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

NITRONE REACTIONS 213
2.6.2. Reduction of Nitrones
Nitrones can be reduced to hydroxylamines (route A), or deoxygenated to the
corresponding imines (route B) (Scheme 2.98).
Reduction of nitrone groups to hydroxylamines occurs readily with sodium
borohydride (201). In particular, the action of NaBH4 on 1-hydroxy-3imidazoline-3-oxides
(268) leads to 1,3-dihydroxyimidazolidines (269), which on
subsequent treatment with hydroxylamine hydrochloride afford 1,2-bishydroxylamines
(270) (Scheme 2.99) (478).
Similarly, nitrones have been reduced to pyrrolines (479).
Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared
from [IrCl(cod)]2, (S)-BINAP, NBun 4 BH4, gives with high enantioselectivity the
corresponding N -hydroxylamines which are important biologically active compounds
and precursors of amines (480). Further reduction of hydroxylamines to
secondary amines or imines can be realized upon treatment with Fe/AcOH (479),
or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature
(481).
R 1
R 2
R 2
R 1
R 3
−
+ O
N
R 3
O
N
−
+
N
OH
H
R 4
Route A
Route B
R 1
R 2
R 1
OH
N
−H 2O
R 3
N
R2 R3 Scheme 2.98
R 1
OH
N
R2 R4 R H
3
[H] NH2OH⋅HCl
EtOH(HCl)
N
OH
R 1 , R 2 , R 3 = H, Alk, Ar, Het etc.
R1 R2 268a–g 269a–g 270a–f
a: R 1 = Ph, R 2 = R 3 = R 4 = Me
b: R 1 = R 2 = R 3 = Me, R 4 = Ph
c: R 1 = Et, R 2 = R 3 = Me, R 4 = Ph
d: R 1 + R 2 = (CH 2) 4, R 3 = Me, R 4 = H
e: R 1 + R 2 = (CH2)4, R 3 = R 4 = H
f: R 1 + R 2 = (CH2)5, R 3 = R 4 = H
g: R 1 = Ph, R 2 = R 3 = Me, R 4 = H
Scheme 2.99
R 3
NHOH
NHOH