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

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

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83 Citations (Scopus)


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
Issue number11
Early online date22 Apr 2003
Publication statusPublished - 30 May 2003
Externally publishedYes


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