Blue-Light-Irradiated Copper-Catalyzed Regio-tunable Double C–H/C–H Cross-Coupling Reaction: A Sustainable Approach to Construct <i>C</i>₂-Indolyl-1,4-naphthoquinones

Double C-H functionalization of unfunctionalized arenes is always challenging due to their inherent chemical inertness. Moreover , enhancing step and atom economy in reaction methodology is highly desirable. Herein, a regio-tunable double C-H/C-H cross-coupling of 1,4-naphthoquinone with indole has been achieved using a Cu(II) catalyst under blue-light irradiation without utilizing any external base, oxidant, or prefunctionalized precursors. Using the presented methodology, an array of high-value-added <i>C</i>₂-indolyl-1,4-quinones and <i>C</i>₂-pyrrolyl-1,4-naphthoquinones were constructed under ambient reaction conditions. Also, four postsynthetic modifications have been made to the synthesized <i>C</i>₂-indolyl-1,4-naphthoquinone. Mechanistic insight from radical trapping, radical scavenging, EPR, and control experiments, well corroborated with DFT studies, suggests that the reaction proceeds by a radical pathway in which 1,4-naphthoquinone forms a highly oxidizing naphthoquinonyl biradical upon blue-light irradiation that further forms an electrophilic naphthoquinone-copper adduct upon interacting with Lewis acid Cu(II). Consequently, electron transfer from electron-rich indole to an oxidizing naphthoquinone-copper adduct leads to a naphthoquinone-copper radical anion adduct and an indolyl radical cation, followed by cross-coupling of both radical ion pairs, affording a 3-(indolyl)-4-oxo-3,4-dihydronaphthalen-1-olate copper adduct by overcoming the barrier energy of +2.08 kcal/mol. This adduct upon oxidation by the excited naphthoquinone enabled <i>C</i>₂-indolyl-1,4-naphthoquinone along with the concomitant release of the copper catalyst.