8248
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2. Voldarsky, L. B.; Reznikov, V. A.; Ovcharenko, V. I.
Synthetic Chemistry of Stable Nitroxides; CRC: Boca
Raton, 1994; p 221.
3. Sviridenko, F. B.; Stass, D. V.; Kobzeva, T. V.; Tretya-
kov, E. V.; Klyatskaya, S. V.; Mshvidobadze, E. V.;
Vasilevsky, S. F.; Molin, Yu. N. J. Am. Chem. Soc. 2004,
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4. (a) Vasilevsky, S. F.; Klyatskaya, S. V.; Korovnikova, O.
L.; Stass, D. V.; Amitina, S. A.; Grigor’ev, I. A.; Elguero,
J. Tetrahedron Lett. 2004, 45, 7741; (b) Vasilevsky, V. F.;
Klyatskaya, S. V.; Korovnikova, O. L.; Stass, D. V.;
Since Cu-free Pd catalysis led to the oxidative homocou-
pling, we investigated the viability of Pd-free Cu-cata-
lyzed version of cross-coupling13 in the next step. We
also utilized the ca. 800-fold greater reactivity of aryl iod-
ides relative to the respective bromides in cross-couplings
with alkynes.14,15 Gratifyingly, we found that the target
acetylenic nitroxyl radicals 11a–c are indeed formed in
70–75% yields in the reactions of hydroxylamine 9 with
terminal aryl- and hetarylacetylenes 10a–c mediated by
the catalytic system CuI–PPh3–K2CO3–DMF.16,17
O
O
N
N
K2CO3, CuI
+
H
R
Ar
R
N
N
10 a-c
O
I
OH
11 a-c
9
H2N
CH3
O
CH3
R:
N
c
a
b
Amitina, S. A.; Grigor’ev, I. A.; Elguero, J. Tetrahedron
2005, 62, 4591.
5. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 50, 4467.
6. (a) Tour, J. M. Chem. Rev. 1996, 96, 537; (b) Martin, R.
E.; Diederich, F. Angew. Chem., Int. Ed. 1999, 38, 1350.
7. Batsanov, A. S.; Collings, J. C.; Fairlamb, I. J. S.;
Holland, J. P.; Howard, J. A. K.; Lin, Z.; Marder, T. B.;
Parsons, A. C.; Ward, R. M.; Zhu, J. J. Org. Chem. 2005,
70, 703.
It is noteworthy that, under these conditions, the dia-
magnetic iodide can be used as a starting material, thus
eliminating the need for the additional step of prepara-
tion of the spin-labeled product. Although the mecha-
nism for the transformation of diamagnetic compound
to the paramagnetic product is so far unknown, it has
been observed that the diamagnetic derivatives are
slowly oxidized to their respective radicals even in the
solid state when stored at room temperature.
8. A recent example: Yin, W.; Srirama Sarma, P. V. V.; Ma,
J.; Han, D.; Chen, J. L.; Cook, J. M. Tetrahedron Lett.
2005, 46, 6363.
In summary, we developed a catalytic Pd-free synthetic
approach to the family of nitroxyls with 3-imidazoline
core and alkyne substituents including aryl and hetaryl
moieties as well as functional groups of both donor
and acceptor character. This approach is likely to be
useful when classic Sonogashira-type cross-coupling
fails due to reoxidation of the catalytic Pd(0) species
by the substrate.
9. (a) Rossi, R.; Carpita, A.; Bigelli, C. Tetrahedron Lett.
1985, 26, 523; (b) Chen, C.; Ai, Z.; Lin, J.; Hong, X.;
Xi, C. Synlett 2006, 2454; (c) Lei, A.; Srivastava, M.;
Zhang, X. J. Org. Chem. 2002, 67, 1969; (d) Liu, Q.;
Burton, D. J. Tetrahedron Lett. 1997, 38, 4371; (e) Li, J.-
H.; Liang, Y.; Zhang, X.-D. Tetrahedron 2005, 61, 1903;
(f) Nguyen, P.; Yuan, Z.; Agocs, L.; Lesley, G.; Marder,
T. B. Inorg. Chim. Acta 1994, 220, 289; Takahashi, A.;
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383.
Acknowledgements
10. (a) Klyatskaya, S. V.; Tretyakov, E. V.; Vasilevsky, S. F.
Russ. Chem. Bull., Int. Ed. 2002, 51, 128; (b) Stroh, C.;
The authors are grateful to Dr. D. V. Stass for measur-
ing the EPR spectra and Dr. S. A. Amitina for a sample
of 1-hydroxy-4-[2-(p-bromophenyl)vinyl]-2,2,5,5-tetra-
methyl-3-imidazoline-3-oxide. This work was supported
by a grant of the Ministry of Education and Science of
Russian Federation No. 2.1.1.4935 (2006–2007), grant
‘Integration’ of SB of the Russian Academy of Sciences
No. 54 (2006–2008) and CRDF RUXO 008-NO-06. Re-
search at Florida State University was sponsored by the
National Science Foundation (CHE-0316598) and
Material Research and Technology (MARTECH)
Center.
Mayor, M.; von Hanish, C. Tetrahedron Lett. 2004, 45,
¨
9623.
11. Method: (i) An example: Solution of phenyl acetylene
(0.05 g, 0.05 ml, 0.47 mmol) in 1 mol of benzene was
added to a mixture of 7 (0.11 g, 0.39 mmol), Et3N (3 ml),
and Pd(PPh3)2Cl2 (0.02 g) in 7 ml of benzene under inert
atmosphere. The mixture is stirred under reflux for 4 h
until the disappearance of phenyl acetylene (TLC control).
After the reaction mixture is filtered through a small pad
of Al2O3, the solvent is removed under reduced pressure.
Crude residue is purified with chromatography on Al2O3
using hexane, benzene, and ethyl acetate as eluents to yield
0.10 g of hydroxylamine 8 (91%), mp 85–86 ꢁC (mplit 85–
87 ꢁC, Volodarskii, L. B.; Grigor’ev, I. A.; Grigor’eva, L.
N.; Kirilyuk, I. A.; Amitina, S. A. Zh. Org. Chem., 1985,
21, 443) and 0.037 g (74%) of dyne 4, mp 85–87 ꢁC (mplit
87–88 ꢁC, Campbell, I. D.; Eglington G. Org. Synth. Coll.
1973, 5, 517). Method: (ii) An example: Solution of phenyl
acetylene (0.03 g, 0.03 ml, 0.28 mmol) in 1 mol of aceto-
nitrile was added to a mixture of 7 (0.16 g, 0.57 mmol),
References and notes
1. Imidazoline Nitroxides; Volodarsky, L. B. Ed., CRC: Boca
Raton, Florida, Synthesis and Properties, 1988; Vol. I, 222
pp and Applications, Vol. II, 160 pp.