Nickel-catalyzed cycloaddition of o -arylcarboxybenzonitriles and alkynes via cleavage of two carbon - Carbon σ bonds

Article abstract of DOI:10.1021/ja203829j

An intermolecular cycloaddition reaction has been developed, where o-arylcarboxybenzonitriles react with alkynes to afford coumarins in the presence of Ni(0)/P(CH₂Ph)₃/MAD as a catalyst. The reaction process displays an unusual mechanistic feature - the cleavage of two independent C - CN and C - CO bonds.

Full text of DOI:10.1021/ja203829j

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Nickel-Catalyzed Cycloaddition of o-Arylcarboxybenzonitriles and
Alkynes via Cleavage of Two CarbonÀCarbon σ Bonds
Kenichiro Nakai, Takuya Kurahashi,* and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
S Supporting Information
b
Table 1. Cycloaddition of 1 and 2a by Nickel Catalysta
ABSTRACT: An intermolecular cycloaddition reaction has
been developed, where o-arylcarboxybenzonitriles react
with alkynes to afford coumarins in the presence of Ni-
(0)/P(CH2Ph)3/MAD as a catalyst. The reaction process
displays an unusual mechanistic feature—the cleavage of
two independent CÀCN and CÀCO bonds.
entry
ligand (mol %)
cocatalyst
R
1
yield (%)b
1
PMe3 (20)
PPh3 (20)
PCy3 (20)
PtBu3 (20)
IMes (20)
MADc
MAD
MAD
MAD
MAD
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
4-Me2N-C6H4- 1a
38
45
68
14
11
80
81
<1
<1
<1
39
99
80
81
65
49
30
<1
9
2
3
he development of chemical transformations involving activa-
T
tion of the carbonÀcarbon σ bond is an ongoing challenge in
organometallic chemistry, because it allows novel transformations
that are difficult to achieve by conventional synthetic methods.1
Herein, we report that o-arylcarboxybenzonitriles 1 react with al-
kynes 2 in the presence of a nickel catalyst to afford coumarins 3;
the reaction proceeds with the cleavage of two carbonÀcarbon σ
bonds and the insertion of alkynes to form two carbonÀcarbon σ
bonds (Scheme 1).2À4
4
5
6
P(CH2Ph)3 (20) MAD
P(CH2Ph)3 (10) MAD
7
8
P(CH2Ph)3 (10)
—
9
P(CH2Ph)3 (10) AlMe3
P(CH2Ph)3 (10) BPh3
10
11
12
13
14
15
16
17
18
19
P(CH2Ph)3 (10) B(C6F5)3 4-Me2N-C6H4- 1a
P(CH2Ph)3 (10) MADd
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
P(CH2Ph)3 (10) MAD
4-Me2N-C6H4- 1a
Scheme 1. Cycloaddition via CÀC σ Bond Cleavage
4-MeO-C6H4-
4-Me-C6H4-
C6H5-
1b
1c
1d
1e
1f
4-CF3-C6H4-
Mesityl-
Me-
1g
1h
Me2N-
Initially, when o-arylcarboxybenzonitrile 1a and 4-octyne
(2a) were treated in the presence of a nickel catalyst, which was
prepared in situ from Ni(cod)2 (10 mol %) and PMe3 (20 mol %)
with methylaluminum bis(2,6-di-tert-butyl-4-methylphen-
oxide) (MAD) as a cocatalyst (30 mol %) in toluene at 120 °C
for 12 h,5 coumarin 3aa was obtained in 38% yield (Table 1,
entry 1). Upon optimization of the nickel catalyst, the cycload-
duct 3aa was obtained in excellent yield; a combination of
Ni(cod)2 and P(CH2Ph)3 was found to be effective in affording
3aa in 80% yield (entry 6). The use of other phosphine ligands or
1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) gave
inferior results (entries 2À5). In optimizing the molecular ratio
of Ni(cod)2 and P(CH2Ph)3 to employ for the reaction, it was
found that a ratio of 1:1 provided 3aa in 81% yield (entry 7). In
the absence of the MAD cocatalyst, the formation of 3aa was not
observed at all (entry 8). The use of Lewis acids such as AlMe3
and BPh3 along with Ni(cod)2/P(CH2Ph)3 as a catalyst com-
pletely retarded the reaction (entries 9 and 10), where-
as the use of B(C6F5)3 as a cocatalyst afforded the desired
cycloadduct 3aa in 39% yield (entry 11).3b The amount of 3aa
a Reactions were carried out using Ni(cod)2 (10 mol %), ligand,
cocatalyst (30 mol %), 1a (0.5 mmol), and 2a (1.5 mmol) in 3 mL of
toluene at 120 °C for 12 h in a sealed tube. b Isolated yields are given.
d
c MAD: methylaluminum bis(2,6-di-tert-butyl-4-methyl-phenoxide).
MAD (60 mol %).
attained quantitative yields on increasing the amount of MAD to
60 mol % (entry 12). With the optimized reaction conditions in
hand, we next evaluated the effects of the o-arylcarboxy group on
1. Benzonitriles consisting of the o-phenylcarboxy moiety with
electron-donating substituents, such as dimethylamino, meth-
oxy, and methyl groups, afforded 3aa in good yields (entries 7,
13, and 14, respectively). Whereas benzonitrile 1d possessing the
o-phenylcarboxy moiety reacted with 2a to afford 3aa in 65%
yield (entry 15), electron-withdrawing trifluoromethyl substituted
o-phenylcarboxybenzonitrile 1e and o-mesitylcarboxybenzonitrile
Received: May 5, 2011
Published: June 20, 2011
r
2011 American Chemical Society
11066
dx.doi.org/10.1021/ja203829j J. Am. Chem. Soc. 2011, 133, 11066–11068
|

Journal of the American Chemical Society
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Scheme 2. Elimination of ArÀCN through Cycloaddition
Table 2. Scope of Nickel-Catalyzed Cycloadditiona
1f reacted with 2a to afford 3aa in lower yields of 49% and 30%,
respectively (entries 16 and 17). Neither o-acetoxybenzonitrile 1g
nor o-carbamoyloxy benzonitrile 1h reacted with 2a to afford
3aa in sufficient yields (entries 18 and 19).
Detailed observations revealed that the present catalytic
reaction proceeded together with the elimination of aryl cyanide
4 (Scheme 2). It was found that the reaction of 1a with 2a
afforded 3aa in 81% yield and 4a in 40% yield. Furthermore,
3-aryl-2-cyano-4-octene 5a, which can be produced by the nickel-
catalyzed addition reaction of 4a with 2a, was observed in 38%
yield.6
In order to demonstrate the scope of this cycloaddition, we
next examined the reaction of 4-octyne (2a) with various o-aryl-
carboxybenzonitriles 1 having different functional groups
(Table 2). Under the optimized reaction conditions, naphthoni-
trile 1i also reacted with 2a to afford 3ia in 99% isolated yield
(entry 1). A range of electron-donating or -withdrawing ring
substituents tolerated the reaction conditions well enough to
furnish the corresponding cycloadducts 3 in good to excellent
yields (entries 2À6). The reaction of 1a with unsymmetrical
alkynes such as 1-methoxy-3-heptyne (2b) and 2-octyne (2c)
afforded products consisting of regioisomers in ratios of 1/1 and
3/2 in 71% and 70% yields, respectively (entries 7 and 8).The
regioselectivity of the cycloaddition with unsymmetrical alkynes
may originate from the steric bulkiness of the substitution on an
alkyne; the reaction of 1a with 4-methyl-2-pentyne (2d) afforded
3ad in 75% yield with a higher regioselectivity (entry 9). The
molecular structure of the major cycloadduct 3ad was deter-
mined through X-ray crystal structure analysis. Moreover, bulky
trimethylsilyl-substituted alkyne 2e reacted with 1c to provide
the adduct 3ce with complete regiocontrol (entry 10). Mono-
aryl-substituted internal alkyne 2f also reacted with 1c to afford
3cf in 90% yield (entry 11). Diphenylacetylene 2g participated in
the reaction with 1c to afford the desired product, 3cg, in 59%
yield (entry 12). However, terminal alkynes such as 1-octyne and
phenylacetylene failed to participate in the reaction, presumably
because of the rapid oligomerization of alkynes. As shown in
Scheme 3, the present nickel-catalyzed cycloaddition can be
applied not only to the synthesis of coumarin 3 but also to that
of quinolone 7. The nickel-catalyzed reaction of alkyne 2a with
o-arylamide-substituted benzonitrile 6a afforded quinolone 7aa
in 83% yield.8
Scheme 3. Nickel-Catalyzed Cycloaddition To Form
Quinolone
a Reactions were carried out using Ni(cod)2 (10 mol %), P(CH2Ph)3 (10
mol %), MAD (30 mol %), 1 (0.5 mmol), and 2 (1.5 mmol) in 3 mL of
toluene at 120 °C for 12 h in a sealed tube. b Isolated yields are given. c MAD
(60 mol %). d Ratio of regioisomers.
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dx.doi.org/10.1021/ja203829j |J. Am. Chem. Soc. 2011, 133, 11066–11068

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COMMUNICATION
In summary, we have developed an unprecedented type of
cycloaddition; o-arylcarboxybenzonitrile reacted with alkynes to
afford coumarins over a nickel catalyst. The reaction represents
the first example of intermolecular cycloaddition involving the
cleavage of two carbonÀcarbon σ bonds of two independent
CÀCN and CÀCO bonds. Efforts to expand the scope of the
reaction and detailed studies to elucidate its underlying mechan-
ism are underway.9
1996, 118, 6305. (b) Kadnikov, D. V.; Larock, R. C. Org. Lett. 2000,
2, 3643. (c) Kadnikov, D. V.; Larock, R. C. J. Org. Chem. 2003, 68, 9423.
(5) (a) Maruoka, K.; Itoh, T.; Yamamoto, H. J. Am. Chem. Soc. 1985,
107, 4573. (b) Maruoka, K.; Araki, Y.; Yamamoto, H. J. Am. Chem. Soc.
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(6) The nickel-catalyzed reaction of 1d with 2a also afforded 3aa in
65% yield along with 3-phenyl-2-cyano-4-octene in 63% yield. This
result may suggest that the electron-donating dimethylamino substitu-
ent on 1a slows down the side reaction; the nickel-catalyzed insertion
reaction of the resulting 4-dimethylaminobenzonitrile 4a to 2a proceeds
at a slower rate than that of benzonitrile. For effects of an electron-
donating substituent on benzonitrile in the nickel-catalyzed insertion
reaction to alkynes, see ref 3a.
(7) The reactions of 4-octyne with o-arylcarboxybromobenzene or o-
arylcarboxyanisole in place of o-arylcarboxybenzonitrile did not afford
any cycloadduct.
(8) For examples of transition-metal-catalyzed reactions for synth-
esis of quinolones, see: (a) Kadnikov, D. V.; Larock, R. C. J. Org. Chem.
2004, 69, 6772. (b) Iwai, T.; Fujihara, T.; Terao, J.; Tsuji, Y. J. Am. Chem.
Soc. 2010, 132, 9602.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures in-
b
cluding spectroscopic and analytical data of the new compounds.
This material is available free of charge via the Internet at http://
pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
tkuraha@orgrxn.mbox.media.kyoto-u.ac.jp; matsubar@orgrxn.
mbox.media.kyoto-u.ac.jp
(9) To probe the nature of the reaction mechanism, the reaction of 8
was performed in the presence of a nickel catalyst. In this case, both
cycloadduct 3aa and aryl cyanide 4a were not obtained at all, and 8 was
recovered quantitatively. This result may indicate that the present
cycloaddition proceeds with the initial elimination of aryl cyanide 4
followed by the reaction with alkyne 2.
’ ACKNOWLEDGMENT
This work was supported by Grants-in-Aid from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan. T.K.
also acknowledges support from the Asahi Glass Foundation,
Kansai Research Foundation, and Toyota Physical and Chemical
Research Institute.
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