Dehydration-type Ti-Claisen Condensation (Carbonhomologation) of α-Heteroatom-substituted Acetates with Alkyl Formates: Utilization as (Z)-Stereodefined Cross-coupling Partners and Application to Concise Synthesis of Strobilurin A

TiCl4-Et3N or -Bu3N reagent conducted a highly (Z)-stereoselective carbon homologation (dehydration type Ti-Claisen condensation) of alkyl alpha-heteroatom (halo and sulfonyloxy)-substituted acetates (XCH2CO2R) with alkyl formates (HCO2R) to afford various alkyl beta-alkoxy-alpha-halo or sulfonyloxy-substituted acrylates (24 examples; 51%-91% yield). Stereoretentive Suzuki-Miyaura, Negishi, and Sonogashira cross-couplings using the obtained methyl beta-methoxy-alpha-halo or sulfonyloxy-substituted acrylates proceeded smoothly to produce a variety of beta-alkoxy-alpha-substituted acrylates in moderate to high yield (35 examples; 29%-99% yield). As a successful application, a 3-step straightforward synthesis of strobilurin A was performed utilizing the present reaction sequence (dehydration type Ti-Claisen condensation and Suzuki-Miyaura crosscoupling), wherein the geometry of the three consecutive olefins (2E,3Z,5E) was completely maintained.