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{κ 2 ( C,N )-C 10 H 6 CH 2 CH(CO 2 Me)NH 2 -2}Cl(CNR)] (R = t Bu ( 1a- t Bu ), Xy (C 6 H 3 Me 2 -2,6) ( 1a-Xy )). Similar complexes ( S )-[Pd{κ 2 ( C, N )-C 8 H 5 N(CH 2 CH(CO 2 Me)NH 2 )-2}Cl(CNR)] (R = t Bu ( 1b- t Bu ), Xy ( 1b-Xy )) are prepared from RNC and a previously reported cyclometalated derivative of l -tryptophan methyl ester, ( S, S )-[Pd 2 {κ 2 ( C, N )-C 8 H 5 N(CH 2 CH(CO 2 Me)NH 2 )-2} 2 (μ-Cl) 2 ] ( B ). Compound 1b-Xy reacts with XyNC to give the iminoacyl complex ( S )-[Pd{κ 2 ( C, N )-C(═NXy)C 8 H 5 N(CH 2 CH(CO 2 Me)NH 2 )-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 ( D; see Chart ) reacts with RNC (R = t Bu, Xy) in refluxing chloroform or toluene to render, depending on the reaction conditions, the cyclic amidines ( 3c- t Bu, 3d-Xy ) or the amidinium salts ( 4b- t Bu, 4c- t Bu, 4c-Xy, 4d- t Bu, 4d-Xy ). The amidines 3a- t Bu and 3a-Xy and the amidinium salts 4a- t Bu and 4a-Xy are synthesized from complexes 1a - t Bu and 1a - Xy . When D reacts with isothiocyanates RNCS (R = Me, To (C 6 H 4 Me-4)), the cyclic amidinium 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 CHCl 3 or CH 2 Cl 2 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-1 H -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- t Bu, 4c- t Bu, 4d- t Bu, 4d-Xy, 4d-Me, 4d-To, and 5a − d have been determined by X-ray diffraction studies.