Multicomponent reactions - Zhu.pdf - Index of

Bn
O
HO 2C
N
H
H 2N
O
+
CHO
O
H
N
H
Scheme 1.32
N
+
O
+
O
H
O
H
N
Ar
92
Ar
OTIPS
NC
MeOH/THF
48 h
67%
OH
1) KHMDS, allyl bromide,
89%, r.t.
2) Ru-catalyst, CH2Cl2, 40°C, 36 h, 69%
3) HF
Ar
. py, 95%
Ar = 4-bromophenyl
H
N O
HN O
OTIPS
benzaldehyde was used as the carbonyl partner, the tandem process was poorly
stereoselective [84].
Both Ugi and Passerini reactions have been explored, using 3-substituted propynoic
acids as dienophiles. The multicomponent adducts 93 have been submitted to
IMDA under different conditions, depending upon the heteroatom X in the tether:
Ugi adducts could be converted smoothly, usually under thermal conditions, to
give 94 as the major stereoisomer (less than 10% of any other stereoisomer detected).
On the contrary, Passerini adducts proved to be unreactive under thermal
conditions, but reacted cleanly under Me2AlCl catalysis to give bicyclic lactones in
a highly stereoselective way (Scheme 1.33) [83].
R 2
CHO
O
R1 +
NC
+
O
Scheme 1.33
OH
R 3 NH2, MeOH, r. t.
X = R 3 N
74-92%
CH 2Cl 2, r. t.
X = O
69-86%
1.6 Other Asymmetric Isonitrile-based Multicomponent Reactions 25
Ar
H
N
Bn
O
H
Bn
O
H
N
H
N O
O H
N
O
H
O
91
R
O X
NH
O
2
R
O
X
2
X = NR3 O
R
: ∆, 24 h,
74-81%
X = O: Me2AlCl,
CH2Cl2, 93
–78°C to r.t.,
68-77%
94
1
OTIPS
O
O
H
N
R 1