Insertion of Isocyanides, Isothiocyanates, and Carbon Monoxide into the Pd-C Bond of Cyclopalladated Complexes Containing Primary Arylalkylamines of Biological and Pharmaceutical Significance. Synthesis of Lactams and Cyclic Amidinium Salts Related to the Isoquinoline, Benzo[g]isoquinoline, and β-Carboline Nuclei

Cyclometalation of 3-(2-naphthyl)-D-alanine methyl ester is achieved by reacting the corresponding hydrochloride salt and Pd(OAc)(2) in a 1: 1 molar ratio (acetonitrile, room temperature, 6 days). Although the chloro-bridged dimer (A) cannot be isolated in a pure form, addition of RNC to the reaction mixture affords the mononuclear derivatives (R)-[Pd{kappa(2)(C,N)-C10H6CH2CH(CO2Me)NH2-2}Cl(CNR)] (R = Bu-t (1a-Bu-t), Xy (C6H3Me2-2,6) (1a-Xy)). Similar complexes (S)-[Pd{kappa(2)(C,N)-C8H5N(CH2CH(CO2Me)NH2)-2}Cl(CNR)] (R = Bu-t (1b-Bu-t), Xy (1b-Xy)) are prepared from RNC and a previously reported cyclometalated derivative Of L-tryptophan methyl ester, (S,S)-[Pd-2{kappa(2)(C,N)-C8H5N(CH2CH(CO2Me)NH2)-2}(2)(mu-Cl)(2)] (B). Compound 1b-Xy reacts with XyNC to give the iminoacyl complex (S)-[Pd(kappa(2)(C,N)- C(=NXy)C8H5N(CH2)CH(CO2Me)NH2)-2} Cl(CNXy)] (2b), whose crystal structure has been determined by X-ray diffraction studies. The cyclopalladated dimer B or those containing phenethylamine (C) or phentermine (1); see Chart 1) reacts with RNC (R = Bu-t, Xy) in refluxing chloroform or toluene to render, depending on the reaction conditions, the cyclic amidines (3c-Bu-t, 3d-Xy) or the amidinium salts (4b-Bu-t, 4c-Bu-t, 4c-Xy, 4d-Bu-t, 4d-Xy). The amidines 3a-Bu-t and 3a-Xy and the amidiniurn salts 4a-Bu-t and 4a-Xy are synthesized from complexes 1a-Bu-t and 1a-Xy. When D reacts with isothiocyanates RNCS (R = Me, To (C6H4Me-4)), the cyclic amidiniurn salts 4d-Me and 4d-To are isolated. Amidinium triflates derived from phentermine with an aryl substituent at the exocyclic nitrogen atom (4d-Xy, 4d-To) present E/Z isomerism in CHCl3 or CH2Cl2 Solution. CO reacts with A-D to give, after depalladation, the corresponding lactams: (R)-1-oxo-3-(methoxycarbonyl)-1,2,3,4-tetrahydrobenzo[g]isoquinoline (5a), (S)-1-oxo-3-(methoxycarbonyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (5b), 1-oxo-1,2,3,4-tetrahydroisoquinoline (5c), and 1-oxo-3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline (5d). The crystal structures of compounds 4b-Bu-t, 4c-Bu-t, 4d-Bu-t, 4d-Xy, 4d-Me, 4d-To, and 5a-d have been determined by X-ray diffraction studies.