Multicomponent reactions - Zhu.pdf - Index of

R 2
52
Scheme 1.20
N R 3
N
O
Scheme 1.21
O
55
Ph
57
53
R1 NC
O R
OH
H
Ph
3
N R1
R2 R
t-Bu
H
3
R
N
H
O
N
CH2Cl
CH3 2 O R3 R 1
+ +
MeOH, r.t.
54
Yield [%] d.r.
98 50 : 50
100 >95 : 5
+
R 1
t-Bu
t-Bu
(C 6H 4)-mCH 3
R 1 NC
R 2
H
H
R 1
cy-C 6H 11
R 3
CH 3
t-Bu
R 2
H
given about the relative configuration of the products. Interestingly, when 2H-1,3benzooxazine
57 was employed, the stereoselectivity dropped to a 59:41 ratio.
In some cases, therefore, 1,3-induction in the Ugi reaction using cyclic imines
seems to be excellent. However, further investigations should be performed in
order to rationalize the results, although it is clear that the position of the chirality
on the imine, together with the hybridization of the carbon atoms in the ring,
seems to play an important role both with regard to the diastereoselectivity and in
determining the preferred face during isonitrile attack.
1.5
Asymmetric Intramolecular Ugi Reactions
+
O R 2
Intramolecular versions of the Ugi reaction, where two of the four functional
groups involved belong to the same molecule, have attracted many scientists for
their ability to generate various heterocycles relevant from a pharmacological point
of view. Among others, reactions with a- and b-aminoacids have been reported
to generate interesting stereochemical outcomes. The possibility of generating
b-lactam rings using b-aminoacids has been known since 1961 as the Ugi fourcenter-three-component
reaction (U-4C-3CR) [60]; the postulated mechanism
OH
1.5 Asymmetric Intramolecular Ugi Reactions 17
Yield [%]
75
67
Yield [%]
75%
d.r.
>95 : 5
93 : 7
d.r.
59 : 41
R 1
56
N
H
O
O R 2
N
O
R 3