Photoredox Minisci-Type Hydroxyfluoroalkylation of Isoquinolines with N-Trifluoroethoxyphthalimide

A straightforward photocatalytic approach has been demonstrated to incorporate a trifluoroethanol unit onto the isoquinolines. Herein, we report N-trifluoroethoxyphthalimide as a hydroxyfluoroalkyl radical precursor, enabling efficient synthesis of trifluoroethanol-substituted heteroarenes. Radical quenching experiments confirmed the involvement of a free-radical pathway under developed photocatalytic conditions. The DFT calculations confirmed the intramolecular 1,2-HAT reactivity of the O centered trifluoroethoxy radical (generated from N-trifluoroethoxyphthalimide under photocatalytic condition) to the C-centered trifluoroethanol radical. Fluorescence quenching studies suggested that isoquinoline was responsible for the quenching of Irphotocatalyst emission. A catalytic cycle involving trifluoroethanol radical reaction with isoquinolines has been proposed.

Automated summary

A photocatalytic approach has been used to introduce a trifluoroethanol unit onto isoquinolines by employing N-trifluoroethoxyphthalimide as a hydroxyfluoroalkyl radical precursor. The involvement of a free-radical pathway was confirmed by radical quenching experiments, and DFT calculations supported the intramolecular 1,2-HAT reactivity of the trifluoroethoxy radical with the trifluoroethanol radical. Fluorescence quenching studies revealed that isoquinoline was responsible for the quenching of Ir photocatalyst emission. A catalytic cycle involving the reaction of trifluoroethanol radical with isoquinolines was proposed.