Chemo- and Regioselective Strategy for the Synthesis of O- and C-Prenylated Resorcinol-Based Natural Products from Vinylogous Esters

We report a novel, efficient, and highly chemo- and regioselective strategy for the synthesis of O- and C-prenylated resorcinol-based bioactive natural products and their analogues, including derricidin, 4'-O-geranylisoliquirtigenin, sofalcone, derricin, isocordoin, 4-hydroxyderricin, crotaorixin, and xanthoangelol. Vinylogous esters and aldehydes were utilized in a single-pot sequence of aldol reaction, aromatization, and oxidation reactions. Terpene-derived resorcinyl ketones, such as O-prenyl/geranyl and C-prenyl/geranyl derivatives, are widely distributed in nature. However, the direct installation of C-prenyl/geranyl groups onto aromatic rings remains challenging, often requiring protecting groups, multistep sequences, Lewis acids, or high-temperature Claisen rearrangements, which suffer from poor regioselectivity and low yields. For the first time, we demonstrate access to these compounds from nonbenzenoid starting materials such as O- and C-prenylated vinylogous esters. This strategy exploits aldehydes as versatile coupling partners and exhibits excellent tolerance toward these fragile terpene moieties as well as a wide range of sensitive functional groups.