Kinetic Resolution of Cyclic Secondary Azides, Using an Enantioselective Copper-Catalyzed Azide-Alkyne Cycloaddition.

An enantioselective copper-catalyzed azide-alkyne cycloaddition (E-CuAAC) is reported by kinetic resolution. Chiral triazoles were isolated in high yield with limiting alkyne (up to 97:3 enantiomeric ratio (er)). A range of substrates were tolerated (>30 examples), and the reaction was scaled to >1 g. The er of a triazole product could be enhanced by recrystallization and the recovered scalemic azide could be racemized and recycled. Recycling the azide allows efficient use of the undesired azide enantiomer.