Synthesis of Halogen Substituted Analogues of Tröger's Base

Halogen substituted analogues of Tröger’s bases 1-8 were synthesized in good to excellent yields from 4-halogen substituted anilines by a Tröger’s base condensation reaction. The condensation was strongly dependent on the reaction conditions. 4-Iodo- and bromoanilines with an electron-donating 2-methyl group were utilized for optimization of the condensation reaction. The condensation reaction, that was never effective with halogen substituted anilines, was subsequently used for 4-haloanilines without the methyl group, affording hitherto inaccessible analogues of Tröger’s base 5-8. In contrast, 2-iodoaniline gave the desired product only in minute yield using the optimized reaction conditions. One example of a palladium-catalyzed cross-coupling reaction of 1 with ethynylmagnesium bromide in 92% yield to give 14 is reported.