Chemistry Reference
In-Depth Information
O
X
O
PhI(OAc)
2
50-75 mol%
R
1
R
2
R
1
R
2
MM200, 30 Hz, 90 min
12
X = Cl: TsNClNa
.
3H
2
O
13
X = Br: TsNHBr
14
N
Ts
15
-(
) X = Cl
H
16
-( ) X = Br
Ts
Na
N
NaOAc
Cl
13
Ph
O
Ts
X
O
O
I
Ts
N
N
PhI(OAc)
2
N
OAc
R
1
R
2
Br
AcO
OAc
B
X
12
PhI
Ts
H
Ts
H
A
N
N
AcOH
X = Cl, Br
H
Br
14
X
R
1
O
O
O
H
Ts
N
R
2
TsNClNa
13
C
l
O
X
O
OAc
C
H
2
O
Ph
R
2
R
1
R
2
X = Cl
N
N
Ts
H
Ts
OAc
R
2
=
OMe,
65%
R
2
= NEt
2
, 52%
99:1
15
-( )
D
-( )
dr
(
anti/syn)
B
r
O
TsNHBr
14
R
1
R
2
X
=
Br
R
1
= Ar
N
Ts
H
R
2
= OMe, OEt, 52-66%
16
-( )
dr
(
anti/syn)
: 91:9
R
2
=
NEt
2
, 48-69%
dr
(
anti/syn)
99:1
Scheme 6.5 Diastereoselective
aminohalogenation
and
plausible
reaction
mechanism.
potassium enolate, which remained stable as shown by spectroscopic an-
alysis. Glycine t-butyl ester Schiff base was selected for the alkylation re-
action due to its higher stability to hydrolysis. In the second step, interaction
with the chiral ammonium salt derived from cinchonidine 20 induced the
reaction of the electrophile R
1
X on a preferential face. Although excellent
yields and exclusive monoalkylation were obtained, the enantiomeric excess
(ee up to 75%) values were lower than those obtained in solution under PTC
conditions. The enantiomeric excess could not be improved by increasing
the amount of catalyst or varying the quantity of base. The ball-milling fre-
quency showed little influence on the measured enantiomeric excess during
the preparation of allylglycine t-butyl ester: at 10 or 20 Hz identical ees(64%)
were obtained, with a further decrease of optical purity at 30 Hz (58% ee).
Despite the diculties associated with temperature control and a high
concentration of reactants, the results demonstrated that asymmetric syn-
thesis in a ball-mill is not a chimera.
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