Iron(V)-oxo species have been proposed as key reactive intermediates in the catalysis of oxygen-activating enzymes and synthetic catalysts. Here, we report the synthesis of [Fe(TAML)(O)]- in nearly quantitative yield, where TAML is a macrocyclic tetraamide ligand. Mass spectrometry, Mössbauer, electron paramagnetic resonance, and x-ray absorption spectroscopies, as well as reactivity studies and density functional theory calculations show that this long-lived (hours at -60 degrees C) intermediate is a spin S = 1/2 iron(V)-oxo complex. Iron-TAML systems have proven to be efficient catalysts in the decomposition of numerous pollutants by hydrogen peroxide, and the species we characterized is a likely reactive intermediate in these reactions.

Small-molecule synthetic homogeneous-oxidation catalysts are normally poorly protected from self-destruction under operating conditions. Achieving design control over both activity and half-life is important not only in advancing the utility of oxidation catalysts, but also in minimizing hazards associated with their use and disposal. Iron(III)-TAML (tetraamido-macrocyclic ligand) oxidant catalysts rapidly activate H(2)O(2) for numerous significant processes, exhibiting high and differing activity and varying half-lives depending upon the TAML design. A general approach is presented that allows for the simultaneous determination of the second-order rate constant for the oxidation of a targeted substrate by the active catalyst (k(II)) and the rate constant for the intramolecular self-inactivation of the active catalyst (k(i)). The approach is valid if the formation of the active catalyst from its resting state and the primary oxidizing agent, measured by the second-order rate constant k(I), is fast and the catalyst concentration is very low, such that bimolecular inactivation pathways can be neglected. If the oxidation process is monitored spectrophotometrically and is set up to be incomplete, the kinetic trace can be analyzed by using the equation ln(lnA(t))/A(infnity)=ln(k(II)/k(i)[Fe(III)](tot)-k(i)t, from which k(II) and k(i) can be determined. Here, A(t) and A(infinity) are absorbances at time t and at the end of reaction (t=infinity), respectively, and [Fe(III)](tot) is the total catalyst concentration. Several tools were applied to examine the validity of the approach by using a variety of different Fe(III)-TAML catalysts, H(2)O(2) and tBuOOH as oxidizing agents, and the dyes safranine O and orange II as target substrates. Learning how catalyst activities (k(II)) and catalyst half-lives (k(i)) can be controlled by ligand design is an important step in creating green catalysts that will not persist in the environment after they have achieved their purpose.

The effect of a 4,6-O-alkylidene acetal on the rate of acid-catalyzed hydrolysis of methyl galactopyranosides and of spontaneous hydrolysis of 2,4-dinitrophenyl galactopyranosides has been studied through the synthesis and hydrolysis of analogs in which O6 is replaced by a methoxymethylene unit in which the methoxy group adopts either an equatorial or an axial position according to the configuration. Consistent with earlier studies under both acid-catalyzed and spontaneous hydrolysis conditions the alkylidene acetal, or its 7-carba analog, retards hydrolysis with respect to comparable systems lacking the cyclic protecting group. The configuration at C7 in the 7-carba analogs does not influence the rate of acid-catalyzed hydrolysis but has a minor influence on the rate of spontaneous hydrolysis of the 2,4-dinitrophenyl galactosides, confirming earlier studies on the role played by the hydroxymethyl group conformation on glycoside reactivity. The benzylidene acetal is found to stabilize the α-anomer of galactopyranose derivatives relative to monocyclic analogs. Reasons for the α-selectivity of 4,6-O-benzylidene-protected galactopyranosyl donors bearing neighboring group-active protecting groups at O2 are discussed.

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Conspectus This Account is aimed at highlighting the recent developments in the N-heterocyclic carbene (NHC)-catalyzed generation of α,β-unsaturated acylazolium intermediates and their subsequent reactivity with (bis)­nucleophiles thereby shedding light on the power of this NHC-bound intermediate in organocatalysis. This key intermediate can be generated by the addition of NHCs to α,β-unsaturated aldehyde or acid derivatives. A wide variety of bisnucleophiles can add across the α,β-unsaturated acylazoliums to form various five and six-membered heterocycles and carbocycles. Moreover, suitably substituted nucleophiles can add to this intermediate and result in valuable products following cascade processes. Employing chiral NHCs in the process can result in the enantioselective synthesis of valuable compounds. In 2013, we developed a unified strategy for the enantioselective synthesis of dihydropyranones and dihydropyridinones by the NHC-catalyzed formal [3 + 3] annulation of 2-bromoenals with readily available 1,3-dicarbonyl compounds or primary vinylogous amides. This reaction takes place under mild conditions with low catalyst loading. Interestingly, employing enolizable aldehydes as the bisnucleophiles in this annulation afforded chiral 4,5-disubstituted dihydropyranones in spite of the competing benzoin/Stetter pathways. Moreover, the use of cyclic 1,3-dicarbonyl compounds such as 4-hydroxy coumarin/pyrazolone afforded the coumarin/pyrazole-fused dihydropyranones. In addition, a [3 + 2] annulation for the synthesis of spiro γ-butyrolactones was demonstrated using 3-hydroxy oxindoles as the bisnucleophile. The interception of α,β-unsaturated acylazolium intermediates with malonic ester derivatives having a γ-benzoyl group resulted in the enantioselective synthesis of functionalized cyclopentenes via a cascade process involving a Michael-intramolecular aldol-β-lactonization-decarboxylation sequence. The use of cyclic β-ketoamides as the coupling partner for catalytically generated α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of spiro-glutarimide and the reaction proceeds in a Michael addition-intramolecular amidation pathway. We have recently demonstrated the enantioselective synthesis of tricyclic δ-lactones with three contiguous stereocenters by the reaction of enals with dinitrotoluene derivatives bearing electron-withdrawing groups, under oxidative conditions. This atom-economic cascade reaction proceeds in a Michael/Michael/lactonization sequence tolerating a range of functional groups. This technique was also used for the N–H functionalization of indoles for the enantioselective synthesis of pyrroloquinolines following the aza-Michael/Michael/lactonization sequence. The use of α-arylidene pyrazolinones as the bisnucleophiles for the tandem generation of dienolate/enolates combined with the NHC-catalyzed generation of α,β-unsaturated acylazoliums resulted in the enantioselective synthesis of pyrazolone-fused spirocyclohexadienones. This formal [3 + 3] annulation proceeds via the vi...

The green title complexes of the type Et4N[V2O3(l-Asal)2] have been synthesized in nearly quantitative yields by one-electron electroreduction (at 0.2 V vs SCE) of V2O3(l-Asal)2 in dichloromethane solution containing tetraethylammonium perchlorate. Here l-Asal2- is the deprotonated salicylaldimine of l-alanine (A = al), l-valine (A = va), or l-phenylalanine (A = pa). Electronic and IR spectra as well as metal reduction potentials (E 1/2 ∼ 0.4 V vs SCE) of the complexes are reported. In Et4N[V2O3(l-alsal)2]·MeCN both the metal atoms have distorted square pyramidal geometry but the metrical differences between the two are considerable. The relative disposition of the two terminal VO groups in the complex is intermediate between cis and trans. The V−O−V angle and V···V distance are 113.2(3)° and 3.067(3) Å, respectively. The two V−O lengths in the V−O−V bridge are very unequal, 1.768(6) and 1.905(7) Å, corresponding to a VV−O−VIV description. Valence localization is consistent with the 51V hyperfine structure of the axial EPR spectra (3d x y 1 ground state) of the whole family of solid complexes:  s = 1/2; g ∥ ∼ 1.95, g ⊥ ∼ 1.98, A ∥ ∼ 180 G, and A ⊥ ∼ 67 G at 300 K. The spectra in frozen (77 K) dichloromethane solution are essentially the same. On the other hand, isotropic room temperature solution spectra of the family have 15 hyperfine lines (g iso ∼ 1.97; A iso ∼ 51 G) revealing that the unpaired electron and hence the metal valence are delocalized over both metal atoms on the X-band EPR time scale. The present results are compared with those of the few other V2O3 3+ complexes known revealing certain patterns. Crystal data for the Et4N[V2O3(l-alsal)2]·MeCN complex are as follows:  chemical formula, C30H41N4O9V2; crystal system, orthorhombic; space group, P212121; a = 9.797(5) Å, b = 12.854(6) Å, c = 27.550(11) Å; Z = 4.

Recent broad-ranging mechanistic studies of FeIII-TAML peroxide activators enable a strategy for designing catalysts with improved (i) hydrolytic and (ii) operational stabilities, (iii) faster activation of H2O2 and other peroxides, and (iv) a pH of highest activity closer to 7. Combining all items of insight leads to [Fe{1-NO2C6H3-3,4-(NCOCMe2NCO)2CF2}(OH2)]- (1a) which exhibits the most desirable technical performance in its class.

The study showed that zinc supplementation had a beneficial impact on the incidence of diarrhea and also weight gain among LBW infants.