Categories: Synthesis of N-Heterocycles, Synthesis of O-Heterocycles >
Synthesis of isoxazoles and benzisoxazoles
Recent Literature
AuCl3-catalyzed cycloisomerization of α,β-acetylenic oximes leads to
substituted isoxazoles in very good yields under moderate reaction conditions.
The methodology is amenable for the selective synthesis of 3-substituted,
5-substituted or 3,5-disubstituted isoxazoles.
C. Praveen, A. Kalyanasundaram, P. T. Perumal, Synlett, 2010,
777-781.
Cycloadditions of copper(I) acetylides to azides and nitrile oxides provide
ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted
isoxazoles, respectively. The process is highly reliable and exhibits an
unusually wide scope with respect to both components. Computational studies
revealed a nonconcerted mechanism involving unprecedented metallacycle
intermediates.
F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless,
V. V. Fokin, J. Am. Chem. Soc., 2005,
127, 210-216.
Various 3-substituted and 3,5-disubstituted isoxazoles have been efficiently
synthesized in good yields by the reaction of N-hydroxyl-4-toluenesulfonamide
with α,β-unsaturated carbonyl compounds. This strategy is associated with
readily available starting materials, mild conditions, high regioselectivity,
and wide scope.
S. Tang, J. He, Y. Sun, L. He, X. She, Org. Lett., 2009,
11, 3982-3985.
The direct regioselective synthesis of 3,5-disubstituted isoxazoles was achieved
through a sequence involving a net bromination of an electron-deficient alkene,
in situ generation of a nitrile oxide, 1,3-dipolar cycloaddition, and loss of
HBr from an intermediate bromoisoxazoline. This one-pot process enables the
direct synthesis of 3,5-disubstituted isoxazoles from electron-deficient
alkenes.
J. Xu, A. T. Hamme II, Synlett, 2008,
919-923.
The consecutive Sonogashira coupling of acid chlorides with terminal alkynes,
followed by 1,3-dipolar cycloaddition under dielectric heating of in situ
generated nitrile oxides from hydroximinoyl chlorides furnishes isoxazoles in
moderate to good yields in the sense of a one-pot three-component reaction.
B. Willy, F. Rominger, T. J. J. Müller, Synthesis, 2008,
293-303.
A large number of functionally substituted 2-alkyn-1-one O-methyl oximes
have been cyclized under mild reaction conditions in the presence of ICl to give
the corresponding 4-iodoisoxazoles in moderate to excellent yields. The
resulting 4-iodoisoxazoles undergo various palladium-catalyzed reactions to
yield 3,4,5-trisubstituted isoxazoles.
J. P. Waldo, R. C. Larock, J. Org. Chem., 2007,
72, 9643-9647.
A thermally promoted cycloaddition between alkynyliodides and nitrile oxides
offers excellent regioselectivity and a broad scope with respect to both
starting materials. Further functionalization of the highly decorated
iodoisoxazole motifs can be achieved via Suzuki cross-coupling.
J. A. Crossley, D. L. Browne, J. Org. Chem., 2010,
75, 5351-5354.
A 1,3-dipolar cycloaddition of phenyl vinylic selenide to nitrile oxides and
subsequent oxidation-elimination furnished 3-substituted isoxazoles with
good yields in a one-pot, two-step transformation.
S.-R. Sheng, X.-L. Liu, Q. Xu, C.-S. Song, Synthesis, 2003, 2763-2764.
The dehydration of primary nitro compounds can be performed by bases in the
presence of dipolarophiles. Among the organic bases examined, DABCO gave the
best results. The reaction is applicable to activated nitro compounds and to
phenylnitromethane and affords isoxazoline derivatives in higher yields
compared with those of other methods. The reaction, however, is not
compatible with nitroalkanes.
L. Cecchi, F. De Sarlo, F. Machetti, Eur. J. Org. Chem., 2006,
4852-4860.
3,5-Disubstituted isoxazoles are regioselectively obtained in good yields by
a mild and convenient one-pot, three-step procedure utilizing a
copper(I)-catalyzed cycloaddition reaction between in situ generated
nitrile oxides and terminal acetylenes.
T. V. Hansen, P. Wu, V. V. Fokin, J. Org. Chem., 2005, 70, 7761-7764.
Pyrazole or isoxazole derivatives are prepared by a palladium-catalyzed four-component coupling of a terminal alkyne, hydrazine (hydroxylamine),
carbon monoxide under ambient pressure, and an aryl iodide.
M. S. M. Ahmed, K. Kobayashi, A. Mori, Org. Lett.,
2005, 7, 4487-4489.
The reaction of
various 2-alkyn-1-one O-methyl oximes with ICl, I2, Br2, or PhSeBr
provided 3,5-disubstituted 4-halo(seleno)isoxazoles
in good to excellent yields under mild reaction conditions.
J. P. Waldo, R. C. Larock, Org. Lett.,
2005, 7, 5203-5205.
A series of 4-alkyl-5-aminoisoxazoles have been synthesized in high yield by
nucleophilic addition of lithiated alkyl nitriles to (α)-chlorooximes.
M. P. Bourbeau, J. T. Rider, Org. Lett.,
2006, 8, 3679-3680.
Various substituted benzisoxazoles have been prepared by a [3 + 2] cycloaddition
of nitrile oxides and arynes. Both highly reactive intermediates, have been
generated in situ by fluoride anion from readily prepared aryne precursors and
chlorooximes. The reaction scope is quite general, affording a novel, direct
route to functionalized benzisoxazoles under mild reaction conditions.
A. V. Dubrovskiy, R. C. Larock., 2010,
12, 1180-1183.
Iron(II) bromide catalyzes the transformation of aryl and vinyl azides with
ketone or methyl oxime substituents into 2,1-benzisoxazoles, indazoles, or
pyrazoles through the formation of an N-O or N-N bond. This transformation
tolerates various functional groups and facilitates access to a range of
benzisoxazoles or indazoles.
B. J. Stokes, C. V. Vogel, L. K. Urnezis, M. Pan, T. G. Driver, Org. Lett., 2010,
12, 2884-2887.
