Regiocontrolled, palladium-catalyzed bisfunctionalization of allenyl esters. Multicomponent coupling approaches to highly substituted alpha,beta-unsaturated delta-lactones.J Org Chem. 2005 Aug 19; 70(17):6848-62.JO
A palladium-catalyzed regioselective bisfunctionalization of allenyl esters with boronic acids (nucleophiles) and aldehydes (electrophiles) was demonstrated. The three-component coupling afforded alpha,beta-unsaturated delta-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-R(1),6-Ph-disubstituted alpha,beta-unsaturated delta-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 alpha,beta-unsaturated delta-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 pi-allylpalladium(II) dimer catalyst featuring an auxiliary allyl ligand derived from beta-pinene, among diverse palladium(II) catalysts, was demonstrated. A catalytic cycle involving an unsymmetrical bis-pi-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%).
