Modular total syntheses of trans-clerodanes and sesquiterpene (hydro)quinones via tail-to-head cyclization and reductive coupling strategies

The trans-clerodanes and sesquiterpene (hydro)quinones are a growing class of natural products that exhibit a wide range of biological activities. Although they are different types of natural products, some of them feature the same trans-decalin core structure. Here, we report the total syntheses of two members of trans-clerodanes, five members of sesquiterpene (hydro)quinones as well as the proposed structure of dysidavarone D via a modular synthetic route. A bioinspired tail-to-head cyclization strategy was developed to syntheses of the trans-decalin architectures by using two diastereochemically complementary radical polyene cyclization reactions catalyzed by Ti(III) and mediated by Mn(III), respectively. The different types of side chains were introduced by challenging nickel catalyzed reductive couplings of sterically hindered alkyl halides. The synthesis of the proposed dysidavarone D proved a wrong structural assignment of the natural product.