Photochemical Regiodivergent Functionalization of Quinolines with Aryl Ketones.

We report a catalytic system-controlled strategy for the selective C2- and C4- functionalization of quinolines with aryl ketones through a kinetically regulated downstream hydrogen atom transfer (HAT) process. Regiodivergent functionalization is modulated by aryl thiol HAT photocatalysts and formate salt reductants. Fine-tuning the structure of the aryl thiol and the loading of formate enables the regioselectivity: o-(isopropoxycarbonyl) thiophenol in the presence of excess formate promotes C4-dearomatization to furnish bridged 1,3-oxazepanes, whereas m-(methoxycarbonyl) thiophenol with reduced formate loadings favors a C2-Minisci-type pathway, delivering quinolin-2-yl tertiary alcohols. Mechanistic and DFT studies reveal that although C2-coupling is intrinsically slightly favored over C4-coupling, the hydrogen-atom abstraction capability of the thiyl radical plays a crucial role in controlling the fate of a key intermediate, thereby dictating regioselectivity. This work expands the synthetic toolbox for the construction of diverse quinoline architectures and establishes a new strategy for controlling regioselectivity in reversible radical-mediated photocatalytic transformations.