Catalytic enantioselective construction of two N-stereogenic centers of ethano- and propano-Tröger's bases

Abstract

Whereas enantioselective methods for constructing carbon stereocenters have been well established, those for creating heteroatomic stereocenters have received less attention. Nitrogen is the most abundant element in the Earth's atmosphere and plays an important role in the biochemical and physiological processes of organisms. However, owing to its rapid pyramidal inversion under general conditions, its stereochemistry has long been overlooked. Here, we report the catalytic enantioselective construction of two conformationally stable N-stereogenic centers of ethano- and propano-Tröger's bases. By using a Pd-catalyzed asymmetric annulative allylic alkylation reaction, various N-chiral ethano- and propano-TBs have been readily prepared in good yields with excellent enantioselectivities. Mechanistic investigations have shown that the two N-stereogenic centers are simultaneously established during intramolecular bridge formation. Furthermore, the synthesized TB products can serve as both an organo-catalyst for the aziridination reaction and a fluorescent/chiroptical probe for pH measurement.