Chemistry Reference
In-Depth Information
t
BuO
2
C
O
t
BuO
2
C
O
R = CO
2
t
Bu
R = H
R
R
base
O
LDA (28%)
BTMG
(2
) (96%)
O
BTMG (
2
) (76%)
DCM
O
O
O
O
β
-R /
α
-R = 4 : 6
β
-R /
α
-R = 5.9 : 1
Me
Me
Me
Me
R = H:
E
-form
R = CO
2
t
Bu:
E / Z
mixture
Scheme 4.17
BTMG (2) catalysed intramolecular Michael addition
this, nitroalkanes have been often used as nucleophiles in TMG (1) catalysed Michael
reactions [46].
Of course, BTMG (2) [47] and TBD (3) [48] similarly work in Michael addition as
powerful catalysts. In the synthesis of lactonamycinwith a hexacyclic ring system, the BCD
tricyclic ring system was effectively constructed by BTMG catalysed intramolecular
Michael addition [49] (Scheme 4.17) (see Scheme 7.6).
AC
2
-symmetrical pentacyclic guanidinium salt like 16 (Figure 4.5) was used for the
conjugate addition of pyrrolidine to
-crotonolactone, in which structural requirement such
as the size of the cavities and substituents on tetrahydropyran rings of the guanidine
catalysts is critical for asymmetric induction [23].
Asymmetric nitro-Michael reactions of methyl vinyl ketone (MVK) in the presence of
bicyclic guanidine with a benzhydryl group led, disappointedly, to low asymmetric
induction (9-12%) [21a] Trials for the reaction of
g
-lactones with
pyrrolidine in the presence of the conjugate acids of a bicyclic guanidine [50] or the
Murphy
a
,
b
-unsaturated
g
-or
d
¼
Me in Scheme 4.7) resulted in the production of racemic
compounds. The latter phase transfer catalyst (PTC) catalyses the nitro-Michael addition of
chalcone but with limited range (70% yield, 23% ee) [24c].
Ma et al. examined guanidine catalysed Michael reaction of tert-butyl glycinate Schiff
base with ethyl acrylate in THF and observed 30% ee as the asymmetric induction when an
acyclic guanidine (2) was used as a catalyst [10b]. Ishikawa et al. succeeded in greatly
improving the asymmetric induction by the use of guanidine 17a, originally prepared based
s guanidine [24a] (R
MeO
OMe
H
H
N
N
+
N
O
O
H
H
Cl
-
16
H
Me
Me
H
Figure 4.5
The structure of a pentacyclic guanidinium salt 16
