Chemistry Reference
In-Depth Information
proposed nine-membered transition state
TS 3
, where PA
1f
serves as a bifunctional
catalyst: The OH in phosphoric acid activated the aldimine as a Brønsted acid and the
phosphoryl oxygen (P=O) activated the nucleophile as a Lewis base, thereby oriented
both nucleophile and electrophile, which increased enantioselectivity (Scheme 3.30).
H
O
i
-Pr
P
OMe
O
O
i
-Pr
OMe
PA
1f
(10 mol %)
HN
m
-Xylene, rt
O
i
-Pr
O
i
-Pr
N
R
P
O
i
-Pr
O
R
H
P
HO
O
i
-Pr
11 examples
72-79% yield
52-90% ee
H
O
i
-Pr
O
i
-Pr
O
*RO
O
P
R
P
*RO
O
H
H
N
PMP
TS 3
Scheme 3.30.
3.5.2. aza - Friedel - Crafts ( F - C ) Reactions
The fi rst organocatalytic aza-F-C reaction of aldimines was reported by Terada and his
coworkers using catalyst PA
1g
[57]. It is remarkable that
N
- boc - protected aryl imines
containing electron-donating or -withdrawing groups at either the
ortho
- ,
meta
- , or
para
-
positions were well tolerated in this condition. Interestingly, the absolute confi guration
of the products was opposite to that found previously in direct Mannich reaction [53]
(Scheme 3.31 ).
PA
1g
(2 mol %)
Boc
Boc
HN
N
O
O
MeO
ClCH
2
CH
2
Cl, -35°C
MeO
Ar
Ar
H
13 examples
80-96% yield
86-97% ee
Scheme 3.31.
The Terada group reported the enantioselective aza-F-C reaction of indoles with
enecarbamates as the precursor of iminium salts [58]. This is the fi rst example of the F-C
reaction initiated by an activation of an electron-rich multiple bond. Use of either pure
regioisomers (
E
) - or (
Z
)-enecarbamate gave the identical product with the same level
