Chemistry Reference
In-Depth Information
+
NaCH(CO
2
Me)
2
OBz
BzO
OBz
(M eO
2
C)
2
HC
OBz
[Pd(
-C
3
H
5
)Cl]
2
(2.5 mol %)
(
R
,
R
)-
DPPBA-5
(1 5 mol %)
THF, 0°C, 1 h
π
[Pd]
98% ee (98%)
+
CPh
3
N
Pd
O
O
Bz O
NH
HN
P
P
CH(CO
2
Me)
2
Ph
2
Ph
2
(
R
,
R
)-
DPPBA-5
(
L1e
)
Scheme 8B.9.
Enantioselective alkylation of a
meso
- diester [37] .
As was pointed out above, Trost applied the allylic substitution at
meso
- substrates
extensively in the fi eld of nucleoside and carbanucleoside synthesis [47]. There are two
general strategies that are schematically described in Scheme 8B.10 (X = O or CH2).
Route A involves fi rst Pd-catalyzed asymmetric allylic amination with a nucleobase,
then regioselective Pd-catalyzed alkylation using a pronucleophile that constitutes a
C
1
-
equivalent, that is, an equivalent of a HOH
2
C
−
or ROOC
−
species. In route B, the order
of the steps is reversed.
ROCO
Base
U
A
ROCO
OCOR
HOH
2
C
Base
U
U
B
"HOH
2
C"
OCOR
U
Scheme 8B.10.
General strategies for the synthesis of nucleosides (U = O) and carbanucleosides
(U = CH
2
).
Several interesting
C
1
-equivalents have been devised. One example is illustrated by
a synthesis of adenosine (Scheme 8B.11) [47]. Acetoxy Meldrum's acid was used here
as the
C
1
-equivalent. The degradation of the corresponding substituent of the product
was carried out by lead tetraacetate oxidation at a late stage of the synthesis. Another
C
1
-nucleophile is represented by sodium [(phenyl-sulfonyl)methylen]nitronate (Scheme
8B.12). The primary alkylation product undergoes a subsequent intramolecular
O
-
alkylation to generate another allylic moiety with a leaving group. This approach was
recently used for a synthesis of adenosine [47] and earlier for a synthesis of (
−
) - carbovir
and aristeromycin [48] .
In conjunction with the synthesis of
-lycorane, Chapsal and Ojima used a small
library of chiral, monodentate phosphoramidites as ligands for desymmetrization of
cyclohex - 2 - en - 1,4 - diyl dibenzoate (Scheme 8B.13 ) [49] . Some of the members of the set
γ
