Oxidation of Cymantrene-Tagged Tamoxifen Analogues: Effect of Diphenyl Functionalization on the Redox Mechanism

Abstract

The oxidations of 1,1'-di-p-anisolyl-2-cymantrenylbutene (3b) and 1,1'-di-p-hydroxyphenyl-2-cymantrenylbutene (3c) were investigated by electrochemical and spectroscopic experiments and by density functional theory (DFT) calculations. Both compounds undergo a reversible one-electron oxidation followed closely by a partially chemically reversible second oxidation (E-1/2 values vs ferrocene: 0.60 and 0.74 V for 3b; 0.63 and 0.78 V for 3c). In comparison to the nonphenyl-functionalized parent, 1,1'diphenyl-2-cymantrenylbutene (3a), 3b,c have lower and more closely spaced oxidation potentials and more rapid follow-up reactions of their dications, 3b(2+) and 3c(2+). Shifts in the calculated charge distributions of the neutral compounds and their singly and doubly oxidized products corroborated trends in the measured shifts of Mn-CO nu(CO) frequencies in assigning the redox sites primarily to the diarylbutene fragment. Upon removal of electrons, the lost charge density is partially compensated by the polarizable cymantrenyl tag. The half-lives of the dications 3b(2+) and 3c(2+) are about 10 s at room temperature in dichloromethane/0.05 M [NBu4][B(C6F5)(4)]. Their follow-up reactions are initiated by loss of a proton either from a hydroxyl group or from the CH2 group of the diarylbutene unit, giving rise to two products having quinone methide structures. Although the initial oxidation sites of cymantrene-tagged diarylbutenes are primarily ligand based and those of ferrocene-tagged diarylbutenes are metal-based, the ultimate oxidation products of their p-OH- or p-OMe-functionalized derivatives are very similar.