Chemistry Reference
In-Depth Information
OH
O
LLA
3
(10 mol %)
SnBu
3
R
R
H
CH
2
Cl
2
, 0°C
7 examples
70-96% yield
95-99% ee
R
R
H
i-Pr
H
O
δ
−
O
O
*L
L*
*L
Ti
Ti
L*
Ti
Ti
i-PrO
i-PrO
O
δ
+
O
Oi-Pr
LLA mechanism
Dual activation mechanism
Scheme 3.15.
Bn
Bn
R
N
LLA
3
(10 mol %)
CH
2
Cl
2
, -40°C
CHO
NaBH
4
EtOH
N
O
O
HO
R
8 examples
62-94% yield
70-97% ee
Scheme 3.16.
[29]. Considering the other possible side reactions, such as 1,2- and 1,4-addition of dia-
zoacetate to α-substituted acroleins, in addition to the cyclopropanation, the yield of
1,3-dipolar cycloaddition products is quite remarkable. This methodology was success-
fully applied to the short synthesis of manzacidin A in fi ve steps, starting from methac-
rolein and ethyl diazoacetate (Scheme 3.17).
Related to the concept of Lewis acid-assisted chiral Lewis acid, the development of
chiral heterometallic catalysts has been studied extensively by the Shibasaki group (Fig.
3.3 ) [30] .
In 2003, they demonstrated the utility of heterobimetallic (HBM) catalysts in an
enantioselective 1,4 - addition of
O
- methoxyamine to enones [31] . They proposed that
two Lewis acidic centers in HBM complex work cooperatively to control the orientations
of both the electrophile and the nucleophile, leading to the highly organized transition
state to provide high enantioselectivity (Fig. 3.4). In a subsequent study, they broadened
the substrate scope to carboxylic acid derivatives [32]. The resulting 1,4-adducts
were successfully transformed into chiral aziridines and β - amino acids, respectively
(Scheme 3.18 ).
The utility of heterometallic catalysts was extended to an enantioselective cyanoe-
thoxycarbonylation of aldehydes with ethyl cyanoformate [33]. Interestingly, it was
found that the addition of three achiral additives was crucial to get high reactivity and
