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

R
H
OH R
N
R
Oxone
K2CO3
OH R
N
O
SYNTHESIS OF NITRONES 133
R
p-TsOH
MeOH
9 10
11
O
1. R 1 CH 2NH 2
2. NaBH 4
MeOH, rt
R
H
H
N
Scheme 2.4
CH 2R 1
4 equiv.H2O2 5 mol % Na2WO4 MeOH, rt
R = Ph, 2-NO 2C 6H 4, 3,4-and-2,3-(MeO) 2C 6H 3;
R 1 = H, Ph, 2,3-(MeO)2C6H3;
Scheme 2.5
R
H
O
N
OH R
N
+
CH 2R 1
Oxidation of secondary amines into nitrones has been extensively studied and
a variety of well-known efÞcient oxidants and catalysts which can be employed
in this process are available. Catalytic oxidation by hydrogen peroxide at room
temperature is carried out by using sodium tungstate (Fig. 2.1) (28–47).
Under suitable conditions, oxidation of N -alkyl-α-amino acids, accompanied
by decarboxylation, has made it possible to carry out regioselective syntheses
of nitrones which were utilized in the synthesis of 1-azabicyclic alkaloids
(Scheme 2.6) (48, 49).
Recently, based on such an oxidative system, the synthesis of nitrone (12)
an inhibitor of 5α-reductase has been carried out (Scheme 2.7) (50). Oxidation
of amines with H2O2 can be catalyzed with peroxotungstophosphate (PCWP)
(51), SeO2 (52–54), and titanium silicalite molecular sieves TS-1 and TS-2
(55, 56).
Quantitative oxidation of secondary amines occurs upon treatment with
Mo(VI) and W(VI) polyperoxo complexes (PPC) of general formula [C5H5N +
(CH2)14CH3]3PO4[MO(O2)2]4 3− (57–60). When studying this reaction by UVand
electron spin resonance (ESR)-spectroscopy, intermediate formation of
nitroxyl radicals was revealed (61). Secondary amines are oxidized in high yields
by using a methyltrioxorhenium (MTO)/H2O2 system (62–64). Moreover, application
of MTO makes it possible to oxidize secondary amines to nitrones upon
treatment with molecular oxygen (65).
In recent years, the use of heterogeneous catalysts Mg-Al LDH (66, 67) and
Mg-Al-O -tBu hydrotalcite (HT-O-tBu), in the oxidation of secondary amines
with hydrogen peroxide, has been reported (68). The reaction appears to proceed
quickly at room temperature, affording high yields. Similarly, it has been found
−
+
O
R
−