Photoredox-Catalyzed Site-Selective Generation of Carbanions from C(sp3 )-H Bonds in Amines

The selective activation of sp3 carbon-hydrogen bonds in the presence of multiple C-H bonds is challenging and remains of supreme importance in chemical research. Late-stage modification of complex molecules via sp3 C-H activation is of high prevalence in organic synthesis. Herein, we describe the activation of a C(sp3 )-H bond in the alpha-position to an amine via a carbanion intermediate. In the presence of several alpha-amine sites, only one specific position is selectively activated. Applying this protocol, the proposed carbanion intermediate was effectively trapped with different electrophiles such as deuterium (D+ ), tritium (T+ ), or carbonyl compounds compiling over 50 examples. Further, this methodology was used to install deuterium or tritium in different drug-derivatives (>10 drugs) at a selected position in a late-stage functionalization. In addition, the protocol is suitable for a gram-scale synthesis, and a detailed mechanistic investigation has been carried out to support our hypothesis.