Rhodium-Catalyzed C(sp2)–H Activation and [3+3] Annulation: Accessing Pyrano[3,2-c]chromene-2,5-diones as TASK-3 Activators

Abstract

Herein, an efficient Rh-catalyzed C–H activation/annulation between α,β-unsaturated amides and coumarin-derived iodonium ylides has been developed, affording novel pyrano[3,2-c]chromene-2,5-diones and analogues in high yields. Most products could be easily isolated by precipitation in ethanol, followed by simple filtration. Additionally, this protocol demonstrated the benefits of environmentally friendly conditions, air compatibility, good functional group compatibility, scale-up synthesis with low catalyst loading, and a recyclable Rh catalyst. Importantly, compounds 3m and 3w demonstrated moderate agonist activity on the TASK-3 channel, with I/I₀ values of 1.7650 ± 0.1058 and 1.400 ± 0.0589, respectively.