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

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 (E1/2 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, 3b2+ and 3c2+. 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 νCO 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 3b2+ and 3c2+ 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.