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

Aryl palladium complexes [Pd­{C₆H₄C­(O)­NRR′-2}­I­(tmeda)] [NRR′ = NH₂ (<b>1a</b>), NHMe (<b>1b</b>), NMe₂ (<b>1c</b>); tmeda = <i>N,N,N</i>′<i>,N</i>′-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{κ²<i>C,O</i>-C₆H₄­C­(O)­NRR′-2}­(tmeda)]­TfO (<b>2a</b>–<b>c</b>) are obtained by iodide abstraction from the appropriate complex <b>1</b> with AgTfO, while the deprotonation of the amide function of <b>1a</b> or <b>1b</b> with KO^<i>t</i>Bu gives the neutral amidate complexes [Pd­{κ²<i>C,N</i>-C₆H₄­C­(O)­NR-2}­(tmeda)] [R = H (<b>3a</b>), Me (<b>3b</b>)]. Complexes <b>2a</b>,<b>b</b> and <b>3a</b>,<b>b</b> react with CO under mild conditions to yield phthalimide (<b>4a</b>) or <i>N</i>-methylphthalimide (<b>4b</b>), whereas the reactions of derivatives <b>1c</b> and <b>2c</b> with CO are very slow and give <i>N</i>¹,<i>N</i>¹,<i>N</i>²,<i>N</i>²-tetramethylphthalamide and phthalic anhydride. The reaction of <b>1b</b> with 1 equiv of XyNC (Xy = 2,6-dimethylphenyl) or ^<i>t</i>BuNC affords Pd(0), (tmedaH)­I, and 3-(2,6-dimethylphenylimino)-2-methylisoindolin-1-one (<b>5b</b>) or 3-(<i>tert</i>-butylimino)-2-methylisoindolin-1-one (<b>5b</b>′), respectively, while complex <b>1c</b> reacts with 3 equiv of XyNC to give <i>trans-</i>[Pd­{C­(NXy)­C₆H₄C­(O)­NMe₂-2}­I­(CNXy)₂] (<b>6</b>). The seven-membered palladacycles [Pd­{κ²<i>C,O</i>-C­(X)C­(X′)­C₆H₄C­(O)­NRR′-2}­(tmeda)]­TfO [NRR′ = NH₂ and X = Ph, X′ = Me (<b>7a</b>); NRR′ = NHMe and X = Ph, X′ = Me (<b>7b</b>), X = X′ = Ph <b>(8b</b>), Et (<b>9b</b>), CO₂Me (<b>10b</b>), X = CO₂Me, X′ = Ph (<b>11b</b>), X = CO₂Et, X′ = Ph (<b>12b</b>); NRR′ = NMe₂ and X = X′ = Ph (<b>8c</b>), Et (<b>9c</b>)] are obtained from the reactions of <b>2a</b>–<b>c</b> with alkynes. Treatment of complexes <b>7a</b>, <b>7b</b>, <b>8b</b>, and <b>9b</b> with CO at room temperature gives the corresponding 2<i>H</i>-benzo­[<i>c</i>]­azepine-1,3-diones (<b>14</b>), 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 <b>11b</b> or <b>12b</b> 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 (<b>15</b>), 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(κ²<i>C,O</i>-C₁₄H₁₃O₅)­(tmeda)] (<b>18</b>) was synthesized by reacting the cationic derivative <b>10b</b> with NaOMe in MeOH. Depalladation of <b>18</b> gives (<i>E</i>)-4-[methoxy­(methoxycarbonyl)­methylene]-2-methylisoquinoline-1,3­(2<i>H</i>,4<i>H</i>)-dione (<b>19</b>)