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In-Depth Information
OH
OH
R
R
N
OR'
OR'
R'O
N
N
N
9
R
H
9
8
H
8
H
N
OH
N
H
Top view of QD-
76
Catalyst: QD-
76
Q-76
R=CH=CH
2
,R'=H,
76a
R=CH=CH
2
,R'=Bn,
76b
R=CH=CH
2
,R'=PHN,
76c
R=CH
2
-CH
3
,R'=PYR,
76d
R=CH=CH
2
,R'=Bz,
76e
R=CH=CH
2
,R'=Ac,
76f
PHN =
Ph
Cl
PYR =
NN
Ph
R=CH=CH
2
,R'=3,5-(CF
3
)
2
C
6
H
3
CO,
76g
O
COOR
3
O
O
76a
(10 mol %)
R
2
R
1
+
NO
2
-20°C, THF
*
NO
2
R
2
OR
3
60
R
1
R = aryl or alkyl
R
2
=OMe,R
3
=Me
58A
R
2
=Me,R
3
=Et
45C
R
2
=OMe,R
3
=Me
61
R
2
=Me,R
3
=Et.
62
94-98% ee, 71-99% yield
91% ee, 93% yield
O
R
3
O
X
R
1
+
X
76a-c
(10 mol %)
R
2
92-99% ee, 74-95% yield
6:1-50:1 d.r.
NO
2
*
R
2
NO
2
*
-20 to 60°C,THF
R
3
R
1
60
O
O
O
O
O
O
O
O
O
O
NC
O
2
N
OR
OR
OR
n = 1, R = Me,
45D
n = 2, R = Et,
45E
O
OR
R'
n
59B
74A
77
45G
45F
Scheme 2B.16.
distance and angle between the acidic and basic center. The high enantioselectivity
afforded by catalysts
76
showed that the rotational C8-C9 bond, instead of compromis-
ing catalyst effi ciency, allowed the catalyst to adopt the optimal conformation to afford
highly effi cient bifunctional catalysis. The next question was: “Does such conformational
fl exibility make the bifunctional catalysts
76
highly general? ”
In a following report published in 2005, Deng and coworkers found that
76
could
promote the conjugate additions of a wide range of trisubstituted carbon nucleophiles
to nitroalkenes
60
in exceedingly high enantioselectivity and diastereoselectivity (Scheme
2B.16) [48]. Based on experimental results obtained from kinetic, conformational, cata-
lyst structure-property studies and product confi guration analysis, they also proposed a
mechanistic model (Fig. 2B.1) [48]. This stereochemical model readily explains how
76
could be both effi cient and general. The authors proposed that various nucleophiles, in
their corresponding enol forms, were activated by a hydrogen-bonding interaction
between the enol and the quinuclidine. Among the various transition states (
78
,
79
, and
