Reactivity of Ortho-Palladated Benzamides toward CO, Isocyanides, and Alkynes. Synthesis of Functionalized Isoindolin-1-ones and 4,5-Disubstituted Benzo[c]azepine-1,3-diones

Aryl palladium complexes [Pd­{C6H4C­(O)­NRR′-2}­I­(tmeda)] [NRR′ = NH2 (1a), NHMe (1b), NMe2 (1c); tmeda = N,N,N′,N′-tetramethylethylenediamine] are prepared by oxidative addition of the corresponding 2-iodophenylbenzamides to “Pd­(dba)2” ([Pd2(dba)3]·dba; dba = dibenzylideneacetone) in the presence of tmeda. Cationic cyclometalated derivatives [Pd­{κ2C,O-C6H4­C­(O)­NRR′-2}­(tmeda)]­TfO (2a–c) are obtained by iodide abstraction from the appropriate complex 1 with AgTfO, while the deprotonation of the amide function of 1a or 1b with KOtBu gives the neutral amidate complexes [Pd­{κ2C,N-C6H4­C­(O)­NR-2}­(tmeda)] [R = H (3a), Me (3b)]. Complexes 2a,b and 3a,b react with CO under mild conditions to yield phthalimide (4a) or N-methylphthalimide (4b), whereas the reactions of derivatives 1c and 2c with CO are very slow and give N1,N1,N2,N2-tetramethylphthalamide and phthalic anhydride. The reaction of 1b with 1 equiv of XyNC (Xy = 2,6-dimethylphenyl) or tBuNC affords Pd(0), (tmedaH)­I, and 3-(2,6-dimethylphenylimino)-2-methylisoindolin-1-one (5b) or 3-(tert-butylimino)-2-methylisoindolin-1-one (5b′), respectively, while complex 1c reacts with 3 equiv of XyNC to give trans-[Pd­{C­(NXy)­C6H4C­(O)­NMe2-2}­I­(CNXy)2] (6). The seven-membered palladacycles [Pd­{κ2C,O-C­(X)C­(X′)­C6H4C­(O)­NRR′-2}­(tmeda)]­TfO [NRR′ = NH2 and X = Ph, X′ = Me (7a); NRR′ = NHMe and X = Ph, X′ = Me (7b), X = X′ = Ph (8b), Et (9b), CO2Me (10b), X = CO2Me, X′ = Ph (11b), X = CO2Et, X′ = Ph (12b); NRR′ = NMe2 and X = X′ = Ph (8c), Et (9c)] are obtained from the reactions of 2a–c with alkynes. Treatment of complexes 7a, 7b, 8b, and 9b with CO at room temperature gives the corresponding 2H-benzo­[c]­azepine-1,3-diones (14), resulting from the insertion of a molecule of CO into the Pd–C bond followed by a C–N reductive coupling. In contrast, the reactions of 11b or 12b with CO in the presence of residual water or 2 equiv of ROH (R = Me, Et) lead to 2-methyl-3-phenylisoindolin-1-one derivatives (15), resulting from a CO insertion followed by an intramolecular aza-Michael addition of the NHMe moiety to the activated vinyl group and subsequent hydrolysis or alcoholysis of the acyl–Pd bond. The neutral complex [Pd­(κ2C,O-C14H13O5)­(tmeda)] (18) was synthesized by reacting the cationic derivative 10b with NaOMe in MeOH. Depalladation of 18 gives (E)-4-[methoxy­(methoxycarbonyl)­methylene]-2-methylisoquinoline-1,3­(2H,4H)-dione (19).