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The 1,3‐dienyl‐5‐alkyl‐6‐oxy motif is widely found in various types of bioactive natural products. However, present synthesis is mainly non‐asymmetric which relied upon different olefination or transition metal‐catalyzed cross‐coupling reactions using enantioenriched precursors. Herein, based upon a newly developed enantioselective α‐alkylation of conjugated polyenoic acids, a variety of 1,3‐dienyl‐5‐alkyl‐6‐oxy motif (with E‐configured internal olefin) was generated as the corresponding α‐adducts in a highly enantioselective and diastereoselective manner. Utilizing 1,3‐dienyl‐5‐alkyl‐6‐oxy motif as key intermediates, we further demonstrated their synthetic potential by expedient total syntheses of three types of natural products (glutarimide antibiotics, α‐pyrone polyketides and Lupin alkaloids) within 4–7 steps. [ABSTRACT FROM AUTHOR]

Capitalizing on the late‐stage diversification of an essential 1,3‐diene intermediate, we describe herein a 9‐step enantioselective total synthesis of (+)‐hyperforin and (+)‐pyrohyperforin, starting from commercially available allylacetone. Our convergent synthesis features a series of critical reactions: 1) an enantioselective deconjugative α‐alkylation of α,β‐unsaturated acid using chiral lithium amides as noncovalent stereodirecting auxiliaries; 2) a HfCl4‐mediated carbonyl α‐tert‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework; 3) an abiotic cascade pyran formation; and 4) a selective 1,4‐semihydrogenation of polyenes. During the course of our synthesis, we also identified a 1,2‐cyclopropanediol overbred intermediate which was responsible for the 1,3‐diene precursor formation through a controlled fragmentation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]