Multicomponent reactions - Zhu.pdf - Index of

N
H
O
N
H
N
O
O N O 62
H
MeOH, –30° C to r.t.
98%, d.r.: 93 : 7
N
H
O
H
N
CO 2Me 65
O
MeOH, –30° C to r.t.
46%, d.r.: 67 : 33
Scheme 1.24
OMe
OMe
N
H
O
Sung et al. [71] attempted to explain the reasons for the observed stereoselectivities
on the basis of the mechanism outlined in Scheme 1.25: it is assumed that the
cyclic intermediate 68 is formed under thermodynamic control and can equilibrate
to the more stable isomer before being attacked by the external nucleophile. When
the aminoacid has a bulky side chain (for example Y ¼ i-Pr), the cyclohexyl intermediate
68 will preferentially dispose this chain in the equatorial position.
Between the two possible diastereoisomers, the most favored one will be that
with R 1 in the equatorial position 68a and therefore this will be formed preferen-
H2N
Y
O
R 1 CHO
R 2 NC
Scheme 1.25
OH
H
N
O
OMe
63 OH
MeOH, –30° C to r.t.
98%, d.r.: 89 : 11
N
H
Ph2P O
H
N
O
OMe
N
H
O
H
N
O
CO2Me 64
MeOH, –30° C to r.t.
81%, d.r.: 83 : 17
66
Cl
67
1) MeOH, –60° C to 0°C, 70%, d.r.: 92 : 8 MeOH, r.t.
2) MeOH, r.t., 90%, d.r.: 91 : 9
d.r.: 74 : 26
Y
Y
O
O
H
O
N
68a
O
N
R1 H
N
R1 R 2
R 2
N
1.5 Asymmetric Intramolecular Ugi Reactions 19
MeOH
MeOH
N
H
O
H
N
O
OMe
OMe
N
H
H
N
R
O
OMe
1
R
O
2
69a
Y
major diastereoisomer
R 2
N
H
O
R 1
H
N
68b 69b
Y
O
minor diastereoisomer
OMe