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 alpha-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 alpha-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, alpha-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, alpha-pyrone polyketides and Lupin alkaloids), completed within 4-7 steps. image