Enantioselective Total Synthesis of Berkeleyone A and Preaustinoids

Abstract Herein we report the first enantioselective total synthesis of 3,5‐dimethylorsellinic acid‐derived meroterpenoids (−)‐berkeleyone A and its five congeners ((−)‐preaustinoids A, A1, B, B1, and B2) in 12–15 steps, starting from commercially available 2,4,6‐trihydroxybenzoic acid hydrate. Based upon the recognition of latent symmetry within D‐ring, our convergent synthesis features two critical reactions: 1) a symmetry‐breaking, diastereoselective dearomative alkylation to assemble the entire carbon core, and 2) a Sc(OTf) 3 ‐mediated sequential Krapcho dealkoxycarbonylation/carbonyl α‐ tert ‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework. We also conducted our preliminary biomimetic investigations and uncovered a series of rearrangements (α‐ketol, α‐hydroxyl‐β‐diketone, etc.) responsible for the biomimetic diversification of (−)‐berkeleyone A into its five preaustinoid congeners.