Regiocontrolled, Palladium-Catalyzed Bisfunctionalization of Allenyl Esters. Multicomponent Coupling Approaches to Highly Substituted α,β-Unsaturated δ-Lactones

A palladium-catalyzed regioselective bisfunctionalization of allenyl esters with boronic acids
(nucleophiles) and aldehydes (electrophiles) was demonstrated. The three-component coupling
afforded α,β-unsaturated δ-lactones under mild conditions and with excellent chemo-, regio-, and
diastereoselectivity. Aromatic, heteroaromatic and vinylic boronic acids (R1B(OH)2) reacted with
ethyl 2,3-butadienoate and benzaldehyde to afford the corresponding 4-R1,6-Ph-disubstituted α,β-unsaturated δ-lactones in 62−78% yields. Lactones derived from aromatic, heteroaromatic, and
vinylic aldehydes were isolated in 51−58% yields, while aliphatic aldehydes were less reactive.
The regiochemistry of bisfunctionalization of allenyl ester homologues remained controlled by the
ester substituent, and the reactions afforded cis-4,5,6-trisubstituted α,β-unsaturated δ-lactones and
esters of (Z)-syn-3,4,5-trisubstituted-5-hydroxy-2-pentenoic acids in combined 47−65% yields. The
superior performance of a π-allylpalladium(II) dimer catalyst featuring an auxiliary allyl ligand
derived from β-pinene, among diverse palladium(II) catalysts, was demonstrated. A catalytic cycle
involving an unsymmetrical bis-π-allylpalladium complex as the key intermediate was proposed,
and the communication highlights the synthetic potential of such intermediates. However, the
efficiency of asymmetry transfer remained low (<20%).