ORGANIC
LETTERS
2011
Vol. 13, No. 23
6272–6275
Iron-Catalyzed Oxidation of Tertiary
Amines: Synthesis of β-1,3-Dicarbonyl
Aldehydes by Three-Component CÀC
Couplings
Weiping Liu,† Jinhua Liu,† Daisuke Ogawa,‡ Yasushi Nishihara,‡ Xingwei Guo,† and
Zhiping Li*,†
Department of Chemistry, Renmin University of China, Beijing 100872, China, and
Division of Chemistry and Biochemistry, Graduate School of Natural Science and
Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530,
Japan
Received October 13, 2011
ABSTRACT
β-1,3-Dicarbonyl aldehydes were synthesized by iron-catalyzed oxidative reactions between 1,3-dicarbonyl compounds and two molecules of
tertiary amines in the presence of tert-butyl hydroperoxide (TBHP). R,β-Unsaturated aldehydes generated by tertiary amine oxidation in situ act as
key intermediates under mild reaction conditions.
Catalytic dehydrogenative oxidation of a CÀH bond
presentsone ofthe mostimportantand useful strategiesfor
achieving a variety of CÀH functionalizations.1,2 The
oxidation of tertiary amines has attracted much interest
fromthe viewpointsof both biochemistryand chemistry.3,4
Imines or iminium ions, selectively generated by oxidation
of the CÀH bond adjacent to a nitrogen atom, are key
intermediates toward various nucleophiles,5 leading to
oxidatively coupled products, which presents an excellent
alternative protocol for the Mannich-type reactions
(Scheme 1, path a).6,7 Recently, we8 have developed an
efficient double alkylation of N-methyl amines, in which
two molecules of nucleophiles were involved in the final
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(b) Xu, X.; Ge, Z.; Cheng, D.; Ma, L.; Lu, C.; Zhang, Q.; Yao, N.; Li, X.
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Y.-F.; Shaukat, A.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem. 2010, 75,
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(e) Shu, X.-Z.; Xia, X.-F.; Yang, Y.-F.; Ji, K.- G.; Liu, X.-Y.; Liang,
Y.-M. J. Org. Chem. 2009, 74, 7464. (f) Tsang, A. S. K.; Todd, M. H.
Tetrahedron Lett. 2009, 50, 1199. (g) Huang, L.; Zhang, X.; Zhang, Y.
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(m) Li, Z.; Li, C.-J. Eur. J. Org. Chem. 2005, 3173. (n) Li, Z.; Li, C.-J.
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† Renmin University of China.
‡ Okayama University.
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D. Science 2006, 312, 67. (c) Dyker, D., Ed. Handbook of CÀH
Transformations: Wiley-VCH: Weinheim, 2005. (d) Special issue on selec-
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(3) (a) Cytochrome P-450, Structure, Mechanism, and Biochemistry,
2nd ed.; Ortiz de Montellano, P. R., Ed.; Plenum Press: New York, 1995.
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r
10.1021/ol202749x
Published on Web 11/04/2011
2011 American Chemical Society