One
isolated example of a Mizoroki-Heck-type alkenylation of
nitrile (34% yield), in which a C-CN bond is cleaved via
oxidative addition to a nickel catalyst, was reported.8
First, we examined the reaction of methyl 4-cyanobenzoate
with several alkenes, including terminal alkenes, cyclic
alkenes, R,ꢀ-unsaturated carbonyl compounds, vinyl acetate,
vinyl ethers, and vinylsilanes, under the conditions we
identified as being suitable for the intramolecular arylation
reaction.6b As a result, the desired Mizoroki-Heck-type
product 2a was obtained in 46% yield, along with the
undesired silylated byproduct 3,6a,b when triethylvinylsilane
(1a) was used as an alkene component (entry 1 in Table 1).
ization of alkenes.9 Inspired by the promising result using
1a, we next optimized the reaction conditions to improve
the selectivity (Table 1). By increasing the amount of 1a (4
equiv to nitrile), the yield of alkenylated product was
improved (entry 2). The choice of the ligand also proved to
affect the selectivity significantly. Among the ligands
examined, P(4-FC6H4)3 proved to be the most effective.10
The effect of the substituents on the silicon atom of
vinylsilanes was also examined (entries 4-7). The use of
vinylsilanes bearing trimethyl-, tert-butyldimethyl-, and
triisopropylsilyl groups, as in 1b-d, lowered the yields of
the corresponding alkenylated products. On the other hand,
the use of triisopropoxylvinylsilane (1e) completely sup-
pressed the formation of 3 and selectively afforded the
alkenylated product 2e. Although 1e proved to be the best
alkene in terms of the yield and selectivity, we were unable
to isolate the pure product 2e due to the difficulty in
separating the byproducts, which were presumably formed
by the oligomerization of 1e. Thus, we decided to employ
1a as an alkene component for further investigation.11
Table 2 shows the scope of the rhodium-catalyzed alk-
enylation of nitriles using 1a. Functional groups, such as
esters (entries 1), ethers (entries 3, 5, 7, and 8), and amines
(entries 4 and 6), and a heteroaromatic ring (entry 12) were
tolerated. The selectivity between alkenylation and silylation
agreed with the trends of electronic and steric effects
observed for our previously reported silylation reaction.6c
Better selectivity for the alkenylation products was observed
with electron-rich substrates due to the relatively slow
silylation reaction (entries 3 and 4). It is important to note
that, although a small amount of silylated products were
formed with several substrates, all the alkenylated products
could successfully be isolated in pure form by standard silica
gel chromatography. In the case of sterically congested
nitriles, the desired alkenylated products were obtained
exclusively, presumably due to the sensitivity of the rate of
silylation to the steric effect6a,b (entries 7-10). Alkenyl
cyanides were also applicable to this catalysis to furnish
dienylsilanes 14 (entry 13).
Table 1. Reaction Optimizationa
A plausible mechanism is illustrated in Scheme 2. A
catalyst precursor A initially reacts with disilane to generate
catalytically active silylrhodium species B. Silicon-assisted
yields (%)b
(5) (a) Gooꢀen, L. J.; Paetzold, J.; Winkel, L. Synlett 2002, 1721. (b)
Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124,
11250. (c) Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433. (d) Tanaka,
D.; Romeril, S. P.; Myers, A. G. J. Am. Chem. Soc. 2005, 127, 10323. (e)
Hu, P.; Kan, J.; Su, W.; Hong, M. Org. Lett. 2009, 11, 2341.
(6) (a) Tobisu, M.; Kita, Y.; Chatani, N. J. Am. Chem. Soc. 2006, 128,
8152. (b) Tobisu, M.; Kita, Y.; Ano, Y.; Chatani, N. J. Am. Chem. Soc.
2008, 130, 15982. (c) Tobisu, M.; Nakamura, R.; Kita, Y.; Chatani, N.
J. Am. Chem. Soc. 2009, 131, 3174.
entry
Si
ligand
2
3
1c
2
3
4
5
6
7
SiEt3 (a)
SiEt3 (a)
SiEt3 (a)
SiMe3 (b)
SitBuMe2 (c)
SiiPr3 (d)
Si(OiPr)3 (e)
P(4-CF3C6H4)3
P(4-CF3C6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
P(4-FC6H4)3
46
60
65
25
36
11
68d
22
28
18
25
14
79
0
(7) For reviews on this topic, see: (a) Fagnou, K.; Lautens, M. Chem.
ReV. 2003, 103, 169. (b) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103,
2829. (c) Miura, T.; Murakami, M. Chem. Commun. 2007, 217.
(8) Nakao, Y.; Yada, A.; Satoh, J.; Ebata, S.; Oda, S.; Hiyama, T. Chem.
Lett. 2006, 35, 790.
a Reaction conditions: methyl 4-cyanobenzoate (0.5 mmol), vinylsilane
(2 mmol), hexamethyldisilane (1 mmol), [RhCl(cod)]2 (0.025 mmol), ligand
(0.05 mmol), ethylcyclohexane (0.5 mL), 130 °C, 15 h. b Isolated yields
based on nitrile. c Run using 1a (1 mmol). d NMR yield.
(9) Tobisu, M.; Hyodo, I.; Onoe, M.; Chatani, N. Chem. Commun. 2008,
6013.
(10) Other ligands examined (ligand (yield of 1a, yield of 2a)): PPh3
(53%, 27%), P(4-MeOC6H4)3 (37%, 31%), P(C6F5)3 (55%, 14%), P(2-
MeC6H4)3 (24%, 74%), PCy3 (22%, 0%), PBu3 (25%, 64%), P(OPh)3 (42%,
42%), bipyridine (25%, 10%), IPr (55%, 28%).
One possible reason for the inapplicability of other alkenes
may be the side reactions initiated by silylrhodation of
alkenes, such as dehydrogenative silylation and oligomer-
(11) For the results using other vinylsilanes, see the Supporting
Information.
Org. Lett., Vol. 12, No. 8, 2010
1865

Table 2. Rh-Catalyzed Alkenylation of Aromatic Nitriles with
Scheme 2. Plausible Mechanism
1aa
The present new variant of the Mizoroki-Heck reaction
can provide a unique strategy for the synthesis of π-conju-
gated molecules. For example, introduction of two different
alkenes to an aromatic ring can be attained by the sequential
alkenylation of 16 via Pd and Rh catalysis (eq 1).
a Reaction conditions: nitrile (0.5 mmol), 1a (2 mmol), hexamethyld-
isilane (1 mmol), [RhCl(cod)]2 (0.025 mmol), P(4-FC6H4)3 (0.05 mmol),
ethylcyclohexane (0.5 mL), 130 °C, 15 h. b Isolated yield of alkenylated
product based on nitrile. Values in the parentheses refer to the yield of the
silylated product. c Run for 30 h. d Run for 40 h. e [RhCl(cod)]2 (0.05 mmol)
and P(4-FC6H4)3 (0.10 mmol) were used. f Mesitylene was used as a solvent.
Starting nitrile was recovered in 45%.
Currently, our decyanative Mizoroki-Heck type reaction
is limited to the synthesis of alkenylsilanes. Nevertheless,
this method should find valuable application in organic
synthesis in view of the versatility of alkenylsilanes as
intermediates.14 Particularly useful is the conversion into
alkenyl bromides, which can be accomplished by the
treatment with NBS at ambient temperature (20f21 in
Scheme 3). The potential utility of the decyanative alkeny-
lation/bromination protocol is demonstrated in the iterative
synthesis15 of oligo(phenylenevinylene)s.16,17 Thus, the
conjugated chain could be extended in a streamlined manner
by repeating the decyanative-Mizoroki-Heck/bromination/
cleavage of a C-CN bond via η2-iminoacyl complex C then
affords arylrhodium D.12 Arylrhodium intermediate D adds
to vinylsilane to form an alkylrhodium complex E, which
affords an alkenylated product, along with rhodium hydride
F via ꢀ-hydrogen elimination. Rhodium hydride F reacts with
disilane to regenerate silylrhodium species B.13 As a minor
pathway, arylrhodium D can react with disilane to afford a
silylated product as we previously reported.6a,b
(12) (a) Taw, F. L.; White, P. S.; Bergman, R. G.; Brookhart, M. J. Am.
Chem. Soc. 2002, 124, 4192. (b) Taw, F. L.; Mueller, A. H.; Bergman,
R. G.; Brookhart, M. J. Am. Chem. Soc. 2003, 125, 9808. (c) Nakazawa,
H.; Kawasaki, T.; Miyoshi, K.; Suresh, C. H.; Koga, N. Organometallics
2003, 23, 117. (d) Itazaki, M.; Nakazawa, H. Chem. Lett. 2005, 34, 1054.
(e) Nakazawa, H.; Kamata, K.; Itazaki, M. Chem. Commun. 2005, 4004.
(f) Nakazawa, H.; Itazaki, M.; Kamata, K.; Ueda, K. Chem. Asian J. 2007,
2, 882. (g) Ochiai, M.; Hashimoto, H.; Tobita, H. Angew. Chem., Int. Ed.
2007, 46, 8192.
(14) Electrophilic substitution: (a) Fleming, I.; Dunogues, J.; Smithers,
R. Org. React. 1989, 37, 57. Addition to aldehydes: (b) Aikawa, K.; Hioki,
Y.-t.; Mikami, K. J. Am. Chem. Soc. 2009, 131, 13922, and references
therein. Coupling with alcohol: (c) Nishimoto, Y.; Kajioka, M.; Saito, T.;
Yasuda, M.; Baba, A. Chem. Commun. 2008, 6396.
(13) An alternative mechanism for the catalyst regeneration from F is
(i) hydrorhodation of 1a to form RhCH2CH2SiEt3, and (ii) the subsequent
ꢀ-silyl elimination to form Rh-SiEt3, which also serves as a catalytically
active species. If this mechanism is operative, the catalytic reaction should
work even with a catalytic amount of disilane. However, the yield of the
alkenylated product significantly decreased as the amount of disilane was
reduced.
(15) (a) Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2009, 48, 3565.
(b) Wang, C.; Glorius, F. Angew. Chem., Int. Ed. 2009, 48, 5240.
(16) For iterative synthesis of oligo(phenylenevinylene)s, see: (a)
Iwadate, N.; Suginome, M. Org. Lett. 2009, 11, 1899. (b) Jørgensen, M.;
Krebs, F. C. J. Org. Chem. 2005, 70, 6004
(17) For the utility of oligo(phenylenevinylene)s in materials, see:
Ajayaghosh, A.; Praveen, V. K. Acc. Chem. Res. 2007, 40, 644
.
.
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Org. Lett., Vol. 12, No. 8, 2010

In summary, we have developed a catalytic system that
allows the Mizoroki-Heck type alkenylation of nitriles via
the cleavage of C-CN bonds. Due to the tolerance of a cyano
group under the standard catalytic cross-coupling conditions,
the present new variant of the Mizoroki-Heck reaction
significantly broadens the range of synthetic strategies for
densely elaborated arenes via orthogonal and iterative
functionalizations. Further development of the catalytic
transformation of C-CN bonds is currently underway in our
laboratory.
Scheme 3. Iterative Synthesis of Oligo(phenylenevinylene)s
Acknowledgment. This work was conducted in affiliation
with the Program for the Promotion of Environmental
Improvement to Enhance Young Researchers’ Independence,
the Special Coordination Funds for Promoting Science and
Technology, MEXT, Japan. Y.K. expresses his special thanks
for JSPS Research Fellowship for Young Scientist for
financial support and The Global COE (center of excellence)
Program “Global Education and Research Center for Bio-
Environmental Chemistry” of Osaka University. We also
thank the Instrumental Analysis Center, Faculty of Engineer-
ing, Osaka University, for their assistance with the HRMS
and elemental analyses.
Supporting Information Available: Experimental details
and spectroscopic data for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
Suzuki-Miyaura coupling sequence, resulting in a tailored
synthesis of asymmetric oligo(phenylenevinylene)s (Scheme
3).
OL100481H
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