Chemistry Reference
In-Depth Information
Substrate
Catalyst
LUMO activation
-
δ
LA
Lewis acid (LA)
(eq 1)
O
O
+
δ
R
R
R
(eq 2)
H
N
R
O
Figure 2A.1.
LUMO-lowering activation with Lewis acid catalysis and iminium catalysis.
O
Me
Me
O
N
Me
Me
Me
H
Ph
X
R
e
Si
Figure 2A.2.
Computational models of imidazolidinone catalyst and corresponding iminium ion.
π-orbital electronics that are inherent to Lewis acid catalysis, that is, LUMO-lowering
activation (Fig. 2A.1 ).
During the development of this activation mode, three parameters were found to be
crucial for both catalyst reactivity and enantioselectivity. Specifi cally, (i) the amine cata-
lyst must be able to undergo effi cient and reversible iminium ion formation, which must
take place with (ii) high levels of geometrical bias and (iii) selective and effective olefi n
π-facial discrimination. These crucial design elements were realized and extensively
developed in a family of readily accessible chiral oxazolidinones (Fig. 2A.2).
As suggested from computer modeling, the catalyst-activated iminium ion was
expected to selectively populate the depicted
E
-isomer to avoid nonbonding interactions
between the substrate olefi n and the catalyst
tert
- butyl group. This geometric constraint
results in the shielding of the olefi n
Si
-face by the benzyl group of the catalyst system,
thus leaving the
Re
- face exposed to enantiocontrolled bond - forming events.
Since its inception, this general mode of activation has found broad applicability in
a wide range of enantioselective transformations. To date, iminium catalysis has been
exploited in more than 50 highly enantioselective protocols, an illustrative selection of
which is delineated in the following subsections.
2A.2.1. Cycloaddition Reactions
Cycloaddition reactions represent a particularly powerful method for the rapid construc-
tion of molecular complexity from relatively simple substrates. In particular, the catalytic
enantioselective Diels-Alder reaction has become a benchmark for the evaluation of
new catalysis concepts, presumably due to the inherent value of this [4 + 2] cycloaddition
