Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

R 1
NO2
R 2
PhSeH
R 1
(EtO)2(O)PCH2OH
NO 2
O
−
R 1
R 2
+
N
SePh
R 3
R 2
[H]
mCPBA
1. Swern oxidation
2. RNHOH
HO
R 1
O
−
R 1
+
NH
N
Scheme 2.37
R 2
R 3
R 2
R
H N
SYNTHESIS OF NITRONES 165
R 3CHO
SePh
SePh
+
−O
P(O)(OEt) 2
Z
Scheme 2.38
a:
b:
c:
d:
+
e:
f:
R 1
Me
H
Me
CO 2Me
Me
O
R 2 R 3
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
R
(EtO) 2(O)P N
+
−O
H
E
2.2.2.2. Synthesis from Oximes Alkylation of oximes at the nitrogen atom
with various reagents seems to be one of the easiest and convenient methods
for synthesizing nitrones. The signiÞcant advantage of this method is that
there is no need to use oxidants, as is shown in Section 2.2.2.1. Electron poor
alkenes, resulting from the activation of electron-accepting groups and action of
electrophiles or metal ions as catalysts, are used as the most available alkylation
agents. The reaction known as Grigg’s nitrone formation, involving formal
Michael addition is widely used (141, 262–285). In most cases, the resulting
nitrones quickly enter into a speciÞc 1,3-cycloaddition reaction. Similar transformations
are observed in the reactions of oximes with alkynes (286, 287).
Therefore, Grigg’s reaction, which seems very effective in using the sequence of
oxime-nitrone-products and 1,3-dipolar cycloaddition, can hardly be considered
as an overall synthetic approach to nitrones. However, under certain conditions,
the resulting nitrones can be isolated. Thus, the reaction of indol-oxime (96)
with methyl acrylate, methyl vinyl ketone, acrylonitrile, and acrylamide gives
indol-nitrones (97) (Scheme 2.39) (288, 289).
Cyclization of oximes containing γ-,δ-, or ω-alkenyl substituents, upon treatment
with N -bromosuccinimide (NBS) or iodine leads in good yields to the
corresponding cyclic nitrones or their dimeric H- bonded hydriodide salts (290).