Asymmetric Total Synthesis of Naturally Occurring (−)-EBC-329 through an ( E )-Selective Cross-Metathesis Reaction

We disclose the first asymmetric synthesis of naturally occurring seco -casbene diterpene (−)-EBC-329. Lipase-mediated enzymatic enantioselective desymmetrization (EED) was employed to fix the cyclopropane-containing (8 R,9 S ) stereocenters in the natural product. An E -selective CM (cross-metathesis) reaction was successfully employed to construct the C 12 –C 13 olefinic unsaturation. A conjugated γ-alkylidene-butenolide, the key partner in the CM reaction, was constructed through a “Pd–Cu” bimetallic cascade cyclization reaction. Late-stage Wittig olefination was employed for the assembly of C 6 –C 7 unsaturated acid functionality. Measurement of the optical rotation value and circular dichroism analysis confirms the absolute configuration of the natural product.