Assessing the impact of electronic and steric tuning of the ligand in the spin state and catalytic oxidation ability of the Fe(II)(Pytacn) family of complexes.

A family of iron complexes with the general formula [Fe(II)((R,R)'Pytacn)(X)2](n+) is described, where (R,R)'Pytacn is the tetradentate ligand 1-[(4-R'-6-R-2-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane, R refers to the group at the α-position of the pyridine, R' corresponds to the group at the γ-position, and X denotes CH3CN or CF3SO3. Herein, we study the influence of the pyridine substituents R and R' on the electronic properties of the coordinated iron center by a combination of structural and spectroscopic characterization using X-ray diffraction, (1)H NMR and UV-vis spectroscopies, and magnetic susceptibility measurements. The electronic properties of the substituent in the γ-position of the pyridine ring (R') modulate the strength of the ligand field, as shown by magnetic susceptibility measurements in CD3CN solution, which provide a direct indication of the population of the magnetically active high-spin S = 2 ferrous state. Indeed, a series of complexes [Fe(II)((H,R)'Pytacn)(CD3CN)2](2+) exist as mixtures of high-spin (S = 2) and low-spin (S = 0) complexes, and their effective magnetic moment directly correlates with the electron-releasing ability of R'. On the other hand, the substitution of the hydrogen atom in the α-position of the pyridine by a methyl, chlorine, or fluorine group favors the high-spin state. The whole family of complexes has been assayed in catalytic C-H and C═C oxidation reactions with H2O2. These catalysts exhibit excellent efficiency in the stereospecific hydroxylation of alkanes and in the oxidation of olefins. Remarkably, R'-substituents have little influence on the efficiency and chemoselectivity of the catalytic activity of the complexes, but the selectivity toward olefin cis-dihydroxylation is enhanced for complexes with R = Me, F, or Cl. Isotopic labeling studies in the epoxidation and cis-dihydroxylation reactions show that R has a definitive role in dictating the origin of the oxygen atom that is transferred in the epoxidation reaction.

Electronic effects on single-site iron catalysts for water oxidation.

Getting in tune: Systematic tuning of the electronic properties of modular non-heme iron coordination complexes can be used to extract important information on the reaction mechanism and intermediates, which, in turn, help to explain the activity of these systems as water oxidation catalysts.

The mechanism of stereospecific C-H oxidation by Fe(Pytacn) complexes: bioinspired non-heme iron catalysts containing cis-labile exchangeable sites.

A detailed mechanistic study of the hydroxylation of alkane C-H bonds using H2O2 by a family of mononuclear non heme iron catalysts with the formula [Fe(II)(CF3SO3)2(L)] is described, in which L is a tetradentate ligand containing a triazacyclononane tripod and a pyridine ring bearing different substituents at the α and γ positions, which tune the electronic or steric properties of the corresponding iron complexes. Two inequivalent cis-labile exchangeable sites, occupied by triflate ions, complete the octahedral iron coordination sphere. The C-H hydroxylation mediated by this family of complexes takes place with retention of configuration. Oxygen atoms from water are incorporated into hydroxylated products and the extent of this incorporation depends in a systematic manner on the nature of the catalyst, and the substrate. Mechanistic probes and isotopic analyses, in combination with detailed density functional theory (DFT) calculations, provide strong evidence that C-H hydroxylation is performed by highly electrophilic [Fe(V)(O)(OH)L] species through a concerted asynchronous mechanism, involving homolytic breakage of the C-H bond, followed by rebound of the hydroxyl ligand. The [Fe(V)(O)(OH)L] species can exist in two tautomeric forms, differing in the position of oxo and hydroxide ligands. Isotopic-labeling analysis shows that the relative reactivities of the two tautomeric forms are sensitively affected by the α substituent of the pyridine, and this reactivity behavior is rationalized by computational methods.

Regioselective oxidation of nonactivated alkyl C-H groups using highly structured non-heme iron catalysts.

Selective oxidation of alkyl C-H groups constitutes one of the highest challenges in organic synthesis. In this work, we show that mononuclear iron coordination complexes Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-MCPP)] (Λ-1P), Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-MCPP)] (Δ-1P), Λ-[Fe(CF(3)SO(3))(2)((S,S,R)-BPBPP)] (Λ-2P), and Δ-[Fe(CF(3)SO(3))(2)((R,R,R)-BPBPP)] (Δ-2P) catalyze the fast, efficient, and selective oxidation of nonactivated alkyl C-H groups employing H(2)O(2) as terminal oxidant. These complexes are based on tetradentate N-based ligands and contain iron centers embedded in highly structured coordination sites defined by two bulky 4,5-pinenopyridine donor ligands, a chiral diamine ligand backbone, and chirality at the metal (Λ or Δ). X-ray diffraction analysis shows that in Λ-1P and Λ-2P the pinene rings create cavity-like structures that isolate the iron site. The efficiency and regioselectivity in catalytic C-H oxidation reactions of these structurally rich complexes has been compared with those of Λ-[Fe(CF(3)SO(3))(2)((S,S)-MCP)] (Λ-1), Λ-[Fe(CF(3)SO(3))(2)((S,S)-BPBP)] (Λ-2), Δ-[Fe(CF(3)SO(3))(2)((R,R)-BPBP)] (Δ-2), Λ-[Fe(CH(3)CN)(2)((S,S)-BPBP)](SbF(6))(2) (Λ-2SbF(6)), and Δ-[Fe(CH(3)CN)(2)((R,R)-BPBP)](SbF(6))(2) (Δ-2SbF(6)), which lack the steric bulk introduced by the pinene rings. Cavity-containing complexes Λ-1P and Λ-2P exhibit enhanced activity in comparison with Δ-1P, Δ-2P, Λ-1, Λ-2, and Λ-2SbF(6). The regioselectivity exhibited by catalysts Λ-1P, Λ-2P, Δ-1P, and Δ-2P in the C-H oxidation of simple organic molecules can be predicted on the basis of the innate properties of the distinct C-H groups of the substrate. However, in specific complex organic molecules where oxidation of multiple C-H sites is competitive, the highly elaborate structure of the catalysts allows modulation of C-H regioselectivity between the oxidation of tertiary and secondary C-H groups and also among multiple methylene sites, providing oxidation products in synthetically valuable yields. These selectivities complement those accomplished with structurally simpler oxidants, including non-heme iron catalysts Λ-2 and Λ-2SbF(6).

An iron catalyst for oxidation of alkyl C-H bonds showing enhanced selectivity for methylenic sites.

Many are called but few are chosen: A nonheme iron complex catalyzes the oxidation of alkyl C-H bonds by using H(2)O(2) as the oxidant, showing an enhanced selectivity for secondary over tertiary C-H bonds (see scheme).

Observation of Fe(V)=O using variable-temperature mass spectrometry and its enzyme-like C-H and C=C oxidation reactions.

Oxo-transfer chemistry mediated by iron underpins many biological processes and today is emerging as synthetically very important for the catalytic oxidation of C-H and C=C moieties that are hard to activate conventionally. Despite the vast amount of research in this area, experimental characterization of the reactive species under catalytic conditions is very limited, although a Fe(V)=O moiety was postulated. Here we show, using variable-temperature mass spectrometry, the generation of a Fe(V)=O species within a synthetic non-haem complex at -40 °C and its reaction with an olefin. Also, with isotopic labelling we were able both to follow oxygen-atom transfer from H(2)O(2)/H(2)O through Fe(V)=O to the products and to probe the reactivity as a function of temperature. This study pioneers the implementation of variable-temperature mass spectrometry to investigate reactive intermediates.

Modeling the cis-oxo-labile binding site motif of non-heme iron oxygenases: water exchange and oxidation reactivity of a non-heme iron(IV)-oxo compound bearing a tripodal tetradentate ligand.

The spectroscopic and chemical characterization of a new synthetic non-heme iron(IV)-oxo species [Fe(IV)(O)((Me,H) Pytacn)(S)](2+) (2, (Me,H)Pytacn=1-(2'-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, S=CH(3)CN or H(2)O) is described. Complex 2 was prepared by reaction of [Fe(II)(CF(3)SO(3))(2)((Me,H) Pytacn)] (1) with peracetic acid. Complex 2 bears a tetradentate N(4) ligand that leaves two cis sites available for binding an oxo group and a second external ligand but, unlike the related iron(IV)-oxo species with tetradentate ligands, it is remarkably stable at room temperature (t(1/2)>2 h at 288 K). Its ability to exchange the oxygen atom of the oxo ligand with water has been analyzed in detail by means of kinetic studies, and a mechanism is proposed on the basis of DFT calculations. Hydrogen-atom abstraction from C-H bonds and oxygen-atom transfer to sulfides by 2 have also been studied. Despite its thermal stability, 2 proves to be a very powerful oxidant that is capable of breaking the strong C-H bond of cyclohexane (bond dissociation energy=99.3 kcal mol(-1)).