ORGANIC
LETTERS
2010
Vol. 12, No. 18
4198-4200
Copper-Catalyzed Rearrangement of
(Z)-Propynal Hydrazones via N-N Bond
Cleavage
Itaru Nakamura,*,†,‡ Naozumi Shiraiwa,‡ Ryo Kanazawa,‡ and Masahiro Terada‡
Research and Analytical Center for Giant Molecules and Department of Chemistry,
Graduate School of Science, Tohoku UniVersity, Sendai 980-8578 Japan
Received July 27, 2010
ABSTRACT
Propynal hydrazones are successfully converted to the corresponding 3-aminoacrylonitriles in the presence of copper catalysts in good to
high yields. As an example, (Z)-N-(hex-2-ynylidene)morpholin-4-amine reacted in the presence of 10 mol % Cu(OAc)2 in acetonitrile at 25 °C
to afford (E)-3-morpholinohex-2-enenitrile ((E)-2 h) in 77% yield via C-N bond formation and subsequent ꢀ-elimination involving cleavage of
N-N and C-H bonds.
π-Acidic metal-catalyzed reactions have gained prominence
in organic synthesis because they efficiently construct highly
elaborate molecules under mild reaction conditions.1 These
transformations often involve cleavage of various σ bonds
such as carbon-hydrogen (C-H), heteroatom-hydrogen
(N-H, O-H), carbon-carbon (C-C), carbon-heteroatom
(C-O,2 C-S,3 and C-N4), and heteroatom-heteroatom
bonds (N-O5 and S-O6), proceeding without loss of any
atoms in the substrate. To the best of our knowledge,
however, π-acid metal-catalyzed reactions via N-N bond
cleavage have rarely been investigated to date, except for
the cyclization of alkynyl azides, in which two of three
nitrogen atoms of the azido group are entirely eliminated
from the starting material as N2 gas after N-N bond
cleavage.7 We envisioned that N-N bond cleavage of
alkynyl hydrazones using a π-acidic metal catalyst would
† Research and Analytical Center for Giant Molecules.
(4) For selected examples, see: (a) Shimada, T.; Nakamura, I.; Yama-
moto, Y. J. Am. Chem. Soc. 2004, 126, 10546. (b) Fu¨rstner, A.; Davies,
P. W. J. Am. Chem. Soc. 2005, 127, 15024. (c) Cariou, K.; Ronan, B.;
Mignani, S.; Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed. 2007,
46, 1881. (d) Istrate, F. M.; Gagosz, F. Org. Lett. 2007, 9, 3181. (e) Takaya,
J.; Udagawa, S.; Kusama, H.; Iwasawa, N. Angew. Chem., Int. Ed. 2008,
47, 4906.
‡ Department of Chemistry.
(1) For selected reviews on π-acidic metal catalysis, see: (a) Fu¨rstner,
A. Chem. Soc. ReV. 2009, 38, 3208. (b) Kirsch, S. F. Synthesis 2008, 3183.
(c) Jime´nez-Nu´n˜ez, E.; Echavarren, A. M. Chem. ReV. 2008, 108, 3326.
(d) Li, Z.; Brouwer, C.; He, C. Chem. ReV. 2008, 108, 3239. (e) Skouta,
R.; Li, C.-J. Tetrahedron 2008, 64, 4917. (f) Bongers, N.; Krause, N. Angew.
Chem., Int. Ed. 2008, 47, 2178. (g) Hashmi, A. S. K. Chem. ReV. 2007,
107, 3180. (h) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817. (i) Fu¨rstner,
A.; Davies, P. W. Angew. Chem., Int. Ed. 2007, 46, 3410. (j) Gorin, D. J.;
Toste, F. D. Nature 2007, 446, 395. (k) Hashmi, A. S. K.; Hutchings, G. J.
Angew. Chem., Int. Ed. 2006, 45, 7896. (l) Zhang, L.; Sun, J.; Kozmin,
S. A. AdV. Synth. Catal. 2006, 348, 2271. (m) Asao, N. Synlett 2006, 1645.
(n) Widenhoefer, R. A.; Han, X. Eur. J. Org, Chem. 2006, 4555. (o) Ma,
S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200.
(5) (a) Trost, B. M.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124, 2528.
(b) Yeom, H.-S.; Lee, E.-S.; Shin, S. Synlett 2007, 2292. (c) Yeom, H.-S.;
Lee, J.-E.; Shin, S. Angew. Chem., Int. Ed. 2008, 47, 7040. (d) Gao, H.;
Zhang, J. AdV. Synth. Catal. 2009, 351, 85. (e) Nakamura, I.; Araki, T.;
Terada, M. J. Am. Chem. Soc. 2009, 131, 2804. (f) Nakamura, I.; Sato, Y.;
Terada, M. J. Am. Chem. Soc. 2009, 131, 4198. (g) Cui, L.; Peng, Y.; Zhang,
L. J. Am. Chem. Soc. 2009, 131, 8394. (h) Hwang, S.; Lee, Y.; Lee, P. H.;
Shin, S. Tetrahedron Lett. 2009, 50, 2305. (i) Ye, L.; Cui, L.; Zhang, G.;
Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258. (j) Yeom, H.-S.; Lee, Y.;
Jeong, J.; So, E.; Hwang, S.; Lee, J.-E.; Lee, S. S.; Shin, S. Angew. Chem.,
Int. Ed. 2010, 49, 1611.
(2) For selected examples, see: (a) Fu¨rstner, A.; Szillat, H.; Stelzer, F.
J. Am. Chem. Soc. 2000, 122, 6785. (b) Fu¨rstner, A.; Stelzer, F.; Szillat, H.
J. Am. Chem. Soc. 2001, 123, 11863.
(3) For selected examples, see: (a) Nakamura, I.; Sato, T.; Yamamoto,
Y. Angew. Chem., Int. Ed. 2006, 45, 4473. (b) Davies, P. W.; Albrecht,
S. J.-C. Angew. Chem., Int. Ed. 2009, 48, 8372.
(6) Shapiro, N. D.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, 4160.
(7) (a) Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 11261. (b) Huo, Z.; Yamamoto, Y. Tetrahedron Lett. 2009, 50, 3651.
10.1021/ol1017504 2010 American Chemical Society
Published on Web 08/18/2010