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

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.