Highly selective metal mediated ortho-alkylation of phenol. First platinum containing organometallic chromane analogues

Abstract

We were able, for the first time, to synthesize and characterize Pt derivatives with a structural shape similar to vitamin E, having a metalla-chromane core. The formation reaction mechanism includes an unexpected highly selective ortho aromatic electrophilic substitution on phenol, operated by [PtCl(η¹-C₂H₄OR)(N–N)], R = Me or Ph, and a final cyclization step. The X-ray structure of one of the new metalla-chromane complexes [Pt(EtPh)(phen)], 1a, (EtPh = 2-(ethan-2′-yl-kC¹)-1-phenolato-kO¹, phen = 1,10-phenanthroline) is reported. Cytotoxicity and Pt uptake measurements, performed on HeLa cancer cells, show an interesting structure–activity correlation for the new metalla-chromane analogues 1a and [Pt(MeOEtPh)(phen)], 1b, (MeOEtPh = 2-(ethan-2′-yl-kC¹)-4-(methoxy)-1-phenolato-kO¹), being the structurally closest to vitamin E and also the most active.