Chemistry Reference
In-Depth Information
N
2
O
H
O
O
42
O
Rh
2
(4
S
-MEOX)
4
41
98% ee
O
O
O
N
2
H
O
44
43
90% ee
Scheme 4.10.
Desymmetrization of adamantanoyl diazoacetates.
O
O
O
O
O
O
Rh
2
(5
S
-MEPY)
4
Me
Me
N
2
CH
2
Cl
2
, 40°C
Me
(
±
)-45
46
47
37% yield
98% ee
34% yield
91% ee
Scheme 4.11.
Reaction of unsymmetrical diazoacetate
45
.
Enantioselective γ-lactone formation via intramolecular C-H insertion of diazoace-
tates has been demonstrated to be a powerful technology in the synthesis of natural
products and pharmaceutical targets (Scheme 4.12), such as (+)-isodeoxypodophyllo-
toxin (
50
) [162,164] , ( − ) - enterolactone (
52
), (
S
) - (+) - imperanene [165] (
54
), and (
R
) - ( − ) -
baclofen [167] (
56
), which have been synthesized with the lactone formation as a key
step catalyzed by Rh
2
(4
S/R
- MPPIM)
4
from the appropriate diazoacetate precursors.
Very high enantioselectivities have been obtained in many applications of this
chemistry.
The intramolecular cyclization with cyclohexyl aryldiazoacetate system
57
(Table 4.6 )
preferably formed the β - lactone system
58
when the azetidinone-based dirhodium(II)
carboxamidate catalysts were used [119]. The same was also observed with carboxylate
catalysts [120]. This is opposite to what was observed with unsubstituted diazoacetate
systems, in which the γ-lactone products were formed exclusively. Chemoselectivities
were high (>97% product selectivity), and the products were formed in 66-69% yield.
However, good control of enantioinduction was not achieved, only 42-51% ee with the
carboxamidate catalysts tested, and 63% ee with Rh
2
(
S
- DOSP)
4
[119,168] . The acyclic
system
60
only formed γ - lactone product
61
(Table 4.7). This reaction was effectively
catalyzed by both Rh
2
(
S
- MEAZ)
4
and Rh
2
(
S
- DOSP)
4
, although the former gave slightly
higher yield and enantiomeric excess (94% yield, 90% ee) [118,119].
