Nucleophilic substitution of (sulfonyloxymethyl)aziridines: an asymmetric synthesis of both isomers of mexiletine

초록

The nucleophilic substitution reactions of 1-[1'(R)-alpha-methylbenzyl]-(2R)- and (2S)-(sulfonyloxy-methyl)aziridines were carried out with various nucleophiles including N-3(-), MeO-, CN-, SCN-, and di-arylcuprates. The reaction pathway is influenced by the stereochemistry of the substrates, nucleophiles, and also the structure of the leaving groups. When the reaction site is less sterically hindered for the reactive nucleophiles to approach to the substrate 1-[1]'(R)-alpha-methylbenzyl]-(2S)-(p-toluenesulfonyloxy-methyl)aziridines, product is obtained as a single isomer while all the other starting materials afford a mixture of two isomers from two different reaction pathways. Application of this method enabled us to prepare both isomers of orally effective antiarrhythmic agent mexiletine. (C) 2008 Elsevier Ltd. All rights reserved.

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