文摘
Reaction of 2 equiv of 1,2-bis((diphenylphosphino)ethynyl)benzene (dppeb, 1) with Pt(cod)Cl2 followed by treatment with N2H4 yields the reduced Pt(0) metalloenediyne, Pt(dppeb)2, 2. This complex is stable to both air oxidation and metal-mediated Bergman cyclization under ambient conditions due to the nearly idealized tetrahedral geometry. Reaction of 2 with 1 equiv of I2 in the presence of excess 1,4-cyclohexadiene (1,4-CHD) radical trap rapidly and near-quantitatively generates the cis-Bergman-cyclized, diiodo product 3 (31P: 未 = 41 ppm, JPt鈥揚 = 3346 Hz) with concomitant loss of 1 equiv of uncyclized phosphine chelate (31P: 未 = 鈭?3 ppm). In contrast, addition of 2 equiv of I2 in the absence of additional radical trap instantaneously forms a metastable Pt(dppeb)22+ intermediate species, 4, that is characterized by 未 = 51 ppm in the 31P NMR (JPt鈥揚 = 3171 Hz) and 谓C鈮 = 2169 cm鈥? in the Raman profile, indicating that it is an uncyclized, bis-ligated complex. Over 24 h, 4 undergoes ligand exchange to form a neutral, square planar complex that spontaneously Bergman cyclizes at ambient temperature to give the crystalline product Pt(dppnap-I2)I2 (dppnap-I2 = (1,4-diiodonaphthalene-2,3-diyl)bis(diphenylphosphine)), 5, in 52% isolated yield. Computational analysis of the oxidation reaction proposes two plausible flattened tetrahedral structures for intermediate 4: one where the phosphine core has migrated to a trans-spanning chelate geometry, and a second, higher energy structure (3.3 kcal/mol) with two cis-chelating phosphine ligands (41掳 dihedral angle) via a restricted alkyne-terminal starting point. While the energies are disparate, the common theme in both structures is the elongated Pt鈥揚 bond lengths (>2.4 脜), indicating that nucleophilic ligand substitution by I鈥?/sup> is on the reaction trajectory to the cyclized product 5. The efficiency of the redox-mediated Bergman cyclization reaction of this stable Pt(0) metalloenediyne prodrug and resulting cisplatin-like byproduct represents an intriguing new strategy for potential dual-threat metalloenediyne therapeutics.