Development of a [3+3] Cycloaddition Strategy toward Functionalized Piperidines

Simon J. Hedley, Wesley J. Moran, David A. Price, Joseph P.A. Harrity

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.

Original languageEnglish
Pages (from-to)4286-4292
Number of pages7
JournalJournal of Organic Chemistry
Volume68
Issue number11
Early online date22 Apr 2003
DOIs
Publication statusPublished - 30 May 2003
Externally publishedYes

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Piperidines
Aziridines
Cycloaddition
Palladium

Cite this

Hedley, Simon J. ; Moran, Wesley J. ; Price, David A. ; Harrity, Joseph P.A. / Development of a [3+3] Cycloaddition Strategy toward Functionalized Piperidines. In: Journal of Organic Chemistry. 2003 ; Vol. 68, No. 11. pp. 4286-4292.
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Development of a [3+3] Cycloaddition Strategy toward Functionalized Piperidines. / Hedley, Simon J.; Moran, Wesley J.; Price, David A.; Harrity, Joseph P.A.

In: Journal of Organic Chemistry, Vol. 68, No. 11, 30.05.2003, p. 4286-4292.

Research output: Contribution to journalArticle

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