Chemistry Reference
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O
TMS
O
R
PA
7a
(down to 0.05 mol %)
R
PhOH (1.1 eq)
Toluene, rt
n
n
10 examples
R = aryl, or alkyl
Quantitative yield
52-90% ee
n = 1, or 2
Scheme 3.52.
3.5.6. Asymmetric Counteranion Directed Catalysis ( ACDC )
In 2006, Mayer and List introduced ACDC as a new concept of enantioselective synthesis
[90]. Using the morpholine salt of chiral anion of PA
1i
as a catalyst, 1,4-transfer hydro-
genation of α , β-unsaturated aldehydes was obtained with high asymmetric induction. The
reduction proceeded via an iminium salt intermediate, wherein phosphate anion effec-
tively shielded one of the enantiofaces of the iminium salt. Later, they extended this
methodology to the reduction of α , β-unsaturated ketones [91]. In particular, they found
that a new class of catalytic salts, in which both cation and anion are chiral, is more effec-
tive for the transfer hydrogenation of α , β - unsaturated ketones (Scheme 3.53 ).
CHO
PA
1i
(20 mol %)
MeO
2
C
CO
2
Me
CHO
morpholine (20 mol %)
Ar
dioxane, 50°C
H
Ar
6 examples
(1.1 eq)
63-90% yield
96- >99% ee
PA
1i
(5 mol %)
O
O
EtO
2
C
CO
2
Et
H
2
N
CO
2
t
-Bu
R
1
R
1
H
i
-Pr
R
2
R
3
R
2
R
3
(5 mol %)
(1.2 eq)
12 examples
Bu
2
O, 60°C
68-99% yield
70-98% ee
48 h
Scheme 3.53.
Recently, the List group successfully applied ACDC to the asymmetric epoxidation
of α , β-unsaturated aldehydes [92]. In previous studies of reductions of enals, the stereo-
genic center is created in the conjugate addition step, whereas in epoxidations of
2,2-disubstituted enals, the initial addition product is achiral. Consequently, they pro-
posed a new catalytic cycle where the subsequent cyclization to iminium ion is the ste-
reogenic center (Scheme 3.54 ).
