Direct Addition of Alcohols to Organonitriles Activated by Ligation to a Platinum(IV) Center

Treatment of trans-[PtCl4(RCN)2] (R = Me, Et) with R‘OH (R‘ = Me, Et, n-Pr, i-Pr, n-Bu) at 45 °C in all cases
allowed the isolation of the trans-[PtCl4{(E)-NHC(R)OR‘}2] imino ester complexes, while the reaction between
cis-[PtCl4(RCN)2] and the least sterically hindered alcohols (methanol and ethanol) results in the formation of cis-[PtCl4{(E)-NHC(R)OR‘}2] (R/R‘ = Me/Me) or trans-[PtCl4{(E)-NHC(Et)OR‘}2] (R‘ = Me, Et), the latter being
formed via thermal isomerization (ROH, reflux, 3 h) of the initially formed corresponding cis isomers. The reaction
between alcohols R‘OH and cis-[PtCl4(RCN)2] (R = Me, R‘ = Et, n-Pr, i-Pr, n-Bu; R = Et; R‘ = n-Pr, i-Pr, n-Bu),
exhibiting greater R/R‘ steric congestion, allowed the isolation of cis-[PtCl4{(E)-NHC(R)OR‘}{(Z)-NHC(R)OR‘}] as the major products. The alcoholysis reactions of poorly soluble [PtCl4(RCN)2] (R = CH2Ph, Ph) performed
under heterogeneous conditions, directly in the appropriate alcohol and for a prolonged time and, for R = Ph, with
heating led to trans-[PtCl4{(E)-NHC(R)OR‘}2] (R = CH2Ph, R‘ = Me, Et, n-Pr, i-Pr; R = Ph, R‘ = Me) isolated
in moderate yields. In all of the cases, in contrast to platinum(II) systems, addition of R‘OH to the organonitrile
platinum(IV) complexes occurs under mild conditions and does not require a base as a catalyst. The formed
isomerically pure (imino ester)Pt(IV) complexes can be reduced selectively, by Ph3PCHCO2Me, to the corresponding
isomers of (imino ester)Pt(II) species, exhibiting antitumor activity, without change in configuration of the imino
ester ligands. Furthemore, the imino esters NHC(R)OR‘ can be liberated from both platinum(IV) and platinum(II)
complexes [PtCln{NHC(R)OR‘}2] (n = 2, 4) by reaction with 1,2-bis(diphenylphosphino)ethane and pyridine,
respectively. All of the prepared compounds were characterized by elemental analyses (C, H, N), FAB mass
spectrometry, IR, and 1H, 13C{1H}, and 195Pt (metal complexes) NMR spectroscopies; the E and Z configurations
of the imino ester ligands in solution were determined by observation of the nuclear Overhauser effect. X-ray
structure determinations were performed for trans-[PtCl4{(E)-NHC(Me)OEt}2] (2), trans-[PtCl4{(E)-NHC(Et)OEt}2] (10), trans-[PtCl4{(E)-NHC(Et)OPr-i}2] (11), trans-[PtCl4{(E)-NHC(Et)OPr-n}2] (12), and cis-[PtCl4{(E)-NHC(Et)OMe}2] (14). Ab initio calculations have shown that the EE isomers are the most stable ones for both
platinum(II) and platinum(IV) complexes, whereas the most stable configurations for the ZZ isomers are less stable
than the respective EZ isomers, indicating an increase of the stability on moving from the ZZ to the EE configurations
which is more pronounced for the Pt(IV) complexes than for the Pt(II) species.