Late-stage Cyclization of Natural Products Enabled by C–C bond Cleavage of Aryl Ketones

We reported herein an efficient palladium-catalyzed method for the construction of the 4-8 membered rings, including benzocyclobutene, indole, indene, indanone, naphthalene, phenanthrene, azepine, and azocine cores, on the aryl moiety of unstrained aryl ketones via C−C cleavage as the key step. A variety of cyclization products were synthesized with excellent functional-group tolerance and high regioselectivity, especially for unsymmetrical alkynes. The late-stage diversification of a series of natural products and pharmaceuticals highlights the synthetic utility of this methodology. Furthermore, multiple dehydroabietic acid (DA)-based derivatives were successfully constructed, leading to the rapid identification of several molecules with significantly enhanced antimicrobial activity.