Ortho Palladation of the Phenethylamines of Biological Relevance l-Tyrosine Methyl Ester and Homoveratrylamine. Reactivity of the Palladacycles toward CO and Isocyanides. Synthesis of the Natural Alkaloid Corydaldine

Palladacycles derived from l-tyrosine methyl ester, (S)-[Pd₂{C,N-C₆H₃CH₂CH­(CO₂Me)­NH₂-2,(OH)-4}₂(μ-Br)₂] (1a-Br), and homoveratrylamine, [Pd₂{C,N-C₆H₂CH₂CH₂NH₂-6,(OMe)₂-3,4}₂(μ-Br)₂] (1b-Br), can be easily prepared in good yield by reacting Pd­(OAc)₂, the corresponding ammonium triflate, and NaBr. Under the same conditions, the reaction of Pd­(OAc)₂ with the free amine affords a low yield of the corresponding acetato complex 1a-OAc or 1b-OAc (the latter only detected in solution). In our hands, the previously reported palladation at the C2 position of homoveratrylamine with Pd­(OAc)₂ is not observed. Instead, a complex mixture is obtained, mainly containing [Pd­(OAc)₂{NH₂CH₂CH₂C₆H₃(OMe)₂-3,4}₂] and minor amounts of 1b-OAc, which reacts with NaBr to afford a new mixture from which [PdBr₂{NH₂CH₂CH₂C₆H₃(OMe)₂-3,4}₂] can be isolated and characterized. These and other adducts can be isolated from Pd­(OAc)₂, homoveratrylamine, and various ligands (PPh₃ and Br^–). 6-Bromohomoveratrylamine reacts with Pd­(dba)₂ in the presence of tmeda to give the complex [Pd­{C,N-C₆H₂CH₂CH₂NH₂-6,(OMe)₂-3,4}­(tmeda)]­Br. Reactions of complexes 1 with acetylacetonato or neutral (PR₃) ligands give products resulting from substitution or bridge-splitting reactions. While 1a-Br reacts with XyNC (1:2 molar ratio) to give (S)-[Pd­{C,N-C₆H₃CH₂CH­(CO₂Me)­NH₂-2,(OH)-4}­Br­(CNXy)], 1b-Br gives [Pd­{C,N-C­(NXy)-C₆H₂CH₂CH₂NH₂-6,(OMe)₂-3,4}­Br­(CNXy)]. (S)-7-Hydroxy-3-(methoxycarbonyl)-3,4-dihydroisoquinolin-1­(2H)-one and 6,7-dimethoxy-3,4-dihydroisoquinolin-1­(2H)-one (corydaldine) have been synthesized through the stoichiometric carbonylation of palladacycles 1a-Br and 1b-Br. The crystal structures of a solvento intermediate in the ortho-metalation reaction of the triflate derivative of l-tyrosine methyl ester and four other complexes have been determined by X-ray diffraction studies.