Mechanisms of Sulfoxidation and Epoxidation Mediated by Iron(III)-Iodosylbenzene Adduct: Electron-Transfer vs. Oxygen-Transfer Mechanism

The mechanisms of sulfoxidation and epoxidation mediated by previously synthesized and characterized iron(III)-iodosylbenzene adduct, FeIII(OIPh) were investigated using para-substituted thioanisole and styrene derivatives as model substrates. Based on detailed kinetic reaction experiments, including the linear free-energy relationships between the relative reaction rates (logkrel) and the σp (4R-PhSMe) with ρ = −0.65 (catalytic) and ρ = −1.13 (stoichiometric), we obtained strong evidence that the stoichiometric and catalytic oxidation of thioanisoles mediated by FeIII(OIPh) species involves direct oxygen transfer. The small negative slope −2.18 from log kobs versus Eox for 4R-PhSMe gives further clear evidence for the direct oxygen atom transfer mechanism. On the contrary, with the linear free-energy relationships between the relative reaction rates (logkrel) and total substituent effect (TE, 4R-PhCHCH2) parameters with slope = 0.33 (catalytic) and 2.02 (stoichiometric), the stoichiometric and catalytic epoxidation of styrenes takes place through a nonconcerted electron transfer (ET) mechanism, including the formation of the radicaloid benzylic radical intermediate in the rate-determining step. On the basis of mechanistic studies, we came to the conclusion that the title iron(III)-iodosylbenzene complex is able to oxygenate sulfides and alkenes before it is transformed into the oxo-iron form by cleavage of the O−I bond.

Significant progress has been made in the last three decades in the understanding and application of nonheme iron complexes in oxidation catalysis. Several ligand systems have been demonstrated as able to form a reactive iron(III)-iodosylarene moiety. Although this part is less commonly examined than the related high-valent oxo congeners, there is no doubt that the iodosylarene entity is a crucial part of the oxidation catalysis in biomimetic model systems. Hence, understanding its properties and reactivity helps tremendously to understand processes in catalytic oxidations. In parallel, highly active and selective catalysts for epoxidation and sulfoxidation have been designed where this moiety is unequivocally involved. To obtain more insight into the mechanisms of the metastable iron(III)-iodosylbenzene mediated sulfoxidation and epoxidation reactions, catalytic and stoichiometric oxidation were carried out using [Fe II (PBI)3](CF3SO3)2 (1) as catalyst and PhIO as oxidant for the catalytic, and the in situ formed Fe III (OIPh) species for the stoichiometric oxidation of thioanisole and styrene derivatives ( Figure 1).

Catalytic Sulfoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
The catalytic activity of the previously synthesized and characterized ferrous complex, [Fe II (PBI)3](OTf)2 (1) was investigated in the oxidation of para-substituted thioanisole derivatives, utilizing PhIO as oxidant. The reactions were carried out under standard, optimal catalytic conditions (1:100:300 ratio for catalyst:oxidant:substrate) in acetonitrile at 293 K. A large excess of substrate was used to minimize over-oxidation of

Catalytic Sulfoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
The catalytic activity of the previously synthesized and characterized ferrous complex, [Fe II (PBI) 3 ](OTf) 2 (1) was investigated in the oxidation of para-substituted thioanisole derivatives, utilizing PhIO as oxidant. The reactions were carried out under standard, optimal catalytic conditions (1:100:300 ratio for catalyst:oxidant:substrate) in acetonitrile at 293 K. A large excess of substrate was used to minimize over-oxidation of the product. It took around 1 h to have about 20-70% yields (based on the oxidant) depending on the substituent on the phenyl ring (Table 1). The iron(II)-catalyzed reactions of thioanisoles produced methyl phenyl sulfoxide derivatives as expected and as a major product in all cases, in addition to one minor product, namely methyl phenyl sulfone derivatives. The effect of electron-donating and electron-withdrawing substituents on the aromatic ring on the relative reactivity has also been studied and showed a significant impact on the catalytic sulfoxidation reaction (Table 1).  2 The product was identified by GC-MS and the yields (based on oxidant) were determined by GC using bromobenzene as internal standard. 3 [Substrate] 0 /[1] 0 . 4

TON/h.
Thioanisols with electron-donating groups, such as -OMe or -Me, on the phenyl ring gave better yields (66% for -OMe and 60% for -Me) than those with electron-withdrawing groups (21% for -NO 2 and 37% for -Cl) (Figure 2a). The highest TON (turn over number) and TOF (turn over frequency) values can be observed for 4-OMe-PhSMe, at 66 and 80 h −1 , respectively ( Figure 2b). depending on the substituent on the phenyl ring (Table 1). The iron(II)-catalyzed reactions of thioanisoles produced methyl phenyl sulfoxide derivatives as expected and as a major product in all cases, in addition to one minor product, namely methyl phenyl sulfone derivatives. The effect of electron-donating and electron-withdrawing substituents on the aromatic ring on the relative reactivity has also been studied and showed a significant impact on the catalytic sulfoxidation reaction (Table 1). Thioanisols with electron-donating groups, such as -OMe or -Me, on the phenyl ring gave better yields (66% for -OMe and 60% for -Me) than those with electron-withdrawing groups (21% for -NO2 and 37% for -Cl) ( The reactivities of para-substituted 4R-PhSMe relative to that of PhSMe were also investigated (Table 1 and Figure 3). It was found that thioanisoles with Hammett treatments of relative reactivities (krel = log(Xf/Xi)/log(Yf/Yi), where Xi and Xf are the initial and final concentration of 4R-PhSMe, and Yi and Yf are the initial and final concentration of PhSMe) of various substituents against σ gave a ρ value of −0.65, which suggests that the behavior of the oxidant generated from 1 and PhIO is mildly electrophilic (Figure 3a). When the logkrel values were plotted against the E 0 ox potentials of 4R-PhSMe, the plot gave a gradient of −1.23 (Figure 3b). The magnitude of these values may be consistent with a direct O-atom transfer from the substrate in the rate-determining step. Much higher values can be observed for an ET (electron transfer) mechanism [31]. The reactivities of para-substituted 4R-PhSMe relative to that of PhSMe were also investigated (Table 1 and Figure 3). It was found that thioanisoles with Hammett treatments of relative reactivities (k rel = log(X f /X i )/log(Y f /Y i ), where X i and X f are the initial and final concentration of 4R-PhSMe, and Y i and Y f are the initial and final concentration of PhSMe) of various substituents against σ gave a ρ value of −0.65, which suggests that the behavior of the oxidant generated from 1 and PhIO is mildly electrophilic (Figure 3a). When the logk rel values were plotted against the E 0 ox potentials of 4R-PhSMe, the plot gave a gradient of −1.23 (Figure 3b). The magnitude of these values may be consistent with a direct O-atom transfer from the substrate in the rate-determining step. Much higher values can be observed for an ET (electron transfer) mechanism [31].  As we noticed before, the reaction of 1 with PhIO results in the formation of reactive Fe III (OIPh) species, which suggests that it may have a key role in the catalytic cycles. To prove this assumption, we followed the formation and decomposition of Fe III (OIPh) intermediate (the rise and fall of their visible chromophores at λmax = 760 nm, as well as the appearance of the forming products (methyl phenyl sulfoxide and methyl phenyl sulfone) during the oxidation reaction of thioanisole, using parallel UV-Vis and GC measurements). The profile of the catalytic process shows the immediate formation and subsequent decomposition of the spectroscopically characterized Fe III (OIPh) species, as well as the formation of the oxidation products that appear parallel to it ( Figure 4).

Stoichiometric Sulfoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
To obtain direct evidence for the involvement of the iron(III)-iodosylbenzene adduct in the sulfoxidation reaction, the stoichiometric reaction of the in situ generated Fe III (OIPh) As we noticed before, the reaction of 1 with PhIO results in the formation of reactive Fe III (OIPh) species, which suggests that it may have a key role in the catalytic cycles. To prove this assumption, we followed the formation and decomposition of Fe III (OIPh) intermediate (the rise and fall of their visible chromophores at λ max = 760 nm, as well as the appearance of the forming products (methyl phenyl sulfoxide and methyl phenyl sulfone) during the oxidation reaction of thioanisole, using parallel UV-Vis and GC measurements). The profile of the catalytic process shows the immediate formation and subsequent decomposition of the spectroscopically characterized Fe III (OIPh) species, as well as the formation of the oxidation products that appear parallel to it ( Figure 4).  As we noticed before, the reaction of 1 with PhIO results in the formation of reactive Fe III (OIPh) species, which suggests that it may have a key role in the catalytic cycles. To prove this assumption, we followed the formation and decomposition of Fe III (OIPh) intermediate (the rise and fall of their visible chromophores at λmax = 760 nm, as well as the appearance of the forming products (methyl phenyl sulfoxide and methyl phenyl sulfone) during the oxidation reaction of thioanisole, using parallel UV-Vis and GC measurements). The profile of the catalytic process shows the immediate formation and subsequent decomposition of the spectroscopically characterized Fe III (OIPh) species, as well as the formation of the oxidation products that appear parallel to it ( Figure 4).

Stoichiometric Sulfoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
To obtain direct evidence for the involvement of the iron(III)-iodosylbenzene adduct in the sulfoxidation reaction, the stoichiometric reaction of the in situ generated Fe III (OIPh)

Stoichiometric Sulfoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
To obtain direct evidence for the involvement of the iron(III)-iodosylbenzene adduct in the sulfoxidation reaction, the stoichiometric reaction of the in situ generated Fe III (OIPh) with various thioanisoles was investigated. The Fe III (OIPh) species was generated with 4 equivalent of PhIO, and the excess of oxidant was removed by filtration. It was found that this intermediate is able to selectively oxidize the thioanisole derivatives, resulting in an almost quantitative formation of the corresponding sulfoxides suggesting a direct O-atom transfer mechanism with two-electron process. The pseudo-first-order rate constants, k obs , in the reaction of Fe III (OIPh) with thioanisoles were determined from the absorbance change at 760 nm ( Figure 5) by monitoring the decrease of the Fe III (OIPh) concentration. The yields of sulfoxides without a significant amount of sulfone formation (~1%) were about 80-90%, indicating that the UV-Vis spectral change corresponds to the OAT process. An isobestic point was observed at~520 nm, indicating that there were no long-lived intermediates during the oxidation reaction ( Figure 5a). The kinetic data show that the reaction is firstorder in the oxidant, Fe III (OIPh) (Figures 5b and 6b), and thioanisole ( Figure 6a). The rates in the presence of excess of thioanisole (300-1500 equivalent) obeyed pseudo-first-order kinetics, and the pseudo-first-order rate constants (normalized with the rate of self-decay process without substrates) increased linearly with the thioanisole concentration ( Figure 6a). The second-order constants, k 2 were evaluated from the slope of the plots of k obs versus [thioanisole] 0 . From this linear plotting, the second-order rate constant (k 2 ) was determined to be 1.69 × 10 −3 M −1 s −1 with E A = 41.93 ± 4.45 kJ mol −1 , ∆H = = 39.41 ± 6.53 kJ mol −1 , ∆S = = −162.15 ± 21.8 J mol −1 K −1 , ∆G = = 86.92 ± 12.91 kJ mol −1 at 293 K ( Figure 7). The obtained value is 2 orders of magnitude smaller than those obtained for Fe IV (O) species with pentadentate poly-pirydil ligands (k 2 = 2.56 × 10 −1 M −1 s −1 with ∆H = = 44 kJ mol −1 , and ∆S = = −100 J mol −1 K −1 at 298 K) [12]. A k rel (PhS(O)Me/PhSMe) value of 0.64 was also determined by comparing an individual reaction with methyl-phenyl-sulfoxide as substrate, with the PhSMe oxidation under identical conditions ( Figure 6a). The k obs and k 2 values are listed in Table 2.
Molecules 2023, 28, x FOR PEER REVIEW 5 of 18 with various thioanisoles was investigated. The Fe III (OIPh) species was generated with 4 equivalent of PhIO, and the excess of oxidant was removed by filtration. It was found that this intermediate is able to selectively oxidize the thioanisole derivatives, resulting in an almost quantitative formation of the corresponding sulfoxides suggesting a direct O-atom transfer mechanism with two-electron process. The pseudo-first-order rate constants, kobs, in the reaction of Fe III (OIPh) with thioanisoles were determined from the absorbance change at 760 nm ( Figure 5) by monitoring the decrease of the Fe III (OIPh) concentration. The yields of sulfoxides without a significant amount of sulfone formation (~1%) were about 80-90%, indicating that the UV-Vis spectral change corresponds to the OAT process. An isobestic point was observed at ~520 nm, indicating that there were no long-lived intermediates during the oxidation reaction ( Figure 5a). The kinetic data show that the reaction is first-order in the oxidant, Fe III (OIPh) (Figures 5b and 6b), and thioanisole ( Figure 6a). The rates in the presence of excess of thioanisole (300-1500 equivalent) obeyed pseudo-first-order kinetics, and the pseudo-first-order rate constants (normalized with the rate of self-decay process without substrates) increased linearly with the thioanisole concentration ( Figure 6a). The second-order constants, k2 were evaluated from the slope of the plots of kobs versus [thioanisole]0. From this linear plotting, the second-order rate constant (k2) was determined to be 1.  Table 2.
(a) (b)    Table 2. Kinetic data for the stoichiometric oxidation of para-substituted thioanisole and methyl phenyl sulfoxide derivatives with Fe III (OIPh) generated in situ by the reaction of 1 with 4 equivalents of PhIO in acetonitrile 1 .      Table 2. Kinetic data for the stoichiometric oxidation of para-substituted thioanisole and methyl phenyl sulfoxide derivatives with Fe III (OIPh) generated in situ by the reaction of 1 with 4 equivalents of PhIO in acetonitrile 1 .   In general, two alternative mechanisms can be proposed for the sulfoxidation of sulfides with oxo-metal complexes, namely direct oxygen atom transfer (OAT) to afford the sulfoxide (pathway a in Scheme 1), and the formation of sulfenium radical via electron transfer (ET) mechanism (pathway b in Scheme 1) [12].  3 In the presence of 5 mmol PhI. 4 In the presence of 10 mmol PhI. 5 In the presence of 50 mmol PhI.
In general, two alternative mechanisms can be proposed for the sulfoxidation of sulfides with oxo-metal complexes, namely direct oxygen atom transfer (OAT) to afford the sulfoxide (pathway a in Scheme 1), and the formation of sulfenium radical via electron transfer (ET) mechanism (pathway b in Scheme 1) [12]. To confirm the mechanism of the reaction as direct OAT rather than electron transfer, we investigated the effect of the substituents in the para position of PhSMe, and the observed kinetic data were treated in terms of the Hammett equation. Electron-attracting substituents in the sulfides reduce the rate of oxidation. The ρ value is −1.13, suggesting that the metal-based oxidant is electrophilic (Figure 8a). By plotting logkobs against the oneelectron oxidation potentials (Eox) of the thioanisols, a linear line with a slope of −2.18 was obtained, which is consistent with a direct OAT mechanism (Figure 8b). These values are of the same order of magnitude, although slightly smaller than the values obtained for Fe IV (O) species with pentadentate poly-pirydil ligands (ρ value is −1.78 and −1.51, respectively), indicating the less electrophilic nature of the Fe III (OIPh) species compared to the oxo-iron(IV) intermediates with similar ligand environment [12,32]. Gradients of much larger magnitude (−8.5 and −10.5) were observed when reactions proceeded through an ET pathway [33]. To confirm the mechanism of the reaction as direct OAT rather than electron transfer, we investigated the effect of the substituents in the para position of PhSMe, and the observed kinetic data were treated in terms of the Hammett equation. Electron-attracting substituents in the sulfides reduce the rate of oxidation. The ρ value is −1.13, suggesting that the metal-based oxidant is electrophilic (Figure 8a). By plotting logk obs against the one-electron oxidation potentials (E ox ) of the thioanisols, a linear line with a slope of −2.18 was obtained, which is consistent with a direct OAT mechanism (Figure 8b). These values are of the same order of magnitude, although slightly smaller than the values obtained for Fe IV (O) species with pentadentate poly-pirydil ligands (ρ value is −1.78 and −1.51, respectively), indicating the less electrophilic nature of the Fe III (OIPh) species compared to the oxo-iron(IV) intermediates with similar ligand environment [12,32]. Gradients of much larger magnitude (−8.5 and −10.5) were observed when reactions proceeded through an ET pathway [33]. Based on these results, we ruled out the participation of the oxo-iron(IV) species, which can be formed by homolytic O-I bond cleavage of iron(III)-iodosyl-benzene adducts, as a reactive intermediate in our stoichiometric and catalytic sulfoxidation reactions. However, we cannot rule out the possibility that the oxo-iron(V) species is formed via heterolytic cleavage of the O-I bond of the iron(III)-iodosyl-benzene adducts in a pre-equilibrium process, and this intermediate participates as a reactive element in the oxidation process. In iron porphyrin systems, an equilibrium exists between an iron(IV) oxo porphyrin π-cation radical complex and an iron(III) iodosylarene porphyrin complex in the presence of iodoarene and it is the iron(IV) center which is the reactive species in olefin epoxidation reactions. [19] If there is an equilibrium between an iron(III)iodosylarene adduct and an iron(V) oxo species, which is formed by OI bond cleavage of the iron(III)-iodosylarene adduct, the presence of an excess amount of iodoarene should decrease the reaction rate. Compound Fe III (OIPh) was employed in the thioanisole oxidation reactions in the presence of PhI (50 equivalent). It was found that the reaction rates were significantly higher than those obtained in the reactions carried out in the absence of PhI (Figure 9). These results demonstrate unambiguously that the iron(III) iodosylarene adduct (Scheme 2), not the iron(V)oxo complex, is the reactive species for the sulfoxidation reactions. When the stoichiometric reaction is carried out with an excess of PhI, a nearly three-fold reaction rate (kobs = 2.459 × 10 −3 s −1 (with 50 mmol PhI) compared to kobs = 0.97 × 10 −3 s −1 (without PhI)) is observed, suggesting that the Fe III (IOPh)-mediated reaction is more favored compared to the oxo-iron(V) species (Figure 9a). The saturation curve clearly shows that the equilibrium is shifted towards the Fe IlI (OIPh) species ( Figure  9b). Based on these results, we ruled out the participation of the oxo-iron(IV) species, which can be formed by homolytic O-I bond cleavage of iron(III)-iodosyl-benzene adducts, as a reactive intermediate in our stoichiometric and catalytic sulfoxidation reactions. However, we cannot rule out the possibility that the oxo-iron(V) species is formed via heterolytic cleavage of the O-I bond of the iron(III)-iodosyl-benzene adducts in a pre-equilibrium process, and this intermediate participates as a reactive element in the oxidation process. In iron porphyrin systems, an equilibrium exists between an iron(IV) oxo porphyrin πcation radical complex and an iron(III) iodosylarene porphyrin complex in the presence of iodoarene and it is the iron(IV) center which is the reactive species in olefin epoxidation reactions [19]. If there is an equilibrium between an iron(III)-iodosylarene adduct and an iron(V) oxo species, which is formed by OI bond cleavage of the iron(III)-iodosylarene adduct, the presence of an excess amount of iodoarene should decrease the reaction rate. Compound Fe III (OIPh) was employed in the thioanisole oxidation reactions in the presence of PhI (50 equivalent). It was found that the reaction rates were significantly higher than those obtained in the reactions carried out in the absence of PhI (Figure 9). These results demonstrate unambiguously that the iron(III) iodosylarene adduct (Scheme 2), not the iron(V)oxo complex, is the reactive species for the sulfoxidation reactions. When the stoichiometric reaction is carried out with an excess of PhI, a nearly three-fold reaction rate (k obs = 2.459 × 10 −3 s −1 (with 50 mmol PhI) compared to k obs = 0.97 × 10 −3 s −1 (without PhI)) is observed, suggesting that the Fe III (IOPh)-mediated reaction is more favored compared to the oxo-iron(V) species (Figure 9a). The saturation curve clearly shows that the equilibrium is shifted towards the Fe IlI (OIPh) species (Figure 9b).
The obtained results are consistent with the results obtained for our catalytic system, based on which the substituent effect tests indicate a direct O-atom transfer from the Fe III (OIPh) intermediate to the substrate in the rate-determining step of both systems (Scheme 2). The mechanism of direct oxygen atom transfer mediated by Fe III (IOPh) and its differences compared to the ET mechanism were also supported by detailed DFT calculations [21]. The obtained results are consistent with the results obtained for our catalytic system, based on which the substituent effect tests indicate a direct O-atom transfer from the Fe III (OIPh) intermediate to the substrate in the rate-determining step of both systems (Scheme 2). The mechanism of direct oxygen atom transfer mediated by Fe III (IOPh) and its differences compared to the ET mechanism were also supported by detailed DFT calculations [21]. Scheme 2. Suggested mechanism for the Fe III (OIPh)-mediated sulfoxidation reaction.

Catalytic Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
Similarly to the catalytic sulfoxidation reaction, the catalytic activity of the [Fe II (PBI)3](OTf)2 (1) was also investigated in the oxidation of para-substituted styrene derivatives, utilizing PhIO as oxidant. The reactions were carried out under standard, optimal catalytic conditions (1:100:300 ratio for catalyst:oxidant:substrate) in acetonitrile at 293 K. The large excess of substrate was used to minimize over-oxidation of the product. It took around 1 h to have about 14-29% yields (based on the oxidant) depending on the substituent on the phenyl ring ( Table 3). The iron(II)-catalyzed reactions of styrenes produced epoxide derivatives as expected, and as a major product in all cases, in addition to one minor product, namely benzaldehyde derivatives (less than 1%). The effect of electron-donating and electron-withdrawing substituents on the aromatic ring on the relative reactivity has also been studied and showed a significant impact on the catalytic epoxidation reaction (Table 1 and Figure 10). Styrenes with both electron-donating (-OMe or -Me) and electron-withdrawing (-Cl or -CN) groups on the phenyl ring gave better  The obtained results are consistent with the results obtained for our catalytic system, based on which the substituent effect tests indicate a direct O-atom transfer from the Fe III (OIPh) intermediate to the substrate in the rate-determining step of both systems (Scheme 2). The mechanism of direct oxygen atom transfer mediated by Fe III (IOPh) and its differences compared to the ET mechanism were also supported by detailed DFT calculations [21]. Scheme 2. Suggested mechanism for the Fe III (OIPh)-mediated sulfoxidation reaction.

Catalytic Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
Similarly to the catalytic sulfoxidation reaction, the catalytic activity of the [Fe II (PBI)3](OTf)2 (1) was also investigated in the oxidation of para-substituted styrene derivatives, utilizing PhIO as oxidant. The reactions were carried out under standard, optimal catalytic conditions (1:100:300 ratio for catalyst:oxidant:substrate) in acetonitrile at 293 K. The large excess of substrate was used to minimize over-oxidation of the product. It took around 1 h to have about 14-29% yields (based on the oxidant) depending on the substituent on the phenyl ring ( Table 3). The iron(II)-catalyzed reactions of styrenes produced epoxide derivatives as expected, and as a major product in all cases, in addition to one minor product, namely benzaldehyde derivatives (less than 1%). The effect of electron-donating and electron-withdrawing substituents on the aromatic ring on the relative reactivity has also been studied and showed a significant impact on the catalytic epoxidation reaction (Table 1 and Figure 10). Styrenes with both electron-donating (-OMe or -Me) and electron-withdrawing (-Cl or -CN) groups on the phenyl ring gave better Scheme 2. Suggested mechanism for the Fe III (OIPh)-mediated sulfoxidation reaction.

Catalytic Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
Similarly to the catalytic sulfoxidation reaction, the catalytic activity of the [Fe II (PBI) 3 ] (OTf) 2 (1) was also investigated in the oxidation of para-substituted styrene derivatives, utilizing PhIO as oxidant. The reactions were carried out under standard, optimal catalytic conditions (1:100:300 ratio for catalyst:oxidant:substrate) in acetonitrile at 293 K. The large excess of substrate was used to minimize over-oxidation of the product. It took around 1 h to have about 14-29% yields (based on the oxidant) depending on the substituent on the phenyl ring ( Table 3). The iron(II)-catalyzed reactions of styrenes produced epoxide derivatives as expected, and as a major product in all cases, in addition to one minor product, namely benzaldehyde derivatives (less than 1%). The effect of electron-donating and electron-withdrawing substituents on the aromatic ring on the relative reactivity has also been studied and showed a significant impact on the catalytic epoxidation reaction (Table 1 and Figure 10). Styrenes with both electron-donating (-OMe or -Me) and electronwithdrawing (-Cl or -CN) groups on the phenyl ring gave better yields (29% for -OMe, 19% for -Me, and 16% for -Cl and 27% for -CN) (Figure 10a). The highest TON (TOF) values can be observed for 4-OMe-PhCHCH 2 ; 59 (59 h −1 ) (Figure 10b).  2 The product was identified by GC-MS and the yields (based on oxidant) were determined by GC using bromobenzene as internal standard. 3 [Substrate] 0 /[1] 0 . 4 TON/h. 5 TE = total substituent effect [33].
Molecules 2023, 28, x FOR PEER REVIEW 10 of 18 yields (29% for -OMe, 19% for -Me, and 16% for -Cl and 27% for -CN) (Figure 10a). The highest TON (TOF) values can be observed for 4-OMe-PhCHCH2; 59 (59 h −1 ) (Figure 10b).  The reactivities of para-substituted 4R-PhCHCH2 relative to that of PhCHCH2 were also investigated (Figures 10 and 11). It was found that styrenes displayed Hammett treatments of relative reactivities (krel = log(Xf/Xi)/log(Yf/Yi), where Xi and Xf are the initial and final concentration of 4R-PhCHCH2, and Yi and Yf are the initial and final concentration of PhCHCH2) of various substituents against σ gave concave Hammett curve, which means that both electron-donating and electron-withdrawing groups on the para-position of the aromatic ring increase the rate of the epoxidation reaction ( Figure  11a). A linear free-energy relationship between the relative rate (logkrel) for the parasubstituted styrene oxidations and the total substituent effect (TE) parameters has been established: ρTE• = +0.33 (Figure 11b) [33]. Based on the obtained results, it can be assumed that the oxidation of aromatic alkenes catalyzed by 1 with PhIO as oxidant takes place through the formation of a rate-limiting radical intermediate. The profile of the catalytic process shows the immediate formation and subsequent decomposition of the spectroscopically characterized Fe III (OIPh) species, as well as the formation of the oxidation products that appear parallel to it (Figure 12). The reactivities of para-substituted 4R-PhCHCH 2 relative to that of PhCHCH 2 were also investigated (Figures 10 and 11). It was found that styrenes displayed Hammett treatments of relative reactivities (k rel = log(X f /X i )/log(Y f /Y i ), where X i and X f are the initial and final concentration of 4R-PhCHCH 2 , and Y i and Y f are the initial and final concentration of PhCHCH 2 ) of various substituents against σ gave concave Hammett curve, which means that both electron-donating and electron-withdrawing groups on the para-position of the aromatic ring increase the rate of the epoxidation reaction (Figure 11a). A linear free-energy relationship between the relative rate (logk rel ) for the para-substituted styrene oxidations and the total substituent effect (TE) parameters has been established: ρ TE • = +0.33 (Figure 11b) [33]. Based on the obtained results, it can be assumed that the oxidation of aromatic alkenes catalyzed by 1 with PhIO as oxidant takes place through the formation of a rate-limiting radical intermediate. The profile of the catalytic process shows the immediate formation and subsequent decomposition of the spectroscopically characterized Fe III (OIPh) species, as well as the formation of the oxidation products that appear parallel to it (Figure 12

Stoichiometric Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
The epoxidation of styrene derivatives with 1 and PhIO as an oxidant was carried out at room temperature under catalytic reaction conditions, and the corresponding epoxides were obtained as the main products in these reactions. Since the product distributions were identical to those observed in the stoichiometric reactions with in situ generated iron(III)-iodosylbenzene adduct, this lead us to suggest that the active oxidizing species responsible for the olefin epoxidation in these catalytic reactions is the iron(III)iodosylbenzene adduct (Figure 12). In order to clarify the elementary step of the catalytic reaction, we performed detailed reaction kinetic measurements. The reactivity of the in situ generated iron(III)-iodosylbenzene was investigated in the epoxidation reaction of styrene derivatives. The Fe III (OIPh) intermediate was generated by the reaction of 1 with 1.2 equivalent of PhIO, and the rate of its decay at 760 nm was measured as a function of the concentration of added styrene derivatives ( Figure 13). An isobestic point was observed at ~520 nm, indicating that there were no long-lived intermediates during the oxidation reaction (Figure 13a). The rates in the presence of a large excess of styrene (300-

Stoichiometric Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
The epoxidation of styrene derivatives with 1 and PhIO as an oxidant was carried out at room temperature under catalytic reaction conditions, and the corresponding epoxides were obtained as the main products in these reactions. Since the product distributions were identical to those observed in the stoichiometric reactions with in situ generated iron(III)-iodosylbenzene adduct, this lead us to suggest that the active oxidizing species responsible for the olefin epoxidation in these catalytic reactions is the iron(III)iodosylbenzene adduct (Figure 12). In order to clarify the elementary step of the catalytic reaction, we performed detailed reaction kinetic measurements. The reactivity of the in situ generated iron(III)-iodosylbenzene was investigated in the epoxidation reaction of styrene derivatives. The Fe III (OIPh) intermediate was generated by the reaction of 1 with 1.2 equivalent of PhIO, and the rate of its decay at 760 nm was measured as a function of the concentration of added styrene derivatives ( Figure 13). An isobestic point was observed at ~520 nm, indicating that there were no long-lived intermediates during the oxidation reaction (Figure 13a). The rates in the presence of a large excess of styrene (300-

Stoichiometric Epoxidation Reaction Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
The epoxidation of styrene derivatives with 1 and PhIO as an oxidant was carried out at room temperature under catalytic reaction conditions, and the corresponding epoxides were obtained as the main products in these reactions. Since the product distributions were identical to those observed in the stoichiometric reactions with in situ generated iron(III)iodosylbenzene adduct, this lead us to suggest that the active oxidizing species responsible for the olefin epoxidation in these catalytic reactions is the iron(III)-iodosylbenzene adduct ( Figure 12). In order to clarify the elementary step of the catalytic reaction, we performed detailed reaction kinetic measurements. The reactivity of the in situ generated iron(III)iodosylbenzene was investigated in the epoxidation reaction of styrene derivatives. The Fe III (OIPh) intermediate was generated by the reaction of 1 with 1.2 equivalent of PhIO, and the rate of its decay at 760 nm was measured as a function of the concentration of added styrene derivatives (Figure 13). An isobestic point was observed at~520 nm, indicating that there were no long-lived intermediates during the oxidation reaction (Figure 13a). The rates in the presence of a large excess of styrene (300-1500 equiv.) obeyed pseudofirst order kinetics −d[Fe III (OIPh)]/dt = k obs [Fe III (OIPh)], where k obs = k sd + k 2 [S] and k sd << k 2 [PhCHCH 2 ]), which is evident from the linear log(absorbance) versus time plots (Figure 13b), and the pseudo-first order rate constants (k obs = k 2 [PhCHCH 2 )] increased proportionally with the substrate concentration (Figure 14a). At constant styrene concentration the linear plot of the reaction rate values (V i = k obs [Fe III (OIPh)]) against the initial concentration of Fe III (OIPh) states that the reaction is first-order with respect to the Fe III (OIPh) concentration (Figure 14b).  (Figure 13b), and the pseudo-first order rate constants (kobs = k2[PhCHCH2)] increased proportionally with the substrate concentration (Figure 14a). At constant styrene concentration the linear plot of the reaction rate values (Vi = kobs[Fe III (OIPh)]) against the initial concentration of Fe III (OIPh) states that the reaction is first-order with respect to the Fe III (OIPh) concentration (Figure 14b).  (Table 4 and Figure 15). This value is an order of magnitude larger than that was found for Fe IV (O) species with pentadentate poly-pirydil ligands (k2 = 2.94 × 10 −4 M −1 s −1 with ΔG ≠ = 93 ± 8 kJ mol −1 at 298 K) [34]. Comparing the obtained values with the values calculated for sulfoxidation, it can be concluded that the epoxidation is slightly more favorable, approximately twice as fast, if the reactions are carried out under the same conditions. The lower ΔG ≠ value obtained for epoxidation is also consistent with the above result. The relatively large and negative entropies are typical of associative processes.  (Table 4 and Figure 15). This value is an order of magnitude larger than that was found for Fe IV (O) species with pentadentate poly-pirydil ligands (k2 = 2.94 × 10 −4 M −1 s −1 with ΔG ≠ = 93 ± 8 kJ mol −1 at 298 K) [34]. Comparing the obtained values with the values calculated for sulfoxidation, it can be concluded that the epoxidation is slightly more favorable, approximately twice as fast, if the reactions are carried out under the same conditions. The lower ΔG ≠ value obtained for epoxidation is also consistent with the above result. The relatively large and negative entropies are typical of associative processes. for the styrene derivatives. From these experiments, the second order rate constant (k 2 ) was determined to be 3.09 × 10 −3 M −1 s −1 with ∆H = = 32 ± 4 kJ mol −1 , ∆S = = −182 ± 14 J mol −1 K −1 , ∆G = = 85 ± 8 kJ mol −1 at 293 K (Table 4 and Figure 15). This value is an order of magnitude larger than that was found for Fe IV (O) species with pentadentate poly-pirydil ligands (k 2 = 2.94 × 10 −4 M −1 s −1 with ∆G = = 93 ± 8 kJ mol −1 at 298 K) [34]. Comparing the obtained values with the values calculated for sulfoxidation, it can be concluded that the epoxidation is slightly more favorable, approximately twice as fast, if the reactions are carried out under the same conditions. The lower ∆G = value obtained for epoxidation is also consistent with the above result. The relatively large and negative entropies are typical of associative processes.   Competitive reactions were also performed with para-substituted styrene derivatives to evaluate the effect of electronic factors on the reaction. Since both electron-donating (-OMe, -Me) and electron-withdrawing (-Cl, -CN) substituents can accelerate the reaction, the correlation of relative reactivity (log krel) on the substituent constants (σ+) of parasubstituted styrenes is not linear, resulting in a concave Hammett curve (16a) [13]. This result is in contrast to the styrene oxidations by oxo-iron(IV) systems, wherein typically linear Hammett correlations of logkrel versus σ+ with ρ+ of ~−2.0 were obtained [14,34]. A linear free-energy relationship was established with ρTE• = +2.02 value between the relative rates (logkrel) of para-substituted styrene oxidations and the total substituent effect (TE, stabilities of the benzylic radicals including spin delocalization and polar effects (Figure 16b) [33]). Competitive reactions were also performed with para-substituted styrene derivatives to evaluate the effect of electronic factors on the reaction. Since both electron-donating (-OMe, -Me) and electron-withdrawing (-Cl, -CN) substituents can accelerate the reaction, the correlation of relative reactivity (log k rel ) on the substituent constants (σ+) of parasubstituted styrenes is not linear, resulting in a concave Hammett curve (16a) [13]. This result is in contrast to the styrene oxidations by oxo-iron(IV) systems, wherein typically linear Hammett correlations of logk rel versus σ+ with ρ+ of~−2.0 were obtained [14,34]. A linear free-energy relationship was established with ρ TE • = +2.02 value between the relative rates (logk rel ) of para-substituted styrene oxidations and the total substituent effect (TE, stabilities of the benzylic radicals including spin delocalization and polar effects (Figure 16b) [33]).  When the stoichiometric reaction is carried out with an excess of PhI, no inhibition was observed, suggesting that the Fe III (IOPh)-mediated reaction is more favored compared to the oxo-iron(V) species. The sensitivity of the k2 values to the para-substituent effect and the concave Hammett curve support the radical mechanism, including the ratelimiting formation of benzyl radical species. If the carbocation ion is the assumed intermediate, a more negative ρ + value is expected in the electrophilic process (~−3.5). The benzylic radical formed then undergoes ring closure to form an epoxide. Since a similar trend and behavior was observed during the catalytic and stoichiometric reactions, the reaction mediated by Fe III (IOPh) intermediate can be considered as an elementary step in the catalytic process.  When the stoichiometric reaction is carried out with an excess of PhI, no inhibition was observed, suggesting that the Fe III (IOPh)-mediated reaction is more favored compared to the oxo-iron(V) species. The sensitivity of the k2 values to the para-substituent effect and the concave Hammett curve support the radical mechanism, including the ratelimiting formation of benzyl radical species. If the carbocation ion is the assumed intermediate, a more negative ρ + value is expected in the electrophilic process (~−3.5). The benzylic radical formed then undergoes ring closure to form an epoxide. Since a similar trend and behavior was observed during the catalytic and stoichiometric reactions, the reaction mediated by Fe III (IOPh) intermediate can be considered as an elementary step in the catalytic process. When the stoichiometric reaction is carried out with an excess of PhI, no inhibition was observed, suggesting that the Fe III (IOPh)-mediated reaction is more favored compared to the oxo-iron(V) species. The sensitivity of the k 2 values to the para-substituent effect and the concave Hammett curve support the radical mechanism, including the rate-limiting formation of benzyl radical species. If the carbocation ion is the assumed intermediate, a more negative ρ + value is expected in the electrophilic process (~−3.5). The benzylic radical formed then undergoes ring closure to form an epoxide. Since a similar trend and behavior was observed during the catalytic and stoichiometric reactions, the reaction mediated by Fe III (IOPh) intermediate can be considered as an elementary step in the catalytic process.

Conclusions
In summary, we reported the catalytic oxidation of thioanisole and styrene derivatives using a non-heme complex, Fe II (PBI) 3 as catalyst and PhIO as oxidant. The catalytic activity was moderate, but proved to be selective for both substrates, producing sulfoxides and epoxides, respectively, as the main products. Based on Hammett correlation for para-substituted thioanisoles, electrophilic iron-based oxidation can be assumed via a direct O-atom transfer mechanism. In contrast, in the case of para-substituted styrenes, a nonconcerted electron transfer mechanism can be proposed through the formation of the radicaloid benzylic radical intermediate in the rate-determining step. The results of the stoichiometric sulfoxidation and epoxidation reactions of the in situ generated Fe III (OIPh) intermediate supported our proposed hypotheses for the investigated catalytic reactions. These results provide further example of metal-oxidant adducts which can transfer their oxygen atom to organic substrates prior to the conversion into metal oxo species. Efforts to develop asymmetric catalyzed oxidation of various alkenes and sulfides of higher technological interest by introducing the chiral moiety to ligands or oxidants as well as their detailed mechanistic aspects are under progress. Future studies will also be focused on elucidating the intriguing reactivity differences between high-and low-spin Fe(III)-iodosylarene complexes. This type of reactivity difference has been demonstrated recently in the reactions of high-and low-spin iron(III)-hydroperoxo and high-valent oxoiron complexes.