Total Synthesis and Late-Stage C–H Oxidations of ent-Trachylobane Natural Products

Herein, we present our studies to construct seven ent-trachylobane diterpenoids by employing a bioinspired two-phase synthetic strategy. The first phase provided enantioselective and scalable access to five ent-trachylobanes, of which methyl ent-trachyloban-19-oate was produced on a 300 mg scale. During the second phase, chemical C–H oxidation methods were employed to enable selective conversion to two naturally occurring higher functionalized ent-trachylobanes. The formation of regioisomeric analogs, which are currently inaccessible via enzymatic methods, reveals the potential as well as limitations of established chemical C–H oxidation protocols for complex molecule synthesis.