9,9-Difluorobispidine Analogues of Cisplatin, Carboplatin, and Oxaliplatin

As part of a comprehensive study of N-unsubstituted bispidines, the novel 9,9-difluorobispidine ( D ) has been synthesized. The compound crystallizes from pentane below 0 °C in the ordered-crystalline phase D-II and undergoes at 0–30 °C a stepwise endothermic phase transition to a dynamically disordered crystalline phase D-I; melting occurs at 227 °C. Single crystalline D-II has been subjected to X-ray structure analysis, revealing association of the molecules to form chains. Reaction of (1,5-hexadiene)PtCl 2 with D affords {C 7 H 10 F 2 (NH) 2 }PtCl 2 ( D1 ), which can be converted by conventional routes to {C 7 H 10 F 2 (NH) 2 }Pt(cbdca)·5H 2 O ( D2 ) and {C 7 H 10 F 2 (NH) 2 }Pt(C 2 O 4 ) ( D3 ). Compound D1 crystallizes solvent-free from water and is isomorphous to the solvent-free parent bispidine analogue ( A1 ). The pentahydrate D2 is isomorphous to the bispidine and 9-oxabispidine homologues ( A2 and C2 ), as shown by X-ray structure analyses. An increased polarity of the bispidine skeleton as a consequence of the high electronegativity of fluorine is seen as the reason for low cytotoxic potency of D1–D3 .