The Contribution of Ligand Flexibility to Metal Center Geometry Modulated Thermal Cyclization of Conjugated Pyridine and Quinoline Metalloenediynes of Copper(I) and Copper(II)

We report the syntheses, reactivities, and structure evaluations of a series of Cu(I) and Cu(II) metalloenediynes of conjugated 1,6-bis(pyridine-3)hex-3-ene-1,5-diyne (PyED, 7) and 1,6-bis(quinoline-3)hex-3-ene-1,5-diyne (QnED, 8) enediyne ligands, as well as their benzoenediyne analogues. Differential scanning calorimetry demonstrates that the [Cu(PyED)₂](NO₃)₂ (11) exhibits a Bergman cyclization temperature (156 °C) which is dramatically reduced from that of the corresponding [Cu(PyED)₂](PF₆) (19) analogue (326 °C), indicating that large differences in the reactivities of these metalloenediynes can be accessed by variations in metal oxidation state. The distorted, 4-coordinate dichloride compound Cu(PyED)(Cl)₂ (15) exhibits a cyclization temperature (265 °C) between those of 11 and 19, suggesting that variation in geometry of the copper center is responsible for the wide range of reactivities. Similar results are obtained for the benzoenediyne and quinoline analogues. The structures of the Cu(II) systems have also been evaluated by a combination of electronic absorption and EPR spectroscopies which reveal tetragonal, 6-coordinate structures for the bis(enediyne) complexes, and tetrahedrally distorted 4-coordinate Cu(enediyne)Cl₂ species. For the bis(quinoline) enediyne derivatives 12 and 14 the larger g-anisotropy (g_∥ = 2.27−2.28; g_⊥ = 2.06−2.07) indicates strong oxygen coordination from counterion. Molecular mechanics/dynamics calculations reveal that the geometries of these metal centers force the alkyne termini to a wide range of distances (3.85−4.20 Å), thereby accounting for the variability in Bergman cyclization temperatures. Overall, the results show that ligand rigidity plays a prominent role in the conformational response of the enediyne to metal center geometry, which results in enhanced variations in the Bergman cyclization temperatures between complexes of different geometries.