Iron-Catalyzed C-H Oxygenation Using Perchlorate Enabled by Secondary Sphere Hydrogen Bonds.

Perchlorate (ClO4-) is a groundwater pollutant that is challenging to remediate. We report a strategy to use Fe(II) tris(2-pyridylmethyl)amine (TPA) complexes featuring appended aniline hydrogen bonds (H-bonds) to promote ClO4- reduction. These complexes facilitate oxygen atom transfer from ClO4- to PPh3 and C-H oxygenation reactions of organic substrates. Catalytic reactions using 15 mol % afforded excellent yields for oxygenation of anthracene and cyclic alkyl aromatics, and this methodology tolerates aryl halides as well as heterocycles containing either O, S, or N.

Appended Lewis Acids Enable Dioxygen Reactivity and Catalytic Oxidations with Ni(II).

We disclose a suite of Ni(II) complexes featuring secondary sphere Lewis acids of varied Lewis acidity and tether lengths. Several of these complexes feature atypical behavior of Ni(II): reactivity with O2 that occurs only in the presence of a tethered Lewis acid. In situ UV-vis spectroscopy revealed that, although adducts are stable at -40 °C, complexes containing 9-borabicyclo[3.3.1]nonane (9-BBN) Lewis acids underwent irreversible oxidative deborylation when warmed to room temperature. We computationally and experimentally identified that oxidative instability of appended 9-BBN moieties can be mitigated using weaker Lewis acids such as pinacolborane (BPin). These insights enabled the realization of catalytic reactions: hydrogen atom abstraction from phenols and room temperature oxygen atom transfer to PPh3.

A metal-free strategy to construct fluoroalkyl-olefin linkages using fluoroalkanes.

We present a metal-free strategy to access fluoroalkyl-olefin linkages from fluoroalkane precursors and vinyl-pinacol boronic ester (BPin) reagents. This reaction sequence is templated by the boron reagent, which induces C-C bond formation upon oxidation. We developed this strategy into a one-pot synthetic protocol using RCF2H precursors directly with vinyl-BPin reagents in the presence of a Brønsted base, which tolerated oxygen- and nitrogen-containing heterocycles, and aryl halogens. We also found that HCF3 (HCF-23; a byproduct of the Teflon industry) and CH2F2 (HCF-32; a low-cost refrigerant) are amenable to this protocol, representing distinct strategies to generate RCF2H and RCF3 molecules. Finally, we demonstrate that the vinyldifluoromethylene products can be readily derivatized, representing an avenue for late-stage modification after installing the fluoroalkyl unit.

A Bidentate Ligand Featuring Ditopic Lewis Acids in the Second Sphere for Selective Substrate Capture and Activation.

We present a ligand platform featuring appended ditopic Lewis acids to facilitate capture/activation of diatomic substrates. We show that incorporation of two 9-borabicyclo[3.3.1]nonane (9-BBN) units on a single carbon tethered to a pyridine pyrazole scaffold maintains a set of unquenched nitrogen donors available to coordinate FeII , ZnII , and NiII . Using hydride ion affinity and competition experiments, we establish an additive effect for ditopic secondary sphere boranes, compared to the monotopic analogue. These effects are exploited to achieve high selectivity for binding NO2 - in the presence of competitive anions such as F- and NO3 - . Finally, we demonstrate hydrazine capture within the second-sphere of metal complexes, followed by unique activation pathways to generate hydrazido and diazene ligands on Zn and Fe, respectively.

Preparation and Functionalization of Mono- and Polyfluoroepoxides via Fluoroalkylation of Carbonyl Electrophiles.

We outline a new synthetic method to prepare mono- and polyfluoroepoxides from a diverse pool of electrophiles (ketones, acyl chlorides, esters) and fluoroalkyl anion equivalents. The initially formed α-fluoro alkoxides undergo subsequent intramolecular ring closure when heated. We demonstrated the versatility of the method through the isolation of 16 mono- and polyfluoroepoxide products. These compounds provide unique entry points for further diversification via either fluoride migration coupled with ring opening, or defluorinative functionalization reactions, the latter of which can be used as a late-stage method to install select bioactive moieties. The reaction sequences described herein provide a pathway to functionalize the commonly observed products formed from 1,2-addition into carbonyl electrophiles.

Nucleophilic strategies to construct -CF2- linkages using borazine-CF2Ar reagents.

Using a Lewis acid-quenched CF2Ph- reagent, we show C-C bond formation through nucleophilic addition reactions to prepare molecules containing internal -CF2- linkages. We demonstrate C(sp2)-C(sp3) coupling using both SNAr reactions and Pd-catalysis. Finally, C(sp3)-C(sp3) bonds are forged using operationally simple SN2 reactions that tolerate medicinally-relevant motifs.

A Borane Lewis Acid in the Secondary Coordination Sphere of a Ni(II) Imido Imparts Distinct C-H Activation Selectivity.

Two borane-functionalized bidentate phosphine ligands that vary in tether length have been prepared to examine cooperative metal-substrate interactions. Ni(0) complexes react with aryl azides at low temperatures to form structurally unusual κ2-(N,N)-N3Ar adducts. Warming these adducts affords products of N2 extrusion and in one case, a Ni-imido compound that is capped by the appended borane. Reactions with 1-azidoadamantane (AdN3) provide a distinct outcome, where a proposed nickel imido intermediate activates the sp2 C-H bonds of arenes, even in the presence of benzylic C-H sites. Combined experimental and computational mechanistic studies demonstrate that the unique reactivity is a consequence of Lewis-acid-induced polarization of the Ni-NR bond, potentially providing a synthetic strategy for chemoselective reaction engineering.

Distinct Reactivity Modes of a Copper Hydride Enabled by an Intramolecular Lewis Acid.

We disclose a 1,4,7-triazacyclononane (TACN) ligand featuring an appended boron Lewis acid. Metalation with Cu(I) affords a series of tetrahedral complexes including a boron-capped cuprous hydride. We demonstrate distinct reactivity modes as a function of chemical oxidation: hydride transfer to CO2 in the copper(I) state and oxidant-induced H2 evolution as well as alkyne reduction.

Hydrazone and Oxime Olefination via Ruthenium Alkylidenes.

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR2 , OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air-stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring-closing reactions with yields up to 88 %.

Substrate Specific Metal-Ligand Cooperative Binding: Considerations for Weak Intramolecular Lewis Acid/Base Pairs.

Metal-ligand cooperative binding modes were interrogated in a series of zinc bis(thiophenoxide) complexes. A weak B-S binding interaction is observed in solution between the weakly Lewis basic thiophenoxide ligands and an appended trialkylborane. The energy of this binding event is dependent upon the strength of the Lewis acid and its proximity to the zinc thiophenoxide.

Late-stage ligand functionalization via the Staudinger reaction using phosphine-appended 2,2'-bipyridine.

The ability of a phosphine-appended-2,2'-bipyridine ligand ((Ph2P)2bpy) to serve as a platform for late-stage ligand modifications was evaluated using tetrahedral (Ph2P)2bpyFeCl2. We employed a post-metalation Staudinger reaction to install a series of functionalized arenes, including those containing Brønsted and Lewis acidic groups. This reaction sequence represents a versatile strategy to both tune the ligand donor properties as well as directly incorporate appended functionality.

Hydrogen-bonded nickel(I) complexes.

A series of nickel(ii) tris(2-pyridylmethyl)amine (TPA) complexes featuring appended hydrogen bonds (H-bonds) to halides (F, Cl, Br) was synthesized and charcterized. Reduction to the nickel(i) state provided access to an unusual nickel(i) fluoride complex stabilized by H-bonds, enabling structural and spectroscopic characterization.

Defluorinative Functionalization of Pd(II) Fluoroalkyl Complexes.

When subjected to arylboranes, anionic trifluoromethyl and difluorobenzyl palladium(II) complexes undergo fluoride abstraction followed by 1,1-migratory insertion. The resulting intermediate fluoroalkyl species can be induced to undergo a subsequent transmetalation and reductive elimination from either an in situ formed fluoroboronate (FB(Ar3)-) or an exogenous boronic acid/ester (ArB(OR)2) and nucleophilic activator, representing a net defluorinative arylation reaction. The latter method enabled a structurally diverse substrate scope to be prepared from either an isolated palladium-CF3 complex, or from Pd(PPh3)4 and other commercially available reagents.

Mobility of Lewis acids within the secondary coordination sphere: toward a model for cooperative substrate binding.

Distance dependence of appended Lewis acids in N2H4 binding and deprotonation was evaluated within a series of zinc complexes. Variation of spacer-length to a tethered trialkylborane Lewis acid revealed distinct preferences for binding and stabilization of the resulting deprotonated N2H3- unit.

Examining the Generality of Metal-Ligand Cooperativity Across a Series of First-Row Transition Metals: Capture, Bond Activation, and Stabilization.

We outline the generality and requirements for cooperative N2H4 capture, N-N bond scission, and amido stabilization across a series of first-row transition metal complexes bearing a pyridine(dipyrazole) ligand. This ligand contains a pair of flexibly tethered trialkylborane Lewis acids that enable hydrazine capture and M-NH2 stabilization. While the Lewis acids are required to bind N2H4, the identity of the metal dictates whether N-N bond scission can occur. The redox properties of the M(II) bis(amidoborane) series of complexes were investigated and reveal that ligand-based events prevail; oxidation results in the generation of a transiently formed aminyl radical, while reduction occurs at the redox-active pyridine(dipyrazole) ligand.

Reductively Stable Hydrogen-Bonding Ligands Featuring Appended CF2-H Units.

We present the development of ligands featuring the unconventional hydrogen bond donor, -CF2H, within a metal's secondary coordination sphere. When metalated with palladium, o-CF2H-functionalized 1,10-phenanthroline provides highly directed H-bonding interactions with Pd-coordinated substrates. Spectroscopic and computational analyses with a series of X-type ligand acceptors (-F, -Cl, -Br, -OR) establish the H-bonding interaction strength for the -CF2H group (∼3 kcal/mol). The synthesis of Pd0/Ni0 complexes and subsequent coupling (Ni) highlight the unique reductive and base compatibility of the -CF2H hydrogen bond donor group.

Tetrahedral iron featuring an appended Lewis acid: distinct pathways for the reduction of hydroxylamine and hydrazine.

We present the preparation of a nitrogen-based bidentate ligand featuring an appended boron Lewis acid as well as its tetrahedral Fe2+ and Zn2+ complexes. These complexes act as platforms for hydrazine and hydroxylamine capture and reduction chemistry.

Tuning ligand field strength with pendent Lewis acids: access to high spin iron hydrides.

Geometrically flexible 9-borabicyclo[3.3.1]nonyl units within the secondary coordination sphere enable isolation of high-spin Fe(ii)-dihydrides stabilized by boron-hydride interactions and a rare example of an isolable S = 3/2 reduction product. The borane-capped Fe(ii)-dihydride: (1) rapidly deprotonates E-H (E = N, O, P, S) bonds to afford borane-stabilized Fe adducts and (2) releases H2 upon exposure to π-acids. The Lewis acids provide an avenue for redox-leveling in analogy to the near constant operating potential for N2 reduction in nitrogenase.

Hydrogen Bonding to a Dinitrogen Complex at Room Temperature: Impacts on N2 Activation.

We report an experimental and computational analysis of the effects of hydrogen bonding to a metal dinitrogen complex. A series of H-bond donors over a wide p Ka range (Δ 20) interact with the nitrogen unit of a ReI-(N2) complex at room temperature. Analysis by 15N NMR, IR spectroscopy, association equilibria, and DFT studies indicates that the H-bonding interaction polarizes and weakens the N-N bond. These results provide insight into the role of the secondary sphere residues in nitrogenase enzymes.

Difluoromethane as a precursor to difluoromethyl borates.

Difluoromethane (CF2H2) is an ecologically-friendly refrigerant which holds promise as a source of CF2H-. However, the weak acidity (pKa = 35-41) and low stability of the conjugate base have prevented its utilization as a chemical feedstock. In this manuscript, we use a Lewis pair approach to deprotonate CF2H2 and capture CF2H- as R3B-CF2H- adducts. One reagent can be used as a base-free Suzuki reagent in palladium-mediated difluoromethylation, where CF2H- transfer is templated by precoordination to an azaborine derived R3B-CF2H- reagent.