Ortho Palladation and Functionalization of l-Phenylalanine Methyl Ester†

The ortho-metalated complex (S,S)-[Pd2{κ2(C,N)-C6H4CH2CH(CO2Me)NH2-2}2(μ-Br)2] (1b) can be prepared by refluxing in acetonitrile equimolecular amounts of Pd(OAc)2 and l-phenylalanine methyl ester hydrochloride, followed by addition of an excess of NaBr. Complex 1b reacts with 4-picoline to give the mononuclear derivative (S)-[Pd{κ2(C,N)-C6H4CH2CH(CO2Me)NH2-2}2Br(NC5H4Me-4)] (2), whose crystal structure has been determined by X-ray diffraction. The precursor of 1b, (S,S)-[Pd2{κ2(C,N)-C6H4CH2CH(CO2Me)NH2-2}2(μ-Cl)2] (1a), could not be isolated in a pure form, but it can be used as the starting material for the synthesis of functionalized derivatives of the phenylalanine methyl ester. Thus, CO and RNC (R = Xy, tBu) insert into the Pd−C bond of 1a to afford, after depalladation, (S)-1-oxo-3-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline (3) and (S)-1-R-3-(methoxycarbonyl)-3,4-dihydroisoquinolinium triflate (R = tBu (4), Xy (5)), respectively. Reaction of complex 1b with bromine or iodine affords trans-(S,S)-[PdBr2{NH2CH(CO2Me)CH2C6H4-X-2}2] (X = Br (6), I (7)), which further reacts with 1,10-phenanthroline (phen) to give [PdBr2(phen)] and (S)-2-X-phenylalanine methyl ester (X = Br (8), I (9)).