Development of a [3+3] cycloaddition strategy toward functionalized piperidines.

Simon J Hedley; Wesley J Moran; David A Price; Joseph P A Harrity

doi:10.1021/jo030002c

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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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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.

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Aziridines Catalysis Combinatorial Chemistry Techniques Cyclization Indicators and Reagents Molecular Structure Palladium Piperidines Journal Article Research Support, Non-U.S. Gov't

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Simon J Hedley, Wesley J Moran, David A Price, Joseph P A Harrity. 2003-05-30. Development of a [3+3] cycloaddition strategy toward functionalized piperidines.. https://doi.org/10.1021/jo030002c

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