Highly Selective Dearomative C3 Deuteration and N-Functionalization of Aza-Heterocycles toward Fsp3-Enriched Motifs

Herein, we disclose the first dearomative C3 selective deuteration and N-deuteroformylation of aza-arenes in a single step, using Hantzsch ester, D2O, and BrCF2CO2K. This methodology clearly enables the synthesis of novel deuterated Fsp3-rich aza-heterocyclic building blocks under mild reaction conditions, besides obviating the need for a catalyst, a base, and/or an acid. This transformation also exhibits a broad substrate scope (∼45 examples) and excellent functional-group tolerance, affording the desired products in excellent yields (up to 95%) along with deuterium incorporation levels of up to 98%. In addition, we present some rare examples of selective partial reductive C3 deuteration and N-deuteroformylation of pyridine derivatives, including late-stage deuteration and functionalization of complex N-heterocycles again under mild conditions. Control experiments and mechanistic studies support the idea that the reaction involves activation of the heteroarene via a zwitterionic difluoromethyl carboxylate intermediate.