Chemistry Reference
In-Depth Information
O
O
Y
Cl
76c
(10-20 mol %)
CN
X
X
+
R
R
Y
H
CN
Toluene, rt
Cl
137
136
76
76
Protonation
R'
N
R'
N
R''O
N
R''O
N
H
H
H
H
H
O
H
O
H
H
O
Nucleophilic addition
H
O
Y
N
N
X
C
C
X
H
R
R
Y
Cl
Cl
T1
T2
O
O
O
CN
CN
CN
Ph
CO
2
Et
CN
74C
74E
74G
74H
dr = 7:1, 91% ee
dr = 20:1, 96% ee
dr = 7:1, 91% ee
dr = 4:1, 88% ee
O
O
O
CN
O
O
t
Bu
O
O
t
Bu
O
O
CF
3
CF
3
COSMe
O
135
45J
45K
45L
dr = 10:1, 93% ee
dr = 17:1, 98% ee
dr = 20:1, 98% ee
dr = 9:1, 94% ee
Scheme 2B.28.
mediate. The synthetic impetus of this investigation was to develop asymmetric tandem
reactions to provide one-pot constructions of 1,3-tertiary-quaternary stereocenters from
simple starting materials. Such structure motifs, although commonly presented in natural
products, are usually built via multistep synthetic sequences.
Deng and coworkers fi rst established that the 6
- OH cinchona alkaloids
83
could
afford high enantioselectivity and diastereoselectivity for the tandem nucleophilic addi-
tion-protonation reaction involving a diverse array of carbon nucleophiles (Scheme
2B.28) [75]. They also showed that with DABCO, this reaction proceeded with hardly
any diastereoselectivity, thereby establishing that catalyst
76
was responsible for both
the enantioselectivity and the diastereoselectivity. This is consistent with a mechanistic
model in which the catalyst serves a dual role, facilitating the enantioselective C- C
bond-forming nucleophilic addition to generate the quaternary stereocenter and effect-
ing the subsequent protonation of the transient enol intermediate to form the tertiary
′
