Chemistry Reference
In-Depth Information
R
1
R
1
[Ox]
N
OH
N
O
R
2
R
2
[Ox] = PbO
2
,MnO
2
,O
2
/Cu
2+
,NaIO
4
,Ag
2
O
1) RMgBr
THF,
−
78
°
C
2) O
2
,Cu(OAc)
2
O
2
/Cu
2+
PhMgBr
Ph
Ph
Ph
Ph
H
H
N
N
N
O
N
O
O
OH
60
123
(25%)
Et
H
3
C
H
3
C
O
O
N
N
MnO
2
NHOH
Et
Et
Et
Et
Et
Et
Et
H
3
C
NH
4
OAc
Et
Et
N
CHCl
3
N
Et
Et
OH
O
61
124
(55%)
O
O
N
N
NaIO
4
N
N
62
125
(72%)
H
2
O / CHCl
3
OH
O
I
I
1)
t-
BuLi, Et
2
O
2)
t-
BuNO, Et
2
O
Ag
2
O
benzene
3) NH
4
Cl, H
2
O
N
N
N
N
Br
Br
OH
OH
O
O
63
58
Scheme 5.24
Oxidation of hydroxylamines to nitroxides
nitroxides (
65
,
66
) using Lai's protocol to prepare hindered morpholinones and piperazinones. Greci
et al
.
132
obtained a series of 2-alkyl-2-phenyl-3,3-dimethylindolines by 1,2-organolithium addition to
2-phenyl-3,3-dimethyl-3
H
-indole. Oxidation of these indolines with mCPBA yielded a series of chiral
indolinic nitroxides (
67
).
Several C
2
-symmetrical chiral nitroxides have been prepared (Scheme 5.26), in which the asymmetric
substituents are either immediately adjacent to the nitrogen on a pyrrolidine or piperidine ring.
30a,c,d
The asymmetric substituents can also be remote from the nitrogen on an azepine
133
or pyrrolidine
ring.
134
A 1 : 2 mixture of meso/(
±
) diastereomers of
N
-benzyl-2,5-dicarboxymethylpyrrolidine treated
with
lithium
diisopropylamide
(LDA)
and
then
with
iodomethane
yields
68
as
a
1 : 6
mixture
of
meso/(
±
)
diastereomers,
which
are
chromatographically
separated.
Deprotection
furnishes
the
pure
69
.
135
Nitrone
70
is obtained by oxidation of (2R,5R)-
2,5-bis(methoxymethyl)pyrrolidine with MeReO
3
/urea.H
2
O
2
. Without purification
70
is converted to
hydroxylamine
71
by the action of phenylmagnesium bromide in tetrahydrofuran. Oxidation of
71
to a nitrone followed by treatment with two equivalents of phenyllithium in tetrahydrofuran yields a
hydroxylamine which is easily oxidized to
72
.
136
The total yield of
72
amounts to 20 %, the enantiomeric
excess is higher than 98 %, the stereochemistry of the addition of phenylmagnesium bromide and
phenyllithium agrees with the stereo-course proposed by Keana.
137
amines, which after oxidation give meso- and (
±
)
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