Selective synthesis of trienes and dienes via nickel-catalyzed intermolecular cotrimerization of acrylates and alkynes

Article abstract of DOI:10.1039/c0cc01754j

Tailoring nickel-catalyzed linear cotrimerization of acrylates and alkynes effectively proceeds to produce trienes and dienes highly selectively.

Full text of DOI:10.1039/c0cc01754j

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Selective synthesis of trienes and dienes via nickel-catalyzed
intermolecular cotrimerization of acrylates and alkynesw
Hiroaki Horie, Takuya Kurahashi* and Seijiro Matsubara*
Received 5th June 2010, Accepted 3rd August 2010
DOI: 10.1039/c0cc01754j
Tailoring nickel-catalyzed linear cotrimerization of acrylates
and alkynes effectively proceeds to produce trienes and dienes
highly selectively.
of IPrꢀHCl, and 11 mol% of tBuOK in 1,4-dioxane afforded
1,3-diene 3aa in 82% yield stereoselectively, along with a trace
amount of 4aa (6%). Under the same reaction conditions,
methyl acrylate (1b) and tert-butyl acrylate (1c) produced the
diene 3 in 71% and 49% yield, along with a triene 4 in 5% and
23% yield, respectively (Table 1 entries 2 and 3). Cotrimerization
of 1a and diarylacetylene 2b also gave the corresponding
1,3-diene 3ab in 82% yield upon slow addition of 2b
(Table 1 entry 4). The reaction of 1a and diarylacetylene 2c,
without slow addition, resulted in the formation of 1,3-diene
3ac in lower yield (Table 1 entry 5, in parentheses). The
reaction of 1a with 2e, with slow addition procedure, greatly
prevents the formation of side product via a [2+2+2]
trimerization of 2e, and 3ae was isolated in 53% yield (Table 1
entry 7). The reaction of 1a with unsymmetrical alkynes, such as
2f and 2g, gave the 1,3-diene 3 in moderate yields consisting of
regioisomers in 1/1 ratios (Table 1 entries 7–9), whereas bulky
tert-butyl substituted alkyne 2h also reacted with 1a to produce
the diene 3ah exclusively in lower yield, but with better regio-
selectivity (Table 1 entry 10). Terminal alkynes, such as 1-octyne
and phenylacetylene, failed to participate in the reaction,
presumably due to rapid oligomerization of the alkynes.
Transition-metal-catalyzed intermolecular cooligomerizations
of alkynes and alkenes that involve an s–p isomerization are
arguably the most important processes in organic syntheses
from an atom-economical point of view. A representative
example would be ruthenium-catalyzed intermolecular
codimerization of alkynes and alkenes to produce 1,4-dienes.1,2
The related transition-metal-catalyzed s–p isomerization, to
construct unsaturated bonds containing acyclic carbon
frameworks, has also been developed extensively; yet, few
reactions for the direct synthesis of p-conjugated compounds
through carbon–carbon bond formation have been reported.3–5
For instance, transition-metal-catalyzed intermolecular liner
cotrimerization between alkenes and alkynes, which leads to
substituted 1,3-dienes or 1,3,5-trienes, is a straightforward
synthetic method; nevertheless, it has not received much
attention so far. We envisaged that such an intermolecular
linear cotrimerization between two molecules of alkenes and
one alkyne to form substituted 1,3-dienes could be achieved by
the following reaction. It would proceed through coordination
of an alkene and an alkyne to a metal center, to form a
metalacyclopentene complex A, and subsequent insertion of
an alkene followed by syn-b-hydride elimination (Scheme 1).6
Herein, we report our success in the nickel-catalyzed synthesis
of 1,3-dienes using such an approach.
In view of the unique product selectivity in the 2 : 1
cotrimerization of two molecules of alkene and one alkyne,
Table 1 Cotrimerization between two molecules of acrylates and one
alkyne to afford 1,3-diene 3a
Entry 1
R
2
R1
R2
3
Yield (%)b
1
2
3
4
5
6
7
8
1a CO2Et 2a Pr
1b CO2Me 2a Pr
1c CO2tBu 2a Pr
Pr
Pr
Pr
3aa 82
3ba 71
3ca 49c,d
Scheme 1
Our investigation began with an attempted 2 : 1 cotrimer-
ization between ethyl acrylate (1a) and 4-octyne (2a). It
was found after thorough screening that a sterically hindered
N-heterocyclic carbene ligand (IPr: 1,3-bis(2,6-diisopropyl-
phenyl) imidazol-2-ylidene) is the most effective for the
cotrimerization to give 1,3-diene 3. The reaction of ethyl
acrylate (1a), 4-octyne (2a), 5 mol% of Ni(cod)2, 10 mol%
1a CO2Et 2b 4-MeO–C6H4 4-MeO–C6H4 3ab 82c,e
1a CO2Et 2c Ph
1a CO2Et 2d 4-F–C6H4
1a CO2Et 2e Ph
1a CO2Et 2f C5H11
1a CO2Et 2g iPr
1a CO2Et 2h tBu
Ph
3ac 68c,e (49)f
3ad 30c,e
4-F–C6H4
Me
Me
Me
Me
3ae 53 (1/1)g,h
3af 50 (1/1)g
3ag 60 (1/1)g
3ah 24 (3/1)g
9
10
a
Reactions were carried out using Ni(cod)2 (5 mol%), IPrꢀHCl
(10 mol%), tBuOK (11 mol%), 1 (2.0 mmol, 2 equiv.) and 2
b
(0.5 mmol) in 2 mL of dioxane at 100 1C for 24 h. Isolated yields
based on alkyne 2. Reaction was carried out using Ni(cod)2
Department of Material Chemistry, Graduate School of Engineering,
Kyoto University, Kyoto 615-8510, Japan.
E-mail: tkuraha@orgrxn.mbox.media.kyoto-u.ac.jp,
matsubar@orgrxn.mbox.media.kyoto-u.ac.jp; Fax: +81 75 383 2461;
Tel: +81 75 383 2462
c
d
(10 mol%), IPrꢀHCl (20 mol%), tBuOK (22 mol%). 1c (3.0 mmol).
e
f
Slow addition of 2 over a period of 20 h. Reaction without slow
g
addition of 2c. Ratio of regioisomers. Slow addition of 2e over a
h
w Electronic supplementary information (ESI) available: Experimental
details and NMR spectra. See DOI: 10.1039/c0cc01754j
period of 40 h. Reaction was carried out for 44 h.
c
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Chem. Commun., 2010, 46, 7229–7231 7229

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Table 2 Cotrimerization between an acrylate and two molecules of
alkynes to afford 1,3,5-triene 4a
Entry
1
R
2
R1 R2
4
Yield (%)b
1
2
3
4
5
1a CO2Et
1b CO2Me
1c CO2tBu
1d C(O)NMe2 2a Pr Pr
1e P(O)(OEt)2 2a Pr Pr
2a Pr Pr
2a Pr Pr
2a Pr Pr
4aa 92
4ba 94
4ca 75
4da 71
4ea 83
6
7
8
9
10
1f CN
2a Pr Pr
2c Ph Ph
2e Ph Me
2i Ph Pr
4fa 22
Scheme 2
1a CO2Et
1a CO2Et
1a CO2Et
1a CO2Et
4ac 77c
4ae 86 (9/1)d
4ai 81 (9/1)d
2j Ph Cyclopropyl 4aj 60 (7/3)d
a
Reactions were carried out using Ni(cod)2 (10 mol%),
P(4-MeO–C6H4)3 (20 mol%), 1 (0.75 mmol, 1.5 equiv.) and 2
b
(1.0 mmol) in 2 mL of MeCN at 80 1C for 24 h. Isolated yields based
on alkyne 2. Reaction was carried out using PCy3 (20 mol%) in place of
c
d
P(4-MeO–C6H4)3 in toluene, 40 1C for 48 h. Ratio of isomers.
produced the corresponding triene 4ea in 83% yield (Table 2
entry 5). The reaction of acrylonitrile (1f) with 2a resulted in
22% yield (Table 2 entry 6). The cotrimerization is also
compatible with aryl-substituted alkynes and afforded trienes.
Ethyl acrylate (1a) reacted with diphenylacetylene (2c) to give
the triene 4ac in 77% isolated yield (Table 2 entry 7). The
reaction of 1a with unsymmetrical alkynes such as 2e and 2i
gave the trienes 4ae and 4ai with high regio- and stereocontrol
in 86% and 81% yields, respectively (Table 2 entries 8 and 9).
Cyclopropyl substituted alkyne 2j also reacted with 1a to
produce the triene 4aj in 60% yield consisting of regioisomers
in a 7/3 ratio (Table 2 entry 10).
Scheme 3
it is reasonable to consider that the catalytic cycle of the
present reaction should consist of oxidative cyclization of
nickel(0) with an alkene 1 and an alkyne 2 to produce the
nickelacyclopentene complex A0 (Scheme 2). The preferential
formation of complex A0 may be attributed to a steric
repulsive interaction between the bulky IPr ligand and the
alkyne 2, which prevents coordination of two molecules of
alkyne 2 to a nickel metal center. Thus, in the case of using a
less sterically hindered N-heterocyclic carbene ligand (IMes:
1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) in place of
IPr, the reaction of 1a with 2a gave 1,3-diene 3aa in 51%
yield along with 1,3,5-triene 4aa in 21% yield (Scheme 3).7,8
It was also found that the reaction of 1a with 2a gave 1,3,5-
triene 4aa in the case of using phosphine ligand regardless of
the steric bulkiness.9,10 The reaction of 1a with 2a, in the
presence of Ni(cod)2 (10 mol%) and PPh3 (20 mol%) in
MeCN gave 1,3,5-triene 4aa exclusively in 75% yield. Lower
amounts of triene 4aa were obtained in the cases of using a
trialkylphosphine, such as PCy3 or PBu3, in place of PPh3
(79% and 45% yields, respectively). The use of P(4-MeO–C6H4)3
instead of PPh3 resulted in 92% yield of the triene 4aa
stereoselectively. A P(4-MeO–C6H4)3/Ni(0) ratio of two is
necessary for the highest catalytic activity, but increasing the
ratio further did not promote the reaction much. Inferior
results were obtained with P(2-MeO–C6H4)3 and P(4-CF3–C6H4)3
(24% and 15%, respectively). The use of bidentate phosphine
ligands, such as dppe and dppf, resulted in low yields of 4aa.
The scope of the cotrimerization of various alkenes with
alkynes is briefly examined and summarized in Table 2. Under
optimized reaction conditions, methyl acrylate (1b) and tert-
butyl acrylate (1c) also produce the triene 4 in 94% and 75%
yield, respectively (Table 2 entries 2 and 3). Acrylamide 1d
reacted with 2a afforded the product 4da in 71% yield (Table 2
entry 4). Cotrimerization of diethyl vinylphosphonate (1e) and 2a
The formation of 1,3,5-triene 4 can be rationalized as arising
from oxidative cyclization of nickel with two molecules of
alkynes (Scheme 4). Insertion of an alkene to the complex
leads to a 7-membered nickelacycle C, which undergoes syn-b-
hydrogen elimination. Following on, reductive elimination
furnishes 1,3,5-triene 4 and regenerates the starting nickel(0)
complex. However, the reaction pathway which involves
nickelacycle A to give nickelacycle C via insertion of an alkyne,
may not be ruled out.
In summary, we demonstrated tailoring cotrimerization of
acrylates and alkynes by tuning the nickel catalyst, to allow
highly selective access to 1,3-dienes and 1,3,5-trienes. It was
found that sterically hindered N-heterocyclic carbene ligands
give 1,3-dienes, while P(4-MeO–C6H4)3 gives 1,3,5-trienes.
Further efforts to expand the scope of the chemistry and
studies of the detailed mechanism are currently underway in
our laboratories.
Scheme 4
c
7230 Chem. Commun., 2010, 46, 7229–7231
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This work was supported by Grants-in-Aid from the
Ministry of Education, Culture, Sports, Science, and Technology,
Japan. T.K. also acknowledges the Asahi Glass Foundation and
the Mizuho Foundation for the Promotion of Sciences. We thank
Prof. S. Ogoshi for valuable discussions on the subject.
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c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 7229–7231 7231