Chemistry Reference
In-Depth Information
R"
N
R'O
R
1
N
X
NO
2
H
H
H
COR
2
O
R
3
H
O
X
H
O
R
2
N
+
O
-
R
1
R
3
78
R"
N
R"
N
R'O
R'O
N
N
H
H
H
H
H
H
O
O
H
O
O
H
H
R
1
X
X
O
N
+
R
2
O
-
N
+
O
-
R
1
R
2
R
3
R
3
O
H
79
80
Figure 2B.1.
80
) leading to the formation of different stereoisomers, transition state assembly
78
is
the most favored. Relative to
78
, transition state
79
is less stable due to fewer hydrogen-
bonding interactions between the nucleophile and the catalyst. On the other hand,
transition state
80
is destabilized due to steric congestions. Furthermore, in transition
state
78
, the variable substituents (R
1
, R
2
, and R
3
) of the donors and acceptors are point-
ing away from the catalyst, which is interacting with the functional groups of the two
substrates through a network of hydrogen bonds. Consequently, alterations of these
substituents are well tolerated by the catalyst as they do not disrupt the networks of
hydrogen-bonding interactions between the catalyst and the substrates (Fig. 2B.1).
An interesting hypothesis, arising from this model, was that catalysts
76
might toler-
ate the replacement of the nitro group with other basic organic functionalities. This
implied that
76
could potentially afford high enantioselectivity and diastereoselectivity
for conjugate addition reactions with a wide range of Michael acceptors other than
nitroalkenes. Subsequent studies guided by this hypothesis indeed led to the develop-
ment of a series of highly enantioselective and diastereoselective asymmetric conjugate
additions with α , β - unsaturated sulfones
81
[49a,d] , ketones
41
[49b], and aldehydes
84
[49c] (Scheme 2B.17). In addition to their implications for bifunctional catalyst design
and development, these synthetic and mechanistic studies of
76
- catalyzed conjugate
additions also established many unprecedented organocatalytic asymmetric transforma-
tions that address important and challenging synthetic problems, such as the construc-
tion of the quaternary stereocenters. Even in comparison with the best chiral metal
