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

• Published in: ACS catalysis Vol. 12; no. 7; pp. 3974 - 3984
• Main Authors: Murugesan, Kathiravan, Donabauer, Karsten, Narobe, Rok, Derdau, Volker, Bauer, Armin, König, Burkhard
• Format: Journal Article
• Language: English
• Published: American Chemical Society 01-04-2022
• Subjects: C−H functionalization; carbanion; photoredox catalysis; site-selectivity; isotope labeling; amino alcohols
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.2c00662

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 α-position to an amine via a carbanion intermediate. In the presence of several α-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.