Chemistry Reference
In-Depth Information
HO
HO
OTMS
cat.
(30 mol %)
Toluene, -78°C
Me
+
HN
N
OMe
CO
2
Me
Me
Ph
Ph
Me
Me
PA
1a
: 57% yield, 0% ee
PA
1b
: >99% yield, 27% ee
PA
1c
: 96% yield, 87% ee
HO
HO
OTMS
PA
1c
(10 mol %)
Toluene, -78°C
H
+
HN
N
OR
2
CO
2
R
2
R
1
Ar
Ar
R
1
11 examples
65-100% yield
86:14 to 100:0
syn
selective
81-96% ee
R
O
H O
O
P
O
O
H
N
R
Ar
H
TS 1
Scheme 3.27.
3,3′ - positions has a benefi cial effect on obtaining high levels of enantioselectivity. In
addition,
N
-hydroxyphenyl-substituted aldimine is critical for asymmetric induction.
DFT calculations were carried out to elucidate the stereoinduction. The reaction seems
to be undertaken through the nine-membered zwitterionic transition state
TS 1
, which
was used originally to explain enantioselectivity [54].
Shortly thereafter, Uraguchi and Terada independently reported that the direct
Mannich reaction of acetoacetone with
N
- boc - protected imines was catalyzed by only
2 mol % of PA
1d
to give the corresponding adducts with high enantioselectivities
(Scheme 3.28 ) [53] .
In 2007, Gong et al. reported the three-component direct Mannich reaction, wherein
phosphoric acids, derived from H
8
-BINOL derivatives, were utilized as catalysts (Fig.
3.6 ) [55] . The one - pot Mannich reactions between
in situ
generated
N
- aryl imines and
cyclic ketones as well as aromatic ketones catalyzed by PA
2a
gave the corresponding
adducts with excellent enantio- and/or diastereoselectivities. The authors postulated that
acid-promoted enolization of the ketone forms the reactive enol, which adds to the
protonated aldimine via
TS 2
(Scheme 3.29 ).
Hydrophosphorylation of aldimines with dialkyl phosphite has been developed by
Akiyama and his colleagues [56]. This process afforded optically active α - amino phos-
phonates in good to high yields and enantioselectivities. Based on the observations, they
