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Table 2 (continued )
formation of iodonium ion 7 is confirmed by the isolation of methyl
ester of p-nitrobenzoic acid as a byproduct in the reaction of
p-nitrobenzaldoxime (Table 2, entry 18). Indeed, nucleophilic ring
opening of iodonium ion 7 by methanol followed by hydrolysis
should afford methyl p-nitrobenzoate as the final product.
In conclusion, we have found a new organocatalytic reaction
for the synthesis of isoxazolines. This catalytic procedure gives
good results for the cyclization of substituted aldoximes and
alkenes. The reaction mechanism most likely involves hypo-
iodous acid, generated in situ by the oxidation of KI by Oxone.
This work was supported by a research grant from the NSF
(CHE-1262479).
Entry Alkene
Aldoxime
Product
3b (%)
17c
18c
19c
1j
2d
74
1a
51d
78
Notes and references
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1j
2e
2a
20
21
a
1a
13
8
The cyclization of alkenes and aldoximes were performed in a MeOH–
H2O mixture at room temperature for 12 h by using alkene 1 (1.2 equiv.),
b
aldoximes 2 (1 equiv.), KI (0.1 equiv.), and Oxone (1.5 equiv.). Isolated
c
d
yields. Reaction was performed for 24 h. Methyl p-nitrobenzoate was
also isolated as a byproduct in 18% yield.
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Scheme 1 Proposed mechanism of KI-catalyzed cyclization.
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additional oxidant. Likewise, oxazoline products were not detected
when the reactions were conducted in the presence of I2 or KI but in
the absence of oxidant. However, we could detect the isoxazoline
product when a combination of I2 and Bu4NOH was used instead of KI
and Oxone under basic conditions.7e The involvement of hypoiodous
acid or hypoiodite anion as active species is in agreement with results
previously reported by both Ishihara’s group and our group.6,8
From these control experiments, we propose the catalytic cycliza-
tion mechanism outlined in Scheme 1. The active iodine species,
hypoiodous acid 6, which is generated from KI and Oxone, reacts
with aldoxime to give the iodonium ion 7, which is then opened by
alkene to give N-iodohydroxy compound 8. Subsequently, the cycli- 8 A. Yoshimura, K. R. Middleton, C. Zhu, V. N. Nemykin and
V. V. Zhdankin, Angew. Chem., Int. Ed., 2012, 51, 8059.
9 (a) D. R. Kelly, S. C. Baker, D. S. King, D. S. de Silva, G. Lord and
J. P. Taylor, Org. Biomol. Chem., 2008, 6, 787; (b) H. Ghosh,
zation of 8 affords the isoxazolidine 9, which undergoes b-elimina-
tion to give the isoxazoline 3 and iodide anion, and the regenerated
iodide anion continues the catalytic cycle. The intermediate
A. Baneerjee, S. K. Rout and B. K. Patel, ARKIVOC, 2011, ii, 209.
c
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