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RESEARCH ARTICLE

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NO₃^● Induced Self-Terminating Radical Oxygenations: Diastereoselective Synthesis of Anellated Pyrrolidines

Arne Stademann ^A and Uta Wille ^B ^C

+ Author Affiliations

- Author Affiliations

^A Institut für Organische Chemie, Christian-Albrechts-Universität Kiel, 24098 Kiel, Germany.

^B School of Chemistry, University of Melbourne, Melbourne VIC 3010, Australia.

^C Corresponding author. Email: uwille@unimelb.edu.au

Australian Journal of Chemistry 57(11) 1055-1066 https://doi.org/10.1071/CH04124
Submitted: 25 June 2004 Accepted: 8 September 2004 Published: 1 November 2004

Abstract

Anellated pyrrolidines 19–22 were obtained through a diastereoselective self-terminating, oxidative radical cyclization cascade by treating the cis-cyclopentyl substituted alkynyl amines 14–18 with photochemically generated nitrate radicals, NO₃^●. A fast and modular access to the starting materials 14–18 was developed, which readily enables variation of the substitution pattern at the pyrrolidine ring formed upon radical cyclization. The diastereoselectivity of this reaction sequence was found to be strongly influenced by the nature of the substituents at the nitrogen atom. This shows that a complex interplay of both steric and stereoelectronic effects orchestrates the stereoselectivity of 5-exo radical cyclizations of highly substituted radicals.

Acknowledgments

Financial support by the Deutsche Forschungsgemeinschaft, the Universität Kiel, and the University of Melbourne is gratefully acknowledged. We thank Professor Dr Ulrich Lüning and the Institut für Organische Chemie, Universität Kiel, for the generous support of this work.

References

[1] M. C. Desai, S. L. Lefkowitz, D. C. Bryce, S. McLean, Bioorg. Med. Chem. Lett. 1994, 15, 1865.
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        and references therein.

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        | Crossref | GoogleScholarGoogle Scholar | However, stabilization of a reaction centre by acceptor or donor substituents, commonly known as capto or dative effects, respectively, is a well accepted concept in chemistry. In the case of radicals, this stabilization is due to orbital interactions between the SOMO and the HOMO (dative) or LUMO (capto), which result in a decrease of the overall energy of the system; see also the following reference.



[34] Density functional calculations on the mechanism of NO₃^● induced, self-terminating radical oxygenations of 1 (X = O) have revealed that the orientation of the nitrate substituent relative to the 5-hexenyl chain has no influence on the diastereoselectivity of the 5-exo cyclization, when R is a non-polar substituent (i.e. methyl); ref. [7].

[35] Formation of 23 could principally be also explained through a 1,3-HAT, followed by 3-exo cyclization, according to 3 → 29 → 30. However, since a 1,3-HAT in radical chemistry is practically unknown (see ref. [31]), we believe that 23 is formed via two subsequent 1,5-HATs, followed by a 3-exo cyclization, as shown in Scheme 5.