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 serie s 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 (QnE D, 8) enediyne ligands, as well as their benzoenediyne analogues. Different ial scanning calorimetry demonstrates that the [Cu(PyED)(2)](NO3)(2) (11) e xhibits a Bergman cyclization temperature (156 degreesC) which is dramatica lly reduced from that of the corresponding [CU(PyED)(2)](PF6) (19) analogue (326 degreesC), indicating that Large differences in the reactivities of t hese metalloenediynes can be accessed by variations in metal oxidation stat e. The distorted, 4-coordinate dichloride compound Cu(PyED)(Cl)(2) (15) exh ibits a cyclization temperature (265 degreesC) between those of 11 and 19. suggesting that variation in geometry of the copper center is responsible f or the wide range of reactivities. Similar results are obtained for the ben zoenediyne and quinoline analogues. The structures of the Cu(II) systems ha ve also been evaluated by a combination of electronic absorption and EPR sp ectroscopies which reveal tetragonal, 6-coordinate structures for the bis(e nediyne) complexes, and tetrahedrally distorted 4-coordinate Cu(enediyne)Cl -2 species. For the bis(quinoline) enediyne derivatives 12 and 14 the large r g-anisotropy (g(\\) = 2.27-2.28; g(perpendicular to) = 2.06-2.07) indicat es strong oxygen coordination from counterion. Molecular mechanics/dynamics calculations reveal that the geometries of these metal centers force the a lkyne termini to a wide range of distances (3.85-4.20 Angstrom), thereby ac counting for the variability in Bergman cyclization temperatures. Overall, the results show that Ligand rigidity plays a prominent role in the conform ational response of the enediyne to metal center geometry, which results in enhanced variations in the Bergman cyclization temperatures between comple xes of different geometries.