Stereodivergent Construction of <i>trans</i> -Decalin-Based Terpenoids

Thousands of highly oxygenated terpenoid natural products contain a common <i>trans</i>-decalin core bearing oxidized substituents in either the equatorial or axial configuration at the C(4) quaternary center. We report an expedient route to a versatile terpenoid building block primed for elaboration into numerous complex natural products. This intermediate is provided from (<i>R</i>)-carvone, a cheap and abundant chiral pool material, in three steps through a diastereodivergent, intramolecular carboborylation reaction. Notably, this method uniquely provides either equatorial or axial functionalized products from a single, common precursor. Identification of optimal ligands required extensive screening efforts, facilitated in part by high-throughput experimentation (HTE) and the construction of an algorithmically guided, combinatorial, in silico library, which identified the highest performing axial-selective ligand. The key interactions responsible for the observed high diastereoselectivity were elucidated with computational analysis, and the synthetic utility of this method was demonstrated in the total synthesis of several diterpenoid natural products.