Chemistry Reference
In-Depth Information
catalysts [50] ,
76
afforded much higher enantioselectivity and diastereoselectivity over
a much broader scope of substrates in conjugate additions to enones
41
and enals
84
.
Notably, cinchona alkaloid
76c
is the fi rst highly enantioselective catalyst for conjugate
additions with
α
,
β
- unsaturated sulfones
81
[49a]. Although a highly enantioselective
amination of
α
- cyanoacetates
74
with dialkyl azadicarboxylate
74
was developed with
β
- ICD (
51
) [46] (Scheme 2B.15 ), catalysts
76
were explored by Deng and coworkers for
this transformation to establish enantioselective access to both enantiomers of adducts
87
, which are valuable chiral building blocks bearing an
N
- substituted tetrasubstituted
stereocenter [51]. As summarized in Scheme 2B.17, in the presence of catalysts QD- and
Q -
76b
, the aminations of
75
proceeded with excellent enantioselectivity to provide
enantioselective access to both enantiomers of adduct
87
. The remarkable ability of
cinchona alkaloids
76
to achieve both highly effi cient stereochemical control and to
tolerate an extremely broad range of Michael donors and acceptors provided further
validation of one of the key design features of
76
, namely the use of a bond of rotational
freedom to link the basic and acidic site.
As part of an extensive investigation, studies to apply catalysts
76
to other asymmetric
reactions were performed in parallel to those directed toward conjugate addition reac-
tions. In 2005, a successful application of
76
in an enantioselective 1,2-addition to car-
bonyls was reported by Deng and coworkers, who realized a highly enantioselective
nitroaldol reaction that is applicable to both alkyl, alkenyl, and aryl
- ketoesters
88
(Scheme 2B.18) [52a]. In addition to their implications in expanding the reaction scope
of
76
, these results provided the fi rst highly enantioselective organocatalytic Henry reac-
tion with ketones. Importantly, with a signifi cantly more general scope than that estab-
lished by metal catalysts [53], this reaction represented important progress in catalytic
asymmetric Henry reactions. The resulting
α
- hydroxyl esters
89
could be transformed
into other synthetically valuable chiral buiding blocks containing tetrasubstituted ste-
reocenters. In recent years, the scope of the
76
-catalyzed Henry reactions was further
α
O
76e
(5 mol %)
HO
NO
2
OEt
R
1
+
CH
3
NO
2
OEt
R
1
CH
2
Cl
2
, -20°C
*
O
23A
88
89
O
93-97% ee, 84-99% yield
R
1
= aryl, alkenyl, alkyl
O
NO
2
76a
or
76c
(5 mol %)
HO
*
CH
3
NO
2
+
R
1
P(O )(OR
2
)
2
R
1
P(O)(OR
2
)
2
THF
90
R
1
23A
91
90-99% ee, 61-93% yield
= aryl, alkyl
NO
2
HO
O
76g
(5 mol %)
*
CH
3
NO
2
R
1
R
2
+
R
1
R
2
CH
2
Cl
2
, -25°C
23A
91
70A
,R
1
=aryl,alkyl;R
2
=CF
3
70B
,R
1
=aryl,alkyl;R
2
=CHF
2
76-99% ee
67-99% yield
Scheme 2B.18.
