E.[5,11,15] Absolutely nothing particular is identified concerning the mechanistic specifics of this
E.[5,11,15] Nothing at all specific is known regarding the mechanistic particulars of this reaction, apart from the statement that “this formal one-electron reduction on the central carbon was quite surprising”.[11] This conclusion continues to be far more convincing if one requires into account the absence of evident and indubitable reductants for the initial reagents. Again, a priori, it seemed unreasonable to predict that the LAIR1 Protein custom synthesis reaction would generate an intermediate that could play the aspect of a decreasing agent. To obtain far better insight into mechanistic information of this approach, we attempted a series of reactions between triarylmethanol six and TFA. Some reaction conditions have been strictly constant with the original protocols, whereas other people involved modifications on the reaction conditions, one example is, the presence or absence of atmospheric oxygen in the reaction vessel as well as the variation in the reaction time inside the array of 66 h. No matter reaction situations, the crude product was by no means a single component, but as an alternative was two big elements quickly observable on TLC plates (see Supporting Information and facts). The goods had been identified as trityl radical five and diamagnetic quinone methide 7 (see Scheme 2), which had been isolated in 526 and 139 yield, respectively (see Exp. Section). Lately, quinoide 7 was reported because the only solution to outcome 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] as well as the reaction of 5 with superoxide, which was generated by a xanthinexanthine oxide system.[16,17] The rationale for this reaction requires the GM-CSF Protein site attack with the O2 at the para carbon on the TAM aryl ring followed by the loss of CO2 in the resulting diamagnetic intermediate and a proton-catalyzed heterolytic cleavage of your O bond on the hydroperoxide group.[16,17] The absence of superoxide or the supply of any other peroxide species indicates that the generation of quinoide 7 by the mechanism described in literature, and above, is extremely improbable in our case. A plausible explanation for the simultaneous formation of trityl five and diamagnetic quinoide 7 might adhere to from what exactly is known in regards to the ready reaction of sterically hindered trityl cations with nucleophiles.[18] Generally, they attack aryl rings at the para position to provide 4-methylenecyclohexa-2,5-diene intermediates analogous to 9 (see Scheme three). Incredibly recently C. Decroos et al. reported the formation of trityl radicals by way of an electron transfer (ET) reaction between 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, and other hemeproteins).[20]European J Org Chem. Author manuscript; obtainable in PMC 2014 April 24.Rogozhnikova et al.PageThis fruitful notion of ET reactions with trityl cations participating as an oxidant delivers the missing link to interpret our results as shown in Scheme 3. The explanation includes the reaction of cation eight with water to yield intermediate cyclohexadiene 9. The decarboxylation of 9 followed by oxidation with cation 8 (or vice versa) gives trityl five and transient trityl 10. The latter needs to be readily oxidized by cation eight together with the eventual formation of quinoide 7 plus the subsequent crop of trityl five. The all round balanced reaction fol.
