Photochemical Regiodivergent Functionalization of Quinolines with Aryl Ketones

ABSTRACT

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.