E.[5,11,15] Nothing specific is known concerning the mechanistic facts of this
E.[5,11,15] Practically nothing specific is identified concerning the mechanistic specifics of this reaction, aside from the statement that “this formal one-electron reduction from the central carbon was very surprising”.[11] This conclusion is still far more convincing if one takes into account the absence of evident and indubitable reductants for the initial reagents. Again, a priori, it seemed unreasonable to predict that the reaction would create an intermediate that could play the PARP2 review aspect of a reducing agent. To gain greater insight into mechanistic particulars of this method, we attempted a series of reactions among triarylmethanol six and TFA. Some reaction situations were strictly consistent using the original protocols, whereas other individuals involved modifications with the reaction conditions, by way of example, the presence or absence of atmospheric oxygen within the reaction vessel along with the variation from the reaction time within the array of 66 h. Irrespective of reaction situations, the crude item was by no means a single component, but instead was two significant components conveniently observable on TLC plates (see Supporting Information). The merchandise were identified as trityl radical five and diamagnetic quinone methide 7 (see Scheme 2), which were isolated in 526 and 139 yield, respectively (see Exp. Section). Recently, quinoide 7 was reported as the only item to result in the oxidative decarboxylation of trityl 5 with nicotinamide adenine dinucleotide phosphate hydride (NADPH)O2, which was catalyzed by rat, pig, and human liver microsomes,[16] and also the reaction of 5 with superoxide, which was generated by a xanthinexanthine oxide program.[16,17] The rationale for this reaction entails the attack from the O2 at the para carbon on the TAM aryl ring followed by the loss of CO2 from the resulting diamagnetic intermediate along with a proton-catalyzed heterolytic cleavage of the O bond with the hydroperoxide group.[16,17] The absence of superoxide or the source of any other peroxide species signifies that the generation of quinoide 7 by the mechanism described in literature, and above, is hugely improbable in our case. A plausible explanation for the simultaneous formation of trityl 5 and diamagnetic quinoide 7 could possibly follow from what exactly is known regarding the ready reaction of sterically hindered trityl cations with nucleophiles.[18] Usually, they attack aryl rings at the para position to provide 4-methylenecyclohexa-2,5-diene intermediates analogous to 9 (see Scheme 3). Pretty recently C. Decroos et al. reported the formation of trityl radicals by way of an electron transfer (ET) reaction involving intermediate methylenecyclohexa-2,5-dienes and trityl cations, which have been generated in situ by oxidation of trityl 5 either by potassium hexachloroiridate(IV)[19] or hydrogen peroxide in the presence of peroxidases (horse radish peroxidase, lactoperoxidase, prostaglandin synthase, as well as other hemeproteins).[20]European J Org Chem. Author manuscript; readily available in PMC 2014 April 24.Rogozhnikova et al.PageThis fruitful PDE5 Accession notion of ET reactions with trityl cations participating as an oxidant provides the missing link to interpret our results as shown in Scheme three. The explanation includes the reaction of cation 8 with water to yield intermediate cyclohexadiene 9. The decarboxylation of 9 followed by oxidation with cation eight (or vice versa) gives trityl five and transient trityl ten. The latter needs to be readily oxidized by cation eight in addition to the eventual formation of quinoide 7 as well as the subsequent crop of trityl 5. The overall balanced reaction fol.
