Nickel-catalyzed decarbonylative cycloaddition of phthalic anhydrides with 1,3-Dienes

Article abstract of DOI:10.1246/cl.2011.322

An intermolecular nickel-catalyzed decarbonylative [4 + 2] cycloaddition has been developed where phthalic anhydrides react with 1,3-dienes to afford substituted 3-vinyldihydroisocoumarins.

Full text of DOI:10.1246/cl.2011.322

doi:10.1246/cl.2011.322
322
Published on the web February 19, 2011
Nickel-catalyzed Decarbonylative Cycloaddition of Phthalic Anhydrides with 1,3-Dienes
Kyohei Fujiwara, Takuya Kurahashi,* and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510
(Received January 13, 2011; CL-110034; E-mail: tkuraha@orgrxn.mbox.media.kyoto-u.ac.jp,
matsubar@orgrxn.mbox.media.kyoto-u.ac.jp)
With the optimized reaction conditions, the scope of the
An intermolecular nickel-catalyzed decarbonylative [4 + 2]
reaction with other 1,3-dienes was examined (Table 2). The
cycloaddition has been developed where phthalic anhydrides react
with 1,3-dienes to afford substituted 3-vinyldihydroisocoumarins.
cycloaddition of 1a with 2,3-dimethyl-1,3-butadiene (2b) gave the
product 3ab in 64% yield (Entry 1). The reaction of 1a with
unsymmetrical 1,3-dienes was also examined. 2-Alkyl-substituted
1,3-diene 2c reacted with 1a to give correspondingly substituted
cycloadduct 3ac in 74% yield (Entry 2). Myrcene (2d) also reacted
with 1a as 1,3-diene to afford cycloadduct 3ad in 73% yield
(Entry 3). The reaction of bulkyl silyl group-substituted 1,3-diene
and phenyl-substituted 1,3-diene with 1a provided cycloadducts
3ae and 3af in 23% and 35% yield, respectively (Entries 4 and 5).
However, 1,1-disubstituted 1,3-dienes, 1,4-disubstituted 1,3-
dienes, and 1-monosubstituted 1,3-dienes, failed to participate in
the reaction.
We next examined the scope of the substituents on phthalic
anhydrides, and results are summarized in Table 3. The reaction
of 4-methylphthalic anhydride (1b) with 2a gave cycloadduct 3ba
in 73% yield as a 1/1 mixture of regioisomers, while the reaction
of 3-methylphthalic anhydride (1c) with 2a afforded 3ca with
complete regio control (Entries 1 and 2). These results may suggest
that the sterically less hindered carbonyl moiety of 1c reacted with
Ni(0) catalyst to afford 3ca regioselectively. Meanwhile, it is
Dihydroisocoumarins are a class of naturally occurring
heterocyclic compounds; their biological and physiological effects
are also of interest.1 A representative synthetic method is intra-
molecular cyclization of homophthalic acid derivatives.2 Mean-
while, transition-metal-catalyzed diversity oriented intermolecular
hetero-annulation to afford dihydroisocoumarins is an attractive
synthetic method, nevertheless, few reactions of 2-iodobenzoic
acid with carbon-carbon double bonds are reported.3 Thus, the
development of alternative methodologies, which would allow
for straightforward access to structurally diverse dihydroisocou-
marins, remains an important research topic. Herein, we would
like to report our results of an unprecedented decarbonylative
cycloaddition of phthalic anhydrides with 1,3-dienes, which may
open the way for a facile divergent synthesis of dihydroisocou-
marins.4-6
We first examined the ligand effects in the decarbonylative
cycloaddition of phthalic anhydride (1a) with 1,2-dimethylene-
cyclohexane (2a) using [Ni(cod)2] as a Ni(0) precursor. The
reaction was performed in refluxing MeCN for 12 h, and the results
are summarized in Table 1. Among the ligands examined, PMe3
gave the best result (90% yield, Entry 1). Trace or lower amounts
of 3aa were obtained in the cases using PMe2Ph, PMePh2, PPh3,
PCy3, and IMes in place of PMe3 (Entries 2-6). In other solvents
such as 1,4-dioxane, tetrahydrofuran (THF), and pyridine, yields
were even lower (Entries 7-9). On addition of ZnCl2 (20 mol %),4a
the yield of 3aa was decreased to 36% (Entry 10).
Table 2. Nickel-catalyzed [4 + 2] cycloaddition of phthalic anhydride 1a
with 1,3-dienes 2a
O
O
[Ni(cod)2] (10 mol%)
PMe3 (40 mol%)
O
R2
+
O
R1
MeCN, reflux, 12 h
R1
R2
O
1a
2
3
Entry
1
2
Diene
3
Product
Yield/%b
64
O
O
O
O
2b
2c
3ab
Table 1. Nickel-catalyzed [4 + 2] cycloaddition of phthalic anhydride 1a
with 1,3-diene 2aa
O
O
[Ni(cod)2] (10 mol%)
Ligand (40 mol%)
O
O
+
O
2
3
74
73
3ac
3ad
Solvent, reflux, 12 h
C7H15
C7H15
O
1a
2a
3aa
Entry
Ligand
Solvent
Additive
Yield/%b
O
O
2d
1
2
3
4
5
6
7
8
9
PMe3
PMe2Ph
PMePh2
PPh3
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
1,4-Dioxane
THF
®
®
®
®
®
®
®
®
®
90
51
41
25
44
<1
50
<1
<1
36
O
O
23
(72 h)
PCy3
4
5
2e
2f
3ae
3af
IMesc
PMe3
PMe3
PMe3
PMe3
SiMe2Ph
SiMe2Ph
Pyridine
MeCN
O
35
d
10
ZnCl2
Ph
Ph
aReactions were carried out using [Ni(cod)2] (10 mol %), ligand
(40 mol %), 1 (0.5 mmol), and 2 (3 mmol) in 20 mL of refluxing
aReactions were carried out using [Ni(cod)2] (10 mol %), PMe3
(40 mol %), 1a (0.5 mmol), and 2 (3 mmol) in 20 mL of refluxing
b
c
solvent for 12 h. Isolated yields. 1,3-Bis(2,4,6-trimethylphenyl)-
d
b
imidazol-2-ylidene. 20 mol %.
MeCN for 12 h. Isolated yields.
Chem. Lett. 2011, 40, 322-323
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

323
3
1
Table 3. The scope of nickel-catalyzed [4 + 2] cycloaddition of phthalic
anhydrides 1 with 1,3-diene 2aa
Ni(0)Ln
O
O
O
O
O
[Ni(cod)2] (10 mol%)
O
O
PMe3 (40 mol%)
O
+
Ni
O
NiLn
R2
L
4
MeCN, reflux, 12 h
R1
R
R
R1
R2
O
7
1
2a
3
O
CO
Entry
1
1
Phthalic anhydride
3
Product
Yield/%b
O
O
NiL
O
O
O
Ni
R
6
5
73
R2
R
1b
3ba
(1/1)c,d
L
O
Me
R1
Me
R2
O
O
O
R1
O
2
2
3
4
1c
1d
1e
3ca
3da
3ea
74d,e
O
Scheme 1. Plausible reaction pathway.
O
Me
Me
O
O
O
1,3-dienes to provide dihydroisocoumarins. The reaction may
realize a facile divergent synthesis of dihydroisocoumarins, which
are widely distributed in nature. Their biological and physiological
effects are also of interest.
57
O
O
(7/3)c,d
MeO
MeO
O
O
O
O
O
O
O
80d,e
O
This work was supported by Grants-in-Aid from MEXT,
Japan. T.K. also acknowledges the Asahi Glass Foundation,
Kansai Research Foundation, and Mizuho Foundation for the
Promotion of Sciences.
O
MeO
MeO
O
99
O
5
6
7
1f
3fa
3ga
3ha
(7/3)c
O
F
F
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1
O
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75
O
O
O
1g
1h
(1/1)c
F
F
O
O
O
O
67
2
O
aReactions were carried out using [Ni(cod)2] (10 mol %), PMe3
(40 mol %), 1 (0.5 mmol), and 2a (3 mmol) in 20 mL of refluxing
MeCN for 12 h. bIsolated yields. cRatio of regioisomers. dReaction
3
4
e
time; 36 h. Single regioisomer.
noteworthy that 3-methoxyphthalic anhydride (1e) also reacted
with 2a to afford 3ea regioselectively in 80% yield (Entry 4). The
effects of 3-methoxy substituents are not clear at the moment,
however we assumed that the selectivity is ascribed to coordina-
tion of oxygen to the nickel center through oxidative addition. The
cycloaddition of 3-fluoro-substituted phthalic anhydride 1f with
2a gave 3fa in 99% yield with a regioselectivity ratio of 7/3
(Entry 5). The reaction of 2,3-naphthalenedicarboxylic anhydride
(1h) with 2a also provides cycloadduct 3ha in 67% yield
(Entry 7).
We propose a plausible mechanism involving oxidative
addition of the more electron-deficient carbonyl moiety of 1 to
Ni(0) bearing electron-rich phosphine ligands, giving the nickela-
cycle 4 (Scheme 1).7,8 Subsequent decarbonylation provides oxa-
nickelacycle 5. Insertion of 2 through the more electron-rich
carbon-carbon double bond to C-Ni bond leads to the more stable
acyclic ³-allylnickel intermediate 7, which undergoes nucleophilic
addition of oxygen to ³-allylnickel at the more substituted carbon
to give 3 and regenerates the starting Ni(0) complex.4e
5
6
7
8
In summary, we have developed a new nickel-catalyzed
decarbonylative [4 + 2] cycloaddition of phthalic anhydrides with
Chem. Lett. 2011, 40, 322-323
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/