amides and carbamates, epoxides, or aziridines, the development
of practical and efficient methods for the preparation of these
target cyclic carbamates, especially those functionalized with
groups sensitive to acid or basic conditions, continue to be of
great interest.
Gold-Catalyzed Synthesis of Alkylidene
2-Oxazolidinones and 1,3-Oxazin-2-ones
Roc´ıo Robles-Mach´ın, Javier Adrio,* and
Juan Carlos Carretero*
As a result of the excellent ability of late transition metals to
activate alkynes toward nucleophilic attack, numerous novel
catalytic cyclizations based on this strategy have been developed
in the last years.6 Especially Au(I)- and Au(III)-catalyzed
processes7 are emerging as an extremely useful tool for the
formation of C-C,8 C-N,9 and C-O10 bonds from alkynes.
Taking into account these precedents and the known Au(III)
cyclization of propargylic amides to oxazoles,10e we envisaged
that 5-alkylidene 2-oxazolidinones and 6-alkylidene 2-oxazi-
nones could be directly prepared by gold-catalyzed cyclization
of the readily available alkynyl carbamates.11
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias,
UniVersidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain
jaVier.adrio@uam.es; juancarlos.carretero@uam.es
ReceiVed March 9, 2006
To test this assumption, we selected as the model substrate
the BOC-protected N-aryl propargylamine 1.12 We were pleased
(4) (a) Das, J.; Rao, C. V. L.; Sastry, T. V. R. S.; Roshaiah, M.; Sankar,
P. G.; Khadeer, A.; Kumar, M. S.; Mallik, A.; Selvakumar, N.; Iqbal, J.;
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A. A.; Hultin, P. G. J. Org. Chem. 2005, 70, 9940-9946. (b) Osa, Y.;
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K. C.; Zhong, Y.-L.; Baran, P. S. Angew. Chem., Int. Ed. 2000, 39, 625-
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(e) Me´ndez, M.; Echavarren, A. M. Eur. J. Org. Chem. 2002, 15-28.
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S. K. Angew. Chem., Int. Ed. 2005, 44, 6990-6993. (b) Hashmi, A. S. K.
Gold Bull. (London) 2004, 37, 51-65. (c) Dyker, G. Angew. Chem., Int.
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(8) For very recent references, see: (a) Ma, S.; Yu, S.; Gu, Z. Angew.
Chem., Int. Ed. 2006, 45, 200-203. (b) Nieto-Oberhuber, C.; Mun˜oz, M.
P.; Lo´pez, S.; Jime´nez-Nu´n˜ez, E.; Nevado, C.; Herrero-Go´mez, E.; Raducan,
M.; Echavarren, A. M. Chem.sEur. J. 2006, 12, 1677-1693. (c) Nieto-
Oberhuber, C.; Lo´pez, S.; Mun˜oz, M. P.; Jime´nez-Nu´n˜ez, E.; Bun˜uel, E.;
Ca´rdenas, D. J.; Echavarren, A. M. Chem.sEur. J. 2006, 12, 1694-1702.
(d) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D. J. Am. Chem.
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J. Am. Chem. Soc. 2004, 126, 4526-4527.
N-Boc-protected alkynylamines are converted into the cor-
responding alkylidene 2-oxazolidinones or 2-oxazinones
under very mild reaction conditions in the presence of 1-5
mol % of a cationic Au(I) complex. The scope of the reaction
is very general, providing the cyclic carbamates in high yield
regardless of the substitution at nitrogen and alkyne terminus.
2-Oxazolidinones and 2-oxazinones are very important struc-
tural motifs in organic synthesis. Part of this interest derives
from their broad use as chiral auxiliaries and amino alcohol
synthons in organic transformations.1,2 In addition, appropriately
substituted natural or synthetic oxazolidinones and oxazinones
have shown outstanding biological properties.3 For instance,
N-aryl oxazolidinones functionalized at the C-5 position have
recently attracted much attention as a new class of completely
synthetic antimicrobial agents, active against multidrug-resistant
gram-positive organisms.4
Although there are a variety of interesting methods for the
synthesis of oxazolidinones and oxazinones from different types
of starting materials,5 such as amino alcohol derivatives, alkenyl
(1) For some reviews on oxazolidinones in asymmetric synthesis, see:
(a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835-876.
(b) Evans, D. A. Aldrichimica Acta 1982, 15, 23-29. For a recent example,
see: (c) Hogan, P. C.; Corey, E. J. J. Am. Chem. Soc. 2005, 127, 15386-
15387.
(2) For the use of 2-oxazinones as synthetic intermediates, see for
instance: (a) Abbas, T. R.; Cadogan, J. I. G.; Doyle, A.; Gosney, I.;
Hodgson, P. K. G.; Howells, G. E.; Hulme, A. N.; Parsons, S.; Sadler, I.
H. Tetrahedron Lett. 1997, 38, 4917-4920. For the synthesis of 1,3-amino
alcohols, see: (b) Bongini, A.; Cardillo, G.; Orena, M.; Porzi, G.; Sandri,
S. Chem. Lett. 1988, 87-90. For biological interest of 1,3-amino alcohols,
see: (c) Benedetti, F.; Norbedo, S. Chem. Commun. 2001, 203-204 and
references therein.
(3) Oxazolidinones: (a) Kim, J. D.; Kim, I. S.; Jin, C. H.; Zee, O. P.;
Jung, Y. J. Org. Lett. 2005, 7, 4025-4028. (b) Mai, A.; Artico, M.; Esposito,
M.; Sbardella, G.; Massa, S.; Befani, O.; Turini, P.; Giovannini, V.;
Mondovi, B. J. Med. Chem. 2002, 45, 1180-1183. Oxazinones: (c) Van
Dang, G.; Rode, B. M.; Stuppner, H. Eur. J. Pharm. Sci. 1994, 2, 331-50.
(d) Sakai, K.; Ichikawa, T.; Yamada, K.; Yamashita, M.; Tanimoto, M.;
Hikita, A.; Ijuin, Y.; Kondo, K. J. Nat. Prod. 1988, 51, 845-850.
(9) For very recent references, see: (a) Kusama, H.; Miyashita, Y.;
Takaya, J.; Iwassawa, N. Org. Lett. 2006, 8, 289-292. (b) Alfonsi, M.;
Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J. Org. Chem. 2005, 70,
2265-2273. (c) Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003,
5, 3349-3352.
(10) For very recent references, see: (a) Genin, E.; Toullec, P. Y.;
Antoniotti, S.; Brancour, C.; Geneˆt, J.-P.; Michelet, V. J. Am. Chem. Soc.
2006, 128, 3112-3113. (b) Antoniotti, S.; Genin, E.; Michelet, V.; Genet,
J.-P. J. Am. Chem. Soc. 2005, 127, 9976-9977. (c) Zhang, L.; Kozmin, S.
A. J. Am. Chem. Soc. 2005, 127, 6962-6963. (d) Kim, N.; Kim, Y.; Park,
W.; Sung, D.; Gupta, A. K.; Oh, C. H. Org. Lett. 2005, 7, 5289-5291. (e)
Hashmi, A. S. K.; Weyrauch, J. P.; Frey, W.; Bats, J. W. Org. Lett. 2004,
6, 4391-4394.
10.1021/jo060520y CCC: $33.50 © 2006 American Chemical Society
Published on Web 05/26/2006
J. Org. Chem. 2006, 71, 5023-5026
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