ORGANIC
LETTERS
2011
Vol. 13, No. 23
6256–6259
A Powerful Palladium-Catalyzed
Multicomponent Process for the
Preparation of Oxazolines and
Benzoxazoles
€
Patrick J. Boissarie, Zoe E. Hamilton, Stuart Lang,* John A. Murphy, and
Colin J. Suckling
WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde,
295 Cathedral Street, Glasgow, G1 1XL United Kingdom
Received October 11, 2011
ABSTRACT
Efficient and convenient three-component couplings of an aryl halide, isocyanide, and an amino alcohol under palladium catalysis provide a range
of oxazolines and benzoxazoles in excellent yield.
The search for novel methods for the preparation of new
and interesting molecules with a greater degree of effi-
ciency is of upmost importance in the continuous devel-
opment of synthetic chemistry. As the molecular targets
increase in complexity the effectiveness of the methods
required to construct these molecules also has to increase,
often with multiple bond-making and/or bond-breaking
processes taking place in one transformation. Multicom-
ponent reactions1 allow for the introduction of atoms
originating from three or more different starting materials
into a final molecule and have long been seen as a way of
incorporating a large degree of diversity into molecular
scaffolds in a single synthetic step.
The benefit of carrying out multicomponent reactions
over conventional multistep sequences includes savings in
the costs of reagents and solvents, along with other materi-
als required for purification and isolation. An additional
advantage is the removal of the need to isolate, often
unstable, intermediates making these one-pot processes
far more powerful than their multistep equivalents.
The use of transition metal complexes as catalysts in
multicomponent processes adds an extra dimension to
these reactions. Due to the wide range of transformations
(2) For some relavent reviews: (a) Balme, G.; Bossharth, E.; Monteiro,
N. Eur. J. Org. Chem. 2003, 4101–4111. (b) Balme, G.; Bouyssi, D.;
Monteiro, N. Pure Appl. Chem. 2006, 231–239. (c) D’Souza, D. M.;
€
Muller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095–1108. (d) Bouyssi, D.;
Montiero, N.; Balme, G. Beilstein J. Org. Chem. 2011, 7, 1387–1406.
(3) For some recent examples: (a) Xu, X.; Cheng, D.; Li, J.; Guo, H.;
Yan, J. Org. Lett. 2007, 9, 1585–1587. (b) Galliford, C. V.; Scheidt, K. A.
J. Org. Chem. 2007, 72, 1811–1813. (c) Stonehouse, J. P.; Chekmarev,
D. S.; Ivanova, N. V.; Lang, S.; Pairaudeau, G.; Smith, N.; Stocks, M. J.;
Sviridov, S. I.; Utkina, L. M. Synlett 2008, 100–104. (d) Xiao, Y.; Zhang,
J. Angew. Chem., Int. Ed. 2008, 47, 1903–1906. (e) Saito, N.; Katayama,
T.; Sata, Y. Org. Lett. 2008, 10, 3829–3832. (f) Mannathan, S.; Jeganmohan,
M.; Cheng, C.-H. Angew. Chem., Int. Ed. 2009, 48, 2192–2195. (g)
Staben, S. T.; Blaquiere, N. Angew. Chem., Int. Ed. 2010, 49, 325–328.
(h) Fusano, A.; Fukuyama, T.; Nishitani, S.; Inouye, T.; Ryu, I. Org.
Lett. 2010, 12, 2410–2413. (i) Yoshida, Y.; Murakami, K.; Yorimitsu,
H.; Oshima, K. J. Am. Chem. Soc. 2010, 132, 8878–8879. (j) Zhou, L.;
Ye, F.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2010, 132, 13590–
13591. (k) Liao, L.; Jana, R.; Urkalan, K. B.; Sigman, M. S. J. Am.
Chem. Soc. 2011, 133, 5784–5787.
(1) For some selected examples: (a) Biginelli, P. Gazz. Chim. Ital.
1893, 23, 360–416. (b) Passerini, M. Gazz. Chim. Ital. 1921, 51, 126–129.
(c) Passerini, M. Gazz. Chim. Ital. 1921, 51, 181–189. (d) Ugi, I.; Meyr,
€
R.; Fetzer, U.; Steinbruckner, C. Angew. Chem. 1959, 71, 373–388. (e)
Ugi, I. Angew. Chem., Int. Ed. 1962, 1, 9–22. (f) Sunderhaus, D.;
Dockendorff, C.; Martin, S. F. Org. Lett. 2007, 9, 4223–4226. (g)
Shaabani, A.; Maleki, A.; Maghimi-Rad, J. J. Org. Chem. 2007, 72,
6309–6311. (h) Hopkin, M. D.; Baxendale, I. R.; Ley, S. V. Synthesis
2008, 1688–1702. (i) Sakhno, Y. I.; Desenko, S. M.; Shishkina, S. V.;
Shishkin, O. V.; Sysoyev, D. O.; Groth, U.; Kappe, C. O.; Chebanov,
V. A. Tetrahedron 2008, 64, 11041–11049. (j) Scheffekaar, R.; Paravidino,
M.; Muilwijk, D.; Lutz, M.; Spek, A. L.; de Kanter, F. J. J.; Orru, R. V. A.;
Ruijter, E. Org. Lett. 2009, 11, 125–128. (k) Brioche, J.; Masson, G.; Zhu, J.
Org. Lett. 2010, 12, 1432–1435.
r
10.1021/ol202725y
Published on Web 11/02/2011
2011 American Chemical Society