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}](N boolean AND N)] (N boolean AND N = N,N,N',N'-tetramethylethylenediamine = tmeda, NRR' = NH2 (la), NHMe (1b), NMe2 (1c); N boolean AND 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) ([Pd-2(dba)(3)]center dot dba; dba = dibenzylideneacetone) in the presence of the N boolean AND N chelating ligand. Cationic cyclometalated derivatives [Pd{kappa C-2,O-C6H4CH2C(O)NRR'-2}-(N boolean AND N)]OTf (N boolean AND N = tmeda, NRR' = NH2 (2a), NHMe (2b), NMe2 (2c); N boolean AND 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 {kappa C-2,N-C6H4CH2C(O)NR-2} (N boolean AND N)] (N boolean AND N = tmeda, R = H (4a), Me (4b); N boolean AND N = dbbpy, R = Me (4b')) are obtained upon deprotonation of the corresponding complex 1 with (KOBu)-Bu-t. 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 boolean AND N)] (N boolean AND N = tmeda, NRR' = NH2 (6a), NHMe (6b), NMe2 (6c); N boolean AND N = dbbpy, NRR' = NHMe (6b')) have been prepared by reacting the corresponding complex 1 with CO at low temperature; when N boolean AND 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)1 (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 boolean AND N)]OTf (N boolean AND N = tmeda, NRR' = NHMe (15b), NMe2 (15c); N boolean AND N = dbbpy, NRR' = NHMe (15b')) are obtained by reacting the appropriate complex 2 with 2 equiv of XyNC.