Chemistry Reference
In-Depth Information
TABLE 4.2. Synthetic Studies toward (
−
) - Astrogorgiadiol
O
O
O
CO
2
Me
Rh(II)-cat.
CO
2
Me
CO
2
Me
N
2
H
H
CH
2
Cl
2
, 20°C
Me
Me
Me
12
13
14
HO
HO
Me
CO
2
Me
H
Me
H
15
Me
(-)-astrogorgiadiol
d . r .
Catalyst
13:14
Yield (%)
26:74
98
Rh
2
(
S
- PTPA)
4
43:57
66
Rh
2
(5
S
- MEPY)
4
36:64
94
Rh
2
(
S
- DOSP)
4
Rh
2
(
S
- biTISP)
2
21:79
38
- ketoester
12
(Table 4.2 ) [156] . The goal was to optimize the
diastereoselectivity of the reaction by screening various catalysts. The optimal selectivity
for
14
was achieved with Rh
2
(
S
- biTISP)
2
, which gave 58% de but with a moderate
yield of 38%. Rh
2
(
S
- PTPA)
4
gave an excellent 98% yield but somewhat lower
diastereoselectivity.
The dirhodium(II)
ortho
- metallated arylphosphines (
7
), developed by Lahuerta,
Perez-Prieto, and coworkers, have been shown to be effective catalysts for the intramo-
lecular C-H insertions of certain diazoketones [102,134,137,138]. Carbenoids derived
from diazoketones are well known for their high reactivity, and, consequently, the
development of enantioselective processes for these reagents has been problematic
[63,128,145,157] . Signifi cant progress has been made with the introduction of the
ortho
-
metallated arylphosphine dirhodium(II) complexes. Wide variations in yield and enan-
tioselectivities were observed with a diversely functionalized set of arylphosphine
ligands, but none of the catalysts appeared to display universal effectiveness [134]. Fur-
thermore, the reactions were sensitive to the functional groups at the insertion site [134].
The best example is shown in Scheme 4.3, where the chloro-substituted system afforded
the cyclopentanone
17
in 74% ee and 87% yield with catalyst
7c
. In general, this system
worked best with electron-withdrawing groups on the aryl portion, suggesting that the
electron-withdrawing substituent deactivates the benzylic C-H bond to achieve a late
transition state for the insertion and hence, increased selectivity [134].
insertion of
α
- diazo -
β
