Synthesis of enantiopure 2,4,8,10-tetrasubstituted Tröger base derivatives

Abstract

Chiral tetramethyl and dibromo-dimethyl substituted Tröger base derivatives are readily prepared in enantiomerically pure forms using camphor sulfonic acid as a resolving agent. The (S,S)-isomers of these derivatives were obtained with 95-99% ee by precipitation using (1S)-(+)-10-camphor sulfonic acid and the partially resolved samples present in the mother liquor were enriched by treatment with (1R)-(-)-10-camphor sulfonic acid to obtain the (R,R)-isomers of tetrasubstituted Tröger base derivatives with 96-99% ee. In the case of 2,8-dibromo-4,10-dimethyl derivative, the (R,R)-isomer was obtained with 96-97% ee from the filtrate fraction after the (S,S)-enantiomer precipitated out. The dibromo derivative is readily functionalized to access a new chiral amine system containing a chiral phenylethylamine moiety.