Visible Light-Induced Cross-Dehydrocoupling of 3-Cyanocoumarins with Unactivated Aliphatic Aldehydes Enables Access to 4-Acylated Coumarins

Abstract

We report visible light-induced cross-dehydrocoupling of 3-cyanocoumarins with unactivated aliphatic aldehydes for the direct synthesis of 4-acylated coumarins. Inexpensive and readily available (n-Bu)4NBr was used as a precursor of the hydrogen atom transfer (HAT) catalyst and [Ir(ppy)2(dtbbpy)PF6] as a photocatalyst. A variety of aldehydes including linear, branched, cyclic, and α,β-unsaturated aliphatic aldehydes were suitable for this reaction yielding the desired acylated coumarin derivatives in 41–98% yields. This method provides a mild, atom-economical, and environmentally friendly synthetic route for the direct acylation of 3-cyanocoumarins. This is the first example so far of C-4 aliphatic acylation of coumarins.

Syntheses, reactivity, and biological applications of coumarins

“…Another straightforward example of C-4 acylation of 3-functionalized coumarins is represented by the visible light-induced cross-dehydrocoupling observed for 3-cyanocoumarin derivatives ( 131 ) during the reaction with aldehydes ( 132 ), discovered by He and others ( Qian et al, 2023 ). The process took advantage of the inexpensive reagent ( n -Bu) 4 NBr and the photocatalyst [Ir(ppy) 2 (dtbbpy)][PF 6 ] ( 133 ) to functionalize the C-4 position of the coumarin with a large panel of acyl substituents derived from aliphatic and α,β-unsaturated aliphatic aldehydes ( 132 ), in good to excellent yields ( Scheme 7 — path b ).…”