Formation of an aza-nickelacycle by reaction of an imine and an alkyne with nickel(0): Oxidative cyclization, insertion, and reductive elimination

Article abstract of DOI:10.1002/anie.200700688

(Chemical Equation Presented) Cyclize, add, reduce: The oxidative cyclization of an imine and an alkyne with nickel(0) followed by the insertion of a second alkyne gives a seven-membered aza-nickelacycle (see scheme). Subsequent reductive elimination yiel

Full text of DOI:10.1002/anie.200700688

Communications
DOI: 10.1002/anie.200700688
Nickel-Catalyzed Cycloaddition
Formation of an Aza-nickelacycle by Reaction of an Imine and an
Alkyne with Nickel(0): Oxidative Cyclization, Insertion, and Reductive
Elimination**
Sensuke Ogoshi,* Haruo Ikeda, and Hideo Kurosawa
In memory Yoshihiko Ito
step. Herein we report the formation of a five-membered aza-
Oxidative cyclization with transition metals is an efficient
method for the simultaneous construction of one carbon–
carbon and two carbon–metal bonds, and a variety of catalytic
reactions involving the oxidative cyclization of two p compo-
nents with a transition metal have been reported to date. For
example, a hetero-nickelacycle derived from an alkyne and an
aldehyde, ketone, or imine is known to play an important role
as a key intermediate in two types of catalytic reactions,[1–3]
namely the formation of allyl alcohols or allyl amines by
reaction of a hetero-nickelacycle with alkylmetal compounds
or reducing reagents[1,2] and the formation of a pyran by
reductive elimination from seven-membered oxa-nickelacy-
cles generated by the insertion of a second alkyne into a
nickeladihydrofuran.[3] A 1,2-dihydropyridine is also a possi-
ble product of the [2+2+2] cycloaddition of two alkynes and
an imine (Scheme 1), although no such reaction has yet been
nickelacycle—a nickelapyrroline—by the oxidative cycliza-
tion of an imine and an alkyne with nickel(0). The insertion of
a second alkyne into this ring to give a seven-membered aza-
nickelacycle—a nickeladihydroazepine—followed by reduc-
tive elimination to give a 1,2-dihydropyridine, as well as the
catalytic application of these reactions, are also discussed.
The reaction of N-(benzenesulfonyl)benzaldimine (1)
with 2-butyne (1equiv) in the presence of [Ni(cod) 2] (cod =
1,5-cyclooctadiene) and PCy3 (Cy = cyclohexyl) at room
temperature for 10 min gives an inseparable mixture of a
nickelapyrroline (2a), a nickeladihydroazepine (3a), and an
h2-iminenickel complex (4; Scheme 2). The addition of an
Scheme 1. A possible reaction between an alkyne and an imine with
nickel(0).
Scheme 2. Reaction of 2-butyne (1 or 2 equiv) and 1 with nickel(0).
reported. The formation of aza-nickelacycles might prove to
be key to the success of this reaction, although thus far only
two nickelacycles containing a nitrogen atom have been
reported.[4,5] Recently we reported the formation of oxa-
nickelacycles by the oxidative cyclization of aldehydes or
ketones and an unsaturated carbon–carbon bond with
nickel(0),[6] therefore the formation of an aza-nickelacycle
from an imine and an alkyne seemed to be the next logical
additional equivalent of 2-butyne (total 2 equiv) to this
reaction mixture generates 3a, the molecular structure of
which was determined by X-ray crystallography (Figure 1), as
the sole product in 95% yield.[7] The coordination of oxygen
[*] Prof. S. Ogoshi, H. Ikeda, Prof. H. Kurosawa
Department of Applied Chemistry, Faculty of Engineering
Osaka University, Suita, Osaka 565-0871 (Japan)
Fax: (+81)6-6879-7394
E-mail: ogoshi@chem.eng.osaka-u.ac.jp
[**] Partial support of this work by the ENEOS Hydrogen Trust Fund and
by a Grant-in-Aid for Scientific Research on Priority Area “Advanced
Molecular Transformations of Carbon Resources” from the Ministry
of Education, Culture, Sports, Science and Technology, Japan is
gratefully acknowledged.
Supporting Information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Figure 1. Molecular structure of 3a.
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Chemie
to nickel might play an important role in the isolation of 3a as
a stable square-planar complex.[8] The molecular structure of
4, in which h2-coordination of the carbon–nitrogen double
bond is observed, was also confirmed by X-ray crystallog-
raphy (Figure 2).[9] As mentioned above, isolation of the five-
much faster than that of diphenylacetylene, which might
explain why 2a is obtained as a mixture with 3a. Heating the
nickeladihydroazepines 3a–c at 1008C promoted the reduc-
tive elimination to give 1,2-dihydropyridine compounds 6a–c,
respectively (Scheme 4). The formation of a 1,2-dihydropyr-
idine by reductive elimination suggested that the develop-
ment of a nickel-catalyzed [2+2+2] cycloaddition reaction of
two alkynes and an imine might be possible.
Scheme 4. Reductive elimination from 3.
The intermolecular [2+2+2] cycloaddition of two alkynes
and 1 in the presence of 10 mol% of [Ni(cod)2] and PMetBu2
at 1008C gave the expected 1,2-dihydropyridine (6a) in 87%
yield (Scheme 5). 3-Hexyne and trimethylsilylacetylene also
Figure 2. Molecular structure of 4.
membered aza-nickelacycle 2a was not possible due to a very
rapid second insertion of 2-butyne to give 3a, therefore a
bulkier alkyne was examined as a carbon-carbon triple bond
component to suppress the formation of the seven-membered
aza-nickelacycle.
The reaction of 1 with diphenylacetylene in the presence
of [Ni(cod)2] and PCy3 at room temperature proceeded to
give the corresponding nickelapyrroline (2b) quantitatively
(Scheme 3). Elemental analysis of 2b confirmed the expected
composition. The coordination of oxygen to nickel is inferred
by analogy with the molecular structure of 3a. The reaction of
4 with diphenylacetylene also gave 2b quantitatively along
with the dissociation of one equivalent of PCy3. The treatment
of 2b with carbon monoxide (5 atm) led to the formation of
the corresponding g-lactam (5), which is also consistent with
the structure of 2b depicted in Scheme 3. The insertion of
diphenylacetylene or 2-butyne into 2b proceeded at room
temperature to give the corresponding nickeladihydroazepine
(3b or 3c, respectively). The insertion of 2-butyne proceeded
Scheme 5. The nickel(0)-catalyzed reaction. TMS=trimethylsilyl.
gave the corresponding 1,2-dihydropyridines (6d and 6e,
respectively). The reaction proceeded catalytically also in the
presence of PCy3, although PMetBu2 gave better results. The
less bulkier or less basic phosphines PnBu3 or P(o-tol)3 (o-
tol = ortho-tolyl) were not efficient for this reaction.
Although the complex Ni0-NHC (NHC = N-heterocyclic
carbene) was also found to be a good catalyst for the
[2+2+2] cycloaddition of two alkynes and a ketone or an
aldehyde, this reaction did not proceed in the presence of 1,3-
bis(2,4,6-trimethylphenyl)imidazol-2-ylidene. To the best of
our knowledge, only one example of the catalytic formation of
a 1,2-dihydropyridine from two alkynes and an imine has
been reported, however, in this example the 1,2-dihydropyr-
idine was an undesired product and was obtained as a
mixture.[10] Thus, our nickel-catalyzed reaction might be very
attractive as a new method for the preparation of 1,2-
dihydropyridines. The reaction might proceed as follows:
oxidative cyclization with nickel(0), which gives rise to a
nickelapyrroline, is followed by the insertion of a second
alkyne to form a nickeladihydroazepine. Reductive elimina-
Scheme 3. Reaction of diphenylacetylene and 1 with nickel(0) followed
by addition of another alkyne (same or different) or CO.
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Communications
tion from this nickeladihydroazepine gives a 1,2-dihydropyr-
[1] Alkyne with an aldehyde/ketone: a) E. Oblinger, J. Montgom-
ery, J. Am. Chem. Soc. 1997, 119, 9065; b) W.-S. Huang, J. Chan,
T. F. Jamison, Org. Lett. 2000, 2, 4221; c) Y. Ni, K. K. D.
Amarasinghe, J. Montgomery, Org. Lett. 2002, 4, 1743;
d) K. M. Miller, W.-S. Huang, T. F. Jamison, J. Am. Chem. Soc.
2003, 125, 3442; e) G. M. Mahandru, G. Liu, J. Montgomery, J.
Am. Chem. Soc. 2004, 126, 3698; f) K. M. Miller, T. F. Jamison, J.
Am. Chem. Soc. 2004, 126, 15342; g) M. Murakami, S. Ashida, T.
Matsuda, J. Am. Chem. Soc. 2005, 127, 6932.
[2] Alkyne with an imine: a) S. J. Patel, T. F. Jamison, Angew. Chem.
2003, 115, 1402; Angew. Chem. Int. Ed. 2003, 42, 1 364; b) S. J.
Patel, T. F. Jamison, Angew. Chem. 2004, 116, 4031; Angew.
Chem. Int. Ed. 2004, 43, 3941.
[3] Two alkynes with an aldehyde/ketone: a) T. Tsuda, T. Kiyoi, T.
Miyane, T. Saegusa, J. Am. Chem. Soc. 1988, 110, 8570; b) T. N.
Tekevac, J. Louie, Org. Lett. 2005, 7, 4037; c) M. Murakami, S.
Ashida, T. Matsuda, J. Am. Chem. Soc. 2006, 128, 2166.
[4] Nickelalactams formed from an alkyne, an isocyanate, and
nickel(0): a) H. Hoberg, B. W. Oster, J. Organomet. Chem. 1982,
234, C35; b) H. Hoberg, B. W. Oster, J. Organomet. Chem. 1983,
252, 359.
idine and regenerates nickel(0). The previously reported
nickel-catalyzed [2+2+2] cycloaddition of alkynes with a
ketone might also proceed by a similar reaction path.[3]
In conclusion, we have demonstrated that the oxidative
cyclization of an imine and an alkyne with nickel(0) gives a
nickelapyrroline and that subsequent insertion of a second
alkyne gives a nickeladihydroazepine. This complex then
undergoes reductive elimination to give a 1,2-dihydropyr-
idine. We have developed this sequential reaction process into
a nickel-catalyzed [2+2+2] cycloaddition of two alkynes and
an imine that yields 1,2-dihydropyridines. This is the first
example of the selective formation of a 1,2-dihydropyridine in
the presence of a transition-metal catalyst. Further studies on
the oxidative cyclization of an imine and unsaturated carbon–
carbon bonds with nickel(0), and on the application of this
process to other catalytic reactions are in progress in our
group.
[5] A nickel-catalyzed reaction of two alkynes and a carbodiimide to
give
a 2-imino-1,2-dihydropyridine has been reported: H.
Experimental Section
Hoberg, G. Burkhart, Synthesis 1979, 525.
Synthesis of 3a: 2-Butyne (276.4 mg, 400 mL, 5.11 mmol) was added
to a solution of [Ni(cod)2] (274.8 mg, 1.00 mmol), PCy3 (288.4 mg,
1.00 mmol), and 1 (244.0 mg, 0.99 mmol) in 5 mL of toluene at room
temperature. The reaction mixture was stirred for 1h, whereupon the
color changed from red to dark red. The reaction mixture was then
concentrated in vacuo to give a red solid. This solid was washed with
hexane to give 467.5 mg of complex 3a (orange solid) in 68% yield.
1H NMR (400 MHz, C6D6): d = 0.87–1.96 (m, 39H; Cy and signals for
[6] a) S. Ogoshi, M.-a. Oka, H. Kurosawa, J. Am. Chem. Soc. 2004,
126, 11082; b) S. Ogoshi, M. Ueta, T. Arai, H. Kurosawa, J. Am.
Chem. Soc. 2005, 127, 12810; c) S. Ogoshi, K.-i. Tonomori, M.-a.
Oka, H. Kurosawa, J. Am. Chem. Soc. 2006, 128, 7077; d) S.
Ogoshi, M. Nagata, H. Kurosawa, J. Am. Chem. Soc. 2006, 128,
5350.
[7] Crystal data for 3a: C39H56NNiO2PS: M = 692.61, brown,
monoclinic, P21/n (no. 14), a = 10.1244(3), b = 21.5519(6), c =
=
=
=
NiC(Me) C(Me)C(Me) (1.09, 3H), NiC(Me) (1.69, 3H), and
17.5944(5) Š, b = 102.400(1)8, V= 3749.5(2) Š3, Z = 4, 1calcd
=
=
NiC(Me) C(Me) (1.95, 3H)), 2.38 (br.s, 3H, Cy), 2.55 (br.s, 3H,
1.227 gcmÀ3, T= 08C, R (Rw) = 0.054 (0.069).
=
NiC(Me) C(Me)C(Me) = C(Me)), 5.07 (s, 1H, CHPh), 6.97–7.02 (m,
[8] K.-i. Fujita, M. Yamashita, F. Puschmann, M. M. Alvarez-
Falcon, C. D. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2006,
128, 9044.
4H), 7.11 (t, JH,H = 7.6 Hz, 2H), 7.31(br.s, 2H), 8.29 ppm (br.d, JH,H
=
6.5 Hz, 2H). 13C NMR (100 MHz, C6D6): d = 15.6 (s), 18.2 (s), 22.2 (s),
24.8 (d, JC,P = 6.1Hz; Cy), 27.2 (s), 28.4 (d, JC,P = 9.9 Hz; Cy), 28.5 (d,
[9] Crystal data for 4: C49H77NNiO2P2S, M = 864.86, brown, mono-
clinic, P21/n (no. 14), a = 10.8288(3), b = 17.5527(4), c =
JC,P = 9.9 Hz; Cy), 30.2 (s), 31.0 (s), 33.6 (d, JC,P = 17.5 Hz; Cy), 60.2 (s,
CHPh), 125.5 (s), 126.5 (s), 127.5 (s), 127.7 (s), 128.3 (s), 128.5 (s),
128.7 (s), 129.1(s), 131.3 (s), 135.5 (s), 135.9 (s), 146.0 ppm (s).
31P NMR (109.4 MHz, C6D6): d = 31.3 ppm (s). Elemental analy-
sis (%) calcd for C39H56NNiO2PS: C 67.63, H 8.15, N 2.02; found: C
67.36, H 8.21, N 2.12.
25.9319(8) Š, b = 99.124(1)8, V= 4866.6(2) Š3, Z = 4, 1calcd
=
1.180 gcmÀ3, T= 08C, R (Rw) = 0.060 (0.097). CCDC 637051
(3a) and CCDC 637052 (4) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Received: February 14, 2007
Published online: May 24, 2007
[10] The catalytic formation of a 1,2-dihydropyridine from two
alkynes and an imine has been reported: P. A. Wender, T. M.
Pedersen, M. J. C. Scanio, J. Am. Chem. Soc. 2002, 124, 15154.
Keywords: alkynes · cycloaddition · imines · metallacycles ·
.
nickel
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Angew. Chem. Int. Ed. 2007, 46, 4930 –4932