Molecular Library Obtained by Allene Insertion into the Pd−C Bond of Cyclopalladated Complexes: Biological and Pharmacological Evaluation

Abstract

A minilibrary of cationic N-heterocycles has been prepared and evaluated. The potential for the preparation was a result of the high versatility of palladium-mediated chemistry. The synthesis of the novel molecules was based on intramolecular quaternization of tertiary amine attached allylpalladium complexes. The steric and electronic factors of the reaction are discussed. The structures of the synthesized molecules made them candidates for precise biological and pharmaco-

Insertion of Allenes into the Pd–C Bond of Ortho-Palladated Primary Arylamines of Biological Relevance: Phenethylamine, Phentermine, (l)-Phenylalanine Methyl Ester, and (l)-Tryptophan Methyl Ester. Synthesis of Tetrahydro-3-benzazepines and Their Salts

“…Pfeffer et al have reported the stoichiometric synthesis of N-heterocycles from allenes and palladacycles containing functionalized pyridines, tertiary anilines, or N , N -dimethyl amines. , For instance, the reaction of [Pd( C , N -C 6 H 4 CH 2 NMe 2 -2)(μ-Cl)] 2 ( 1h ; Scheme ) with 1,1-dimethyl­allene in the presence of PPh 3 affords the isoquinolinium salt Q . It was proposed that this reaction occurred through (1) formation of an η 3 -allyl complex, in which the NMe 2 group was not coordinated to the metal, and (2) nucleophilic attack of the free amino group to the less-hindered external carbons of the allylic moiety.…”

“…There is a study of a seven-membered palladacycle derived from (2-ethynylphenyl)-N,N-dimethylmethanamine. 11 Therefore, we also report here the first insertion reactions of allenes into the Pd−C bond of ortho-palladated primary amines.…”

“…Allenes insert into the Pd–C aryl bonds to give η 3 -allyl complexes in which a new bond forms between the previously metalated carbon and the central carbon of the allene moiety. − These insertion reactions have been widely investigated because they are the key step in the palladium-catalyzed coupling reactions of 1,2-dienes and aryl halides to afford carbo- and heterocycles. ,− We report here a study of the reactivity toward allenes of six-membered palladacycles derived from amines of biological relevance, such as as phenethylamine, phentermine, ( l )-phenylalanine methyl ester, and ( l )-tryptophan methyl ester, the functionalization of which was also an objective of the work. There are just a few examples of insertion reactions of allenes into the Pd–C aryl bond of stable κ 2 ( C , N )-palladacycles. , These include mainly five-membered cyclometalated complexes derived from α-tetralone ketimine, benzo[ h ]quinoline, 2-phenylpyridine, , N , N -dimethylbenzylamine, N , N -dimethylnaphthylamine, and N , N -dimethylpropargylamines, although there are two examples containing six-membered derivatives of 2-benzylpyridine and N -phenyl- N -(2-pyridyl)-amine. , As the latter amine is bonded to Pd through the pyridine group, our study represents the first devoted to the reactivity of six-membered cyclopalladated amines toward allenes. There is a study of a seven-membered palladacycle derived from (2-ethynylphenyl)- N , N -dimethylmethanamine .…”

“…There are just a few examples of insertion reactions of allenes into the Pd–C aryl bond of stable κ 2 ( C , N )-palladacycles. , These include mainly five-membered cyclometalated complexes derived from α-tetralone ketimine, benzo[ h ]quinoline, 2-phenylpyridine, , N , N -dimethylbenzylamine, N , N -dimethylnaphthylamine, and N , N -dimethylpropargylamines, although there are two examples containing six-membered derivatives of 2-benzylpyridine and N -phenyl- N -(2-pyridyl)-amine. , As the latter amine is bonded to Pd through the pyridine group, our study represents the first devoted to the reactivity of six-membered cyclopalladated amines toward allenes. There is a study of a seven-membered palladacycle derived from (2-ethynylphenyl)- N , N -dimethylmethanamine . Therefore, we also report here the first insertion reactions of allenes into the Pd–C bond of ortho-palladated primary amines.…”

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

“…Due to these adverse effects, research moved on to second and third-generation platinum compounds like carboplatin [1] and oxaliplatin [4], respectively, as well as to other metal complexes with improved pharmacological properties [5,6]. Among the non-platinum metal complexes studied for cancer treatment, palladium(II) derivatives were readily chosen due to their structural analogy with those containing Pt(II) [4,7].…”