Lewis Acid Integrated Bifunctional Covalent Organic Framework for Photocatalytic Regioselective C3-Carbonylation of Indoles

Abstract

The regioselective carbonylation of indoles have attracted significant recent attention owing to the ubiquitous presence of indole derivatives in pharmaceuticals and natural products. Aldehydes are very appealing as effective carbonylation sources; however, methods to activate aldehydes toward successful incorporation into indoles are scarce. Moreover, there is no available report on heterogeneous, solid-state catalysts for this transformation from an aldehyde substrate. To tackle the problem, we synthesized a bipyridine-based COF bearing Lewis-acidic groups (BF2–Bpy–DHTA COF) in a one-step, presynthetic process, increasing the oxidizing ability of the COF matrix by tuning the valence band position. A dense array of −BF2 units, incorporated via a presynthetic modification strategy, ensures essentially quantitative coordination to bipyridines. The improved light-absorbing properties, effective charge separation and migration, and embedded Lewis acidity make BF2–Bpy–DHTA COF a potent catalyst for the one-pot carbonylation of indoles under mild conditions. This intuitive design circumvents several prior synthetic limitations, including the use of exotic enzyme-photocatalyst hybrids, acids, and high-temperature synthesis of Mannich adducts. Interestingly, BF2–Bpy–DHTA COF exhibits high recyclability, yielding consistently 3-formylindole products across eight consecutive photocatalytic cycles. Most importantly, this design eliminates the repeated use of external Lewis acids, enabling truly catalytic conditions, while establishing a fundamentally new methodology for the synthesis of C3-carbonylated indoles, distinct from previously reported approaches.