The introduction of a trifluoromethyl (CF₃) group can dramatically improve a compound's biological properties. Despite the well-established importance of trifluoromethylated compounds, general methods for the trifluoromethylation of alkyl C-H bonds remain elusive. Here we report the development of a dual-catalytic C(sp³)-H trifluoromethylation through the merger of light-driven, decatungstate-catalysed hydrogen atom transfer and copper catalysis. This metallaphotoredox methodology enables the direct conversion of both strong aliphatic and benzylic C-H bonds into the corresponding C(sp³)-CF₃ products in a single step using a bench-stable, commercially available trifluoromethylation reagent. The reaction requires only a single equivalent of substrate and proceeds with excellent selectivity for positions distal to unprotected amines. To demonstrate the utility of this new methodology for late-stage functionalization, we have directly derivatized a broad range of approved drugs and natural products to generate valuable trifluoromethylated analogues. Preliminary mechanistic experiments reveal that a 'Cu-CF₃' species is formed during this process and the critical C(sp³)-CF₃ bond-forming step involves the copper catalyst. 

Privileged chiral catalyst scaffolds are highly useful in chemical synthesis such as drug preparation. Substituted phenol ligands are among the most frequently used scaffolds. However, the preparation of chiral phenol ligands commonly involves tedious synthetic procedures. Herein, we describe a facile strategy to prepare potent chiral bisphenols (BPOLs) through the desymmetrizing asymmetric ortho-halogenation. Both theoretical and experimental studies were conducted in order to shed light on the mechanistic picture. The halogen handles in the BPOL products are manipulated to yield unsymmetrical chiral BPOL ligands, which are potential privileged catalyst scaffolds and have been applied in other asymmetric catalytic reactions.