Chemistry Reference
In-Depth Information
TABLE 8B.59. Cross - Coupling of Cinnamyl Substrates with Organozinc Reagents
R
1
R
2
Zn
+
Ar
X
R
1
Ar
CuX/
L
Solvent, T
Ar
b
l
Yield
(%)
e e
(%)
Entry
Ar
R
X
CuX
Ligand
Solvent
T ( ° C)
b
:
l
1
P h
neo
-
Pent
Cl
CuBr
SMe
2
L70
THF
−
90
68
95:5
82
2
4 - CF
3
Ph
neo
-
Pent
Cl
CuBr
SMe
2
L70
THF
−
90
72
97:3
87
3
3 - Thienyl
neo
-
Pent
Cl
CuBr
SMe
2
L70
THF
− 90
70
94:6
63
4
P h
neo
-
Pent
Cl
CuBr
SMe
2
L70
THF
25
n.d.
n.d.
25
5
P h
neo
-
Pent
Cl
CuBr
SMe
2
L71
THF
− 30
82
98:2
96
6
Ph
Pent
Cl
CuBr
SMe
2
L71
THF
− 30
88
98:2
65
7
P h
i
- Bu
Cl
CuBr
SMe
2
L71
THF
− 30
86
98:2
72
65
a
8
Ph
Bu
Br
CuBr
SMe
2
(
R
,
R
,
aS
) -
L59
Diglyme
−
40
84:16
71
70
a
9
Ph
Et
Br
CuBr
SMe
2
(
R
,
R
,
aS
) -
L59
Diglyme
−
40
84:16
77
10
Ph
Et
Br
CuOTf
L72
THF
n.d.
93:7
86
−
60
11
Ph
Br
CuOTf
L72
THF
n.d.
97:3
88
i
- Pr
−
60
12
4 - MePh
Et
Br
CuOTf
L73
Diglyme
n.d.
88:12
74
−
30
a
Conv.
n.d., not determined.
In 2001, Ferringa et al. investigated the addition of dialkylzinc in the presence of
phosphoramidite ligands (
R
,
R
,
aS
) -
L59
(Fig. 8B.36) [359]. On screening the reaction
conditions, they were able to optimize the diethylzinc addition in highly polar solvents,
such as diglyme, up to 77% ee. Similar results were obtained with other alkyl reagents
(entries 8 and 9). By switching to CuOTf as another Cu source, the selectivities could
also be increased in THF (entries 10 and 11), especially with the partly hydrogenated
ligand (
L72
) [297]. Zhou et al. reported on their results obtained with the spirophosphor-
amidite
L73
in 2003 [360]. The selectivities obtained with this ligand were comparable
to those with (
R
,
R
,
aS
) -
L59
(entry 12).
While most ligand optimizations were carried out with (substituted) cinnamyl halides,
Woodward et al. investigated substrates derived from Morita-Baylis-Hillman reactions
[361]. First experiments were carried out with binaphthol ligand
L74
(Fig. 8B.38 ), which
gave moderate ees with several aryl-substituted substrates (Table 8B.60, entry 1); the
