Highly efficient total synthesis of Δ-PGJ2, 15-deoxy-Δ-PGJ2, and their analogues

Palladium-catalyzed reaction of TBS ether of 4-cyclopentene-1,3-diol monoacetate (>95% ee) with an anion derived from methyl malonate and a base such as t-BuOK and LDA proceeded highly efficiently and reproducibly. The product obtained in >90% isolated yield was transformed in five steps into the key cyclopentenone possessing the α-chain at the γ position. Aldol reaction of this enone with the ω-chain aldehyde afforded the aldol adduct, and exposure of the derived mesylate to Al₂O₃ furnished the cross-conjugated dienone of the full structure. Finally, functional group manipulation furnished Δ¹²-PGJ₂ efficiently. Similarly, 15-deoxy-Δ^12,14-PGJ₂, 5,6-acetylene analogues, and a 5,6-dihydro analogue were synthesized.