Design of pincer complexes based on (methylsulfanyl)acetic/propionic acid amides with ancillary S‐ and N‐donors as potential catalysts and cytotoxic agents

Abstract

Pincer complexes featuring readily tunable tridentate ligand frameworks comprise one of the most actively studied classes of organometallic and metalorganic compounds and find extensive use in catalysis, organic synthesis, materials science, and other fields of chemistry and allied disciplines. Currently growing attention is devoted to non-classical ligand scaffolds, such as functionalized carboxamides, which offer multiple options for directed structural modifications. In this study, the reactions of (methylsulfanyl)acetyl and propanoyl chlorides with 2-(aminomethyl)pyridine, 2-(2-aminoethyl)pyridine, 8aminoquinoline and 2-(diphenylthiophosphoryl)aniline afford a series of new pincer-type ligands based on functionalized carboxamides. The ligands obtained readily undergo direct cyclopalladation under the action of PdCl 2 (NCPh) 2 in dichloromethane at room temperature, resulting in Pd(II) pincer complexes with N,N,S-and S,N,S-donor sets. Importantly, some of the cyclopalladated derivatives can also be produced efficiently under solvent-free conditions according to the approach recently developed by our group. The complexes obtained have been tested for cytotoxicity against several human cancer cell lines and catalytic activity in the model Suzuki reaction. The results have been compared to those for the related Pd(II) pincer complexes to define the main structure-activity relationships and to outline the most promising structures for further investigations. Yield: 87 mg (95%). M.p. > 225°C (dec.). 1 H NMR (400.13 MHz, CDCl 3 , δ, ppm): 2.73 (ddd, 1H, CH 2 , 2 J HH = 1.9 Hz, 3 J HH = 16.8 Hz, 3 J HH = 7.3 Hz), 3.15 (ddd, 1H, CH 2 S(O), 2 J HH = 2.2 Hz, 3 J HH = 16.8 Hz, 3 J HH = 11.4 Hz), 3.36 (ddd, 1H, CH 2 , 2 J HH = 1.9 Hz, 3 J HH = 13.0 Hz, 3 J HH = 11.4 Hz), 3.47 (ddd, 1H, CH 2 S(O), 2 J HH = 2.2 Hz, 3 J HH = 13.0 Hz, 3 J HH = 7.3 Hz), 3.51 (s, 3H, Me), 5.03 and 5.22 (ABq, 2H, CH 2 Py, J AB = 20.3 Hz), 7.35-7.39 (m, 1H, H(C4)), 7.48 (d, 1H, H(C2), 3 J HH = 7.9 Hz), 7.91 (dt, 1H, H(C3), 3 J HH = 7.9 Hz, 4 J HH = 1.6 Hz), 9.05 (d, 1H, H(C5), 3 J HH = 5.4 Hz).13

Heteroleptic Palladium(II) Complexes of Thiazolinyl‐picolinamide Derived N∩N∩N Pincer Ligand: An Efficient Catalyst for Acylative Suzuki Coupling Reactions

“…[13,33] However, late transition metal amido complexes have been found to be potential catalysts for many organic transformations including transfer hydrogenation to an unsaturated substrate and coupling reactions (Figure 1). [34][35][36][37][38][39][40][41][42][43][44][45][46] The intrinsic structure of the pincer ligands allows the development of late transition metal amido complexes and to explore their catalytic activities. [47,48] Palladium-catalyzed cross-coupling reactions are important and pioneering methodology for producing the C sp 2 À C sp 2 , C sp 2 À N and C sp 2 À O in the synthesis of industrially important valueadded molecules and other natural products, bioactive compounds, polymers, and materials.…”

Halide exchange studies of novel Pd(ii) NNN-pincer complexes

“…Pincer metal complexes in which three donor sites of the ligand stabilize a planar metal center have been studied extensively. Variations to the so-called ECE type ligand (Chart 1) where E symbolizes coordination through anking NR 2 , PR 2 , SR, SeR or OR groups afford complexes with applications especially in catalysis [1][2][3][4][5][6][7][8] but also in other elds including sensing, 6,9-12 materials science [13][14][15][16][17][18][19] and medicinal chemistry. 18,20 Among various metals, palladium is one of the most studied owing mainly to its importance in organic synthesis.…”

“…Variations to the so-called ECE type ligand (Chart 1) where E symbolizes coordination through anking NR 2 , PR 2 , SR, SeR or OR groups afford complexes with applications especially in catalysis [1][2][3][4][5][6][7][8] but also in other elds including sensing, 6,9-12 materials science [13][14][15][16][17][18][19] and medicinal chemistry. 18,20 Among various metals, palladium is one of the most studied owing mainly to its importance in organic synthesis. While formation of a carbon-palladium bond provides stability, replacing carbon with other elements such as Si, P, N have been shown to lead to signicant changes in reactivity and an lead to signicant developments in catalysis 4,8,[21][22][23][24][25][26][27] and cytotoxicity studies.…”

“…While formation of a carbon-palladium bond provides stability, replacing carbon with other elements such as Si, P, N have been shown to lead to signicant changes in reactivity and an lead to signicant developments in catalysis 4,8,[21][22][23][24][25][26][27] and cytotoxicity studies. 18,20,[28][29][30][31][32] A key factor in reactivity is the general lability of the fourth coordination site. For instance, the nature of the monodentate ligand (L) at the fourth coordination site has been shown to provide remarkable control over the electronic structures of palladium and platinum complexes with NCN pincer ligands.…”

“…While formation of a carbon–palladium bond provides stability, replacing carbon with other elements such as Si, P, N have been shown to lead to significant changes in reactivity and an lead to significant developments in catalysis 4,8,21–27 and cytotoxicity studies. 18,20,28–32 …”