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

Aryl palladium complexes [Pd{C6H4CH2C(O)NRR′-2}I(N∧N)] (N∧N = N,N,N′,N′-tetramethylethylenediamine = tmeda, NRR′ = NH2 (1a), NHMe (1b), NMe2 (1c); N∧N = 4,4′-di-tert-butyl-2,2′-bipyridyl (dbbpy), NRR′ = NHMe (1b′)) are prepared by oxidative addition of the corresponding 2-(2-iodophenyl)acetamide to “Pd(dba)2” ([Pd2(dba)3]·dba; dba = dibenzylideneacetone) in the presence of the N∧N chelating ligand. Cationic cyclometalated derivatives [Pd{κ2C,O-C6H4CH2C(O)NRR′-2}(N∧N)]OTf (N∧N = tmeda, NRR′ = NH2 (2a), NHMe (2b), NMe2 (2c); N∧N = dbbpy, R = NHMe (2b′)) are obtained by reacting the appropriate complex 1 with AgOTf. The reaction of 2b′ with PPh3 affords [Pd{C6H4CH2C(O)NHMe-2}(dbbpy)(PPh3)]OTf (3b′). Neutral amidate complexes of the type [Pd{κ2C,N-C6H4CH2C(O)NR-2}(N∧N)] (N∧N = tmeda, R = H (4a), Me (4b); N∧N = dbbpy, R = Me (4b′)) are obtained upon deprotonation of the corresponding complex 1 with KOtBu. The complex [Pd{C6H4CH2C(O)NHMe-2}{CH(CN)2}(dbbpy)] (5b′) has been prepared by reacting 4b′ with malononitrile. Acyl derivatives [Pd{C(O)C6H4CH2C(O)NRR′-2}I(N∧N)] (N∧N = tmeda, NRR′ = NH2 (6a), NHMe (6b), NMe2 (6c); N∧N = dbbpy, NRR′ = NHMe (6b′)) have been prepared by reacting the corresponding complex 1 with CO at low temperature; when N∧N = tmeda, prolonged reaction times and high temperatures lead to Pd(0) and isoquinoline-1,3(2H,4H)-dione (7a), a 1:2 mixture of 2-methylisoquinoline-1,3(2H,4H)-dione (7b) and 3-(dimethylamino)-1H-2-benzopyran-1-one (8b), or 3-(methylamino)-1H-2-benzopyran-1-one (8c), respectively. Similar results are obtained from the reactions of 2a−c with CO under much milder conditions, while 2b′ reacts with CO in acetone to give the isochroman-1-one derivative N,3,3-trimethyl-1-oxo-3,4-dihydro-1H-2-benzopyrane-4-carboxamide (9). While the reaction of 1b′ with 1 equiv of XyNC (Xy = 2,6-dimethylphenyl) gives the iminoacyl complex [Pd{C(NXy)C6H4CH2C(O)NHMe-2}I(dbbpy)] (10b′), the homologous products from the tmeda derivative 1a, 1b, or 1c decompose, giving Pd(0) and 1-(2,6-dimethylphenylimino)-1,2-dihydroisoquinolin-3(4H)-one (11a), 1-(2,6-dimethylphenylimino)-2-methyl-1,2-dihydroisoquinolin-3(4H)-one (11b), or 1-(2,6-dimethylphenylimino)-3-(N,N-dimethylamino)-1H-2-benzopyrane (12c), respectively. The reaction of 1a or 1b′ with 3 equiv of XyNC affords trans-[Pd{C(NXy)C6H4CH2C(O)NHR-2}I(CNXy)2] (R = H (13a), Me (13b)); the protonation of 13b with HOTf leads to [Pd{C(NHXy)C6H4CH2C(O)NH2)-2}I(CNXy)2]OTf (14a). Complexes [Pd{C(NXy)C6H4{C6H4CH2C(O)NRR′-2}-2}(CNXy)(N∧N)]OTf (N∧N = tmeda, NRR′ = NHMe (15b), NMe2 (15c); N∧N = dbbpy, NRR′ = NHMe (15b′)) are obtained by reacting the appropriate complex 2 with 2 equiv of XyNC.