Piridinas n-oxidos

FULL PAPER
DOI: 10.1002/ejoc.200800338

Synthesis of New Polycyclic γ- and δ-Lactones upon Activation of, and Nucleophilic Additions to, Diazines: Influence of the Activating Agents
A. Garduno-Alva,[a] Y. Xu,[b][‡] N. Gualo-Soberanes,[a] J. Lopez-Cortes,[a] H. Rudler,*[b] A. Parlier,[b] M. C. Ortega-Alfaro,[c] C. Alvarez-Toledano,[a] and R. A. Toscano[a]
Keywords: Lactones / Azo compounds /Cyclization / Silyl enol ethers / Polycycles
The reaction of bis(trimethylsilyl)ketene acetals 2 with Nheterocycles containing either one or two nitrogen atoms in the presence of triflic anhydride has been examined and the structures of the resulting products compared with those obtained by using methyl chloroformate as the activating agent. Whereas pyridine, pyrazine, quinoxaline and pyrimidineled to the same type of fused δ- or γ-lactones 4, 6, 8, 10 and 11 as with methyl chloroformate, the behaviour of pyridazine appeared to be peculiar. In the presence of methyl chloroformate, this heterocycle led to δ-lactones 16 via stable dihydropyridazines, with triflic anhydride, the direct formation of γ-lactones 20 was observed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany,2008)

Introduction
The use of ketene acetals as potential 1,3-dinucleophiles has emerged as a very powerful method for the synthesis of lactones from both simple aromatic compounds as well as from aza-aromatics.[1] Whereas in the first case the activation of the aromatic substrates was the result of the coordination of their double bonds to a transition metal, in the second case the activation ofthe aza-aromatics occurred through the nitrogen atoms via the formation of pyridinium salts. These transformations were first carried out on pyridine and its derivatives: it is a two-step process giving isolable intermediate monoaddition products, carboxylic acid substituted dihydropyridines.[2] These could be oxidized in a non-biomimetic way to afford tetrahydropyridine-fused δlactones.[1b,3]Among the oxidizing agents X+, the more efficient are derived from HCl, I2, Br2 and ArCO3H (Scheme 1). Both the monoaddition products, the various dihydropyridines, and the diaddition products, the fused lactones, might be considered potentially important from a biological point of view.[4] No less important as far as their biological
[a] Instituto de Quimica, Universidad Nacional Autonoma deMéxico (UNAM), Circuito Exterior s/n, Ciudad Universitaria, 04510 México D.F., México [b] Laboratoire de Chimie Organique, UMR CNRS 7611, Université P. M. Curie, Case 47, 4 place Jussieu, 75252 Paris Cedex 5, France Fax: +33-1-44273787 E-mail: henri.rudler@upmc.fr [c] Facultad de Quimica, Universidad Nacional Autonoma de México (UNAM), Circuito Exterior s/n, Ciudad Universitaria, 04510 México D.F.,México [‡] Present address: Aster Print Pigments, Shanghai, China 3714

Scheme 1.

implications are concerned are diazine derivatives, which could be obtained by similar means: pyrazine and quinoxaline were even more straightforward as the presence of two nitrogen atoms, which might both be activated towards nucleophilic addition upon interaction with alkyl chloroformates, allowed for the directformation of γ-lactones upon successive, formal additions of the two termini of the dinucleophiles to the two carbon–nitrogen double bonds of these substrates[1b,5] (Scheme 2).

Scheme 2.

The purpose of this paper is to show that the double nucleophilic addition reaction of ketene acetals, which leads to lactones, can be extended to other diazines such as pyrimidine and pyridazine, but that thecourse of the reaction may be dependent on the nature of the nitrogen-activating agent. Therefore, we shall first make a comparison between the behaviour of two types of activating agents, alkyl chloroformates and triflic anhydride [(CF3SO2)2O], in the reacEur. J. Org. Chem. 2008, 3714–3723

© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

New Polycyclic γ- and δ-Lactones

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