Synthesis of 1,4-Diazabicyclo[3.3.1]nonan-6-ones

Daniel Kracht; Susumu Saito; Bernhard Wünsch

doi:10.1071/CH09206

RESEARCH ARTICLE

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Synthesis of 1,4-Diazabicyclo[3.3.1]nonan-6-ones

Daniel Kracht ^A , Susumu Saito ^B and Bernhard Wünsch ^A ^C

+ Author Affiliations

- Author Affiliations

^A Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Hittorfstraße 58–62, D-48149 Münster, Germany.

^B Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464–8602, Japan.

^C Corresponding author. Email: wuensch@uni-muenster.de

Australian Journal of Chemistry 62(12) 1684-1689 https://doi.org/10.1071/CH09206
Submitted: 10 April 2009 Accepted: 14 July 2009 Published: 10 December 2009

Abstract

1,4-Diazabicyclo[3.3.1]nonanes (aza-morphans) represent conformationally constrained piperazine derivatives. Herein, we report a six-step synthesis of the benzyl and allyl substituted bicyclic ketones 3a and 3b, which represent interesting building blocks for the synthesis of conformationally restricted receptor ligands. The key steps of the synthesis are the regioselective addition of ethyl acrylate to the piperazine 8, the sodium hexamethyldisilazide-induced Dieckmann cyclization of the diesters 10, and the decarboxylation of the enol esters 11 with dilute HCl. The complete sequence is only successful when a benzyl (10a) or allyl moiety (10b) is attached to N-1, since the tosyl derivative 10f failed to give a Dieckmann cyclization product, and the decarboxylation failed with the acyl derivatives 11c and 11d.

Acknowledgement

This work was performed within the International Research Training Group ‘Complex Functional Systems in Chemistry: Design, Synthesis and Applications’ in collaboration with the University of Nagoya. Financial support of this IRTG by the Deutsche Forschungsgemeinschaft is gratefully acknowledged.

References

Synthesis of 1,4-Diazabicyclo[3.3.1]nonan-6-ones

Abstract

Acknowledgement

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