A Regioselective Approach to Accessing Trisubstituted Pyrrolo[2,3-d][1,2,3]triazoles via an Orthogonal Protection Strategy

The first access to N-2, N-4-disubstituted pyrrolo[2,3-d][1,2,3]triazoles is reported herein. The series was generated using an orthogonal protecting group strategy from N-1, N-4-disubtituted pyrrolo[2,3-d][1,2,3]triazoles. N-Arylation by Ullman–Goldberg cross-coupling was achieved to explore the reactivity of the pyrrole core and to design N-4-substituted pyrrolo[2,3-d][1,2,3]triazole derivatives. Next, a transition-catalyst-free N-arylation methodology was implemented to achieve N-2 arylation of the triazole moiety. Each arylation strategy was optimized, and a representative library of various aryl iodines or bis-aryl iodonium salts was employed to establish the scope and limitations of each method.