Investigations into the Mechanism of Inter- and Intramolecular Iron-Catalyzed [2 + 2] Cycloaddition of Alkenes.

Mechanistic studies are reported on the inter- and intramolecular [2 + 2] alkene cycloadditions to form cyclobutanes promoted by (tricPDI)Fe(N2) (tricPDI = 2,6-(2,4,6-tricyclopentyl)C6H2N = CMe)2C5H3N). A combination of kinetic measurements, freeze-quench 57Fe Mössbauer and infrared spectroscopic measurements, deuterium labeling studies, natural abundance 13C KIE studies, and isolation and characterization of catalytically relevant intermediates were used to gain insight into the mechanism of both inter- and intramolecular [2 + 2] cycloaddition reactions. For the stereo- and regioselective [2 + 2] cycloaddition of 1-octene to form trans-1,2-dihexylcyclobutane, a first-order dependence on both iron complex and alkene was measured as well as an inverse dependence on N2 pressure. Both 57Fe Mössbauer and infrared spectroscopic measurements identified (tricPDI)Fe(N2)(η2-1-octene) as the catalyst resting state. Rate-determining association of 1-octene to (tricPDI)Fe(η2-1-octene) accounts for the first order dependence of alkene and the inverse dependence on N2. Heavy atom 13C/12C kinetic isotope effects near unity also support post rate-determining C-C bond formation. By contrast, the intramolecular iron-catalyzed [2 + 2] cycloaddition of 1,7-octadiene yielded cis-bicyclo[4.2.0]octane in 92:8 d.r. and a first order dependence on the iron precursor and zeroth order behavior in both diene and N2 pressure were measured. A pyridine(diimine) iron trans-bimetallacycle was identified as the catalyst resting state and was isolated and characterized by X-ray diffraction and 1H NMR and 57Fe Mössbauer spectroscopies. Dissolution of the iron trans-bimetallacycle in benzene-d6 produced predominantly the cis-cyclobutane product, establishing interconversion between the trans and cis metallacycles during the catalytic reaction and consistent with a Curtin-Hammett kinetic regime. A primary 13C/12C kinetic isotope effect of 1.022(4) was measured at 23 °C, consistent with irreversible unimolecular reductive elimination to form the cyclobutane product. Despite complications from competing cyclometalation of chelate aryl substituents, deuterium labeling experiments were consistent with unimolecular C-C reductive elimination that occurred either by a concerted pathway or a radical rebound sequence that is faster than C-C bond rotation.

Nickel-Catalyzed Asymmetric Alkene Hydrogenation of α,ß-Unsaturated Esters: High-Throughput Experimentation-Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation.

A highly active and enantioselective phosphine-nickel catalyst for the asymmetric hydrogenation of α,ß-unsaturated esters has been discovered. The coordination chemistry and catalytic behavior of nickel halide, acetate, and mixed halide-acetate with chiral bidentate phosphines have been explored and deuterium labeling studies, the method of continuous variation, nonlinear studies, and kinetic measurements have provided mechanistic understanding. Activation of molecular hydrogen by a trimeric (Me-DuPhos)3Ni3(OAc)5I complex was established as turnover limiting followed by rapid conjugate addition of a nickel hydride and nonselective protonation to release the substrate. In addition to reaction discovery and optimization, the previously unreported utility high-throughput experimentation for mechanistic elucidation is also described.

Cobalt-Catalyzed [2π + 2π] Cycloadditions of Alkenes: Scope, Mechanism, and Elucidation of Electronic Structure of Catalytic Intermediates.

Aryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, ((R)PDI)CoN2, are effective precatalysts for the intramolecular [2π + 2π] cycloaddition of α,ω-dienes to yield the corresponding bicyclo[3.2.0]heptane derivatives. The reactions proceed under mild thermal conditions with unactivated alkenes, tolerating both amine and ether functional groups. The overall second order rate law for the reaction, first order with respect to both the cobalt precatalyst and the substrate, in combination with electron paramagnetic resonance (EPR) spectroscopic studies established the catalyst resting state as dependent on the identity of the precatalyst and diene substrate. Planar S = ½ κ(3)-bis(imino)pyridine cobalt alkene and tetrahedral κ(2)-bis(imino)pyridine cobalt diene complexes were observed by EPR spectroscopy and in the latter case structurally characterized. The hemilabile chelate facilitates conversion of a principally ligand-based singly occupied molecular orbital (SOMO) in the cobalt dinitrogen and alkene compounds to a metal-based SOMO in the diene intermediates, promoting C-C bond-forming oxidative cyclization. Structure-activity relationships on bis(imino)pyridine substitution were also established with 2,4,6-tricyclopentyl-substituted aryl groups, resulting in optimized catalytic [2π + 2π] cycloaddition. The cyclopentyl groups provide a sufficiently open metal coordination sphere that encourages substrate coordination while remaining large enough to promote a challenging, turnover-limiting C(sp(3))-C(sp(3)) reductive elimination.

Synthesis and electronic structure of bis(imino)pyridine iron metallacyclic intermediates in iron-catalyzed cyclization reactions.

The bis(imino)pyridine iron dinitrogen compound, ((iPr(TB))PDI)Fe(N2)2 ((iPr(TB))PDI = 2,6-(2,6-(i)Pr2-C6H3-N═C-(CH2)3)2(C5H1N)) is an effective precatalyst for the [2π + 2π] cycloaddition of diallyl amines as well as the hydrogenative cyclization of N-tosylated enynes and diynes. Addition of stoichiometric quantities of amino-substituted enyne and diyne substrates to ((iPr(TB))PDI)Fe(N2)2 resulted in isolation of catalytically competent bis(imino)pyridine iron metallacycle intermediates. A combination of magnetochemistry, X-ray diffraction, and Mössbauer spectroscopic and computational studies established S = 1 iron compounds that are best described as intermediate-spin iron(III) (SFe = 3/2) antiferromagnetically coupled to a chelate radical anion (SPDI = 1/2). Catalytically competent bis(imino)pyridine iron diene and metallacycles relevant to the [2π + 2π] cycloaddition were also isolated and structurally characterized. The combined magnetic, structural, spectroscopic, and computational data support an Fe(I)-Fe(III) catalytic cycle where the bis(imino)pyridine chelate remains in its one-electron reduced radical anion form. These studies revise a previous mechanistic proposal involving exclusively ferrous intermediates and highlight the importance of the redox-active bis(imino)pyridine chelate for enabling catalytic cyclization chemistry with iron.

Complexes with redox-active ligands: synthesis, structure, and electrochemical and photophysical behavior of the Ru(II) complex with TTF-annulated phenanthroline.

Ru(II) complexes with chelating ligands, 4',5'-ethylenedithiotetrathiafulvenyl[4,5-f][1,10]phenanthroline (L1), 1,3-dithiole-2-thiono[4,5-f][1,10]phenanthroline (L2), and 1,3-dithiole-2-ono[4,5-f][1,10]phenanthroline (L3), have been prepared and their structural, electrochemical, and photophysical properties investigated. Density functional theory (DFT) calculations indicate that the highest occupied molecular orbital of [Ru(bpy)2(L1)](PF6)2 (1) is located on the tetrathiafulvalene (TTF) subunit and appears ~0.6 eV above the three Ru-centered d orbitals. In agreement with this finding, 1 exhibits three reversible oxidations: the two at lower potentials take place on the TTF subunit, and the one at higher potential is due to the Ru(3+)/Ru(2+) redox couple. Complexes [Ru(bpy)2(L2)](PF6)2 (2) and [Ru(bpy)2(L3)](PF6)2 (3) exhibit only the Ru(3+)/Ru(2+)-related oxidation. The optical absorption spectra of all complexes reveal a characteristic metal-to-ligand charge transfer (MLCT) band centered around 450 nm. In addition, in the spectrum of 1 the MLCT band is augmented by a low-energy tail that extends beyond 500 nm and is attributed to the intraligand charge transfer (ILCT) transition of L1, according to time-dependent DFT calculations. The substantial decrease in the luminescence quantum yield of 1 compared to those of 2 and 3 is attributed to the reductive quenching of the emissive state via electron transfer from the TTF subunit to the Ru(3+) center, thus allowing nonradiative relaxation to the ground state through the lower-lying ILCT state. In the presence of O2, complex 1 undergoes a photoinduced oxidative cleavage of the central C═C bond of the TTF fragment, resulting in complete transformation to 3. This photodegradation process was studied with (13)C NMR and optical absorption spectroscopy.

Heteroleptic Fe(II) complexes of 2,2'-biimidazole and its alkylated derivatives: spin-crossover and photomagnetic behavior.

Three iron(II) complexes, [Fe(TPMA)(BIM)](ClO(4))(2)⋅0.5H(2)O (1), [Fe(TPMA)(XBIM)](ClO(4))(2) (2), and [Fe(TPMA)(XBBIM)](ClO(4))(2)⋅0.75CH(3)OH (3), were prepared by reactions of Fe(II) perchlorate and the corresponding ligands (TPMA=tris(2-pyridylmethyl)amine, BIM=2,2'-biimidazole, XBIM=1,1'-(α,α'-o-xylyl)-2,2'-biimidazole, XBBIM=1,1'-(α,α'-o-xylyl)-2,2'-bibenzimidazole). The compounds were investigated by a combination of X-ray crystallography, magnetic and photomagnetic measurements, and Mössbauer and optical absorption spectroscopy. Complex 1 exhibits a gradual spin crossover (SCO) with T(1/2) =190 K, whereas 2 exhibits an abrupt SCO with approximately 7 K thermal hysteresis (T(1/2) =196 K on cooling and 203 K on heating). Complex 3 is in the high-spin state in the 2-300 K range. The difference in the magnetic behavior was traced to differences between the inter- and intramolecular interactions in 1 and 2. The crystal packing of 2 features a hierarchy of intermolecular interactions that result in increased cooperativity and abruptness of the spin transition. In 3, steric repulsion between H atoms of one of the pyridyl substituents of TPMA and one of the benzene rings of XBBIM results in a strong distortion of the Fe(II) coordination environment, which stabilizes the high-spin state of the complex. Both 1 and 2 exhibit a photoinduced low-spin to high-spin transition (LIESST effect) at 5 K. The difference in the character of intermolecular interactions of 1 and 2 also manifests in the kinetics of the decay of the photoinduced high-spin state. For 1, the decay rate constant follows the single-exponential law, whereas for 2 it is a stretched exponential, reflecting the hierarchical nature of intermolecular contacts. The structural parameters of the photoinduced high-spin state at 50 K are similar to those determined for the high-spin state at 295 K. This study shows that N-alkylation of BIM has a negligible effect on the ligand field strength. Therefore, the combination of TPMA and BIM offers a promising ligand platform for the design of functionalized SCO complexes.

Bis(imino)pyridine iron dinitrogen compounds revisited: differences in electronic structure between four- and five-coordinate derivatives.

The electronic structures of the four- and five-coordinate aryl-substituted bis(imino)pyridine iron dinitrogen complexes, ((iPr)PDI)FeN(2) and ((iPr)PDI)Fe(N(2))(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CMe)(2)C(5)H(3)N), have been investigated by a combination of spectroscopic techniques (NMR, Mössbauer, X-ray Absorption, and X-ray Emission) and DFT calculations. Homologation of the imine methyl backbone to ethyl or isopropyl groups resulted in the preparation of the new bis(imino)pyridine iron dinitrogen complexes, ((iPr)RPDI)FeN(2) ((iPr)RPDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CR)(2)C(5)H(3)N; R = Et, (i)Pr), that are exclusively four coordinate both in the solid state and in solution. The spectroscopic and computational data establish that the ((iPr)RPDI)FeN(2) compounds are intermediate spin ferrous derivatives (S(Fe) = 1) antiferromagnetically coupled to bis(imino)pyridine triplet diradical dianions (S(PDI) = 1). While this ground state description is identical to that previously reported for ((iPr)PDI)Fe(DMAP) (DMAP = 4-N,N-dimethylaminopyridine) and other four-coordinate iron compounds with principally σ-donating ligands, the d-orbital energetics determine the degree of coupling of the metal-chelate magnetic orbitals resulting in different NMR spectroscopic behavior. For ((iPr)RPDI)Fe(DMAP) and related compounds, this coupling is strong and results in temperature independent paramagnetism where a triplet excited state mixes with the singlet ground state via spin orbit coupling. In the ((iPr)RPDI)FeN(2) family, one of the iron singly occupied molecular orbitals (SOMOs) is essentially d(z(2)) in character resulting in poor overlap with the magnetic orbitals of the chelate, leading to thermal population of the triplet state and hence temperature dependent NMR behavior. The electronic structures of ((iPr)RPDI)FeN(2) and ((iPr)PDI)Fe(DMAP) differ from ((iPr)PDI)Fe(N(2))(2), a highly covalent molecule with a redox noninnocent chelate that is best described as a resonance hybrid between iron(0) and iron(II) canonical forms as originally proposed in 2004.

Iron-Catalyzed Vinylsilane Dimerization and Cross-Cycloadditions with 1,3-Dienes: Probing the Origins of Chemo- and Regioselectivity.

The selective, intermolecular, homodimerization and cross-cycloaddition of vinylsilanes with unbiased 1,3-dienes, catalyzed by a pyridine-2,6-diimine (PDI) iron complex is described. In the absence of a diene coupling partner, vinylsilane hydroalkenylation products were obtained chemoselectively with unusual head-to-head regioselectivity (up to >98% purity, 98:2 E/Z). In the presence of a 4- or 2-substituted diene coupling partner, under otherwise identical reaction conditions, formation of value-added [2+2]- and [4+2]-cycloadducts, respectively, was observed. The chemoselectivity profile was distinct from that observed for analogous α-olefin dimerization and cross-reactions with 1,3-dienes. Mechanistic studies conducted with well-defined, single-component precatalysts (MePDI)Fe(L2) (where MePDI = 2,6-(2,6-Me2-C6H3N═CMe)2C5H3N; L2 = butadiene or 2(N2)) provided insights into the kinetic and thermodynamic factors contributing to the substrate-controlled regioselectivity for both the homodimerization and cross cycloadditions. Diamagnetic iron diene and paramagnetic iron olefin complexes were identified as catalyst resting states, were characterized by in situ NMR and Mössbauer spectroscopic studies, and were corroborated with DFT calculations. Stoichiometric reactions and computational models provided evidence for a common mechanistic regime where competing steric and orbital-symmetry requirements dictate the regioselectivity of oxidative cyclization. Although distinct chemoselectivity profiles were observed in cross-cycloadditions with the vinylsilane congeners of α-olefins, these products arose from metallacycles with the same connectivity. The silyl substituents ultimately governed the relative rates of ß-H elimination and C-C reductive elimination to dictate final product formation.

TTF-Annulated phenanthroline and unexpected oxidative cleavage of the C=C bond in its ruthenium(II) complex.

Tetrathiafulvalene (TTF) and 1,10-phenanthroline have been fused together via a simple and efficient synthetic procedure that provides a new bidentate ligand, 4',5'-ethylenedithiotetrathiafulvenyl[4,5-f][1,10]phenanthroline (EDT-TTF-phen, 1). Its ruthenium(II) complex exhibits a unique packing of TTF subunits in the solid state. In an acetonitrile solution, [Ru(bpy)(2)(1)](PF(6))(2) undergoes facile oxidative cleavage of the C=C double bond, which cannot be observed in the dark or under anaerobic conditions. This points to the photocatalytic role played by the ruthenium(II) chromophore in this conversion.

ORGANIC CHEMISTRY. Iron-catalyzed intermolecular [2+2] cycloadditions of unactivated alkenes.

Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal-catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks.

Cobalt precursors for high-throughput discovery of base metal asymmetric alkene hydrogenation catalysts.

Asymmetric hydrogenation of alkenes is one of the most widely used methods for the preparation of single enantiomer compounds, especially in the pharmaceutical and agrochemical industries. For more than four decades, precious metal complexes containing rhodium, iridium, and ruthenium have been predominantly used as catalysts. Here, we report rapid evaluation of libraries of chiral phosphine ligands with a set of simple cobalt precursors. From these studies, base metal precatalysts have been discovered for the hydrogenation of functionalized and unfunctionalized olefins with high enantiomeric excesses, demonstrating the potential utility of more earth-abundant metals in asymmetric hydrogenation.

High-Activity Iron Catalysts for the Hydrogenation of Hindered, Unfunctionalized Alkenes.

The activity of aryl-substituted bis(imino)pyridine and bis(arylimidazol-2-ylidene)pyridine iron dinitrogen complexes has been evaluated in a series of catalytic olefin hydrogenation reactions. In general, more electron donating chelates with smaller 2,6-aryl substituents produce more active iron hydrogenation catalysts. Establishment of this structure-activity relationship has produced base metal catalysts that exhibit high turnover frequencies for the hydrogenation of unfunctionalized, tri- and tetrasubstituted alkenes, one of the most challenging substrate classes for homogenous hydrogenation catalysts.

Bis(imino)pyridine Iron Dinitrogen Compounds Revisited: Differences in Electronic Structure Between Four- and Five-Coordinate Derivatives.

The electronic structures of the four- and five-coordinate aryl-substituted bis(imino)pyridine iron dinitrogen complexes, ((iPr)PDI)FeN(2) and ((iPr)PDI)Fe(N(2))(2) ((iPr)PDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CMe)(2)C(5)H(3)N), have been investigated by a combination of spectroscopic techniques (NMR, Mössbauer, X-ray Absorption and X-ray Emission) and DFT calculations. Homologation of the imine methyl backbone to ethyl or isopropyl groups resulted in the preparation of the new bis(imino)pyridine iron dinitrogen complexes, ((iPr)RPDI)FeN(2) ((iPr)RPDI = 2,6-(2,6-(i)Pr(2)-C(6)H(3)-N=CR)(2)C(5)H(3)N; R = Et, (i)Pr), that are exclusively four coordinate both in the solid state and in solution. The spectroscopic and computational data establish that the ((iPr)RPDI)FeN(2) compounds are intermediate spin ferrous derivatives (S(Fe) = 1) antiferromagnetically coupled to bis(imino)pyridine triplet diradical dianions (S(PDI) = 1). While this ground state description is identical to that previously reported for ((iPr)PDI)Fe(DMAP) (DMAP = 4-N,N-dimethylaminopyridine) and other four-coordinate iron compounds with principally σ-donating ligands, the d-orbital energetics determine the degree of coupling of the metal-chelate magnetic orbitals resulting in different NMR spectroscopic behavior. For ((iPr)RPDI)Fe(DMAP) and related compounds, this coupling is strong and results in temperature independent paramagnetism where a triplet excited state mixes with the singlet ground state via spin orbit coupling. In the ((iPr)RPDI)FeN(2) family, one of the iron SOMOs is essentially d(z2) in character resulting in poor overlap with the magnetic orbitals of the chelate, leading to thermal population of the triplet state and hence temperature dependent NMR behavior. The electronic structures of ((iPr)RPDI)FeN(2) and ((iPr)PDI)Fe(DMAP) differ from ((iPr)PDI)Fe(N(2))(2), a highly covalent molecule with a redox non-innocent chelate that is best described as a resonance hybrid between iron(0) and iron(II) canonical forms as originally proposed in 2004.