Effect of 6,6'-Substituents on Bipyridine-Ligated Ni Catalysts for Cross-Electrophile Coupling.

A family of 4,4'-tBu2-2,2'-bipyridine (tBubpy) ligands with substituents in either the 6-position, 4,4'-tBu2-6-Me-bpy (tBubpyMe), or 6 and 6'-positions, 4,4'-tBu2-6,6'-R2-bpy (tBubpyR2; R = Me, iPr, sBu, Ph, or Mes), was synthesized. These ligands were used to prepare Ni complexes in the 0, I, and II oxidation states. We observed that the substituents in the 6 and 6'-positions of the tBubpy ligand impact the properties of the Ni complexes. For example, bulkier substituents in the 6,6'-positions of tBubpy better stabilized (tBubpyR2)NiICl species and resulted in cleaner reduction from (tBubpyR2)NiIICl2. However, bulkier substituents hindered or prevented coordination of tBubpyR2 ligands to Ni0(cod)2. In addition, by using complexes of the type (tBubpyMe)NiCl2 and (tBubpyR2)NiCl2 as precatalysts for different XEC reactions, we demonstrated that the 6 or 6,6' substituents lead to major differences in catalytic performance. Specifically, while (tBubpyMe)NiIICl2 is one of the most active catalysts reported to date for XEC and can facilitate XEC reactions at room temperature, lower turnover frequencies were observed for catalysts containing tBubpyR2 ligands. A detailed study on the catalytic intermediates (tBubpy)Ni(Ar)I and (tBubpyMe2)Ni(Ar)I revealed several factors that likely contributed to the differences in catalytic activity. For example, whereas complexes of the type (tBubpy)Ni(Ar)I are low spin and relatively stable, complexes of the type (tBubpyMe2)Ni(Ar)I are high-spin and less stable. Further, (tBubpyMe2)Ni(Ar)I captures primary and benzylic alkyl radicals more slowly than (tBubpy)Ni(Ar)I, consistent with the lower activity of the former in catalysis. Our findings will assist in the design of tailor-made ligands for Ni-catalyzed transformations.

Scaffold-Oriented Asymmetric Catalysis: Conformational Modulation of Transition State Multivalency during a Catalyst-Controlled Assembly of a Pharmaceutically Relevant Atropisomer.

A new class of superbasic, bifunctional peptidyl guanidine catalysts is presented, which enables the organocatalytic, atroposelective synthesis of axially chiral quinazolinediones. Computational modeling unveiled the conformational modulation of the catalyst by a novel phenyl urea N-cap, that preorganizes the structure into the active, folded state. A previously unanticipated noncovalent interaction involving a difluoroacetamide acting as a hybrid mono- or bidentate hydrogen bond donor emerged as a decisive control element inducing atroposelectivity. These discoveries spurred from a scaffold-oriented project inspired from a fascinating investigational BTK inhibitor featuring two stable chiral axes and relies on a mechanistic framework that was foreign to the extant lexicon of asymmetric catalysis.

Iron(iv) alkyl complexes: electronic structure contributions to Fe-C bond homolysis and migration reactions that form N-C bonds from N2.

High-valent iron alkyl complexes are rare, as they are prone to Fe-C bond homolysis. Here, we describe an unusual way to access formally iron(iv) alkyl complexes through double silylation of iron(i) alkyl dinitrogen complexes to form an NNSi2 group. Spectroscopically validated computations show that the disilylehydrazido(2-) ligand stabilizes the formal iron(iv) oxidation state through a strongly covalent Fe-N π-interaction, in which one π-bond fits an "inverted field" description. This means that the two bonding electrons are localized more on the metal than the ligand, and thus an iron(ii) resonance structure is a significant contributor, similar to the previously-reported phenyl analogue. However, in contrast to the phenyl complex which has an S = 1 ground state, the ground state of the alkyl complex is S = 2, which places one electron in the π* orbital, leading to longer and weaker Fe-N bonds. The reactivity of these hydrazido(2-) complexes is dependent on the steric and electronic properties of the specific alkyl group. When the alkyl group is the bulky trimethylsilylmethyl, the formally iron(iv) species is stable at room temperature and no migration of the alkyl ligand is observed. However, the analogous complex with the smaller methyl ligand does indeed undergo migration of the carbon-based ligand to the NNSi2 group to form a new N-C bond. This migration is followed by isomerization of the hydrazido ligand, and the product exists as two isomers that have distinct η1 and η2 binding of the hydrazido group. Lastly, when the alkyl group is benzyl, the Fe-C bond homolyzes to give a three-coordinate hydrazido(2-) complex which is likely due to the greater stability of a benzyl radical compared to that for methyl or trimethylsilylmethyl. These studies demonstrate the availability of a hydrocarbyl migration pathway at formally iron(iv) centers to form new N-C bonds directly to N2, though product selectivity is highly dependent on the identity of the migrating group.

Three-Coordinate Nickel and Metal-Metal Interactions in a Heterometallic Iron-Sulfur Cluster.

Biological multielectron reactions often are performed by metalloenzymes with heterometallic sites, such as anaerobic carbon monoxide dehydrogenase (CODH), which has a nickel-iron-sulfide cubane with a possible three-coordinate nickel site. Here, we isolate the first synthetic iron-sulfur clusters having a nickel atom with only three donors, showing that this structural feature is feasible. These have a core with two tetrahedral irons, one octahedral tungsten, and a three-coordinate nickel connected by sulfide and thiolate bridges. Electron paramagnetic resonance (EPR), Mössbauer, and superconducting quantum interference device (SQUID) data are combined with density functional theory (DFT) computations to show how the electronic structure of the cluster arises from strong magnetic coupling between the Ni, Fe, and W sites. X-ray absorption spectroscopy, together with spectroscopically validated DFT analysis, suggests that the electronic structure can be described with a formal Ni1+ atom participating in a nonpolar Ni-W σ-bond. This metal-metal bond, which minimizes spin density at Ni1+, is conserved in two cluster oxidation states. Fe-W bonding is found in all clusters, in one case stabilizing a local non-Hund state at tungsten. Based on these results, we compare different M-M interactions and speculate that other heterometallic clusters, including metalloenzyme active sites, could likewise store redox equivalents and stabilize low-valent metal centers through metal-metal bonding.

An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids.

Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides 38 and 49 (13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines.

An Asymmetric Aromatic Finkelstein Reaction: A Platform for Remote Diarylmethane Desymmetrization.

A first-of-its-kind enantioselective aromatic Finkelstein reaction is disclosed for the remote desymmetrization of diarylmethanes. The reaction operates through a copper-catalyzed C-I bond-forming event, and high levels of enantioselectivity are achieved through the deployment of a tailored guanidinylated peptide ligand. Strategic use of transition-metal-mediated reactions enables the chemoselective modification of the aryl iodide products; thus, the synthesis of a diverse set of otherwise difficult-to-access diarylmethanes with excellent levels of selectivity is realized from a common intermediate. A mixed experimental/computational analysis of steric parameters and substrate conformations identifies the importance of remote conformational effects as a key to achieving high enantioselectivity in this desymmetrization reaction.

Valence Delocalization and Metal-Metal Bonding in Carbon-Bridged Mixed-Valence Iron Complexes.

The carbide ligand in the iron-molybdenum cofactor (FeMoco) in nitrogenase bridges iron atoms in different oxidation states, yet it is difficult to discern its ability to mediate magnetic exchange interactions due to the structural complexity of the cofactor. Here, we describe two mixed-valent diiron complexes with C-based ketenylidene bridging ligands, and compare the carbon bridges with the more familiar sulfur bridges. The ground state of the [Fe2 (µ-CCO)2 ]+ complex with two carbon bridges (4) is S= 1 / 2 ${{ 1/2 }}$ , and it is valence delocalized on the Mössbauer timescale with a small thermal barrier for electron hopping that stems from the low Fe-C force constant. In contrast, one-electron reduction of the [Fe2 (µ-CCO)] complex with one carbon bridge (2) affords a mixed-valence species with a high-spin ground state (S= 7 / 2 ${ 7/2 }$ ), and the Fe-Fe distance contracts by 1 Å. Spectroscopic, magnetic, and computational studies of the latter reveal an Fe-Fe bonding interaction that leads to complete valence delocalization. Analysis of near-IR intervalence charge transfer transitions in 5 indicates a very large double exchange constant (B) in the range of 780-965 cm-1 . These results show that carbon bridges are extremely effective at stabilizing valence delocalized ground states in mixed-valent iron dimers.

Comparative study of CO2 insertion into pincer supported palladium alkyl and aryl complexes.

The insertion of CO2 into metal alkyl bonds is a crucial elementary step in transition metal-catalyzed processes for CO2 utilization. Here, we synthesize pincer-supported palladium complexes of the type (tBuPBP)Pd(alkyl) (tBuPBP = B(NCH2PtBu2)2C6H4-; alkyl = CH2CH3, CH2CH2CH3, CH2C6H5, and CH2-4-OMe-C6H4) and (tBuPBP)Pd(C6H5) and compare the rates of CO2 insertion into the palladium alkyl bonds to form metal carboxylate complexes. Although, the rate constant for CO2 insertion into (tBuPBP)Pd(CH2CH3) is more than double the rate constant we previously measured for insertion into the palladium methyl complex (tBuPBP)Pd(CH3), insertion into (tBuPBP)Pd(CH2CH2CH3) occurs approximately one order of magnitude slower than (tBuPBP)Pd(CH3). CO2 insertion into the benzyl complexes (tBuPBP)Pd(CH2C6H5) and (tBuPBP)Pd(CH2-4-OMe-C6H4) is significantly slower than any of the n-alkyl complexes, and CO2 does not insert into the palladium phenyl bond of (tBuPBP)Pd(C6H5). While (tBuPBP)Pd(CH2CH3) and (tBuPBP)Pd(CH2CH2CH3) are resistant to ß-hydride elimination, we were unable to synthesize complexes with n-butyl, iso-propyl, and tert-butyl ligands due to ß-hydride elimination and an unusual reductive coupling, which involves the formation of new C-B bonds. This reductive process also occurred for (tBuPBP)Pd(CH2C6H5) at elevated temperature and a related process involving the formation of a new H-B bond prevented the isolation of (tBuPBP)PdH. DFT calculations provide insight into the relative rates of CO2 insertion and indicate that steric factors are critical. Overall, this work is one of the first comparative studies of the rates of CO2 insertion into different metal alkyl bonds and provides fundamental information that may be important for the development of new catalysts for CO2 utilization.

A Guide to Tris(4-Substituted)-triphenylmethyl Radicals.

Triphenylmethyl (trityl, Ph3C•) radicals have been considered the prototypical carbon-centered radical since their discovery in 1900. Tris(4-substituted)-trityls [(4-R-Ph)3C•] have since been used in many ways due to their stability, persistence, and spectroscopic activity. Despite their widespread use, existing synthetic routes toward tris(4-substituted)-trityl radicals are not reproducible and often lead to impure materials. We report here robust syntheses of six electronically varied (4-RPh)3C•, where R = NMe2, OCH3, tBu, Ph, Cl, and CF3. The characterization reported for the radicals and related compounds includes five X-ray crystal structures, electrochemical potentials, and optical spectra. Each radical is best accessed using a stepwise approach from the trityl halide, (RPh)3CCl or (RPh)3CBr, by controllably removing the halide with subsequent 1e- reduction of the trityl cation, (RPh)3C+. These syntheses afford consistently crystalline trityl radicals of high purity for further studies.

Dinitrogen Binding and Functionalization from a Low-Coordinate Alkynyliron Complex.

Alkynyl complexes of low-coordinate transition metals offer a sterically open environment and interesting bonding opportunities. Here, we explore the capacity of iron(I) alkynyl complexes to bind N2 and isolate a N2 complex including its X-ray crystal structure. Silylation of the N2 complex gives an isolable, formally iron(IV) complex with a disilylhydrazido(2-) ligand, but natural bond orbital analysis indicates that an iron(II) formulation is preferable. The structure of this compound is similar to an earlier reported phenyl complex in which phenyl migration forms a new N-C bond, but the alkynyl group does not migrate. DFT calculations are used to test the possible reasons why the alkynyl is resistant to migration, and these show that the large Fe-C bond energy in the alkynyl complex is a factor that could contribute to the lack of migration.

Independent Tuning of the pKa or the E1/2 in a Family of Ruthenium Pyridine-Imidazole Complexes.

Two series of RuII(acac)2(py-imH) complexes have been prepared, one with changes to the acac ligands and the other with substitutions to the imidazole. The proton-coupled electron transfer (PCET) thermochemistry of the complexes has been studied in acetonitrile, revealing that the acac substitutions almost exclusively affect the redox potentials of the complex (|ΔE1/2| ≫ |ΔpKa|·0.059 V) while the changes to the imidazole primarily affect its acidity (|ΔpKa|·0.059 V ≫ |ΔE1/2|). This decoupling is supported by DFT calculations, which show that the acac substitutions primarily affect the Ru-centered t2g orbitals, while changes to the py-imH ligand primarily affect the ligand-centered π orbitals. More broadly, the decoupling stems from the physical separation of the electron and proton within the complex and highlights a clear design strategy to separately tune the redox and acid/base properties of H atom donor/acceptor molecules.

Generality-oriented optimization of enantioselective aminoxyl radical catalysis.

Catalytic enantioselective methods that are generally applicable to a broad range of substrates are rare. We report a strategy for the oxidative desymmetrization of meso-diols predicated on a nontraditional catalyst optimization protocol by using a panel of screening substrates rather than a singular model substrate. Critical to this approach was rational modulation of a peptide sequence in the catalyst incorporating a distinct aminoxyl-based active residue. A general catalyst emerged, providing high selectivity in the delivery of enantioenriched lactones across a broad range of diols, while also achieving up to ~100,000 turnovers.

Aspartyl ß-Turn-Based Dirhodium(II) Metallopeptides for Benzylic C(sp3)-H Amination: Enantioselectivity and X-ray Structural Analysis.

Amination of C(sp3)-H bonds is a powerful tool to introduce nitrogen into complex organic frameworks in a direct manner. Despite significant advances in catalyst design, full site- and enantiocontrol in complex molecular regimes remain elusive using established catalyst systems. To address these challenges, we herein describe a new class of peptide-based dirhodium(II) complexes derived from aspartic acid-containing ß-turn-forming tetramers. This highly modular system can serve as a platform for the rapid generation of new chiral dirhodium(II) catalyst libraries, as illustrated by the facile synthesis of a series of 38 catalysts. Critically, we present the first crystal structure of a dirhodium(II) tetra-aspartate complex, which unveils retention of the ß-turn conformation of the peptidyl ligand; a well-defined hydrogen-bonding network is evident, along with a near-C4 symmetry that renders the rhodium centers inequivalent. The utility of this catalyst platform is illustrated by the enantioselective amination of benzylic C(sp3)-H bonds, in which state-of-the-art levels of enantioselectivity up to 95.5:4.5 er are obtained, even for substrates that present challenges with previously reported catalyst systems. Additionally, we found these complexes to be competent catalysts for the intermolecular amination of N-alkylamides via insertion into the C(sp3)-H bond α to the amide nitrogen, yielding differentially protected 1,1-diamines. Of note, this type of insertion was also observed to occur on the amide functionalities of the catalyst itself in the absence of the substrate but did not appear to be detrimental to reaction outcomes when the substrate was present.

Catalytic reduction of dinitrogen to ammonia using molybdenum porphyrin complexes.

Porphyrin complexes are well-known in O2 and CO2 reduction, but their application to N2 reduction is less developed. Here, we show that oxo and nitrido complexes of molybdenum supported by tetramesitylporphyrin (TMP) are effective precatalysts for catalytic N2 reduction to ammonia, verified by 15N2 labeling studies and other control experiments. Spectroscopic and electrochemical studies illuminate some relevant thermodynamic parameters, including the N-H bond dissociation free energy of (TMP)MoNH (43 ± 2 kcal mol-1). We place these results in the context of other work on homogeneous N2 reduction catalysis.

Dynamic effects on ligand field from rapid hydride motion in an iron(ii) dimer with an S = 3 ground state.

Hydride complexes are important in catalysis and in iron-sulfur enzymes like nitrogenase, but the impact of hydride mobility on local iron spin states has been underexplored. We describe studies of a dimeric diiron(ii) hydride complex using X-ray and neutron crystallography, Mössbauer spectroscopy, magnetism, DFT, and ab initio calculations, which give insight into the dynamics and the electronic structure brought about by the hydrides. The two iron sites in the dimer have differing square-planar (intermediate-spin) and tetrahedral (high-spin) iron geometries, which are distinguished only by the hydride positions. These are strongly coupled to give an S total = 3 ground state with substantial magnetic anisotropy, and the merits of both localized and delocalized spin models are discussed. The dynamic nature of the sites is dependent on crystal packing, as shown by changes during a phase transformation that occurs near 160 K. The change in dynamics of the hydride motion leads to insight into its influence on the electronic structure. The accumulated data indicate that the two sites can trade geometries by rotating the hydrides, at a rate that is rapid above the phase transition temperature but slow below it. This small movement of the hydrides causes large changes in the ligand field because they are strong-field ligands. This suggests that hydrides could be useful in catalysis not only due to their reactivity, but also due to their ability to rapidly modulate the local electronic structure and spin states at metal sites.

Mechanism of Nitrogen-Carbon Bond Formation from Iron(IV) Disilylhydrazido Intermediates during N2 Reduction.

We recently reported a reaction sequence that activates C-H bonds in simple arenes as well as the N-N triple bond in N2, delivering the aryl group to N2 to form a new N-C bond (Nature 2020, 584, 221). This enables the transformation of abundant feedstocks (arenes and N2) into N-containing organic compounds. The key N-C bond forming step occurs upon partial silylation of N2. However, the pathway through which reduction, silylation, and migration occurred was unknown. Here, we describe synthetic, structural, magnetic, spectroscopic, kinetic, and computational studies that elucidate the steps of this transformation. N2 must be silylated twice at the distal N atom before aryl migration can occur, and sequential silyl radical and silyl cation addition is a kinetically competent pathway to a formally iron(IV)-NN(SiMe3)2 intermediate that can be isolated at low temperature. Kinetic studies show its first-order conversion to the migrated product, and DFT calculations indicate a concerted transition state for migration. The electronic structure of the formally iron(IV) intermediate is examined using DFT and CASSCF calculations, which reveal contributions from iron(II) and iron(III) resonance forms with oxidized NNSi2 ligands. The depletion of electron density from the Fe-coordinated N atom makes it electrophilic enough to accept the incoming aryl group. This new pathway for the N-C bond formation offers a method for functionalizing N2 using organometallic chemistry.

Synthesis and Surface Attachment of Molecular Re(I) Complexes Supported by Functionalized Bipyridyl Ligands.

Eleven 2,2'-bipyridine (bpy) ligands functionalized with attachment groups for covalent immobilization on silicon surfaces were prepared. Five of the ligands feature silatrane functional groups for attachment to metal oxide coatings on the silicon surfaces, while six contain either alkene or alkyne functional groups for attachment to hydrogen-terminated silicon surfaces. The bpy ligands were coordinated to Re(CO)5Cl to form complexes of the type Re(bpy)(CO)3Cl, which are related to known catalysts for CO2 reduction. Six of the new complexes were characterized using X-ray crystallography. As proof of principle, four molecular Re complexes were immobilized on either a thin layer of TiO2 on silicon or hydrogen-terminated silicon. The surface-immobilized complexes were characterized using X-ray photoelectron spectroscopy, IR spectroscopy, and cyclic voltammetry (CV) in the dark and for one representative example in the light. The CO stretching frequencies of the attached complexes were similar to those of the pure molecular complexes, but the CVs were less analogous. For two of the complexes, comparison of the electrocatalytic CO2 reduction performance showed lower CO Faradaic efficiencies for the immobilized complexes than the same complex in solution under similar conditions. In particular, a complex containing a silatrane linked to bpy with an amide linker showed poor catalytic performance and control experiments suggest that amide linkers in conjugation with a redox-active ligand are not stable under highly reducing conditions and alkyl linkers are more stable. A conclusion of this work is that understanding the behavior of molecular Re catalysts attached to semiconducting silicon is more complicated than related complexes, which have previously been immobilized on metallic electrodes.

Imine Directed Cp*RhIII -Catalyzed N-H Functionalization and Annulation with Amino Amides, Aldehydes, and Diazo Compounds.

A multicomponent annulation that proceeds by imine directed Cp*RhIII -catalyzed N-H functionalization is disclosed. The transformation affords piperazinones displaying a range of functionality and is the first example of transition metal-catalyzed multicomponent N-H functionalization. A broad range of readily available α-amino amides, including those derived from glycine, α-substituted, and α,α-disubstituted amino acids, were effective inputs and enabled the incorporation of a variety of amino acid side chains with minimal racemization. Branched and unbranched alkyl aldehydes and various stabilized diazo compounds were also efficient reactants. The piperazinone products were further modified through efficient transformations. Mechanistic studies, including X-ray crystallographic characterization of a catalytically competent five-membered rhodacycle with imine and amide nitrogen chelation, provide support for the proposed mechanism.

Desulfurization and N2 Binding at an Iron Complex Derived from the C-S Activation of Benzothiophene.

Metal insertion into the C-S bonds of thiophenes is a facile route to interesting polydentate ligand scaffolds with C and S donors. Here, we describe iron-mediated C-S activation of a diphenylphosphine-functionalized benzothiophene proligand. Metalation of the proligand with "tetrakis(trimethylphosphine)iron" gives an initial five-coordinate, diamagnetic iron(II) species with two PMe3 ligands and a dianionic PCS pincer ligand. Upon one-electron reduction, a reactive anionic iron(I) complex is formed. This species then undergoes deep-seated changes, notably cleavage of C-S and C-P bonds in the supporting ligand. Substantial coordination sphere alterations accompany the ligand C-S bond activation, including loss of a sulfur anion from the S-Fe-C metallacycle and reorganization of the two PMe3 ligands. The resulting desulfurized six-coordinate PCC iron complex also has an N2 ligand trans to the vinyl C. Reducing this complex then cleaves a C-P bond in the appended diphenylphosphine, giving a phosphido arm. These ligand transformations demonstrate novel approaches to pincers with thiolates and phosphides, which would be difficult to synthesize using typical methods through free ligand salts.

Electrocatalytic, Homogeneous Ammonia Oxidation in Water to Nitrate and Nitrite with a Copper Complex.

Electrocatalytic ammonia oxidation at room temperature and pressure allows energy-economical and environmentally friendly production of nitrites and nitrates. Few molecular catalysts, however, have been developed for this six- or eight-electron oxidation process. We now report [Cu(bipyalk)]+, a homogeneous electrocatalyst that realizes the title reaction in water at 94% Faradaic efficiency. The catalyst exhibits high selectivity against water oxidation in aqueous media, as [Cu(bipyalk)]+ is not competent for water oxidation.