Synthesis and Reactivity of Ortho-Palladated 3‑Phenylpropanamides. Insertion of CO, XyNC, and Alkynes into the Pd–C Bond. Synthesis of Seven- and Nine-Membered Palladacycles and Benzazepine- and Benzazonine-Based Heterocycles

Aryl palladium complexes [Pd­{C6H4(CH2)2C­(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 3-(2-iodophenyl)­propanamides to “Pd­(dba)2” ([Pd2(dba)3]·dba; dba = dibenzylideneacetone) in the presence of tmeda. The cationic seven-membered palladacycles [Pd­{κ2C,O-C6H4(CH2)2C­(O)­NRR′)-2}­(tmeda)]­TfO (2a–c) are obtained by reacting 1a–c with AgTfO. Neutral amidate complexes of the type [Pd­{κ2C,N-C6H4(CH2)2C­(O)­NR)-2}­(tmeda)] [R = H (3a), Me (3b)] are obtained upon deprotonation of the amide function in 1a or 1b with KOtBu. The reaction of 1a with CO at room temperature affords the stable acyl derivative [Pd­{C­(O)­C6H4(CH2)2C­(O)­NH2-2}­I­(tmeda)] (4), while 2a gives Pd, (tmedaH)­TfO, and 4,5-dihydro-2H-benzo­[c]­azepine-1,3-dione (5a). Compound 5a can also be obtained in high yield by treating the amidate complex 3a with CO, while a low yield of 2-methyl-4,5-dihydro-2H-benzo­[c]­azepine-1,3-dione (5b) was obtained from 3b under the same conditions. Complexes 1a–c react with 3 equiv of XyNC to give trans-[Pd­{C­(NXy)­C6H4(CH2)2C­(O)­NRR′-2}­I­(CNXy)2] [NRR′ = NH2 (6a), NHMe (6b), NMe2 (6c)]. By refluxing a CHCl3 solution of 6a or 1a and XyNC in 1:1 molar ratio, mixtures of 1-(2,6-dimethylphenylimino)-1,2,4,5-tetrahydrobenzo­[c]­azepin-3-one (7a) and 2-(2-cyanoethyl)-N-(2,6-dimethylphenyl)­benzamide (8a) are obtained. Complexes 2a–c react with alkynes in 1:1 molar ratio to give nine-membered palladacycles of the type [Pd­{κ2C,O-C­(X)C­(X)­C6H4(CH2)2C­(O)­NRR′-2}­(tmeda)]­TfO [NRR′ = NH2, X = Ph (9a), C6H4nBu-4 (10a), C6H4Br-4 (11a), CO2Me (12a); NRR′ = NHMe, X = Ph (9b); NRR′ = NMe2, X = Ph (9c)]. The reaction of 2a with an excess of 3-hexyne gives the complex [Pd­{η3-C6H4(C4Et4)­(CH2)2C­(O)­NH2}­(tmeda)]­TfO (13), containing a spirocyclic ligand coordinated to Pd through a η3-allylic bond. The derivatives 9a, 10a and 11a react with CO at 50 °C in CHCl3 to give colloidal Pd, (tmedaH)­TfO, and the corresponding 6,7-disubstituted 1,2-dihydro-4H-benzo­[e]­azonine-3,5-diones (14, 15, 16), which result from a CO insertion/C–N reductive coupling sequence.