Multicomponent reactions - Zhu.pdf - Index of

Although various chiral glycosyl aldehydes with a direct attachment of the carbonyl
group to the anomeric center showed low diastereoselectivity [52], a moderate
stereoselectivity was observed in the condensation of 45 with methyl isocyanoacetate,
propionic acid and a solid-supported amine [53].
1.4.4
Chiral Cyclic Imines
Only a few examples of U-3CRs involving chiral cyclic imines have been reported
to date.
N
1
R 1
OAr
+
H
H
sec-Bu
N
H
+
OAr
Scheme 1.17
CN
R 1
O
R 2
Ph
BocNH-CH2 BocNH-CH2 attack from
top face
R 2 CO 2
OR 3
47
R 3
Et
Et
Me
N
H
R 2 CO 2H
OAr
O
MeOH,
80°C
O
cis : trans
63 : 37
55 : 45
67 : 33
R 2
1.4 Asymmetric Intermolecular Ugi Reactions 15
Isocyanide insertion
with inversion
Condensations employing 2-pyrrolines with the chirality on C-3 [8, 54] or C-5
[55] showed only moderate stereoselectivity.
In the first case the best combination of reagents gave a 2:1 cis:trans mixture
(60% yield, Ar ¼ p-cyanophenyl) [54]. To the best of our knowledge this represents
the only example involving cyclic imines, in which the prevailing stereoisomer is
the cis one. The observed stereoselectivity can be explained, according to the authors
of that work if the reaction follows mechanism B or C to give preferentially
the bicyclic hydrogen-bonded intermediate 47 after attack of the carboxylate from
the side opposite to the OAr group. This intermediate, both kinetically and thermodynamically
favored, finally undergoes insertion of the isocyanide with inversion to
give the cis isomer.
A reversal of stereoselectivity, with a ratio usually in the range 2:1, was observed
when 5-substituted-2-pyrrolines were used [55]. 2,5-Pyrrolidines 48 and 49 (Scheme
OAr
H
N
46a
N
O
O Ph
OAr
+
46b
N
O
O Ph
46a
H
N
R 1
R 1
CO2R 3
CO2R 3