ORGANIC
LETTERS
2013
Vol. 15, No. 7
1560–1563
Ag- and Au-Catalyzed Addition of
Alcohols to Ynimides: β‑Regioselective
Carbonylation and Production of Oxazoles
Takuya Sueda,* Arisa Kawada, Yumi Urashi, and Naoki Teno
Faculty of Pharmaceutical of Sciences, Hiroshima International University,
5-1-1 Hirokoshingai, Kure City, Hiroshima 737-0112, Japan
Received February 5, 2013
ABSTRACT
Metal-catalyzed reactions of ynimides with alcohols to afford β-ketoimides and oxazoles are demonstrated. The triple bond of ynamides is
generally activated by mineral acids or metal salts to lead to the regioselective addition of nucleophiles at the R-C-atom, because of the inherent
electronic bias. In contrast, the two neighboring carbonyl groups of ynimides decrease the electron density of the triple bond and the nucleophiles
attack the carbonyl C-atom.
Coinage metal catalysts such as silver1 and gold2 salts
interact with the CÀC triple bond of alkynes to allow the
addition of various nucleophiles. For regioselective trans-
formations, intramolecular reactions have generally been
applied. In the case of intermolecular versions of the
reaction with unsymmetrical internal alkynes, mixtures of
regioisomers have been generated in most cases, accompanied
by a Markovnikov type addition.3 In contrast to such simple
alkynes, the inherent electronic bias of ynamides4 is perhaps
the feature needed to ensure the R-regioselective addition of
nucleophiles.5 Therefore, not only has the utility of ynamides
as the equivalent of ynamines been recognized in recent years,
but also their usefulness in the regioselective functionalization
of triple bonds in organic transformations has been signifi-
cantly expanded (Scheme 1).
We have recently reported the Cu-catalyzed coupling of
alkynyl(triaryl)bismuthonium salts with imides to furnish
the first reliable synthetic method of ynimides.6a More
recently, Davies has reported the first catalytic procedure
for the synthesis of N-alkynylphthalimides directly from
terminal alkynes.6c The electron-donating ability of the
N-atom to the triple bond still present in ynimides allows
for the R-regioselective carbonylation with acidic water
(see Supporting Information (SI)).
Compared with ynamides, the presence of two carbonyl
groups on the N-atom of ynimides decreases the electron
density of the triple bond, lowering the reactivity toward
electrophiles and protons. Instead, the neighboring carbonyl
carbons would become more electrophilic, as indicated
by the facile dephthalimidation with various nucleophiles
to give the free amino group. Thus, in the presence of an
appropriate metal catalyst, nucleophiles should add to the
neighboring carbonyl groups of ynimides, followed by
(1) For a review, see: Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev.
2008, 108, 3149.
(2) For representative reviews, see: (a) Krause, N.; Winter, C. Chem.
ꢀ
Rev. 2011, 111, 1994. (b) Corma, A.; Leyva-Perez, A.; Sabater, M. J.
Chem. Rev. 2011, 111, 1657. (c) Belmont, P.; Parker, E. Eur. J. Org.
Chem. 2009, 6075. (d) Patil, N. T.; Yamamoto, Y. Chem. Rev. 2008, 108,
3395. (e) Li, Z.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239. (f)
€
Arcadi, A. Chem. Rev. 2008, 108, 3266. (g) Furstner, A.; Davies, P. W.
Angew. Chem., Int. Ed. 2007, 46, 3410. (h) Hashmi, A. S. K. Chem. Rev.
2007, 107, 3180. (i) Hashmi, A. S. K.; Hutchings, G. J. Angew. Chem.,
Int. Ed. 2006, 45, 7896.
(3) For examples: (a) Santos, L. L.; Ruiz, V. R.; Sabater, M. J.;
Corma, A. Tetrahedron 2008, 64, 7902. (b) Fukuda, Y.; Utimoto, K.
J. Org. Chem. 1991, 56, 3729.
(4) For representative reviews, see: (a) Evano, G.; Jouvin, K.; Coste,
A. Synthesis 2013, 45, 17. (b) Dekorver, K. A.; Li, H.; Lohse, A. G.;
Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev. 2010, 110, 5064.
(c) Evano, G.; Coste, A.; Louvin, K. Angew. Chem., Int. Ed. 2010, 49,
2840. (d) Mulder, J. A.; Kurtz, K. C. M.; Hsung, R. P. Synlett 2003, 1379.
(5) For the Au-catalyzed R-regioselective addition of nucleophiles to
ynamides, see: (a) Davis, P. W.; Cremonesi, A.; Martin, N. Chem.
Commun. 2011, 47, 379. (b) Li, C.; Zhang, L. Org. Lett. 2011, 13, 1738.
(6) (a) Sueda, T.; Oshima, A.; Teno, N. Org. Lett. 2011, 13, 3996. For
a recent report for ynimides, see: (b) Souto, J. A.; Becker, P. B.; Iglesias,
€
(c) Kramer, S.; Dooleweerdt, K.; Lindhardt, A. T.; Rorrlander, M.;
~
Skrydstrup, T. Org. Lett. 2009, 11, 4208. (d) Couty, S.; Meyer, C.; Cossy,
J. Angew. Chem., Int. Ed. 2006, 45, 6726.
A.; Muniz, K. J. Am. Chem. Soc. 2012, 134, 15505. (c) Alford, J. S.;
Davies, M. L. Org. Lett. 2012, 14, 6020.
r
10.1021/ol400338x
Published on Web 03/15/2013
2013 American Chemical Society