Replacing the Z-phenyl Ring in Tamoxifen(®) with a para-Connected NCN Pincer-Pt-Cl Grouping by Post-Modification †

Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C(6)H(2)(CH(2)NMe(2))(2)-2,6](–), R = C(O)H, C(O)Me and C(O)Et), X = Cl(–) or Br(–)) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen(®) itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen(®) derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with (1)H-, (13)C{(1)H}- and (195)Pt{(1)H}-NMR, IR, exact mass MS and elemental analysis.