C.-J. Li, K. Itami et al.
[3] For reviews on the reactions of C H bonds, see: a) V. Ritleng, C.
e) L. C. Campeau, D. R. Stuart, K. Fagnou, Aldrichimica Acta 2007,
are described. Under the influence of tBuOOtBu, pyridine
N-oxide derivatives react with alkanes to furnish the corre-
sponding cross-coupling products (alkylated nitrogen hetero-
cycles) in good yields. We believe that the present oxidative
À
cross-coupling reactions at two different C H bonds not
only contributes to the realization of “greener” synthesis,
but also unlocks opportunities for markedly different strat-
egies in chemical synthesis. Moreover, in view of the current
strict guidelines limiting transition-metal levels in pharma-
[4] For selected recent examples, see: a) L. Ackermann, A. Althammer,
121, 6616; c) F. Kakiuchi, S. Kan, K. Igi, N. Chatani, S. Murai, J.
donck, A. H. M. de Vries, P. C. J. Kamer, J. G. de Vries, P. W. N. M.
Liang, J. G. Lei, J. J. Li, D. H. Wang, X. Chen, I. C. Naggar, C. Guo,
128, 12634; s) R. Giri, N. Maugel, J. J. Li, D. H. Wang, S. P. Breazza-
ceuticals,[16] the realization of C C bond-forming reactions
À
without using a transition metal is noteworthy. The elucida-
tions of reaction mechanism and full scope of present meth-
odology are the focus of ongoing research efforts.
Experimental Section
A representative experimental procedure (4a and 5a): A reaction vessel
was charged with pyridine N-oxide (1a, 47.5 mg, 0.5 mmol), tert-butyl
peroxide (3a, 146 mg, 1.0 mmol) and cyclohexane (2a, 1.0 mL,
9.2 mmol). Then the reaction vessel was sealed and the resulting solution
was stirred at 1358C for 15 h. After cooling to room temperature, the re-
sulting mixture was removed in vacuo and the residue was purified by
column chromatography (SiO2, hexane/ethyl acetate 6:1) to give 4a
(75 mg, 58%) and 5a (21 mg, 12%) as pale yellow oils.
Data for 4a: 1H NMR (400 MHz, CDCl3): d=7.16–7.12 (m, 1H), 7.03–
7.02 (m, 2H), 3.55–3.47 (m, 2H), 2.04–2.00 (m, 4H), 1.83–1.73 (m, 6H),
1.53–1.41ACHTUNGTRENNUNG
(m, 4H), 1.29–1.17 ppm (m, 6H); 13C NMR (100 MHz, CDCl3):
d=156.7, 125.4, 120.2, 38.1, 31.2, 26.7, 26.6 ppm; IR (liquid film): n˜ =
3076, 2912, 2846, 1520, 1442, 1389, 1230, 835, 749 cmÀ1; MS (EI): m/z
(%): 259, 242 (100), 214, 188, 175, 158, 144, 119, 91, 77; HRMS calcd for
C17H25NO: 259.1936; found: 259.1933.
Data for 5a: 1H NMR (400 MHz, CDCl3): d=6.85 (s, 2H), 3.56–3.48 (m,
2H), 2.45–2.41 (m, 1H), 2.05–2.01 (m, 4H), 1.84–1.72 (m, 11H), 1.58–
1.42 (m, 4H), 1.32–1.18 ppm (m, 11H); 13C NMR (100 MHz, CDCl3): d=
155.9, 146.1, 118.4, 43.8, 38.2, 33.9, 31.4, 26.8, 26.6, 26.1 ppm; IR (liquid
film): n˜ =2925, 2846, 1553, 1454, 1415, 1270, 1237, 845 cmÀ1; MS (EI):
m/z (%): 341, 324 (100), 296, 270, 257, 214; HRMS calcd for C23H35NO:
341.2719; found: 341.2716.
C.-J. Li, Green Chem. 2007, 9, 1047; j) Z. Li, D. S. Bohle, C.-J. Li,
The experiments in Tables 2 and 3 were carried out analogously. All
products were purified by column chromatography and characterized by
NMR spectroscopy and standard/high-resolution mass spectrometry.
129, 12072; f) T. Dohi, M. Ito, K. Morimoto, M. Iwata, Y. Kita,
1301; g) T. A. Dwight, N. R. Rue, D. Charyk, R. Josselyn, B.
11904; j) J.-B. Xia, S.-L. You; Organometallics 2007, 26, 4869; k) G.
Cai, Y. Fu, Y. Li, X. Wan, Z.-J. Shi, J. Am. Chem. Soc., 2007, 129,
7666.
Acknowledgements
We are grateful to PRESTO program of Japan Science and Technology
Agency (to K.I.), a Grant-in-Aid for Scientific Research from MEXT,
Japan (to K.I.), Canada Research Chair (Tier I) foundation (to C.J.L.),
the NSF-EPA joint program for a Sustainable Environment (to C.J.L.),
and NSERC (to C.J.L.) for support of our research. S.Y. is a recipient of
the JSPS Predoctoral Fellowships for Young Scientists.
À
À
Keywords: alkanes · C C coupling · C H activation ·
nitrogen heterocycles
[1] P. T. Anastas, J. C. Warner, Green Chemistry: Theory and Practice,
Oxford University Press, New York, 1998.
[2] S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M.
336
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 333 – 337