Guanidine catalyzed enantioselective desymmetrization of meso-aziridines

Abstract

Chiral guanidine was easily synthesized in two steps from commercially available (1R,2R)-1-amino-2-indanol. It was found to be an efficient Br?nsted base catalyst for the enantioselective desymmetrization of meso N-acyl aziridines with benzenethiols. High yields (90-94%) and enantioselectivities (88-95% ee) were achieved. The enantiopure 1,2-difunctionalized products obtained can be used to generate chiral allylic amides via simple transformations. Desymmetrization of cis-N-tosyl-aziridine-2,3-dicarboxylates with arenethiols was also developed as a direct synthetic approach towards ?-substituted aspartates, with ees up to 90%. The nucleophile scope of the chiral guanidine catalyzed desymmetrization of meso-aziridines was expanded to include carbamodithioic acid, which was generated in situ from an amine and CS2. Moderate to high yields (up to 98%) and good enantioselectivities (up to 90% ee) were also achieved. The optical purity of the ring-opened products could be enhanced to excellent ee values (up to 99%) after a single recrystallization. This is the first time on the use of carbamodithioic acid as a nucleophile in the asymmetric ring opening of aziridines. The methodology also provided a novel and practical protocol for the synthesis of enantiomerically enriched ?-amino sulfonic acids.