Functionalized analogues of Tröger's base: scope and limitations of a general synthetic procedure and facile, predictable method for the separation of enantiomers

A major stumbling block in the applications of enantiomerically pure Tröger's base analogues is their poor availability. We have therefore developed a facile method for the enantioseparation of functionalized Tröger's base analogues possessing various substitution patterns. The systematic separation of a library comprising 36 representatives on the commercially available Whelk O1 chiral stationary phase provided valuable information on structure–enantioselectivity relationships. A mechanistic explanation of observed relationships allows one to predict whether or not enantioseparation of a given, perhaps yet unknown derivative of Tröger's base will be feasible. In addition, we provide a detailed report on the scope and limitations of the general synthetic protocol employing anilines and paraformaldehyde in CF3COOH, as well as some considerations concerning the mechanism of formation of Tröger's base analogues.

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