Chemistry Reference
In-Depth Information
R
3
R
3
+
+
R
1
R
1
N
N
OR
2
R
2
O
X
X
N
N
1
2
a
: R
1
=Ph, R
2
=PhCH
2
, R
3
=vinyl, X=Br
b
: R
1
=9-anthracenyl, R
2
=H, R
3
=vinyl, X=Cl
c
: R
1
=9-anthracenyl, R
2
=allyl, R
3
=vinyl, X=Br
d
: R
1
=9-anthracenyl, R
2
=benzyl, R
3
=vinyl, X=Br
e
: R
1
=9-anthracenyl, R
2
=allyl, R
3
=vinyl, X=OH
f
: R
1
=9-anthracenyl, R
2
=allyl, R
3
=ethyl, X=OH
g
: R
1
=9-anthracenyl, R
2
=benzyl, R
3
=ethyl, X=Br
h
: R
1
= 4-iodophenyl, R
2
=H, R
3
=vinyl, X=Br
i
: R
1
=4-CF
3
-phenyl, R
2
=H, R
3
=vinyl, X=Br
j
: R
1
=phenyl, R
2
=H, R
3
=vinyl, X=Br
Fig. 10.3
Quaternary Cinchonine
(1)
and Cinchonidine
(2)
Based PTC.
R''
R''
N
N
X
X
N
N
a
R' = H, R'' = CH=CH
2
, R''' = H
b
R' = H, R'' = CH
2
-CH
3
, R''' = H
c
R' = OMe, R'' = CH=CH
2
, R''' = H
d
R' = H, R'' = CH=CH
2
, R''' = Bn
e
R' = H, R'' = CH
2
-CH
3
, R''' = Bn
f
R' = H, R'' = CH=CH
2
, R''' = CH
2
-CH=CH
2
g
R' = H, R'' = C
2
H
5
, R''' = H
OR'''
OR'''
Anth
Anth
R'
R'
1
2
Scheme 10.33
R
R
Ph
O
Ph
Ph
Ph
RX, PTC
O
deprotection
OH
N
t-
Bu
N
t-
Bu
N
Ph
O
Ph
O
O
Scheme 10.34
the Schiff base of glycine with benzophenone as a
protected and activated building block. This substrate
could be alkylated or dialkylated under PTC condi-
tions to yield, after deprotection, a variety of amino
acids (Scheme 10.33).
Using compound
1a
as catalyst (Fig. 10.3) and
50% NaOH at 5°C, up to 81% ee could be obtained
(RX = benzyl bromide) [217]. In the same reaction
99.5% ee was reported by Corey [218], who applied
solid caesium hydroxide hydrate as a base at -78°C
in the presence of catalyst
1c
in methylene chloride.
Lygo [219] with RX = benzyl bromide used catalysts
1b
and
2b
in an aqueous KOH/toluene system at
25°C to achieve high yields (89-91% ee) of the
R-
and
S
-isomers, respectively. Bis(a-amino acid) esters
were prepared similarly (ee > 95%) using dibro-
moalkanes as alkylating agents. Dityrosine and isodi-
tyrosine likewise were prepared [220]. Intriguingly,
similarly high enantiomeric excesses could be
obtained in a homogeneous system using neutral
non-ionic, soluble phosphazene bases [221]. Chin-
chilla
et al.
[222] alkylated cinchonidine and cincho-
nine with Merrifield resin. The resulting materials
were applied in the enantioselective alkylation
according to Scheme 10.34. The cinchonidine-based
catalyst yielded the
S
-isomer whereas the cinchonine
analogue gave the
R
-isomer. Both were obtained in
up to 90% ee.
Another strategy to functionalise amino acids
using the Schiff base of glycine was developed via
the Michael addition. This was demonstrated by
Corey, who reacted the latter with acrylonitrile in
the presence of catalyst
1c
to yield a precursor for
the synthesis of (
S
)-ornithine (Scheme 10.35) [223].
Catalyst
1c
was utilised also with similar Michael
additions of cyclohexenone and chalcone and also
in the aldol and nitroaldol reactions of aldehydes. A
typical example (Scheme 10.36) was the stereose-
lective synthesis of an amprenavir (an HIV protease
inhibitor) intermediate [224].
