Asymmetric synthesis via aziridinium ions: exploring the stereospecificity of the ring opening of aziridinium ions and a formal synthesis of (−)-swainsonine

The use of aziridinium ions in two different projects is described. First, the stereospecificity of the ring opening of aziridinium ions with MeNH2 as a route to chiral diamines has been explored. When the aziridinium ion contained a phenyl or para-methoxyphenyl substituent, stereospecific ring opening occurred. In contrast, switching the para-methoxy group to a para-N,N-dimethylamino group gave a racemic diamine product. Second, starting from N-Boc pyrrolidine, asymmetric lithiation-trapping-ring expansion (via an aziridinium ion) was used to synthesise a piperidine alcohol. In this way, a formal synthesis of (−)-swainsonine was completed.

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N-[(1R)-(4-Methoxyphenyl)-2-(1-pyrrolidinyl)ethyl]-N-methylamineC14H22N2OEr >97:3[α]D = −73.2 (c 1.0, CHCl3)Source of chirality: prepared from (R)-styrene oxideAbsolute configuration: (1R)

(1R,2S)-2-(1-Hydroxyallyl)pyrrolidine-1-carboxylic acid tert-butyl esterC12H21NO3Er 96:4[α]D = −51.4 (c 1.0, CHCl3)Source of chirality: asymmetric deprotonationAbsolute configuration: (1R,2R)

(1S,2S)-2-(1-Hydroxyallyl)pyrrolidine-1-carboxylic acid tert-butyl esterC12H21NO3Er 98:2[α]D = −67.1 (c 1.0, CHCl3)Source of chirality: asymmetric deprotonationAbsolute configuration: (1S,2S)