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 KO^tBu. 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.