Visible-light-driven net-1,2-hydrogen atom transfer of amidyl radicals to access β-amido ketone derivatives

Chem Sci. 2024 Dec 3. doi: 10.1039/d4sc04997g. Online ahead of print.

Abstract

Hydrogen atom transfer (HAT) processes provide an important strategy for selective C-H functionalization. Compared with the popularity of 1,5-HAT processes, however, net-1,2-HAT reactions have been reported less frequently. Herein, we report a unique visible-light-mediated net-1,2-HAT of amidyl radicals for the synthesis of β-amido ketone derivatives. Single-electron transfer (SET) to N-aryloxy amides generates nitrogen-centered radicals (N˙), which undergo a rare net-1,2-HAT to form carbon-centered radicals (C˙). The C-centered radicals are then captured by silyl enol ethers on the way to β-amido ketones. A series of β-amido ketone derivatives (33 examples, up to 97% yield) were prepared with good functional group tolerance demonstrating the synthetic utility of this method. Mechanistic studies, including EPR, radical trapping experiments, deuterium labeling and KIE measurements, suggest an intramolecular radical net-1,2-HAT pathway.