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

Abstract

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)](NO(3))(2) (11) exhibits a Bergman cyclization temperature (156 degrees C) which is dramatically reduced from that of the corresponding [Cu(PyED)(2)](PF(6)) (19) analogue (326 degrees 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 degrees 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)Cl(2) species. For the bis(quinoline) enediyne derivatives 12 and 14 the larger g-anisotropy (g( parallel) = 2.27-2.28; g( perpendicular) = 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 A), 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.

Unique Metal‐Diyne, ‐Enyne, and ‐Enediyne Complexes: Part of the Remarkably Diverse World of Metal‐Alkyne Chemistry

“…Subsequent complexation with Cu(II) or Zn(II) generates macrocyclic complexes that exhibit cyclization temperatures by DSC, which are sensitive to the structure of metal site. The more rigid macrocyles containing Cu(II) or Zn(II) tend toward more planar-tetragonal structures based on correlation to previous studies (552,553) and undergo reaction between 120 and 140 C in the solid state. As the size of the macrocle increases, the Zn(II) derivative adopts a more distorted geometry, increasing the cyclization temperature to $160 C, while the Cu(II) structure remains planar-tetragonal.…”

“…29). Despite the apparent clarity of mechanism, the Buchwald study reported one negative result; the Hg 2þ compound did not The notion that metal geometry could be responsible for the disparate reactivities of the tetrahedral d 10 Hg 2þ versus square-planar d 8 Pd 2þ and Pt 2þ compounds was presented and demonstrated in four subsequent studies; two involving the 1,2-bis(diphenylphosphinoethynyl)benzene enediyne ligand with various d 10 metals (550,551), and two describing a previously unreported bis(pyridyl) enediyne where the bond between the two rings (e.g., Scheme 86) was removed to allow for enhanced conformational flexibility and response to changes in metal geometry (552,553). The bis(pyridyl) enediyne analogues also show a pronounced reactivity based on the geometry of the metal.…”

Geometric and Electronic Control of Thermal Bergman Cyclization

“…The cyclization temperature is nearly identical to those reported for other [Cu(N) 4 ] 2+ metalloenediyne constructs whose tetragonal X···Cu(N 4 )···X structures have been characterized by EPR, ligand field region electronic absorption spectroscopy, and molecular mechanics calculations. 119,122 The cyclization temperature for the Zn(II) analog 89, however, is slightly higher (148 °C) than that observed for the Cu(II) complex 88. Since the Bergman cyclization temperature for 89 is between that expected for a planar or tetrahedral [Zn(N) 4 ] 2+ structure, a distorted 4-coordinate or 5-coordinate square pyramidal geometry with an axial CH 3 COO -or H 2 O ligand would explain the elevated Bergman cyclization temperature for 89.…”

A novel rearrangement of fluorescent human thymidylate synthase inhibitor analogues in ESI tandem mass spectrometry

“…Azidomethylanthracenes, Z1, Z2, and Z3, and 3-ethynylquinoline A2 have previously been described in the literature [5,21,22]. Compounds A1, A5, A6, and A9 have been prepared by reaction between propargyl bromide and the corresponding amines or alcohols under basic conditions.…”