Chiral Phosphinophenyloxazolines Bearing Alkoxymethyl Substituents: Synthesis and Application in the Palladium Catalyzed Allylic Substitution Reactions

Abstract

The chiral phosphine-oxazoline ligands 3 and 4 bearing 4-alkoxymethyl substituents on the oxazoline ring with (R)-configuration were prepared from L-serine methyl ester in 66% and 33% yields, respectively. Along this synthetic pathway, the b-hydroxylamides derived from L-serine methyl ester and 2-halobenzoyl chlorides were expediently converted to the corresponding oxazolines by using diethylaminosulfur trifluoride as the activation agent. Potassium diphenylphosphide was the reagent of choice for replacing the bromine atom on the phenyl ring, giving the desired oxazoline-phosphine ligands 3 and 4. Together with [Pd(h 3allyl)Cl]2, ligands 3 and 4 induced an enantioselective allylic substitution reaction of 1,3-diphenyl-2-propenyl acetate by dimethyl malonate. Although ligands 3 and 4 exhibit the (R)-configuration, differing from the (S)-configuration of Pfaltz-Helmchen-Williams phosphine-oxazoline ligands, all these ligands led to the same enantiotopic preference in the allylic substitution reaction. To facilitate the recovery and reuse of the phosphine-oxazoline ligand, immobilization on Merrifield resin was attempted, albeit in low loading.