Chemistry Reference
In-Depth Information
Ph
Me
N
Me
Et
Ph
N
N
H
Et
HO
14
(0.1 equiv)
RCHO
(1 equiv)
+
CH
3
NO
2
(1.5 equiv)
NO
2
R
THF, -65 ˚C, 9 h
R =
i
Bu: 33% (54% ee)
R = Ph: 31% (33% ee)
Scheme 4.14
Examples of guanidine catalysed asymmetric nitroaldol reactions
acetophenone or acyclic ketones do not work as electrophiles because of no reaction or
predominant self condensation, respectively. This method has been applied to Henry
reactions using sugar derivatives [41]. PS-TBD was also proven to be an efficient catalyst.
In 1994, the first guanidine catalysed asymmetric nitroaldol reaction was reported [10a].
Treatment of pivalaldehydewith nitromethane in tetrahydrofuran (THF) afforded an adduct
in 33% yield with 54% ee when N,N-diethyl-N
0
,N
00
-bis[(1S)-1-phenylethyl]guanidine (14)
was used. (Scheme 4.14).
TheMurphy
Me in Scheme 4.7) also catalyses the nitroaldol reaction
of isobutylaldehyde and nitromethane to give an adduct in 52% yield but with low ee (20%)
[24c].
Several enantiopure guanidines were studied as the catalysts for the Henry reaction of
dibenzylamino aldehydes with nitromethane. (R)-1-(1-Naphthyl)ethylamine-derived gua-
nidine catalysed the reactions of L-isoleucine-derived aldehydes with good diastereos-
electivity [42].
Catalytic enantio- and diastereoselective nitroaldol reactions were explored by using
designed guanidine-thiourea bifunctional organocatalysts like 15 (Figure 4.4) under mild
and operationally simple biphasic conditions. These catalytic asymmetric reactions have a
broad substrate generality with respect to the variety of aldehydes and nitroalkanes [43]. On
the basis of studies of structure and catalytic activity relationships, a plausible guanidine-
thiourea cooperative mechanism and a transition state of the catalytic reactions are
proposed.
s guanidine 10 (R
¼
R
1
R
2
Cl
-
+
N
N
N
N
N
Ar
H
H
Ar
S
R
3
S
R
3
15
Ar = 3,5
-
(CF
3
)
2
C
6
H
3
Figure 4.4
Structure of guanidine-thiourea bifunctional organocatalyst 15
