Highly Enantioselective Construction of Sterically Hindered α-Allyl-α-Aryl Lactones via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Abstract

Pd-catalyzed decarboxylative asymmetric allylic alkylation has been developed for sterically hindered α-aryl, β-oxo-allyl ester lactone substrates. Pb-mediated α-arylation of the β-oxo-allyl ester was used as the key step to synthesize the substrates for catalysis in moderate to high yields. Optimization studies for decarboxylative asymmetric allylic alkylations (DAAA) were conducted using δ-valerolactone-derived α-aryl β-oxo-allyl ester with 2,4,6-trimethoxyphenyl as the aryl substituent. Using (R,R)-ANDEN-phenyl Trost as the chiral ligand, enantioselectivities of up to >99% ee and 98% ee were achieved with the six-membered and five-membered lactone substrates, respectively. Bulky aryl groups containing di-ortho substitutions and naphthyl groups gave the highest enantioselectivities. This synthetic route allows for the simple modification of aryl groups, giving highly enantioselective access to important structural motifs.