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R
L
O
R
L
O
N
N
N
NHBu
N
NHBu
O
R
N
O
Ph
OH
L77a
R
L
= CH
2
c
-Hex, R =
n
-Bu
b
R
L
= CH
2
CO
2
t
-Bu, R = CH
2
i
-Pr
O
i
-Pr
L76a
R
L
=
c
-Hex
b
R
L
=
t
-Bu
Figure 8B.39.
Peptide-based ligands used in allylic alkylations.
TABLE 8B.61. Reaction of Allyl Phosphates in the Presence of Peptide-Based Ligands
R
1
R
2
Zn
R
OPO(OEt)
2
γ
Cu-Cat./
L
THF, T
R
Entry
R
R
1
Ligand
R
L
CuX
T ( ° C)
Yield (%)
ee (%)
1
P h
E t
L76a
c -
Hex
CuCN
−
78
34
66
2
4 - NO
2
Ph
Et
L76a
c -
Hex
CuCN
−
78
73
75
3
2 - NO
2
Ph
Et
L76b
t
- Bu
CuCN
−
78
85
87
4
M e
L77a
Cu(OTf)
2
80
90
CO
2
t
- Bu
- CH
2
c -
Hex
−
50
5
E t
L77a
Cu(OTf)
2
68
97
CO
2
t
- Bu
- CH
2
c -
Hex
−
50
6
AcO(CH
2
)
4
L77a
Cu(OTf)
2
85
95
CO
2
t
- Bu
- CH
2
c -
Hex
−
50
7
P h
E t
L77b
Cu(OTf)
2
61
95
CH
2
CO
2
t
- Bu
−
15
8
2 - NO
2
Ph
Et
L77b
CH
2
CO
2
t
- Bu
Cu(OTf)
2
−
15
95
95
9
4 - CF
3
Ph
AcO(CH
2
)
4
L77b
CH
2
CO
2
t
- Bu
Cu(OTf)
2
−
15
62
84
10
Ph
Et
L78
—
Cu(OTf)
2
−
78
93
40
of allyl phosphates with several dialkylzinc species (Table 8B.61). These ligands were
found by an intense combinatorial ligand screening and gave good results with (substi-
tuted) cinnamyl phosphates.
As reported previously by Dubner and Knochel [357], electron-withdrawing groups
at the aromatic ring increased the yield and enantiomeric excess, while the ligand with
the sterically demanding
t
-butyl side chain gave the best results (Table 8B.61, entries
1-3). Fortunately, this protocol is not limited to simple cinnamyl substrates and Et
2
Zn
additions, but can also be applied to other zinc reagents and higher substituted allyl
phosphates. This allows the stereoselective synthesis of quaternary stereogenic centers,
as nicely illustrated in the total synthesis of sporochnol (Scheme 8B.99).
By replacing the pyridine ring by a phenol or a naphthol ring system, the substrate
spectrum could be enlarged also to α , β - unsaturated esters [363] . Especially good regi-
oselectivities were obtained with
t
- butyl esters ( γ / α > 20:1) and the enantiomeric excesses
were always ≤90% (entries 4-6). In principle, this ligand type could also be applied to
cinnamyl substrates if a
t
-butyl glutamate is incorporated into the ligand (
L77b
) [364] .
