Ortho Palladation and Functionalization of l-Phenylalanine Methyl Ester

Abstract

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, t Bu) 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)).

Synthesis and Reactivity of Ortho-Palladated Phenylacetamides. Intramolecular C−N vs C−O Reductive Coupling after CO or XyNC Insertion into the Pd−C Bond. Synthesis of Isoquinoline- and Isocoumarin-Based Heterocycles

“…Chemical shifts are referred to internal TMS ( 1 H and 13 C{ 1 H}) or external 85% H 3 PO 4 ( 31 P{ 1 H}). The assignments of the 1 H and 13 C{ 1 H} NMR spectra were made with the help of HMBC and HMQC experiments. Inserted and coordinated XyNC are denoted by XyNC i and XyNC c , respectively, and the C 6 H 4 aryl group is denoted as Ar. Melting points were determined on a Reichert apparatus and are uncorrected.…”

“…Anal. Calcd for C 14 13 [Pd{C 6 H 4 CH 2 C(O)NHMe-2}{CH(CN) 2 }(dbbpy)] (5b 0 ). To a solution of 4b 0 (95.6 mg, 0.183 mmol) in CH 2 Cl 2 (10 mL) was added malononitrile (12.2 mg, 0.185 mmol), and the mixture was stirred for 1 h. The resulting colorless solution was concentrated (1 mL), and n-pentane (30 mL) was slowly added, whereupon a colorless solid precipitated, which was filtered off, washed with n-pentane (3 Â 5 mL), and vacuum-dried to give 5b 0 3 0.25H 2 …”

“…This type of reactions have been widely studied, as they are involved in the synthesis of acyl [10][11][12][13][14][15] and iminoacyl 11,[13][14][15][16][17][18][19][20] palladium complexes and also in many stoichiometric and catalytic syntheses of organic compounds. [13][14][15][20][21][22] We report in this work that, depending on the substituents on the amidic nitrogen, these insertion reactions lead to isoquinoline-or isocoumarin-based heterocycles resulting from intramolecular C-N or C-O couplings. Both types of heterocyclic structures are present in numerous natural products and biologically active molecules, and both the development of suitable synthetic strategies and the study of their pharmacological activity are the subjects of intensive research.…”

Antitumor and antimycobacterial activities of cyclopalladated complexes: X-ray structure of [Pd(C2,N-dmba)(Br)(tu)] (dmba =N,N-dimethylbenzylamine, tu = thiourea)

“…0.03 Å longer than those found in related complexes [23,26], but shorter than the predicted value of 2.081 Å (based on the sum of the covalent radii for C(sp 2 ) and Pd, 0.771 and 1.31 Å, respectively) [27]. The Pd-Br distance of 2.566(2) Å is significantly longer than the sum of the covalent radii (2.45 Å) [27] but lies in the range of 2.568(1)-2.546(1) Å obtained for similar complexes containing the Pd-Br bond trans to the carbometallated site [28,29].…”

Reactions of m-chloroperoxybenzoic acid with dimeric cyclopalladated complexes derived from 2-phenyl-2-oxazolines

“…Reactions at the C-Pd bond of cyclopalladated complexes (CPCs) [1][2][3][4][5] (e.g., phosphination [6][7][8][9][10], chlorination [11][12][13][14], iodination [15][16][17][18][19], bromination [15,16], acetoxylation [20][21][22][23][24][25] and other transformations [15,[26][27][28][29][30][31]) represent an attractive method for highly regioselective functionalization of organic compounds. These Pd-mediated transformations are gaining importance as a synthetic method, providing access to new organic and organometallic compounds not readily available by other methods.…”