Iron-Catalyzed Highly Enantioselective cis-Dihydroxylation of Trisubstituted Alkenes with Aqueous H2 O2.

Reliable methods for enantioselective cis-dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis-α-[FeII (2-Me2 -BQPN)(OTf)2 ], which bears a tetradentate N4 ligand (Me2 -BQPN=(R,R)-N,N'-dimethyl-N,N'-bis(2-methylquinolin-8-yl)-1,2-diphenylethane-1,2-diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron-deficient alkenes were efficiently oxidized to chiral cis-diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H2 O2 ) as oxidant under mild conditions. Experimental studies (including 18 O-labeling, ESI-MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis-FeV (O)2 reaction intermediate as an active oxidant. This cis-[FeII (chiral N4 ligand)]2+ /H2 O2 method could be a viable green alternative/complement to the existing OsO4 -based methods for asymmetric alkene dihydroxylation reactions.

Selective catecholamine detection in living cells by a copper-mediated oxidative bond cleavage.

The development of a new triggered-release system for selective detection of catecholamines in biological samples including living cells is reported. Catecholamines are a class of tightly regulated hormones and neurotransmitters in the human body and their dysregulation is implicated in various neurodegenerative diseases. It is highly challenging to selectively sense and detect catecholamines in a complex biological environment due to their small size, non-specific molecular shape and trivial chemical properties. In this study, a copper-based, catecholamine-triggered oxidation that releases a fluorescent reporter is described. The probe is highly sensitive and selective for detecting changes in catecholamine levels in aqueous buffer, human plasma, and cellular models of neuronal differentiation and Parkinson's disease. This new catecholamine sensing strategy features chemical reactivity as part of small molecule recognition as opposed to the conventional use of a well-designed host for reversible binding.

Intramolecular Nitrene Insertion into Saturated C-H-Bond-Mediated C-N Bond Cleavage of a Coordinated NHC Ligand.

Ruthenium(II) complexes bearing a tridentate bis(N-heterocyclic carbene) ligand reacted with iminoiodanes (PhI=NR) resulting in the formation of isolable ruthenium(III)-amido intermediates, which underwent cleavage of a C-N bond of the tridentate ligand and formation of an N-substituted imine group. The RuIII -amido intermediates have been characterized by 1 H NMR, UV/Vis, ESI-MS, and X-ray crystallography. DFT calculations were performed to provide insight into the reaction mechanism.

Chiral cis-iron(ii) complexes with metal- and ligand-centered chirality for highly regio- and enantioselective alkylation of N-heteroaromatics.

Iron-catalyzed highly regio- and enantioselective organic transformations with generality and broad substrate scope have profound applications in modern synthetic chemistry; an example is herein described based on cis-FeII complexes having metal- and ligand-centered chirality. The cis-ß FeII(N4) complex [FeII(L)(OTf)2] (L = N,N'-bis(2,3-dihydro-1H-cyclopenta-[b]quinoline-5-yl)-N,N'-dimethylcyclohexane-1,2-diamine) is an effective chiral catalyst for highly regio- and enantioselective alkylation of N-heteroaromatics with α,ß-unsaturated 2-acyl imidazoles, including asymmetric N1, C2, C3 alkylations of a broad range of indoles (34 examples) and alkylation of pyrroles and anilines (14 examples), all with high product yields (up to 98%), high enantioselectivity (up to >99% ee) and high regioselectivity. DFT calculations revealed that the "chiral-at-metal" cis-ß configuration of the iron complex and a secondary π-π interaction are responsible for the high enantioselectivity.

cis-Oxoruthenium complexes supported by chiral tetradentate amine (N4) ligands for hydrocarbon oxidations.

We report the first examples of ruthenium complexes cis-[(N4)RuIIICl2]+ and cis-[(N4)RuII(OH2)2]2+ supported by chiral tetradentate amine ligands (N4), together with a high-valent cis-dioxo complex cis-[(N4)RuVI(O)2]2+ supported by the chiral N4 ligand mcp (mcp = N,N'-dimethyl-N,N'-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine). The X-ray crystal structures of cis-[(mcp)RuIIICl2](ClO4) (1a), cis-[(Me2mcp)RuIIICl2]ClO4 (2a) and cis-[(pdp)RuIIICl2](ClO4) (3a) (Me2mcp = N,N'-dimethyl-N,N'-bis((6-methylpyridin-2-yl)methyl)cyclohexane-1,2-diamine, pdp = 1,1'-bis(pyridin-2-ylmethyl)-2,2'-bipyrrolidine)) show that the ligands coordinate to the ruthenium centre in a cis-α configuration. In aqueous solutions, proton-coupled electron-transfer redox couples were observed for cis-[(mcp)RuIII(O2CCF3)2]ClO4 (1b) and cis-[(pdp)RuIII(O3SCF3)2]CF3SO3 (3c'). Electrochemical analyses showed that the chemically/electrochemically generated cis-[(mcp)RuVI(O)2]2+ and cis-[(pdp)RuVI(O)2]2+ complexes are strong oxidants with E° = 1.11-1.13 V vs. SCE (at pH 1) and strong H-atom abstractors with DO-H = 90.1-90.8 kcal mol-1. The reaction of 1b or its (R,R)-mcp counterpart with excess (NH4)2[CeIV(NO3)6] (CAN) in aqueous medium afforded cis-[(mcp)RuVI(O)2](ClO4)2 (1e) or cis-[((R,R)-mcp)RuVI(O)2](ClO4)2 (1e*), respectively, a strong oxidant with E(RuVI/V) = 0.78 V (vs. Ag/AgNO3) in acetonitrile solution. Complex 1e oxidized various hydrocarbons, including cyclohexane, in acetonitrile at room temperature, affording alcohols and/or ketones in up to 66% yield. Stoichiometric oxidations of alkenes by 1e or 1e* in t BuOH/H2O (5 : 1 v/v) afforded diols and aldehydes in combined yields of up to 98%, with moderate enantioselectivity obtained for the reaction using 1e*. The cis-[(pdp)RuII(OH2)2]2+ (3c)-catalysed oxidation of saturated C-H bonds, including those of ethane and propane, with CAN as terminal oxidant was also demonstrated.

cis-Dioxorhenium(V/VI) Complexes Supported by Neutral Tetradentate N4 Ligands. Synthesis, Characterization, and Spectroscopy.

A series of cis-dioxorhenium(V) complexes containing chiral tetradentate N4 ligands, including cis-[ReV(O)2(pyxn)]+ (1; pyxn = N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)cyclohexane-1,2-diamine), cis-[ReV(O)2(6-Me2pyxn)]+ (cis-2), cis-[ReV(O)2(R,R-pdp)]+ (3; R,R-pdp = 1,1'-bis((R,R)-2-pyridinylmethyl)-2,2'-bipyrrolidine), cis-[ReV(O)2(R,R-6-Me2pdp)]+ (4), and cis-[ReV(O)2(bqcn)]+ (5; bqcn = N,N'-dimethyl-N,N'-di(quinolin-8-yl)cyclohexane-1,2-diamine), were synthesized. Their structures were established by X-ray crystallography, showing Re-O distances in the range of 1.740(3)-1.769(8) Å and O-Re-O angles of 121.4(2)-124.8(4)°. Their cyclic voltammograms in MeCN (0.1 M [NBu4]PF6) display a reversible ReVI/V couple at E1/2 = 0.39-0.49 V vs SCE. In aqueous media, three proton-coupled electron transfer reactions corresponding to ReVI/V, ReV/III, and ReIII/II couples were observed at pH 1. The Pourbaix diagrams of 1·OTf, 3·OTf, and 5·OTf have been examined. The electronic absorption spectra of the cis-dioxorhenium(V) complexes show three absorption bands at around 800 nm (600-1730 dm3 mol-1 cm-1), 580 nm (1700-5580 dm3 mol-1 cm-1), and 462-523 nm (3170-6000 dm3 mol-1 cm-1). Reaction of 1 with Lewis acids (or protic acids) gave cis-[ReV(O)(OH)(pyxn)]2+ (1·H+), in which the Re-O distances are lengthened to 1.788(5) Å. Complex cis-2 resulted from isomerization of trans-2 at elevated temperature. cis-[ReVI(O)2(pyxn)](PF6)2 (1'·(PF6)2) was obtained by constant-potential electrolysis of 1·PF6 in MeCN (0.1 M [NBu4]PF6) at 0.56 V vs SCE; it displays shorter Re-O distances (1.722(4), 1.726(4) Å) and a smaller O-Re-O angle (114.88(18)°) relative to 1 and shows a d-d transition absorption band at 591 nm (ε = 77 dm3 mol-1 cm-1). With a driving force of ca. 75 kcal mol-1, 1' oxidizes hydrocarbons with weak C-H bonds (75.5-76.3 kcal mol-1) via hydrogen atom abstraction. DFT and TDDFT calculations on the electronic structures and spectroscopic properties of the cis-dioxorhenium(V/VI) complexes were performed.

Highly Enantioselective Iron-Catalyzed cis-Dihydroxylation of Alkenes with Hydrogen Peroxide Oxidant via an Fe(III) -OOH Reactive Intermediate.

The development of environmentally benign catalysts for highly enantioselective asymmetric cis-dihydroxylation (AD) of alkenes with broad substrate scope remains a challenge. By employing [Fe(II) (L)(OTf)2 ] (L=N,N'-dimethyl-N,N'-bis(2-methyl-8-quinolyl)-cyclohexane-1,2-diamine) as a catalyst, cis-diols in up to 99.8 % ee with 85 % isolated yield have been achieved in AD of alkenes with H2 O2 as an oxidant and alkenes in a limiting amount. This "[Fe(II) (L)(OTf)2 ]+H2 O2 " method is applicable to both (E)-alkenes and terminal alkenes (24 examples >80 % ee, up to 1 g scale). Mechanistic studies, including (18) O-labeling, UV/Vis, EPR, ESI-MS analyses, and DFT calculations lend evidence for the involvement of chiral Fe(III) -OOH active species in enantioselective formation of the two C-O bonds.

Water oxidation catalysed by iron complex of N,N'-dimethyl-2,11-diaza[3,3](2,6)pyridinophane. Spectroscopy of iron-oxo intermediates and density functional theory calculations.

The macrocyclic [FeIII(L1)Cl2]+ (1, L1 = N,N'-dimethyl-2,11-diaza[3,3](2,6)pyridinophane) complex is an active catalyst for the oxidation of water to oxygen using [NH4]2[CeIV(NO3)6] (CAN), NaIO4, or Oxone as the oxidant. The mechanism of 1-catalysed water oxidation was examined by spectroscopic methods and by 18O-labelling experiments, revealing that FeIV[double bond, length as m-dash]O and/or FeV[double bond, length as m-dash]O species are likely to be involved in the reaction. The redox behaviour of 1 and these high-valent Fe[double bond, length as m-dash]O species of L1 has been examined by both cyclic voltammetry and density functional theory (DFT) calculations. In aqueous solutions, the cyclic voltammograms of 1 at different pH show a pH-dependent reversible couple (E 1/2 = +0.46 V vs. SCE at pH 1) and an irreversible anodic wave (E pa = +1.18 V vs. SCE at pH 1) assigned to the FeIII/FeII couple and the FeIII to FeIV oxidation, respectively. DFT calculations showed that the E value of the half reaction involving [FeV(L1)(O)(OH)]2+/[FeIV(L1)(O)(OH2)]2+ is +1.42 V vs. SCE at pH 1. Using CAN as the oxidant at pH 1, the formation of an FeIV[double bond, length as m-dash]O reaction intermediate was suggested by ESI-MS and UV-vis absorption spectroscopic measurements, and the rate of oxygen evolution was linearly dependent on the concentrations of both 1 and CAN. Using NaIO4 or Oxone as the oxidant at pH 1, the rate of oxygen evolution was linearly dependent on the concentration of 1, and a reactive FeV[double bond, length as m-dash]O species with formula [FeV(L1)(O)2]+ generated by oxidation with NaIO4 or Oxone was suggested by ESI-MS measurements. DFT calculations revealed that [FeV(L1)(O)2]+ is capable of oxidizing water to oxygen with a reaction barrier of 15.7 kcal mol-1.

[Fe(F20 TPP)Cl]-catalyzed amination with arylamines and {[Fe(F20 TPP)(NAr)](PhI=NAr)} + . Intermediate assessed by high-resolution ESI-MS and DFT calculations.

Amination of CH bonds catalyzed by transition metal complexes via nitrene/imide insertion is an appealing strategy for CN bond formation, and the use of iminoiodinanes, or their in situ generated forms from 'PhI(OAc)2 +primary amides (such as sulfonamides, sulfamates, and carbamates)', as nitrogen sources for the amination reaction has been well documented. In this work, a 'metal catalyst+PhI(OAc)2 +primary arylamines' amination protocol has been developed using [Fe(F20 TPP)Cl] (H2 F20 TPP=meso-tetrakis(pentafluorophenyl)porphyrin) as a catalyst. This catalytic method is applicable for both intra- and intermolecular amination of sp(2) and sp(3) CH bonds (>27 examples), affording the amination products, including natural products such as rutaecarpine, in moderate-to-good yields. ESI-MS analysis and DFT calculations lend support for the involvement of {[Fe(F20 TPP)(NC6 H4 -p-NO2 )](PhI=NC6 H4 -p-NO2 )} + . intermediate in the catalysis.

Anti-cancer iron(II) complexes of pentadentate N-donor ligands: cytotoxicity, transcriptomics analyses, and mechanisms of action.

Two cytotoxic iron(II) complexes [Fe(L)(CH3 CN)n ](ClO4 )2 (L=qpy for Fe-1 a, Py5 -OH for Fe-2 a) were synthesized. Both complexes are stable against spontaneous demetalation and oxidation in buffer solutions. Cyclic voltammetry measurements revealed the higher stability of Fe-2 a (+0.82 V vs Fc) against Fe(II) to Fe(III) oxidation than Fe-1 a (+0.57 V vs Fc). These two complexes display potent cytotoxicity at micromolar level against a panel of cancer cell lines (Fe-1 a=0.8-3.1 µM; Fe-2 a=0.6-3.4 µM), and induce apoptosis that involves caspase activation. Transcriptomic and Connectivity Map analyses revealed that the changes of gene expression induced by Fe-1 a and Fe-2 a are similar to that induced by ciclopirox, an antifungal compound whose mode of action involves formation of intracellular cytotoxic iron chelates. Both Fe-1 a and Fe-2 a caused cellular nuclear DNA damage, as revealed by Comet assay and H2 AX immunofluorescence experiments. The cytotoxicity is associated with production of reactive oxygen species (for Fe-1 a), cell cycle regulation, and stress kinase pathways. The relative contributions of these to the overall cytotoxic mechanism is significantly affected by the structure of penta-N-donor ligand.

Density functional theory calculations on oxidative C-C bond cleavage and N-O bond formation of [Ru(II)(bpy)2(diamine)](2+) via reactive ruthenium imide intermediates.

DFT calculations are performed on [Ru(II)(bpy)2(tmen)](2+) (M1, tmen = 2,3-dimethyl-2,3-butanediamine) and [Ru(II)(bpy)2(heda)](2+) (M2, head = 2,5-dimethyl-2,5-hexanediamine), and on the oxidation reactions of M1 to give the C-C bond cleavage product [Ru(II)(bpy)2(NH=CMe2)2](2+) (M3) and the N-O bond formation product [Ru(II)(bpy)2(ONCMe2CMe2NO)](2+) (M4). The calculated geometrical parameters and oxidation potentials are in good agreement with the experimental data. As revealed by the DFT calculations, [Ru(II)(bpy)2(tmen)](2+) (M1) can undergo oxidative deprotonation to generate Ru-bis(imide) [Ru(bpy)2(tmen-4 H)](+) (A) or Ru-imide/amide [Ru(bpy)2(tmen-3 H)](2+) (A') intermediates. Both A and A' are prone to C-C bond cleavage, with low reaction barriers (ΔG(≠)) of 6.8 and 2.9 kcal mol(-1) for their doublet spin states (2)A and (2)A', respectively. The calculated reaction barrier for the nucleophilic attack of water molecules on (2)A' is relatively high (14.2 kcal mol(-1)). These calculation results are in agreement with the formation of the Ru(II)-bis(imine) complex M3 from the electrochemical oxidation of M1 in aqueous solution. The oxidation of M1 with Ce(IV) in aqueous solution to afford the Ru(II)-dinitrosoalkane complex M4 is proposed to proceed by attack of the cerium oxidant on the ruthenium imide intermediate. The findings of ESI-MS experiments are consistent with the generation of a ruthenium imide intermediate in the course of the oxidation.

[Fe(III)(TF4DMAP)OTf] catalysed anti-Markovnikov oxidation of terminal aryl alkenes to aldehydes and transformation of methyl aryl tertiary amines to formamides with H2O2 as a terminal oxidant.

Anti-Markovnikov oxidation of terminal aryl alkenes to aldehydes and transformation of N-methyl aryl tertiary amines to formamides with H2O2 as a terminal oxidant under mild conditions have been achieved with moderate to good product yields using [Fe(III)(TF4DMAP)OTf] as catalyst.

Nonheme iron mediated oxidation of light alkanes with oxone: characterization of reactive oxoiron(IV) ligand cation radical intermediates by spectroscopic studies and DFT calculations.

The oxidation of light alkanes that is catalyzed by heme and nonheme iron enzymes is widely proposed to involve highly reactive {Fe(V)=O} species or {Fe(IV)=O} ligand cation radicals. The identification of these high-valent iron species and the development of an iron-catalyzed oxidation of light alkanes under mild conditions are of vital importance. Herein, a combination of tridentate and bidentate ligands was used for the generation of highly reactive nonheme {Fe=O} species. A method that employs [Fe(III)(Me3tacn)(Cl-acac)Cl](+) as a catalyst in the presence of oxone was developed for the oxidation of hydrocarbons, including cyclohexane, propane, and ethane (Me3tacn=1,4,7-trimethyl-1,4,7-triazacyclononane; Cl-acac=3-chloro-acetylacetonate). The complex [Fe(III)(Tp)2](+) and oxone enabled stoichiometric oxidation of propane and ethane. ESI-MS, EPR and UV/Vis spectroscopy, (18)O labeling experiments, and DFT studies point to [Fe(IV)(Me3tacn)({Cl-acac}(.+))(O)](2+) as the catalytically active species.