A general synthesis of 2-alkoxy-2-phenylpropanoic acids

A preparation of a variety of 2-alkoxy-2-phenylpropanoic acids in two steps is described. Epoxidation of α-methylstyrene with mCPBA in methanol or primary alcohol solvents proceeded with an acid-catalyzed in situ ring opening reaction to give the corresponding 2-alkoxy-2-phenyl-1-propanols in 28–91% yield. Lower yields were realized with secondary (22–58%) and tertiary (14%) alcohols. These alcohols were cleanly oxidized to the corresponding carboxylic acids using a mild Heynsʹ oxidation (O2, Pt/C) in generally good to excellent yields (25–92%). The derived (S)-α-methylbenzylamide diastereomers are nearly all well separated by capillary GC, and the use of this method to determine the enantiomeric purity of brucine-resolved 2-methoxy-2-phenylpropanoic acid was demonstrated.