ORGANIC
LETTERS
2012
Vol. 14, No. 3
708–711
Tandem MigrationÀCarboalkoxylation of
o-Isocyanophenyl Acetals Leading to
Benzoxazoles
Takashi Okitsu, Kenta Nagase, Nobuhiko Nishio, and Akimori Wada*
Department of Organic Chemistry for Life Science, Kobe Pharmaceutical University,
4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan
a-wada@kobepharma-u.ac,jp
Received November 28, 2011
ABSTRACT
An efficient approach to benzoxazoles via tandem migrationÀcarboalkoxylation of o-isocyanophenyl acetals has been developed. Both a Lewis
acid and base are essential for this reaction, and the BF3 OEt2/2,4,6-collidine combination is the best choice for cooperative transformation.
3
Benzoxazoles are an important class of aromatic com-
pounds and have been used for biologically active mole-
cules and fluorescent sensors.1 Because of their usefulness,
numerous efficient methods for the synthesis of benzo-
xazoles have been developed, including the condensation
of 2-aminophenols with carboxylic acid derivatives.2 To
date, transition-metal-catalyzed CÀH functionalizations
of benzoxazoles have been reported and those elegant and
straightforward approaches can create CÀC bonds directly,
even sp3 carbon centers.3
Recently, we have explored a versatile synthesis for
benzofurans by iodocyclization of ethoxyethyl ethers to
alkynes.4 During the course of our studies into the iodine-
mediated cyclization using isonitriles instead of alkynes
asthe substrates, we found that the reaction of isocyano-
phenyl acetal 1a with bis(2,4,6-collidine)iodonium(I)
hexafluorophosphate [I(coll)2PF6] and BF3 OEt2 af-
3
forded 2-(R-alkoxyalkyl)benzoxazole 2a in 79% yield
and iodinated benzoxazole 3a was not obtained (eq 1).
Isonitrile compounds are often used for multicompo-
nent reactions such as Ugi’s four-component reaction
and Passerini’s three-component reaction,5 and in gen-
eral, they are transferred to amide groups through
carboalkoxylations. Isonitriles are also converted to a
component of heteroaromatic rings such as indoles,6
benzofurans,7 imidazoles,8 and oxazoles.9 While ben-
zoxazoles can be prepared via carboalkoxylation of un-
stable o-isocyanophenols,10 this variant accompanied by
€
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J. 2000, 6, 3321–3329.
(6) Deyrup, J. A.; Vestling, M. M.; Hagen, W. V. Tetrahedron 1969,
25, 1467–1478.
(7) Bossio, R.; Marcaccini, S.; Paoli, P.; Pepino, R.; Polo, C. Synthe-
sis 1991, 999–1000.
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10.1021/ol203175a
Published on Web 01/17/2012
2012 American Chemical Society