Application of crystallization-induced asymmetric transformation to a general, scalable method for the resolution of 2,8-disubstituted Tröger's base derivatives.

A general method for the gram scale resolution of 2-substituted and 2,8-disubstituted Tröger's base (TB) derivatives in 63-91% yield has been achieved through the application of crystallization-induced asymmetric transformation (CIAT). Enantiomeric ratios of the resolved TB derivatives range from 99.1:0.9 to >99.5:0.5. Among the Tröger's base compounds resolved are four synthetically valuable bromo and iodo derivatives.