Chemistry Reference
In-Depth Information
EtO
OEt
P
O
O
R
s
R
s
L
n
Zn
O
R
H
H
O
N
R
l
OPO(OEt)
2
R
l
N
NH
n
-Bu
R
H
N
O
C
u
N
O
NH
n
-Bu
H
O
C
u
O
alkyl
H
AlkylZn
alkyl
AlkylZn
A
B
Scheme 8B.100.
Proposed mechanism for the copper-catalyzed allylic alkylation with peptide
ligands.
TABLE 8B.62. Desymmetrization of
meso
- Substrates
R
2
Zn
(EtO)
2
OPO
OPO(OEt)
2
OPO(OEt)
2
n
n
CuOTf/
L
,
Toluene, THF, T
R
Entry
n
R
Ligand
T ( ° C)
Yield (%)
ee (%)
Confi g.
1
1
M e
L79
− 78
40
94
(
S
,
S
)
2
1
E t
L79
− 78
88
88
(
S
,
S
)
3
1
P h
L79
− 78
60
68
(
S
,
R
)
4
1
Me
(
R,R,aS
) -
L59
0
54
87
(
R
,
R
)
5
1
Et
(
R,R,aS
) -
L59
− 40
98
87
(
R
,
R
)
6
2
Et
(
R,R,aS
) -
L59
−
40
77
90
(
R
,
R
)
7
3
Et
(
R,R,aS
) -
L59
−
40
85
98
(
R
,
R
)
By combining the sulfonamide subunit with salicylaldimines such as in
L79
, they
found an excellent ligand for regioselective (γ / α 99:1) desymmetrizations of cyclic
meso
-
compounds [366]. Best results were obtained from the cyclopentenyl substrate (
n
= 0)
with Me
2
Zn (94% ee), while the corresponding ethyl and phenyl reagents showed a
lower selectivity (Table 8B.62, entries 1-3). Reaction of Et
2
Zn with the corresponding
cyclohexenyl substrate (
n
= 1) gave S
N
2 ′ products from either inversion or retention,
depending on the solvent and ligand used. The problem with the larger ring substrates
could be solved by using Feringa's phosphoramidite ligand (
S
,
S
,
aR
) -
L59
(Fig. 8B.36 )
[367]. The enantiomer of this ligand (
R,R,aS
) -
L59
gave excellent enantiomeric excess
with various ring sizes and dialkylzinc reagents (entries 4-7). Interestingly, herewith also
the cyclohexenyl substrate gave a mixture of the inversion and the retention product,
while with the fi ve- and six-membered ring, only inversion was observed.
In parallel to these peptide-based ligands, Hoveyda et al. developed bidentate diami-
nocarbene-based ligands (NHC) such as
L80
(Fig. 8B.42) as effi cient chiral promoters
for acyclic alkylations [368]. This ligand was found to be superior to the peptide-based
ligand. The catalyst loading could be reduced to 2 mol % and the catalyst was suitable
also for the generation of quaternary stereogenic centers. Best results were obtained by
