Transcript Aminides 01 - heterobetainas.uah.es

Synthesis of Substituted Pyridinium N-Aminides
by Sonogashira Reactions
Córdoba López, Marta; Izquierdo Ceinos, Mª Luisa; Alvarez-Builla, Julio*.
Departamento de Química Orgánica, Universidad de Alcalá, 28871- Alcalá de Henares, Madrid, Spain.
E-mail address: [email protected]
Introduction
Palladium-catalyzed cross-coupling Sonogashira reaction is one of the most important methods for the formation of C-C bonds.1 Particularly, alkynes are useful
building blocks in organic synthesis and a representative functional group in many natural and bioactive compounds. In the last year, our program has been related with the
synthetic utility of N-(azin-2’-yl)pyridinium aminides 1, as building blocks in the synthesis of azine derivatives, using Sonogashira reaction (Scheme 1).
Halogenation of pyridinium N-(pyridin-2’-yl)aminide 1 can be regioselectively achieved in the 5’-position of the pyridine with N-halosuccinimide in equimolar amount.2
The synthesis of substituted N-aminides 3 has been performed by treatment the N-(5’-iodopyridin-2’-yl)pyridinium aminide 2 with the corresponding acetylene in the
presence of 1,4-diazabiciclo[2.2.2]octane (DABCO) and a palladium salt (Scheme 1).3 Additionally, a new environmentally friendly methodology has been developed carrying
out the reaction under microwave irradiation.4
Sonogashira reaction have been performed in three different conditions; one using conventional heating and two using microwaves. Modifications in the solvent from
acetonitrile to water do not improve the final result because the formation of compound 3 was detected in some cases.
A) Pd(OAc)2, DABCO, 
+N
N
+N
1.1 eq. NIS
N
N
-
R
N
CH3CN
2
R
3
+N
N
R
Scheme 1
N
B) Pd2(PPh3)2, DABCO
Mw 10min, 60ºC
I
1
+N
N
H2O
C) Pd2(PPh3)2, DABCO
3
Mw 15min, 70ºC
N
+
R
Compound
R
Method
Yield (%)
Compound
Method
R
Yield (%)
R
3a
3b
(Me)3-Si
(i Pr)3-Si
B
C
46
A
B
C
48
22
A
B
C
3g
CF3
3c
S
A
B
C
CF3
3d
3e
Me
3f
MeO
A
B
C
A
B
C
27
75
43
45
69
65
25
68
61
25
47
57
Compound
3i
21
15
40
18
4b
3
A
B
21
57
4c
7
S
NH2
Me
Yield (%)
A
B
C
CF3
3j
R
4a
3h
A
B
C
30
60
39
4
Me
A
B
C
N
27
10
4d
CF3
Me
O
3k
H
A
B
C
9
22
43
10
CF3
5
4e
CF3
Method A: Aminide 2 (1mmol), alkyne (2 mmol), Pd(OAc)2 (5mmol %) and DABCO (6 mmol) in acetonitrile as solvent at 40ºC for
24 h. Method B: Aminide 2 (1mmol), alkyne (2 mmol), DABCO (6 mmol), PdCl2(PPh3)2 (5mmol %) in acetonitrile as solvent at
60ºC for 10 minutes using MW. Method C: Aminide 2 (1mmol), alkyne (2 mmol), DABCO (6 mmol), PdCl2(PPh3)2 (5mmol %) in
water as solvent at 70ºC for 15 minutes using MW.
Method C: Aminide 2 (1mmol), alkyne (2 mmol), DABCO (6
mmol), PdCl2(PPh3)2 (5mmol %) in water as solvent at 70ºC for 15
minutes using MW.
Conclusion
In this communication we report the synthesis of a series of N-(5’-alkynylpiridin-2’-yl) pyridinium aminides, through a copper- and fosfine-free method, based on a
catalytic system Pd(II)/DABCO, and using either conventional heating or microwaves.4
The use of another solvent non-toxic and non-flammable like water in presence of DABCO and Pd2(PPh3)2 in microwaves generates the Sonogashira coupling products,
together with unexpected side products as a result of addition over the alkyne.
Acknowledgment
Financial support by the CTQ2008-05027/BQU (2008-2011) and a grant, by Universidad de Alcalá (Spain) (M.C.) are gratefully acknowledged.
References
1. Yin, L.; Liebscher, J. Chem. Rev. 2007, 107, 133-173.
2. Burgos, C.; Delgado, F.; García-Navío, J. L.; Izquierdo, M. L.; Álvarez-Builla, J. Tetrahedron 1995, 31, 8649-8654.
3. Li, J.H.; Liang, Y.; Xie, Y.X. J. Org.Chem. 2005, 70, 4393-4396..
4. Kappe, O.C. Angew. Chem. Ed. 2004, 43, 6250-6284.