Synthesis of 2,5-Diazabicyclo[2.2.2]octanes by Dieckmann Analogous Cyclization
Ralph Holl A , Mareike Dykstra A , Martin Schneiders B , Roland Fröhlich B , Masato Kitamura C , Ernst-Ulrich Würthwein B and Bernhard Wünsch A DA Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Hittorfstraße 58-62, 48149 Münster, Germany.
B Organisch-Chemisches Institut der Westfälischen Wilhelms-Universität Münster, Corrensstr. 40, 48149 Münster, Germany.
C Department of Chemistry, Graduate School of Science, Nagoya University, Furo, Chikusa, Nagoya 464-8602, Japan.
D Corresponding author. Email: wuensch@uni-muenster.de
Australian Journal of Chemistry 61(11) 914-919 https://doi.org/10.1071/CH08350
Submitted: 14 August 2008 Accepted: 29 September 2008 Published: 5 November 2008
Abstract
Starting with (S)-aspartate, methyl (S)-2-[1-allyl-4-(4-methoxybenzyl)-3,6-dioxopiperazin-2-yl]acetate 10 was synthesized in a four-step synthesis. Deprotonation of 10 and subsequent trapping of the first cyclization product led to the bicyclic mixed acetal 13 in 15% yield. The low yield of 13, compared with the yield of the corresponding glutamate derivatives, is explained by the higher energy (strain) of the bicyclo[2.2.2]octane system and the lower conformational flexibility of the shorter acetate side chain. The formation of a six-membered Na+-chelate 12 as intermediate is responsible for the high diastereoselectivity of the cyclization step.
Acknowledgements
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.
[1]
M. Weigl,
B. Wünsch,
Org. Lett. 2000, 2, 1177.
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
| Crossref | GoogleScholarGoogle Scholar |
[18]
[19]
