Chemistry Reference
In-Depth Information
reaction, the use of
N
- trifl yl phosphamides improved both reactivities and enantioselec-
tivities. It is interesting that while the Lewis acid-catalyzed Nazarov reactions provide
mainly the
trans
products, the methodology primarily generates
cis
products. The
Rueping group later extended the application of this acid to the enantioselective Michael
addition of indole with
-ketoesters [87]. This is not only the fi rst
example of a Brønsted acid-catalyzed activation of
β
,
γ
- unsaturated
α
α
,
β
- unsaturated carbonyl com-
pounds, but it also provides the corresponding
-keto esters in good yields and with
excellent enantioselectivities. More recently, Rueping et al. further expanded the appli-
cation of these highly reactive phosphoramides to the fi rst enantioselective carbonyl-ene
reaction of
α
α
-ketoesters to afford a range of substituted
α
- hydroxyesters in good yields
with excellent enantioselecitivities (Scheme 3.51 ) [88] .
O
O
O
O
O
ent
-PA
6c
(2 mol
%)
CHCl
3
, 0°C
R
1
O
R
1
R
1
R
2
R
2
R
2
11 examples
45-92% yield
1.5:1 to >99:1
cis
selective
86-93% ee (
cis
)
90-98% ee (
trans
)
R
1
CO
2
R
2
O
R
3
PA
6d
(5 mol %)
CH
2
Cl
2
, -75°C
O
R
3
R
1
CO
2
R
2
N
Me
Me
10 examples
43-88% yield
80-92% ee
F
3
C
O
OH
PA
6e
(1 mol %)
o
-Xylene, 10°C
CO
2
Et
R
R
R = aryl
F
3
C
CO
2
Et
17 examples
55-95% yield
92-97% ee
Scheme 3.51.
Cheon and Yamamoto thereafter prepared
N
- trifl yl thio- and selenophosphoramides
and reported the fi rst metal - free Br ø nsted acid - catalyzed asymmetric protonation reac-
tions of silyl enol ethers using a chiral Brønsted acid in the presence of achiral Brønsted
acid media [89]. Interestingly, replacement of sulfur and selenium into the
N
- trifl yl
phosphoramide increases both reactivities and enantioselectivities for protonation reac-
tions. It is appealing that the catalyst loading for the protonation could be decreased to
0.05 mol % without any signifi cant loss of enantioselectivity (Scheme 3.52).
