Chemistry Reference
In-Depth Information
RBr, 5N NaOH
O
O
N
C
NOBn
N
C
TBAB, CH
2
Cl
2
, 20
°
C
NOBn
S
S
O
O
R
O
O
R = Benzyl (Bn), 99% yield, > 95%
de
R =
p
-nitrobenzyl, 98% yield, > 95%
de
R = propargyl, 95% yield, > 95%
de
Scheme 10.13
SMe
SMe
O
O
O
O
N
N
Me
Me
SMe
SMe
i-
PrBr, MeCN, TBAB
3 eq LiOH, 6 eq Li
Cl
NN
NN
-20
°
C, 1 h
Me
Ph
Me
Ph
90% yield, 84%
de
Scheme 10.14
1. K
2
CO
3
, TEBA, rt
2. NaOH, MeOH
COOH
O
Me
3
+ CH
3
NO
2
O
O
2
N
3
BzO
BzO
1. SOCl
2
2. BzO-NH
2
, Et
3
N, r
t
N
R
N
H
t-
BuOK, RX, Aliquat, 50
°
C
O
O
3
3
O
2
N
O
2
N
HO
HCOONH
4
, Pd/
C
MeOH, reflux
N
H
RX = CH
3
I,
n
-C
4
H
9
Br,
n
-C
8
H
17
Br
overall yield 20-35%
O
3
O
2
N
Scheme 10.15
Carbon alkylation of N-protected glycinate ester
with RCHFCH
2
Br afforded—after deprotection and
hydrolysis—a series of g-fluoro-a-amino acids [91].
The alkylation step was achieved using 50% aqueous
sodium hydroxide and TEBA as a catalyst. A highly
diastereo- and chemoselective monoalkylation of an
N
-(b-oximino)acyl compound (Scheme 10.13) was
reported by Miyabe [92], who used 10% TBAB in a
5 N NaOH/CH
2
Cl
2
biphasic system at 25°C.
1,5-Dimethyl-4-phenylimidazolidin-2-one-derived
iminic glycinimides also were alkylated diastereo-
selectively (Scheme 10.14) by alkyl iodides and by
Michael acceptors in the presence of TBAB and an
LiOH/LiCl mixture [93].
N-Alkylation of a benzyl-ether-protected trihy-
droxamic acid was carried out by Labidalle
et al
. [94].
The multistep synthesis combined a triple PTC
Michael reaction of nitromethane with methyl acry-
late, followed, after reaction with
O
-benzylhydroxy-
lamine, by a PTC N-alkylation using potassium
t
-butoxide base and Aliquat 336 catalyst at 50°C
(Scheme 10.15).
Arylation of phenylacetonitrile was reported by
a team from Janssen [95]. In a description of a
scaleable process for the synthesis of the aromatase
inhibitor R83842, these authors copiously demon-
strated the advantages of PTC methodology over tra-
ditional synthetic strategies. Thus, the use of KMnO
4
,
