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Synlett 2015; 26(10): 1357-1360
DOI: 10.1055/s-0034-1380552
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of Annulated and Spirocyclic Butenolide Derivatives by Condensation of Malonates with Cyclic α-Hydroxy β-Dicarbonyl Compounds

Barhiem Schickmous
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uni-oldenburg.de
,
Thorsten Klüner
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uni-oldenburg.de
,
Jens Christoffers*
Institut für Chemie, Carl von Ossietzky Universität Oldenburg, 26111 Oldenburg, Germany   Email: jens.christoffers@uni-oldenburg.de
› Author Affiliations
Further Information

Publication History

Received: 08 January 2015

Accepted after revision: 19 March 2015

Publication Date:
23 April 2015 (online)

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Abstract

Cyclocondensation of alicyclic and heterocyclic α-hydroxy β-dicarbonyl compounds with dimethyl malonate gives bicyclic butenolide derivatives. The reaction sequence is catalyzed by 4-(N,N-dimethylamino)pyridine and consists of two processes: Knoevenagel condensation followed by transesterification. Depending on the chemical nature of the β-dicarbonyl moiety (oxoester, diketone or α-acetyl lactone or lactam), products with either annulated or spirocyclic constitution are obtained.

Keywords

annulation - heterocycles - Knoevenagel reaction - lactones - spiro compounds

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1380552. It includes experimental procedures and spectroscopic data for all new compounds as well as copies for NMR spectra.
  • Supporting Information
 

  • References and Notes

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  • 13 The reason for the selectivity switch from annulated to spirocyclic product remains unclear. Actually, one might assume that the prolonged reaction times and elevated temperatures clearly indicate that all products are formed under thermodynamic control. This seems to be evident for the formation of annulated product 7h, with the six-membered ring, which is approximately 36 kJ·mol–1 more stable then the corresponding spirocycle, as DFT calculations indicated.15 Nevertheless, for starting material 6i, with a seven-membered ring, the annulated product is thermodynamically also slightly more stable than spirocycle 8a, although this effect is less pronounced (20 kJ·mol–1). The latter case is therefore clearly a result of kinetic control. We were, however, unable to detect or identify any reaction intermediates that could shed light on this selectivity switch.
  • 14 CCDC-1031225 (7h) and 1031226 (8a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336033.
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