Sequential insertion of alkynes and CO or isocyanides into the Pd-C bond of cyclopalladated phenylacetamides. Synthesis of eight-membered palladacycles, benzo[d]azocine-2,4(1 H,3 H)-diones, and highly functionalized acrylonitrile and acrylamide derivatives

Article abstract of DOI:10.1021/om300151n

The cyclopalladated complexes [Pd{κ²C,O-C ₆H₄CH₂C(O)NRR′-2}(tmeda)]TfO [R = R′ = H (1a), R = Me, R′ = H (1b), R = R′ = Me (1c)] react with alkynes XC≡CX′ in 1:3 molar ratio to give the eight-membered palladacycles [Pd{κ²C,O-C(X)C(X′)C₆H ₄CH₂C(O)NRR′-2}(tmeda)]TfO [R = R′ = H and X = X′ = Ph (2aa), CO₂Me (2ab), Et (2ac) or X = Ph, X′ = Me (2ad); R = Me, R′ = H and X = X′ = Ph (2ba), CO₂Me (2bb), Et (2bc) or X = Ph, X′ = Me (2bd); R = R′ = Me and X = X′ = Ph (2ca)]. The treatment of complexes 2aa, 2ac, 2ad, 2ba, 2bc, and 2bd with CO at 50 °C affords the corresponding benzo[d]azocine-2,4(1H,3H)-diones (3), which result from the insertion of a molecule of CO into the Pd-C bond and subsequent C-N reductive coupling and formation of (tmedaH)TfO. The reaction of 2ab with CO in MeOH gives (MeO₂C)₂CC(CO ₂Me)C₆H₄CH₂C(O)NH₂-2 (4ab). Complexes 2aa and 2ab react with 1 equiv of R″NC 1:1 to give [Pd{C(X)C(X′)C₆H₄CH₂C(O)NH ₂-2}(CNR″)(tmeda)]TfO [R″ = t-Bu, X = X′ = Ph (5a), CO₂Me (5b); R = Xy, X = X′ = Ph (5a′), CO₂Me (5b′)]. While 2aa reacts with 1 equiv of R″NC in refluxing CHCl ₃ to give a low yield of the compound XyHNC(O)C(Ph)C(Ph)C ₆H₄CH₂C(O)NH₂-2 (6a) when R″ = Xy, the complex 2aa, 2ba, or 2ca affords the acrylonitrile derivative NCC(Ph)C(Ph)C₆H₄CH₂C(O)NRR′-2 [R = R′ = H (7a), R = Me, R′ = H (7b), R = R′ = Me (7c)] when R″ = t-Bu; alternatively, the latter derivatives can be obtained by refluxing in situ generated solutions of the corresponding cyano complexes [Pd{C(Ph)C(Ph)C₆H₄CH₂C(O)NRR′-2}(CN) (tmeda)] in CHCl₃. The intermediate cyano complex with R = R′ = H (8) has been isolated and characterized. The reactions of 2aa, 2ba, 2ca, and 2ac with 4 equiv of XyNC give [Pd₃(CNXy)₆] and mixtures from which the compounds XyNHC(O)C(Ph)C(Ph)C₆H₄CH ₂CN-2 (9, from 2aa), XyNHC(O)C(Ph)C(Ph)C₆H ₄CH₂C(O)NRR′-2 [R = Me, R′ = H (6b), R = R′ = Me (6c), from 2ba or 2ca, respectively], or [Pd{C(NXy)C(Et)C(Et) C₆H₄CH₂CN-2}Cl(CNXy)₂] (10, from 2ac) can be isolated. The crystal structures of 2aaη2Et₂O, 3aa, 3ac, 8, 9, and 10 have been determined.