Unified Synthesis of Unconventional α-Polyhalogenated Amines Through Hydroaminoalkylation.

We report a unified method for the synthesis of α-polyhalomethyl amines from alkenes and alkynes, enabled by readily available hemiaminal reagents. This operationally simple transformation allows for the introduction of not only well-established CF3 and CF2H groups, but also the synthetically (and medicinally) underexplored CF2Cl and CFClH motifs-thereby broadening access to previously inaccessible chemical space of halogenated amine scaffolds. The method displays broad substrate scope and functional-group tolerance while operating under mild conditions. Late-stage functionalization of drug-like derivatives of Oxaprozin, Erlotinib, and Ibuprofen (among others) is reported.