Highly stereoselective and efficient synthesis of ω-heterofunctional di- and trienoic esters for Horner-Wadsworth-Emmons reaction via alkyne hydrozirconation and Pd-catalyzed alkenylation

In situ OH metalation with iBu2AlH and hydrozirconation with HZrCp2Cl of HOCH2CCH, (E)-HOCH2CHCHCCH, and HOCH2CCCH3 followed by Pd-catalyzed alkenyl-alkenyl coupling with (E)-BrCHCHCO2Et and (E)-BrCHC(Me)CO2Et using PEPPSI-IPr (7) as a catalyst provides a highly efficient and selective (⩾98% all-E) route to ω-hydroxy di- and trienoic acid esters (1a-6a). The corresponding phosphonate esters (1c-4c) of ⩾98% isomeric purity can be obtained via conventional bromination-phosphonation in >80% yields. As expected, their carbonyl olefination is ca. 85-90% E-selective with alkyl aldehydes but ⩾98% E-selective with PhCHO and some α,β-unsaturated aldehydes under the conditions used.

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