15NRORC: An Azine Labeling Protocol

A practical method for the synthesis of ¹⁵N-labeled azines with a high degree of isotopic enrichment is described. Activation of azine heterocycles with an electron-deficient arene allows for the facile substitution of the nitrogen atom with a specifically designed ¹⁵N-labeled reagent that undergoes a canonical ANRORC-type mechanism. A wide range of azines can be converted to their corresponding ¹⁵N isotopologs using this method, and it also allows for dearomative access to reduced heterocyclic congeners. A short dearomative formal synthesis of ¹⁵N-solifenacin is accomplished as well to demonstrate a practical application of this method for generating labeled pharmaceuticals.