K. S. Kanyiva et al. / Tetrahedron Letters 50 (2009) 3463–3466
3465
Table 3
R3
R4
NR1
R4
Optimization of reaction conditions for C(5)-alkenylation of imidazolesa
N
Ni(cod)2 (3 mol%)
R3
N
NMe
R1
1 + 2
1 + 2
Ligand (12 mol%)
LA (6 mol%)
Pr
Pr
H
R3 R4
LnNi
N+R1
D'
+
2a
N
NMe
N
NMe
Me
3ea
N
N+R1
toluene, 100 oC, 1 h
Al
(1.0 mmol)
H
Me
1e
(3.0 mmol)
LnNi
H
N
R3 R4
R2 = H
LnNi(0)
Al
N
N+R1
R2
B
Al
R2
D
+
R3
R4
R2 = Me, Ph, Si
L = PCyp3
Yield of 3eab (%)
L = P(t-Bu)3
Entry
Ligand
LA
A
1
2
3
4
PCyp3
AlMe3
AlMe3
AlMe3
ZnMe2
59 (55)c
59
12
R3
R4
Al N N+R1
P(i-Pr)3
P(t-Bu)3
PCyp3
Al = AlMe3
R3
LnNi H
NiLn
51
H
N
N+R1
R2
C'
R4
C
Al
a
All the reactions were carried out with 1e (3.0 mmol) and 2a (1.0 mmol) in the
presence of Ni(cod)2 (3 mol %), a ligand (12 mol %), and LA (6 mol %) in toluene
(0.68 mL).
b
Estimated by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard.
Isolated yield after 1.5 h, E/Z = >99:1.
Scheme 1. Plausible mechanism.
c
ent alkenylation reactions allow efficient synthesis of a diverse
range of substituted imidazoles with high atom economy. Current
efforts are directed to develop direct C–H functionalization reac-
tions of other substrates by the cooperative catalysis.
Table 4
Nickel/AlMe3-catalyzed C(5)-alkenylation of 2-substituted imidazolesa
Ni(cod)2 (3 mol%)
PCyp3 (12 mol%)
AlMe3 (6 mol%)
R3 R4
NMe
H
Acknowledgments
R3
R4
+
N
NMe
N
toluene, 100 oC
R1
R1
This work has been supported by Grant-in-Aid for Creative Sci-
entific Research and that for Priority Area ‘Chemistry of Concerto
Catalysis’ from MEXT. K.S.K. acknowledges Honjo International
Scholarship Foundation for financial support.
3
1
2
(3.0 mmol) (1.0 mmol)
R1 = Ph (1f)
SiMe2t-Bu (1g)
R3, R4 = Me, i-Pr (2f)
Me, t-Bu (2g)
Supplementary data
Entry
1
1
2
Time (h)
Major product
Yieldb (%)
E/Zc
Pr
Pr
Supplementary data associated (detailed experimental proce-
dures including spectroscopic and analytical data) with this Letter
1f
2a
2
81 (3fa)
>95:5
N
N
NMe
Ph
Pr
Pr
References and notes
2
1g
1e
1e
1e
2a
2e
2f
1
42 (3ga)
63 (3ee)
75 (3ef)
71 (3eg)
96:4
NMe
SiMe2t-Bu
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Hex
SiMe3
3d
31
4
>95:5
>95:5
>95:5
N
N
N
NMe
Me
Me
i-Pr
4
NMe
Me
Me
t-Bu
5
2g
4
NMe
Me
a
Unless otherwise stated, all the reactions were carried out with 1 (3.0 mmol)
and 2 (1.0 mmol) in the presence of Ni(cod)2 (3 mol %), PCyp3 (12 mol %), and AlMe3
(6 mol %) in toluene (0.68 mL).
b
Isolated yields of isomerically pure products based on 2 as the limiting reagent.
c
Estimated by 1H NMR analysis of a crude product.
d
Ni(cod)2 (10 mol %), PCyp3 (40 mol %), and AlMe3 (20 mol %) were used.
In conclusion, we have demonstrated regio- and stereoselective
alkenylation of imidazoles by nickel/LA binary catalysis. The pres-