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

Abstract

In situ OH metalation with i Bu 2AlH and hydrozirconation with HZrCp 2Cl of HOCH 2C CH, ( E)-HOCH 2CH CHC CH, and HOCH 2C CCH 3 followed by Pd-catalyzed alkenyl–alkenyl coupling with ( E)-BrCH CHCO 2Et and ( E)-BrCH C(Me)CO 2Et 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.