Novel, Mercury-Free Synthetic Pathway for Trifluoromethylthio-Substituted Metallocenes

A novel synthetic pathway for trifluoromethylthioferrocene (3), which does not involve the use of toxic mercury­(II)-based reagents, is described. The novel approach involves first the treatment of the commercially available bromoferrocene (1a) with NaSCN in the presence of copper­(+I) to yield thiocyanatoferrocene (1), and then the reaction of 1 with the Rupper-Prakash reagent and tetrabutylammonium fluoride (TBAF) to give 3 in an overall yield of 60%. This approach could be extended for the preparation of thiocyanato-(4) and trifluoromethylthio-ruthenocene (7), which are herein both reported for the first time. Interestingly, diferrocenyl disulfide (2a) and diruthenocenyl disulfide (5) could be isolated as side-products during the synthesis of 3 and 7, respectively. All new compounds were unambiguously characterized by 1H, 13C, and 19F NMR spectroscopy, mass spectrometry, cyclic voltammetry, elemental analysis, as well by X-ray crystallography for 1, 4, 4b, 5, 6, and 7. 1–7 were further tested for their toxic activity on cervical cancer (HeLa) and noncancerous (MRC-5) cell lines. All organometallic compounds were found either to be nontoxic or to have a moderate toxicity toward the cell lines used in this study.