Phase-Transfer Catalyzed Asymmetric Arylacetate Alkylation
Phenethyl arylacetates are alkylated under phase-transfer conditions with cinchona catalysts with alkyl halides in high yield with excellent enantioselectivity (84–99% ee) following recrystallization. Cinchonidine (CD) derived catalyst gave the (R)-product and cinchonine (CN) catalyst produced the (S)-product. The phenethyl (PE) ester group is removed, using ammonium formate and catalytic Pd/C, to give alkylated carboxylic acid products in high selectivity. The utility of the approach is demonstrated by a direct synthesis of (S)-naproxen™.
Andrus, M. B.; Harper, K. C.; Christiansen, M. A.; Binkley, M. A. “Phase-Transfer Catalyzed Asymmetric Arylacetate Alkylation.” Synfacts, 2009, 8, 920.