Effect of Substituted Pyridine Co-Ligands and (Diacetoxyiodo)benzene Oxidants on the Fe(III)-OIPh-Mediated Triphenylmethane Hydroxylation Reaction

Iodosilarene derivatives (PhIO, PhI(OAc)2) constitute an important class of oxygen atom transfer reagents in organic synthesis and are often used together with iron-based catalysts. Since the factors controlling the ability of iron centers to catalyze alkane hydroxylation are not yet fully understood, the aim of this report is to develop bioinspired non-heme iron catalysts in combination with PhI(OAc)2, which are suitable for performing C-H activation. Overall, this study provides insight into the iron-based ([FeII(PBI)3(CF3SO3)2] (1), where PBI = 2-(2-pyridyl)benzimidazole) catalytic and stoichiometric hydroxylation of triphenylmethane using PhI(OAc)2, highlighting the importance of reaction conditions including the effect of the co-ligands (para-substituted pyridines) and oxidants (para-substituted iodosylbenzene diacetates) on product yields and reaction kinetics. A number of mechanistic studies have been carried out on the mechanism of triphenylmethane hydroxylation, including C-H activation, supporting the reactive intermediate, and investigating the effects of equatorial co-ligands and coordinated oxidants. Strong evidence for the electrophilic nature of the reaction was observed based on competitive experiments, which included a Hammett correlation between the relative reaction rate (logkrel) and the σp (4R-Py and 4R’-PhI(OAc)2) parameters in both stoichiometric (ρ = +0.87 and +0.92) and catalytic (ρ = +0.97 and +0.77) reactions. The presence of [(PBI)2(4R-Py)FeIIIOIPh-4R’]3+ intermediates, as well as the effect of co-ligands and coordinated oxidants, was supported by their spectral (UV–visible) and redox properties. It has been proven that the electrophilic nature of iron(III)-iodozilarene complexes is crucial in the oxidation reaction of triphenylmethane. The hydroxylation rates showed a linear correlation with the FeIII/FeII redox potentials (in the range of −350 mV and −524 mV), which suggests that the Lewis acidity and redox properties of the metal centers greatly influence the reactivity of the reactive intermediates.

Although great efforts have been made to fine-tune the reactivity of iron-oxo complexes in oxidation reactions by modifying the structural and electronic properties of the metal center, there are few studies in the literature on other reactive intermediates such as Fe III -OIPh, Fe III -OOH, and Fe III -OOR species.In many cases, due to their Janus face, these intermediates not only participate in reactions as precursor complexes of Fe IV = O or Fe V = O intermediates but can also participate in oxidation processes as active species [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44].Since the redox properties of catalysts and their intermediates play a special role in redox reactions, such as in hydrogen atom transfer (HAT) and oxygen atom transfer (OAT), it is therefore important to examine what factors influence the reactivity of these complexes.In the case of high valence metal oxo species, it has been shown that the reactivity can be influenced not only by the oxidation and spin state of the metal center(s) but also by the nature of the supporting ligands, including the axial and equatorial co-ligands.[45][46][47][48][49][50][51][52][53][54][55][56][57].Terminal oxidants, such as the insoluble, polymeric PhIO and the organic solvent-soluble PhI(OAc) 2 , can be used as mild oxidants in many metal complex-catalyzed oxygenation processes, where their main role is the formation of high-valent metal-oxo intermediates, but in many cases the formation and active role of Fe III -OIPh complexes in the oxidation reactions was also confirmed [29][30][31][32][33][42][43][44].
Previous studies have shown that iron(II) complexes with PBI-type ligands (PBI = 2-(2pyridyl)benzimidazole) can be used as precursors to produce a number of reactive intermediates believed to be involved in iron-based oxidation processes.With their help, both the [(PBI) 4 (Solvent) 2 Fe III 2 (µ-O 2 )] 4+ [58][59][60][61][62] and the [(PBI) 2 (Solvent or additives)Fe III (OIPh)] 3+ intermediates can be synthesized by the use of H 2 O 2 , and PhIO (or PhI(OAc) 2 ), respectively [42][43][44].The structure of the above intermediates was assumed based on UV-VIS, EPR, and rRaman measurements [43].Thanks to the ligands, the advantage of these systems is that both the iron(II) precursors and the formed high-valent intermediates have favorable thermal stability, enabling their detailed characterization, the investigation of their spectral and redox properties, and the effect of these characteristics on their reactivity.Considering the results so far, it can be said that the above complexes are suitable as catalysts for the oxygenation of thioanisoles and other compounds containing C-H and C=C bonds with PhIO or its more soluble and mild oxygen source derivative, PhI(OAc) 2 , or deformylation of various aldehydes in a nucleophilic reaction with H 2 O 2 .As a result of previous catalytic studies, it was established that in the case of OAT reactions, such as sulfoxidation and epoxidation, the yield of the reactions can be significantly increased if monodentate pyridines with electron-withdrawing groups are used as equatorial ligands for the catalytically active [(PBI) 2 (4R-Py)Fe III (OIPh)] 3+ .Based on the detailed mechanistic studies, the linear free energy (Hammett equations) relationships through the positive ρ-value obtained for the co-ligands indicate that the reactive intermediate of the above reactions is electrophilic [44].
The aim of this report is to study the catalytic and stoichiometric oxidation reactions involving C-H activation using the sample substrate triphenylmethane, namely to study the effect of monodentate 4R-pyridine ligands and 4R'-PhIO (from 4R'-PhI(OAc) 2 ) terminal oxidants with electron-withdrawing and electron donor substituents (Scheme 1).Our further aim is to compare the HAT (this study) and the previously published processes [44] mediated by [(PBI) 2 (4R-Py)Fe III (OIPh)] 3+ intermediates based on the kinetic and catalytic results.

Effect of Equatorial Ligands on the Fe III OIPh-Mediated Oxidation of Triphenylmethane
In this report, we wanted to investigate the effect of equatorial pyridines (4R-py; R = -CH3, -H, -C(O)C6H5, -C(O)CH3, -CN) and the oxidant 4R'-PhI(OAc)2 (R = -OCH3, -CH3, H, -Cl, -C(O)CH3) in catalytic oxidation processes that involve C-H activation, using 1 as catalyst and triphenylmethane as model substrate.In order to compare the systems with OAT and C-H activation, we used the previously observed optimal conditions with a catalystadditive-oxidant-substrate ratio of 1:10:100:300, in acetonitrile at 323 K for 4 h [62].The catalyst-co-ligand ratio was chosen to be 1:10 based on the maximum shift of the characteristic λmax of the Fe III (OIPh) species due to pyridine additives [62].As a mild oxygen source, PhI(OAc)2 has the advantage of not damaging the catalysts and showing no

Effect of Equatorial Ligands on the Fe III OIPh-Mediated Oxidation of Triphenylmethane
In this report, we wanted to investigate the effect of equatorial pyridines (4R-py; R = -CH 3 , -H, -C(O)C 6 H 5 , -C(O)CH 3 , -CN) and the oxidant 4R'-PhI(OAc) 2 (R = -OCH 3 , -CH 3 , H, -Cl, -C(O)CH 3 ) in catalytic oxidation processes that involve C-H activation, using 1 as catalyst and triphenylmethane as model substrate.In order to compare the systems with OAT and C-H activation, we used the previously observed optimal conditions with a catalyst-additive-oxidant-substrate ratio of 1:10:100:300, in acetonitrile at 323 K for 4 h [62].The catalyst-co-ligand ratio was chosen to be 1:10 based on the maximum shift of the characteristic λ max of the Fe III (OIPh) species due to pyridine additives [62].As a mild oxygen source, PhI(OAc) 2 has the advantage of not damaging the catalysts and showing no noticeable reactivity with the substrate [63].According to our previous studies, the formation of the more oxidizing PhIO can be explained by the reaction of PhI(OAc) 2 with a trace amount of water [64].Based on the blank experiments, it can be said that no hydroxylated products were formed in the absence of either the catalyst or PhI(OAc) 2 .At first glance, it is clear that the catalytic activity of the iron salt [Fe II (CH 3 CN) 4 (OTf) 2 ] is negligible (conversion = 10.27%).In the case of [Fe II (PBI) 3 ](OTf) 2 (1), a 2.5-fold increase in activity was observed with a conversion value of 24.71% (TOF = 6.17 h −1 ) (Figure 1).The results of the comprehensive screening of [Fe(PBI) 3 ](OTf) 2 with and without pyridines are shown in Table 1.As expected, triphenylmethanol was the only oxidized product without any other byproducts after 4 h.Based on the obtained conversion values, it can be concluded that the pyridine derivatives have a significant effect on the test reactions.In the case of pyridine (1:py = 1:10), the conversion value increased by 1.5 times (37.12%;TOF = 9.28 h −1 ).The effect of electron-donating (-CH 3 ) and electron-withdrawing (-CN, -C(O)C 6 H 5 , -C(O)CH 3 ) substituents of pyridines on the reactivity was also investigated in competitive experiments, and a significant effect on catalytic oxidation of triphenylmethane was shown (Table 1 and Figure 2a), where the 4-CN-pyridine resulted in the highest (83.00%,TOF = 20.75 h −1 ), and 4-Me-pyridine gave the lowest conversion with 19.98% (TOF = 4.99 h −1 ).The effect is remarkable, which can be attributed to the increased electrophilicity of the ([(PBI) 2 (4R-Py)Fe III OIPh] 3+ ) species due to the electron-withdrawing pyridine ligand.
Summarizing the results of the competitive experiments and comparing them with the results of the sulfoxidation and epoxidation experiments, it can be said that the value hydroxylation of triphenylmethane with PhI(OAc) 2 in the presence of para-substituted pyridines in acetonitrile at 323 K 1 .

Entry
Co-Ligand Conversion (%) Summarizing the results of the competitive experiments and comparing them with the results of the sulfoxidation and epoxidation experiments, it can be said that the value obtained for co-ligands (ρ = +0.97) is much higher than the value obtained for sulfoxidation (ρ = +0.16),which indicates that the oxidation reaction involving C-H activation is much more sensitive to the electrophilic nature of the intermediate as the sulfoxidation reaction described by the direct oxygen transfer (DOT) mechanism [62].Considering the previous results of the oxidation of cis-cyclooctene (ρ = 0.95) and cis-and trans-stilbene (ρ = 0.59 and +0.46, respectively) under the same conditions, it can be said that both the C-H activation and the epoxidation with nonconcerted ET mechanism are greatly influenced by the electrophilic character of the reactive intermediate (oxidant) [44].Unfortunately, hydrocarbons with a higher BDE value (such as PhCH3) did not give the reaction under the given conditions.

Effect of Co-Oxidant (4R'-PhI(OAc)2) on the Fe III OIPh-Mediated Oxidation of Triphenylmethane
As noted earlier, the reaction of 1 with PhIO leads to reactive Fe III (OIPh) formations, suggesting that it may play a key role in the catalytic cycles.This is also supported by the UV-Vis spectrum of the catalytic reaction mixture, where the rise and fall of their characteristic chromophores at λmax = 700-760 nm (depending on the pyridines used as co-ligand) Summarizing the results of the competitive experiments and comparing them with the results of the sulfoxidation and epoxidation experiments, it can be said that the value obtained for co-ligands (ρ = +0.97) is much higher than the value obtained for sulfoxidation (ρ = +0.16),which indicates that the oxidation reaction involving C-H activation is much more sensitive to the electrophilic nature of the intermediate as the sulfoxidation reaction described by the direct oxygen transfer (DOT) mechanism [62].Considering the previous results of the oxidation of cis-cyclooctene (ρ = 0.95) and cisand trans-stilbene (ρ = 0.59 and +0.46, respectively) under the same conditions, it can be said that both the C-H activation and the epoxidation with nonconcerted ET mechanism are greatly influenced by the electrophilic character of the reactive intermediate (oxidant) [44].Unfortunately, hydrocarbons with a higher BDE value (such as PhCH 3 ) did not give the reaction under the given conditions.

Effect of Co-Oxidant (4R'-PhI(OAc) 2 ) on the Fe III OIPh-Mediated Oxidation of Triphenylmethane
As noted earlier, the reaction of 1 with PhIO leads to reactive Fe III (OIPh) formations, suggesting that it may play a key role in the catalytic cycles.This is also supported by the UV-Vis spectrum of the catalytic reaction mixture, where the rise and fall of their characteristic chromophores at λ max = 700-760 nm (depending on the pyridines used as co-ligand) is clearly visible.After that, we wanted to investigate the effect of the electron-donating and electron-withdrawing groups introduced into the co-oxidant (4R'-PhI(OAc) 2 , where R' = -OCH 3 , -CH 3 , -H, -Cl, and -C(O)CH 3 ) on the catalytic oxidation of triphenylmethane with 1.Before the detailed investigation of the catalytic system, we studied the formation kinetics of Fe III OIPh-4R' adducts, with special attention paid to the role of the substituents on the co-oxidant.The rates in the presence of excess of PhI(OAc) 2 (10 equivalent) obeyed pseudo-first-order kinetics.The pseudo-first-order rate constants, k obs , in the reaction of 1 with 4R-PhI(OAc) 2 (R' = -OCH 3 , -CH 3 , -H, -Cl, and -C(O)CH 3 ) were determined from the absorbance change at 760 nm (Table 2 and Figure 3a).Based on the obtained data, the fastest adduct formation was observed for 4R-PhI(OAc) 2 containing an electron-donating substituent (0.637 s −1 for -OCH 3 ), while for the electron-withdrawing group -C(O)Me was the slowest (0.187 s −1 ).The observed kinetic data were treated based on the Hammett equation, from which the value of ρ was −0.63 (Figure 3b).Since the formation of the adduct in the case of PhIO is orders of magnitude faster than in the case of PhI(OAc) 2 , based on the negative ρ-value, it can be assumed that the rate-determining step is the formation of PhIO by the proton-assisted hydrolysis of PhI(OAc) 2 , which means that the higher electron density of the I(OAc) 2 group increases the reaction rate.on the co-oxidant.The rates in the presence of excess of PhI(OAc)2 (10 equivalent) obeyed pseudo-first-order kinetics.The pseudo-first-order rate constants, kobs, in the reaction of 1 with 4R-PhI(OAc)2 (R' = -OCH3, -CH3, -H, -Cl, and -C(O)CH3) were determined from the absorbance change at 760 nm (Table 2 and Figure 3a).Based on the obtained data, the fastest adduct formation was observed for 4R-PhI(OAc)2 containing an electron-donating substituent (0.637 s −1 for -OCH3), while for the electron-withdrawing group -C(O)Me was the slowest (0.187 s −1 ).The observed kinetic data were treated based on the Hammett equation, from which the value of ρ was −0.63 (Figure 3b).Since the formation of the adduct in the case of PhIO is orders of magnitude faster than in the case of PhI(OAc)2, based on the negative ρ-value, it can be assumed that the rate-determining step is the formation of PhIO by the proton-assisted hydrolysis of PhI(OAc)2, which means that the higher electron density of the I(OAc)2 group increases the reaction rate.To investigate the effect of the oxidant, the catalytic oxidation of triphenylmethane was carried out with 1 and 4R'-PhI(OAc)2 (R' = -OCH3, -CH3, -H, -Cl, and -C(O)CH3) derivatives under the conditions used for the study of the effect of co-ligands earlier (catalyst-oxidant-substrate ratio is 1:100:300 in acetonitrile at 323 K).
As evident in Table 3, the catalytic oxidation of triphenylmethane was affected by the substituents on the oxidant, 4R'-PhI(OAc)2 used.For example, the 4-C(O)CH3-PhI(OAc)2 resulted in the highest (45.75%), and the 4-CH3O-PhI(OAc)2 gave the lowest conversion To investigate the effect of the oxidant, the catalytic oxidation of triphenylmethane was carried out with 1 and 4R'-PhI(OAc) 2 (R' = -OCH 3 , -CH 3 , -H, -Cl, and -C(O)CH 3 ) derivatives under the conditions used for the study of the effect of co-ligands earlier (catalyst-oxidant-substrate ratio is 1:100:300 in acetonitrile at 323 K).
As evident in Table 3, the catalytic oxidation of triphenylmethane was affected by the substituents on the oxidant, 4R'-PhI(OAc) 2 used.For example, the 4-C(O)CH 3 -PhI(OAc) 2 resulted in the highest (45.75%), and the 4-CH 3 O-PhI(OAc) 2 gave the lowest conversion value with 13.87% for the hydroxylation of triphenylmethane (Figure 4a).The effect is also remarkable and can be traced back to the increased electrophilicity of the [(PBI) 2 (CH 3 CN)Fe III OIPh-4R'] 3+ species, due to the electron-withdrawing substituents of the PhIO oxidant, which is consistent with the results obtained for pyridine co-ligands.
The relative rates (k rel ) for the [Fe II (PBI) 3 ](OTf) 2-catalyzed hydroxylation of triphenylmethane with substituted iodosobenzene diacetates (4R-PhI(OAc) 2 , R = -OCH 3 , -CH 3 , -H, -Cl, and -C(O)CH 3 ) was determined by measuring the formation of triphenylmethanol by GC. Figure 4b shows a linear correlation (R = 0.99) of log k rel versus Hammett σ p constants in the competitive reactions (Figure 4b).The slope (ρ) of the plot is +0.77, which means that the reaction of electron-deficient intermediates is much more favored.This value is similar to the value obtained for substituted pyridines (ρ = +0.97),which confirms the importance of the electrophilic feature of the [(PBI) 2 (CH 3 CN)Fe III OIPh-4R'] 3+ intermediate.  Reaction conditions: see experimental section. 2 The product was identified by GC-MS and the yields (based on oxidant) were determined by GC using bromobenzene as internal standard.-Cl, and -C(O)CH3) was determined by measuring the formation of triphenylmethanol by GC. Figure 4b shows a linear correlation (R = 0.99) of log krel versus Hammett σp constants in the competitive reactions (Figure 4b).The slope (ρ) of the plot is +0.77, which means that the reaction of electron-deficient intermediates is much more favored.This value is similar to the value obtained for substituted pyridines (ρ = +0.97),which confirms the importance of the electrophilic feature of the [(PBI)2(CH3CN)Fe III OIPh-4R'] 3+ intermediate.  Reaction conditions: see experimental section. 2 The product was identified by GC-MS and the yields (based on oxidant) were determined by GC using bromobenzene as internal standard. 3

Effect of Equatorial Ligands on the Fe III OIPh-Mediated Stoichiometric Oxidation of Triphenylmethane
As a possible elementary step of the catalytic reaction, we wanted to investigate the stoichiometric oxidation of the in situ formed iron(III)-iodosylbenzene adduct with triphenylmethane, with particular attention paid to the effect of pyridine co-ligands.Based on our previous results [62], for the full formation of [(PBI)2(4R-Py)Fe IlI OIPh] 3+ (R = -CH3, -H, C(O)CH3, -C(O)Ph, and -CN) in the reaction of 1 with PhI(OAc)2, the optimal amount of co-ligands (10 equivalents) was determined by titration.The λmax values of the

Effect of Equatorial Ligands on the Fe III OIPh-Mediated Stoichiometric Oxidation of Triphenylmethane
As a possible elementary step of the catalytic reaction, we wanted to investigate the stoichiometric oxidation of the in situ formed iron(III)-iodosylbenzene adduct with triphenylmethane, with particular attention paid to the effect of pyridine co-ligands.Based on our previous results [62], for the full formation of [(PBI) 2 (4R-Py)Fe IlI OIPh] 3+ (R = -CH 3 , -H, C(O)CH 3 , -C(O)Ph, and -CN) in the reaction of 1 with PhI(OAc) 2 , the optimal amount of co-ligands (10 equivalents) was determined by titration.The λ max values of the [(PBI) 2 (4R-Py)Fe IlI OIPh] 3+ complexes are shown in Table 4 [62].The observed hypochromic shift in the near IR region clearly indicated the coordination of the pyridine ligands, as well as their electronic effect on the electrophilicity of the active species, based on the observed trend of the Hammett correlation between the λ max −1 (at 700-760 nm) and the Hammett constants (σ p ) [62].These results imply that the effect of the ligands appears in the redox properties of the intermediates, as well as in their redox potential values, which may be consistent with our previous spectroscopic results.  2 Reactions were followed by UV-Vis spectroscopy at 700-760 nm.

Figure 2 .
Figure 2. [Fe II (PBI) 3 ](OTf) 2 -catalyzed hydroxylation of triphenylmethane with PhI(OAc) 2 in the presence of para-substituted pyridines in acetonitrile at 323 K: (a) the calculated conversion (=TON) values for para-substituted pyridines.(b) Hammett plot of logk rel against the σ p of para-substituted pyridines. [1]0 = 1 × 10 −3 M, [PhI(OAc) 2 ] 0 = 1 × 10 −1 M, [Ph 3 CH] 0 = 3 × 10 −1 M, [pyridine] 0 = 1 × 10 −2 M. The relative rates (k rel ) for the [Fe II (PBI) 3 ](OTf) 2 -catalyzed hydroxylation of triphenylmethane in the presence of para-substituted pyridines (4R-Py, R = -CH 3 , H, -C(O)C 6 H 5 , -C(O)CH 3 and CN) was determined by measuring the formation of triphenylmethanol by GC. Figure 2b depicts a linear correlation (R = 0.96) of log k rel versus Hammett σ p constants in the competitive [Fe II (PBI) 3 ](OTf) 2 -catalyzed hydroxylation reaction.The slope (ρ) of the plot is +0.97, clearly indicating that the electron-deficient intermediates are much more reactive than the electron-rich species, which is consistent with the involvement of an electrophilic oxidant, probably a putative [(PBI) 2 (4R-Py)Fe III OIPh] 3+ intermediate.Summarizing the results of the competitive experiments and comparing them with the results of the sulfoxidation and epoxidation experiments, it can be said that the value obtained for co-ligands (ρ = +0.97) is much higher than the value obtained for sulfoxidation (ρ = +0.16),which indicates that the oxidation reaction involving C-H activation is much more sensitive to the electrophilic nature of the intermediate as the sulfoxidation reaction described by the direct oxygen transfer (DOT) mechanism[62].Considering the previous results of the oxidation of cis-cyclooctene (ρ = 0.95) and cisand trans-stilbene (ρ = 0.59 and +0.46, respectively) under the same conditions, it can be said that both the C-H activation and the epoxidation with nonconcerted ET mechanism are greatly influenced by the electrophilic character of the reactive intermediate (oxidant)[44].Unfortunately, hydrocarbons with a higher BDE value (such as PhCH 3 ) did not give the reaction under the given conditions.

Table 4 .
Summary of kinetic data for the stoichiometric oxidation of triphenylmethane with [(PBI) 2 Fe III (OIPh)(4R-Py)] intermediates generated in situ by the reaction of 1 with Ph(IOAc) 2 and 4R-Py derivatives in acetonitrile at 293 K 1 .