Photoredox Minisci-Type Hydroxyfluoroalkylation of Isoquinolines with <i>N</i>-Trifluoroethoxyphthalimide
Ankita Thakur, Shiv Shankar Gupta, Ankit Kumar Dhiman, Upendra Sharma
Abstract
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 Ir-photocatalyst emission. A catalytic cycle involving trifluoroethanol radical reaction with isoquinolines has been proposed.