Pd−Catalyzed MIA−Directed Methoxylation of Phenylalanines: A Combined Experimental and Computational Study

Abstract The direct methoxylation of substituted phenylalanines has been accomplished via methoxyiminoacyl (MIA)-mediated Pd-catalyzed C–H functionalization. A diverse array of ortho-methoxylated phenylalanine derivatives are efficiently generated in good to high yields. KIE study has shown that the oxhydryl cleavage step is the rate-limiting step. The computational data show that the participation manner of methanol has a great influence on the energy barriers of transition states during the C(sp2)–O formation stage. The pathway containing stepwise deprotonation and reductive elimination is superior to that of a concerted deprotonation-methoxylation.