Enantioselective Synthesis of the 1,3‐Dienyl‐5‐Alkyl‐6‐Oxy Motif: Method Development and Total Synthesis

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. Method development and total synthesis have resulted in the enantioselective synthesis of the 1,3‐dienyl‐5‐alkyl‐6‐oxy motif, and thus expedient total syntheses of three types of natural products (glutarimide antibiotics, α‐pyrone polyketides and Lupin alkaloids), completed within 4–7 steps.