Sayanti Chatterjee

Olefincis-Dihydroxylation and Aliphatic CH Bond Oxygenation by a Dioxygen-Derived Electrophilic Iron-Oxygen Oxidant

Many iron-containing enzymes involve metal-oxygen oxidants to carry out O2-dependent transformation reactions. However, the selective oxidation of C-H and C=C bonds by biomimetic complexes using O2 remains a major challenge in bioinspired catalysis. The reactivity of iron-oxygen oxidants generated from an Fe(II)-benzilate complex of a facial N3 ligand were thus investigated. The complex reacted with O2 to form a nucleophilic oxidant, whereas an electrophilic oxidant, intercepted by external substrates, was generated in the presence of a Lewis acid. Based on the mechanistic studies, a nucleophilic Fe(II)-hydroperoxo species is proposed to form from the benzilate complex, which undergoes heterolytic O-O bond cleavage in the presence of a Lewis acid to generate an Fe(IV)-oxo-hydroxo oxidant. The electrophilic iron-oxygen oxidant selectively oxidizes sulfides to sulfoxides, alkenes to cis-diols, and it hydroxylates the C-H bonds of alkanes, including that of cyclohexane.

Reactivity of an Iron–Oxygen Oxidant Generated upon Oxidative Decarboxylation of Biomimetic Iron(II) α-Hydroxy Acid Complexes

Three biomimetic iron(II) α-hydroxy acid complexes, [(Tp(Ph2))Fe(II)(mandelate)(H2O)] (1), [(Tp(Ph2))Fe(II)(benzilate)] (2), and [(Tp(Ph2))Fe(II)(HMP)] (3), together with two iron(II) α-methoxy acid complexes, [(Tp(Ph2))Fe(II)(MPA)] (4) and [(Tp(Ph2))Fe(II)(MMP)] (5) (where HMP = 2-hydroxy-2-methylpropanoate, MPA = 2-methoxy-2-phenylacetate, and MMP = 2-methoxy-2-methylpropanoate), of a facial tridentate ligand Tp(Ph2) [where Tp(Ph2) = hydrotris(3,5-diphenylpyrazole-1-yl)borate] were isolated and characterized to study the mechanism of dioxygen activation at the iron(II) centers. Single-crystal X-ray structural analyses of 1, 2, and 5 were performed to assess the binding mode of an α-hydroxy/methoxy acid anion to the iron(II) center. While the iron(II) α-methoxy acid complexes are unreactive toward dioxygen, the iron(II) α-hydroxy acid complexes undergo oxidative decarboxylation, implying the importance of the hydroxyl group in the activation of dioxygen. In the reaction with dioxygen, the iron(II) α-hydroxy acid complexes form iron(III) phenolate complexes of a modified ligand (Tp(Ph2)*), where the ortho position of one of the phenyl rings of Tp(Ph2) gets hydroxylated. The iron(II) mandelate complex (1), upon decarboxylation of mandelate, affords a mixture of benzaldehyde (67%), benzoic acid (20%), and benzyl alcohol (10%). On the other hand, complexes 2 and 3 react with dioxygen to form benzophenone and acetone, respectively. The intramolecular ligand hydroxylation gets inhibited in the presence of external intercepting agents. Reactions of 1 and 2 with dioxygen in the presence of an excess amount of alkenes result in the formation of the corresponding cis-diols in good yield. The incorporation of both oxygen atoms of dioxygen into the diol products is confirmed by (18)O-labeling studies. On the basis of reactivity and mechanistic studies, the generation of a nucleophilic iron-oxygen intermediate upon decarboxylation of the coordinated α-hydroxy acids is proposed as the active oxidant. The novel iron-oxygen intermediate oxidizes various substrates like sulfide, fluorene, toluene, ethylbenzene, and benzaldehyde. The oxidant oxidizes benzaldehyde to benzoic acid and also participates in the Cannizzaro reaction.

Catalytic and regiospecific extradiol cleavage of catechol by a biomimetic iron complex.

An iron(III)-catecholate complex of a facial tridentate ligand reacts with dioxygen in the presence of ammonium acetate-acetic acid buffer to cleave the aromatic C-C bond of 3,5-di-tert-butylcatechol regiospecifically resulting in the formation of an extradiol product with multiple turnovers.

Functional models of α-keto acid dependent nonheme iron oxygenases: synthesis and reactivity of biomimetic iron(II) benzoylformate complexes supported by a 2,9-dimethyl-1,10-phenanthroline ligand

Two biomimetic iron(II) benzoylformate complexes, [LFeII(BF)2] (2) and [LFeII(NO3)(BF)] (3) (L is 2,9-dimethyl-1,10-phenanthroline and BF is monoanionic benzoylformate), have been synthesized from an iron(II)–dichloro complex [LFeIICl2] (1). All the iron(II) complexes have been structurally and spectroscopically characterized. The iron(II) center in 2 is coordinated by a bidentate NN ligand (2,9-dimethyl-1,10-phenanthroline) and two monoanionic benzoylformates to form a distorted octahedral coordination geometry. One of the benzoylformates binds to the iron in 2 via both carboxylate oxygens but the other one binds in a chelating bidentate fashion via one carboxylate oxygen and the keto oxygen. On the other hand, the iron(II) center in 3 is ligated by one NN ligand, one bidentate nitrate, and one monoanionic chelating benzoylformate. Both iron(II) benzoylformate complexes exhibit the facial NNO donor environment in their solid-state structures. Complexes 2 and 3 are stable in noncoordinating solvents under an inert atmosphere, but react with dioxygen under ambient conditions to undergo oxidative decarboxylation of benzoylformate to benzoate in high yields. Evidence for the formation of an iron(IV)–oxo intermediate upon oxidative decarboxylation of benzoylformate was obtained by interception and labeling experiments. The iron(II) benzoylformate complexes represent the functional models of α-keto acid dependent oxygenases.

Hydroxylation versus Halogenation of Aliphatic C−H Bonds by a Dioxygen‐Derived Iron–Oxygen Oxidant: Functional Mimicking of Iron Halogenases

An iron-oxygen intermediate species generated in situ in the reductive activation of dioxygen by an iron(II)-benzilate complex of a monoanionic facial N3 ligand, promoted the halogenation of aliphatic C-H bonds in the presence of a protic acid and a halide anion. An electrophilic iron(IV)-oxo oxidant with a coordinated halide is proposed as the active oxidant. The halogenation reaction with dioxygen and the iron complex mimics the activity of non-heme iron halogenases.

Oxygenative Aromatic Ring Cleavage of 2-Aminophenol with Dioxygen Catalyzed by a Nonheme Iron Complex: Catalytic Functional Model of 2-Aminophenol Dioxygenases

2-Aminophenol dioxygenases catalyze the oxidative ring cleavage of 2-aminophenol to 2-picolinic acid using O2 as the oxidant. Inspired by the reaction catalyzed by these nonheme iron enzymes, a biomimetic iron(III)-2-amidophenolate complex, [(tBu-L(Me))Fe(III)(4,6-di-tBu-AP)](ClO4) (1a) of a facial tridentate ligand (tBu-L(Me) = 1-[bis(6-methyl-pyridin-2-yl)-methyl]-3-tert-butyl-urea and 4,6-di-tBu-H2AP = 2-amino-4,6-di-tert-butylphenol) bearing a urea group have been isolated. The complex reacts with O2 to cleave the C-C bond of 4,6-di-tBu-AP regioselectively and catalytically to afford 4,6-di-tert-butyl-2-picolinic acid. An iron(II)-chloro complex [(tBu-L(Me))Fe(II)Cl2(MeOH)] (1) of the same ligand also cleaves the aromatic ring of 4,6-di-tBu-AP catalytically in the reaction with O2. To assess the effect of urea group on the ring cleavage reaction of 2-aminophenol, two iron complexes, [(BA-L(Me))2Fe(II)2Cl4] (2) and [(BA-L(Me))Fe(III)(4,6-di-tBu-AP)](ClO4) (2a), of a tridentate ligand devoid of urea group (BA-L(Me) = benzyl-[bis(6-methyl-pyridin-2-yl)-methyl]-amine) have been isolated and characterized. Although the iron complexes (1 and 1a) of the ligand with urea group display catalytic reaction, the iron complexes (2 and 2a) of the ligand without urea group do not exhibit catalytic aromatic ring fission reactivity. The results support the role of urea group in directing the catalytic reactivity exhibited by 1 and 1a.

Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity.

Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant.

Aliphatic C‐C Bond Cleavage of α‐Hydroxy Ketones by a Dioxygen‐Derived Nucleophilic Iron‐Oxygen Oxidant

A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O2 , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid. The O2 -dependent aliphatic C-C bond cleavage of α-hydroxy ketones containing no α-C-H bond bears similarity to the lyase activity of the heme enzyme, cytochrome P450 17A1 (CYP17A1).

Bioinspired Olefin cis-Dihydroxylation and Aliphatic C–H Bond Hydroxylation with Dioxygen Catalyzed by a Nonheme Iron Complex

A mononuclear iron(II)-α-hydroxy acid complex [(TpPh,Me)FeII(benzilate)] (TpPh,Me = hydrotris(3-phenyl-5-methylpyrazol-1-yl)borate) of a facial tridentate ligand has been isolated and characterized to explore its catalytic efficiency for aerial oxidation of organic substrates. In the reaction between the iron(II)-benzilate complex and O2, the metal-coordinated benzilate is stoichiometrically converted to benzophenone with concomitant reduction of dioxygen on the iron center. Based on the results from interception experiments and labeling studies, different iron-oxygen oxidants are proposed to generate in situ in the reaction pathway depending upon the absence or presence of an external additive (such as protic acid or Lewis acid). The five-coordinate iron(II) complex catalytically cis-dihydroxylates olefins and oxygenates the C-H bonds of aliphatic substrates using O2 as the terminal oxidant. The iron(II) complex exhibits better catalytic activity in the presence of a Lewis acid.