An unexpected disproportional reaction of 2H-azirines giving (1E,3Z)-2-aza-1,3-dienes and aromatic nitriles in the presence of nickel catalysts

Article abstract of DOI:10.1039/c2cc30745f

An unprecedented nickel-catalysed disproportional reaction of 2,3-diaryl-2H-azirines forming azabutadienes and aromatic nitriles was discovered. This reaction involves the cleavage of two bonds of the 2H-azirine framework, which provides a novel type of transformation of 2H-azirines.

Full text of DOI:10.1039/c2cc30745f

View Article Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
ChemComm
Cite this: Chem. Commun., 2012, 48, 3554–3556
www.rsc.org/chemcomm
COMMUNICATION
An unexpected disproportional reaction of 2H-azirines giving
(1E,3Z)-2-aza-1,3-dienes and aromatic nitriles in the
presence of nickel catalystsw
Kazuhiro Okamoto, Ayano Mashida, Masahito Watanabe and Kouichi Ohe*
Received 2nd February 2012, Accepted 22nd February 2012
DOI: 10.1039/c2cc30745f
An unprecedented nickel-catalysed disproportional reaction
of 2,3-diaryl-2H-azirines forming azabutadienes and aromatic
nitriles was discovered. This reaction involves the cleavage of
two bonds of the 2H-azirine framework, which provides a novel
type of transformation of 2H-azirines.
C–N bond cleavage (Scheme 1b) catalysed by the nickel complex
and also by palladium, rhodium, and iron complexes to generate
a nitrenoid species,5 producing an indole as a result of an
intramolecular nitrene insertion into the C–H bond of the arene.
2H-Azirines are highly strained three-membered N-heterocyclic
compounds. Various ring-opening reactions using the strain release
have been reported.1 For example, the C–C bonds of 2H-azirines
are cleaved under irradiation to generate nitrile ylides, which
undergo 1,3-dipolar cycloaddition reactions shown in Scheme 1a.2
Furthermore, vinyl nitrenoid intermediates are formed by the
C–N bond cleavage in many of the transition metal-catalysed
ring-opening reactions of 2H-azirines (Scheme 1b).3–7 On the
other hand, to our knowledge, there is no report of the generation
of carbenoid species and nitriles through the cleavage of both
C–C and C–N bonds of 2H-azirines (Scheme 1c). Herein, we report
a nickel-catalysed disproportionation reaction of 2H-azirines
that involves a two-bond cleavage giving (1E,3Z)-2-aza-1,
3-dienes together with aromatic nitriles in a 1 : 1 ratio.
ð1Þ
ð2Þ
Next, a reaction of 2,3-diphenyl-2H-azirine 1b in the
presence of 10 mol% of Ni(cod)2 and 20 mol% of PCy3 in
benzene-d6 was performed at room temperature. The 2H-azirine
starting reactant 1b disappeared within 15 min, and the 1H NMR
spectrum of the reaction mixture showed that (1E,3Z)-1,3,
4-triphenyl-2-aza-1,3-butadiene 3b9 and benzonitrile 4b were
obtained, both in 50% yield (eqn (2)). This unexpected result
inspired us to investigate the reactivity of azirines towards
nickel complexes having a range of ligands.
During the course of our study on transition metal-catalysed
reactions involving nitrene species generated from nitrogen-
containing heterocycles,8 the azirine 1a, bearing two phenyl
groups at the 2-position on the 2H-azirine ring, reacted in the
presence of a nickel catalyst to afford indole 2a in a 45% yield
(eqn (1)). This result indicates that the azirine undergoes a
The reactivity of azirines towards the formation of the
2-azabutadiene 3b and the nitrile 4b strongly depends on the
nature of ligands on the central nickel catalyst. Table 1
summarizes the ligand effect in this reaction. Moderate yields
were obtained (56–64%) when tri(sec-alkyl)phosphines such as
tricyclohexylphosphine (PCy3), triisopropylphosphine (PiPr3),
and tricyclopentylphosphine (PCyp3) were used (entries 1–3).
Among ligands examined, PCyp3 gave an acceptable yield of
2-azabutadiene. 2-Azabutadiene 3b was isolated in 48% yield
under optimized conditions (entry 4). N-Heterocyclic carbene
(NHC) ligand IPr was also effective for the present reaction
(entry 5). Surprisingly, the use of other phosphine ligands or
other NHC ligands resulted in quite low yields.
Scheme 1 Ring-opening reactions of 2H-azirines.
Department of Energy and Hydrocarbon Chemistry, Graduate School of
Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510,
Japan. E-mail: ohe@scl.kyoto-u.ac.jp
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2cc30745f
We carried out 2,3-diaryl-2H-azirines reactions under identical
conditions. Irrespective of substituents on aryl groups, the corres-
ponding 2-azabutadienes and aromatic nitriles were obtained in
c
3554 Chem. Commun., 2012, 48, 3554–3556
This journal is The Royal Society of Chemistry 2012

View Article Online
Table 1 Nickel-catalysed formation of azadiene 3b from azirine 1ba
Entry
Ligand
X
Conversionb (%)
Yieldb (%)
1
2
PCy3
PiPr3
PCyp3
PCyp3
IPr
PBu3
PtBu3
PPh3
IMes
dmpe
dippf
20
20
20
20
20
20
20
20
20
10
10
100
100
100
100
100
34
40
38
100
100
80
56
60
62
64 (48)d
54
4
8
6
14
8
3
4c
5
6
7
8
9
10
11
4
a
The reaction was carried out with azirine 1b (0.20 mmol), Ni(cod)2
b
(10 mol%), ligand (X mol%) in toluene (1.5 mL). The yields were
Scheme 2
A
proposed catalytic cycle for the nickel-catalyzed
disproportionation of azirines.
determined by 1H NMR using 1,4-dioxane as an internal standard.
c
d
molecule of azirine 3 on the carbene complex D forms the
azirinium ylide E with the elimination of an aromatic nitrile
4,14 followed by a C–N bond cleavage to give the azadiene 3
with regeneration of the low-valence nickel.
The reaction was carried out at 40 1C. Isolated yield.
moderate yields (Table 2, 48–58%). Regiochemistry was almost
perfect, Ar1 groups being distributed to the 3-position of azadienes
and Ar2 groups being distributed to both 1,4-positions of azadienes
in each reaction. The stereochemistry of the azadienes was deduced
from that of known compounds reported in the literature.10
Azabutadienes are formally considered to be produced from
two different species generated by different pathways. One is a
carbenoid species generated by a 2H-azirine two-bond cleavage
(Scheme 1a), and the other is a vinylnitrenoid species formed by
a 2H-azirines C–N bond cleavage (Scheme 1b). We assumed
that the 2-azabutadienes were obtained by the formation of
nickel–carbene complexes11 by way of a 2H-azirine two-bond
cleavage followed by a carbene addition/ring-opening reaction
to produce another 2H-azirine.12,13
This reaction mechanism indicates that a crossover reaction
between two different 2H-azirines possibly takes place. As
expected, the reaction of the azirines 1d and 1f gave the
crossover products 3df and 3df0 as well as the corresponding
azadienes 3d and 3f (eqn (3)).
The most plausible catalytic cycle is shown in Scheme 2.
First, oxidative addition of the 2H-azirine 1 to a low-valence
nickel species gives the four-membered azanickelacyclobutene C,
which readily undergoes ring opening to yield the nickel–carbene
complex D. Subsequently, the nucleophilic attack of another
Table 2 Nickel-catalysed formation of azadienes 3 from azirines 1a
ð3Þ
In marked contrast to the reaction catalysed by nickel, a
palladium-catalysed reaction of 2H-azirine 1b did not afford
any 2-azadiene 3b; instead, two dimerization products 5b and
6b were obtained in 57% and 26% yield, respectively
(eqn (4)).15 On the basis of the reported mechanism involving
the ring opening of 2H-azirines,16 the dimerization reaction
could proceed through a vinyl nitrene–palladium complex,
which would be formed by oxidative addition of the azirine 1b
to a low-valence palladium species (see also Scheme 1b).
Yield of 3b Yield of 4c
Entry Azirine Ar1
Ar2
(%)
(%)
1
1a
1b
1c
1d
1e
Ph
4-tBuC6H4
Ph
Ph
48
58
54
48
—
60
48
42
—
2d
3e
4e
5
4-MeOC6H4 Ph
4-ClC6H4
Ph
Ph
4-ClC6H4 51
a
The reaction was carried out with azirine 1 (0.20 mmol), Ni(cod)2
b
(10 mol%), and PCyp3 (20 mol%) in toluene (1.5 mL). Isolated
c
1
yield. The yields were determined by H NMR using 1,4-dioxane as
d
an internal standard. Ni(cod)2 (15 mol%) and PCyp3 (30 mol%)
e
were used. Ni(cod)2 (20 mol%) and PCyp3 (40 mol%) were used.
ð4Þ
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 3554–3556 3555

View Article Online
In summary, we have found an unusual nickel-catalysed
disproportional reaction of 2,3-diaryl-2H-azirines affording
(E,Z)-2-aza-1,3-butadienes together with aromatic nitriles. In
contrast, a palladium-catalysed reaction of the azirine gave
two types of dimerization products. Further investigations on
the interception of the reactive species in the present reaction
with other unsaturated molecules such as alkenes are underway.
This work was financially supported by Global COE
Program ‘‘Integrated Materials Science’’ of Kyoto University
from MEXT, administrated by JSPS, Japan.
(d) A. Padwa and T. Stengel, Tetrahedron Lett., 2004, 45, 5991;
(e) D. A. Candito and M. Lautens, Org. Lett., 2010, 12, 3312.
8 K. Okamoto, T. Oda, S. Kohigashi and K. Ohe, Angew. Chem.,
Int. Ed., 2011, 50, 11470.
9 (a) A. Dehnel, J. P. Finet and G. Lavielle, Synthesis, 1977, 474;
(b) F. Palacios, C. Alonso and G. Rubiales, J. Org. Chem., 1997,
62, 1146.
10 Both aryl groups on the 2H-azirine backbone are necessary for this
reaction. Nickel-catalysed reactions of 2-methyl-3-phenyl-2H-azirine
or 3-methyl-2-phenyl-2H-azirine did not give the corresponding
azadienes at all.
11 (a) D. J. Mindiola and G. L. Hillhouse, J. Am. Chem. Soc., 2002,
124, 9976; (b) R. Waterman and G. L. Hillhouse, J. Am. Chem.
Soc., 2003, 125, 13350; (c) J. Barluenga, P. Barrio, L. A. Lo
M. Tomas, S. Garcıa-Granda and C. Alvarez-Rua, Angew. Chem.,
Int. Ed., 2003, 42, 3008; (d) J. Barluenga, R. Vicente, P. Barrio,
L. A. Lopez and M. Tomas, J. Am. Chem. Soc., 2004, 126, 5974;
(e) J. C. del Amo, M. J. Mancheno, M. Gomez-Gallego and
M. A. Sierra, Organometallics, 2004, 23, 5021; (f) J. Barluenga,
P. Barrio, L. Riesgo, L. A. Lopez and M. Tomas, J. Am. Chem.
Soc., 2007, 129, 14422.
´
pez,
Notes and references
´
´
´
1 For reviews: (a) D. J. Anderson and A. Hassner, Synthesis, 1975,
483; (b) T. L. Gilchrist, Aldrichimica Acta, 2001, 34, 51;
(c) F. Palacios, A. M. O. de Retana, E. M. de Marigorta and
J. M. de los Santos, Eur. J. Org. Chem., 2001, 2401; (d) A. Padwa,
Comprehensive Heterocyclic Chemistry III, Elsevier, Ltd., Amsterdam,
2008, pp. 1–104.
´
´
´
´
´
12 (a) L. S. Hegedus, A. Kramer and C. Yijun, Organometallics, 1985,
4, 1747; (b) A. F. Khlebnikov, M. S. Novikov and A. A. Amer,
Tetrahedron Lett., 2004, 45, 6003; (c) A. F. Khlebnikov,
A. A. Amer, R. R. Kostikov, J. Magull and D. Vidovic, Russ. J.
Org. Chem. (Transl. of Zh. Org. Khim.), 2006, 42, 515.
13 We have developed the rhodium-catalysed carbene-transfer reactions
via furylcarbene complexes from carbonyl–ene–yne compounds. For
reviews, see: K. Ohe and K. Miki, J. Synth. Org. Chem. Jpn., 2009,
67, 1161. We have found that the 2H-azirines also reacted with
carbonyl–ene–yne compounds to give 2-azabutadienes as a carbene-
addition/ring-opening reaction product. K. Okamoto, A. Mashida,
M. Watanabe, K. Ohe, 91st Annual Meeting of the Chemical Society
of Japan, Kanagawa, Japan, March 29, 2011, 4C8-33, abstract
vol. IV, p. 1426.
14 Aromatic nitriles may inhibit the nickel catalysis. The nickel-
catalyzed reaction of azirine 1b under the same reaction conditions
with the addition of 1.0 equiv. of p-tolunitrile gave only 8% of
azadiene 3b.
15 Azirine dimers 5b and 6b were obtained as single stereoisomers,
respectively, although relative configurations were not determined.
16 A palladium-catalyzed carbonylative reaction of 2H-azirines giving
b-lactams was reported by Alper et al. They considered that the
reaction proceeded through the insertion of carbon monooxide
into the azirine dimer like 5b. See ref. 4b,c.
2 (a) B. Singh and E. F. Ullman, J. Am. Chem. Soc., 1967, 89, 6911;
(b) B. Singh, A. Zweig and J. B. Gallivan, J. Am. Chem. Soc., 1972,
94, 1199; (c) A. Padwa and J. Smolanoff, J. Am. Chem. Soc., 1971,
93, 548.
3 (a) H. Alper and S. Wollowitz, J. Am. Chem. Soc., 1975, 97, 3541;
(b) K. Hayashi, K. Isomura and H. Taniguchi, Chem. Lett., 1975,
1011; (c) H. Alper and J. E. Prickett, J. Chem. Soc., Chem.
Commun., 1976, 983.
4 (a) T. Sakakibara and H. Alper, J. Chem. Soc., Chem. Commun.,
1979, 458; (b) H. Alper, C. P. Perera and F. R. Ahmed, J. Am.
Chem. Soc., 1981, 103, 1289; (c) H. Alper and C. P. Perera,
Organometallics, 1982, 1, 70.
5 (a) K. Isomura, K. Uto and H. Taniguchi, J. Chem. Soc., Chem.
Commun., 1977, 664; (b) S. Chiba, G. Hattori and K. Narasaka,
Chem. Lett., 2007, 36, 52; (c) S. Jana, M. D. Clements, B. K. Sharp
and N. Zheng, Org. Lett., 2010, 12, 3736.
6 (a) H. Alper, J. E. Prickett and S. Wollowitz, J. Am. Chem. Soc.,
1977, 99, 4330; (b) T. Izumi and H. Alper, Organometallics, 1982,
1, 322; (c) S. Auricchio, A. Bini, E. Pastormerlo and
A. M. Truscello, Tetrahedron, 1997, 53, 10911.
7 (a) A. Inada and H. Hefmgartner, Helv. Chim. Acta, 1982, 65, 1489;
(b) N. P. Reddy, Y. Uchimaru, H.-J. Lautenschlager and M. Tanaka,
Chem. Lett., 1992, 45; (c) S. Auricchio, S. Grassi, L. Malpezzi,
A. S. Sartori and A. M. Truscello, Eur. J. Org. Chem., 2001, 1183;
c
3556 Chem. Commun., 2012, 48, 3554–3556
This journal is The Royal Society of Chemistry 2012