Chemistry Reference
In-Depth Information
extended by Zhao, Bandini, and others to other ketones such as
90
and
70
(Scheme
2B.18 ) [52b,c] .
An enantioselective Freidel-Crafts reaction of indoles and carbonyls catalyzed by
76c
was reported in 2006 by Deng and coworkers (Scheme 2B.19) [54]. High enantiose-
lectivity was established for reactions of various indoles
92
with various carbonyls such
as aryl aldehydes
16A
and aryl pyruvates
88
. However, attempts to extend the high
enantioselectivity to simple aliphatic aldehydes and ketones have not yet been met with
success.
HO
X
R
1
*
76c
(10 mol %)
O
R
2
R
2
+
rt-70°C
H
H
R
1
X
1
88:
X=CO
2
Et, R = H, Ar, alkynyl
92
16A:
X = H, R = Ar
93A:
X = H 82-93% ee, 60-96% yield
93B:
X=CO
2
Et 81-99% ee, 52-97% yield
1
Scheme 2B.19.
In another signifi cant expansion of the reaction scope of
76
, Deng and coworkers
documented the fi rst effi cient asymmetric Diels-Alder reaction with 2-pyrones
94
(Scheme 2B.20) [55]. It is noteworthy that 2-pyrones
94
presented a class of synthetically
useful but inactive diene substrates for Diels-Alder reactions. As illustrated in a pro-
posed stereochemical model presented in Scheme 2B.20, Deng and coworkers postu-
lated that, in addition to directing the substrates toward the formation of
exo
-
96
in high
enantioselectivity and diastereoselectivity, the simultaneous activation of both the
pyrone diene
94
and the dienophile
95
by catalyst
76c
was critical in addressing the well-
known activity issues associated with D-A reactions of 2-pyrones
94
[55] .
Toste and coworkers reported a synthetically interesting enantioselective fragmenta-
tion reaction, which also expanded the scope of catalysts
76
. Specifi cally, Toste and
others showed that catalyst
76f
was very effective in the promotion of an asymmetric
Kornblum-DeLaMare reaction, which produces optically active γ - hydroxyl enone
99
from cyclic
meso
- peroxides
98
(Scheme 2B.21) [56]. In contrast to the bond-forming
reactions with electrophiles and nucleophiles, this reaction fragments the
meso
- peroxide
enantioselectively to form a chiral product. In the proposed stereochemical model, the
C6′ - OH of
76f
activates the peroxide bond as an acid while the basic quinuclidine depro-
tonates the acidic C-H. With this two-point interaction, the catalyst also induces the
enantioselectivity by directing the peroxide
98
to adopt an orientation with its bulky
substituents pointing to open space.
As outlined in the fi rst report of
76
as a highly effi cient chiral catalyst, Deng and
coworkers' studies were inspired by Wynberg's pioneering studies of natural cinchona
alkaloids as acid-base bifunctional catalysts and Hatakeyama's success in the use of the
6′-OH as an acidic center to activate aldehydes in the asymmetric Morita-Baylis-Hill-
man reaction with β - ICD
51
. At the same time, catalysts
76
are designed to specifi cally
address two key issues, inadequate acidity and conformational infl exibility, which
prevent the natural cinchona alkaloids and β - ICD
51
, respectively, from becoming highly
effi cient yet general chiral acid-base bifunctional catalysts. The importance in addressing
