Chemistry Reference
In-Depth Information
lactam as the minor product when the reaction is catalyzed by Rh
2
(4
S
- MEOX)
4
. Only
moderate enantiomeric induction is observed for both products in these cases (65-80%
ee) [188]. If R is an alkoxy group, the adjacent C-H bond is signifi cantly more activated
for C-H insertion, and
- lactam product
67
is observed exclusively in excellent yield
(97%) and moderate enantiomeric excess (78% ee). When using an electron-withdraw-
ing ester group as R,
γ
-lactam formation is heavily suppressed due to the deactivating
infl uence of this group on the adjacent site. Rh
2
(4
S
- MEOX)
4
gives preferably the achiral
product
69
derived from insertion into the
tert
-butyl group on the nitrogen. The major
chiral product
68
was formed with 46% ee. The pyrrolidine-based catalyst Rh
2
(5
S
-
MEPY)
4
gave even more selectivity for the achiral product
69
(89% selectivity). Inter-
estingly, the selectivity could be tuned toward the
γ
- lactam product
68
with the use of
Rh
2
(4
S
- BNOX)
4
, which gave 88% product selectivity. The degree of enantiocontrol
was, however, poor for both products
67
and
68
in this case (16 and 20% ee, respec-
tively). This shows that the infl uence of the catalyst can be crucial in this chemistry, and
these examples also highlight how subtle changes in catalyst structure can greatly infl u-
ence the carbenoid intermediate structure [188]. For the more complicated system
70
(Scheme 4.14), mixtures of
β
-lactams as well as intramolecular cyclopropanation
of the phenyl ring were observed [166]. The best selectivity was obtained with Rh
2
(5
S
-
MEPY)
4
, which afforded
β
- and
γ
- lactam product
71
in 71% yield and with a moderate 85%
ee. Also, a 4% yield of the intramolecular cyclopropanation product was observed in
this case [166] .
γ
Ph
O
Ph
O
O
Rh
2
(5
S
-MEPY)
4
CH
2
Cl
2
, 40°C
71% yield
85% ee
O
N
2
O
O
N
N
Ph
Ph
7
7
Scheme 4.14.
Intramolecular C -H insertion of system
70
.
In contrast to the moderate enantioselectivities observed for acyclic diazoacetamides,
excellent enantiocontrol can be obtained for cyclic systems (Table 4.9) [189]. For azacy-
cloheptane
72
(
n
= 1), the formation of β - lactam
73
was greatly favored (99% selectivity)
in 67% yield and with remarkable enantiomeric excess (97% ee) when catalyzed by
Rh
2
(5
S
- MEPY)
4
. Rh
2
(4
S
- MEOX)
4
gave similar results but somewhat lower levels of
enantioinduction (92% ee) [189]. The best catalyst for the azacyclooctane system
72
(
n
= 2) was Rh
2
(4
S
- MEOX)
4
, but the γ - lactam product
74
was major in this case with
98% ee. It seems that the conformational restriction imposed by smaller rings prevents
the formation of γ-lactams; however, the eight-membered ring is large enough to accom-
modate this transition state as well as β-lactam formation. If the reaction is conducted
in refl uxing dichloroethane, an almost complete loss of regioselectivity can be observed
[189]. In the cyclization of enantiopure diazoacetopyrrolidine
75
(Scheme 4.15 ), remark-
able double stereodifferentiation was obtained to produce heterobicyclic system
76
in
86% yield and 96% de [143]. This intermediate was used in a facile synthesis of the
pyrrolizidine base (− ) - heliotridane (
77
) [143] .
Carbenoids derived from α - methoxycarbonyl - α - diazoacetamides
78
(Table 4.10 ) can
effectively form the corresponding β - lactam
80
when R is a
tert
- butyl group with Rh
2
(
S
-
