Copper-Catalyzed C(sp)-H α-Acetylation: Generation of Quaternary Centers.

α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in natural products and pharmaceuticals. We report the α-acetylation of C(sp)-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CHR at RT with BuOOBu as oxidant via copper(I) -diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles.

Copper catalyzed benzylic sp C-H alkenylation.

The prenyl group is present in numerous biologically active small molecule drugs and natural products. We introduce benzylic C-H alkenylation of substrates Ar-CH with alkenylboronic esters (CH)OB-CH[double bond, length as m-dash]CMe as a pathway to form prenyl functionalized arenes Ar-CHCH[double bond, length as m-dash]CMe. Mechanistic studies of this radical relay catalytic protocol reveal diverse reactivity pathways exhibited by the copper(ii) alkenyl intermediate [Cu]-CH[double bond, length as m-dash]CMe that involve radical capture, bimolecular C-C bond formation, and hydrogen atom transfer (HAT).

Thiol and HS-Mediated NO Generation from Nitrate at Copper(II).

Reduction of nitrate is an essential, yet challenging chemical task required to manage this relatively inert oxoanion in the environment and biology. We show that thiols, ubiquitous reductants in biology, convert nitrate to nitric oxide at a Cu(II) center under mild conditions. The β-diketiminato complex [ClNN]Cu(κ-ONO) engages in O-atom transfer with various thiols (RSH) to form the corresponding copper(II) nitrite [Cu](κ-ON) and sulfenic acid (RSOH).

Electrocatalytic Ammonia Oxidation by a Low-Coordinate Copper Complex.

Molecular catalysts for ammonia oxidation to dinitrogen represent enabling components to utilize ammonia as a fuel and/or source of hydrogen. Ammonia oxidation requires not only the breaking of multiple strong N-H bonds but also controlled N-N bond formation. We report a novel β-diketiminato copper complex [PrNN]Cu-NH ([Cu]-NH ()) as a robust electrocatalyst for NH oxidation in acetonitrile under homogeneous conditions.

Lewis acid-assisted reduction of nitrite to nitric and nitrous oxides via the elusive nitrite radical dianion.

Reduction of nitrite anions (NO) to nitric oxide (NO), nitrous oxide (NO) and ultimately dinitrogen (N) takes place in a variety of environments, including in the soil as part of the biogeochemical nitrogen cycle and in acidified nuclear waste. Nitrite reduction typically takes place within the coordination sphere of a redox-active transition metal. Here we show that Lewis acid coordination can substantially modify the reduction potential of this polyoxoanion to allow for its reduction under non-aqueous conditions (-0.

NO Coupling at Copper to -Hyponitrite: NO Formation via Protonation and H-Atom Transfer.

Copper nitrite reductases (CuNIRs) convert NO to NO as well as NO to NO under high NO flux at a mononuclear type 2 Cu center. While model complexes illustrate N-N coupling from NO that results in symmetric -hyponitrite [Cu]-ONNO-[Cu] complexes, we report NO assembly at a single Cu site in the presence of an external reductant Cp*M (M = Co, Fe) to give the first copper -hyponitrites [Cp*M]{[Cu](κ-ON)[Cu]}. Importantly, the κ-N-bound [Cu] fragment may be easily removed by the addition of mild Lewis bases such as CNAr or pyridine to form the spectroscopically similar anion {[Cu](κ-ON)}.

Copper(ii) ketimides in sp C-H amination.

Commercially available benzophenone imine (HN[double bond, length as m-dash]CPh) reacts with β-diketiminato copper(ii) -butoxide complexes [Cu]-O Bu to form isolable copper(ii) ketimides [Cu]-N[double bond, length as m-dash]CPh. Structural characterization of the three coordinate copper(ii) ketimide [MeNN]Cu-N[double bond, length as m-dash]CPh reveals a short Cu-N distance (1.700(2) Å) with a nearly linear Cu-N-C linkage (178.

Uncovering Redox Non-innocent Hydrogen-Bonding in Cu(I)-Diazene Complexes.

The life-sustaining reduction of N to NH is thermoneutral yet kinetically challenged by high-energy intermediates such as NH. Exploring intramolecular H-bonding as a potential strategy to stabilize diazene intermediates, we employ a series of [TpCu](μ-NH) complexes that exhibit H-bonding between pendant aromatic N-heterocycles (Het) such as pyridine and a bridging -NH ligand at copper(I) centers. X-ray crystallography and IR spectroscopy clearly reveal H-bonding in [TpCu](μ-NH) while low-temperature H NMR studies coupled with DFT analysis reveals a dynamic equilibrium between two closely related, symmetric H-bonded structural motifs.

Mechanism of O-Atom Transfer from Nitrite: Nitric Oxide Release at Copper(II).

Nitric oxide (NO) is a key signaling molecule in health and disease. While nitrite acts as a reservoir of NO activity, mechanisms for NO release require further understanding. A series of electronically varied β-diketiminatocopper(II) nitrite complexes [Cu](κ-ON) react with a range of electronically tuned triarylphosphines PAr that release NO with the formation of O═PAr.

Thionitrite and Perthionitrite in NO Signaling at Zinc.

NO and H S serve as signaling molecules in biology with intertwined reactivity. HSNO and HSSNO with their conjugate bases SNO and SSNO form in the reaction of H S with NO as well as S-nitrosothiols (RSNO) and nitrite (NO ) that serve as NO reservoirs. While HSNO and HSSNO are elusive, their conjugate bases form isolable zinc complexes TpZn(SNO) and TpZn(SSNO) supported by tris(pyrazolyl)borate ligands.

Quantification of Ni-N-O Bond Angles and NO Activation by X-ray Emission Spectroscopy.

A series of β-diketiminate Ni-NO complexes with a range of NO binding modes and oxidation states were studied by X-ray emission spectroscopy (XES). The results demonstrate that XES can directly probe and distinguish end-on vs side-on NO coordination modes as well as one-electron NO reduction. Density functional theory (DFT) calculations show that the transition from the NO 2s2s σ* orbital has higher intensity for end-on NO coordination than for side-on NO coordination, whereas the 2s2s σ orbital has lower intensity.

Three-Coordinate Copper(II) Alkynyl Complex in C-C Bond Formation: The Sesquicentennial of the Glaser Coupling.

Copper(II) alkynyl species are proposed as key intermediates in numerous Cu-catalyzed C-C coupling reactions. Supported by a β-diketiminate ligand, the three-coordinate copper(II) alkynyl [Cu]-C≡CAr (Ar = 2,6-ClCH) forms upon reaction of the alkyne H-C≡CAr with the copper(II) -butoxide complex [Cu]-OBu. In solution, this [Cu]-C≡CAr species cleanly transforms to the Glaser coupling product ArC≡C-C≡CAr and [Cu](solvent).

Lewis Acid Coordination Redirects S-Nitrosothiol Signaling Output.

S-Nitrosothiols (RSNOs) serve as air-stable reservoirs for nitric oxide in biology. While copper enzymes promote NO release from RSNOs by serving as Lewis acids for intramolecular electron-transfer, redox-innocent Lewis acids separate these two functions to reveal the effect of coordination on structure and reactivity. The synthetic Lewis acid B(C F ) coordinates to the RSNO oxygen atom, leading to profound changes in the RSNO electronic structure and reactivity.

Tris(pyrazolyl)borate Copper Hydroxide Complexes Featuring Tunable Intramolecular H-Bonding.

A modular synthesis provides access to a series of new tris(pyrazolyl)borate ligands TpK that possess a single functionalized pendant pyridyl (py) or pyrimidyl (pyd) arm designed to engage in tunable intramolecular H-bonding to metal-bound functionalities. To illustrate such H-bonding interactions, a series of [TpCu](μ-OH) (-) complexes were synthesized from the corresponding TpCu-OAc (-) complexes. Single crystal X-ray structures of three new dinuclear [TpCu](μ-OH) complexes reveal H-bonding between the pendant heterocycle and bridging hydroxide ligands while the donor arm engages the copper center in an unusual monomeric TpCu-OH complex.

Copper-Catalyzed C(sp )-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity.

Undirected C(sp )-H functionalization reactions often follow site-selectivity patterns that mirror the corresponding C-H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C-H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C-H bonds over tertiary and benzylic C-H sites.

Nitrosyl Linkage Isomers: NO Coupling to NO at a Mononuclear Site.

Linkage isomers of reduced metal-nitrosyl complexes serve as key species in nitric oxide (NO) reduction at monometallic sites to produce nitrous oxide (NO), a potent greenhouse gas. While factors leading to extremely rare side-on nitrosyls are unclear, we describe a pair of nickel-nitrosyl linkage isomers through controlled tuning of noncovalent interactions between the nitrosyl ligands and differently encapsulated potassium cations. Furthermore, these reduced metal-nitrosyl species with N-centered spin density undergo radical coupling with free NO and provide a N-N coupled cis-hyponitrite intermediate whose protonation triggers the release of NO.

Three-Coordinate Copper(II) Aryls: Key Intermediates in C-O Bond Formation.

Copper(II) aryl species are proposed key intermediates in Cu-catalyzed cross-coupling reactions. Novel three-coordinate copper(II) aryls [Cu]-CF supported by ancillary β-diketiminate ligands form in reactions between copper(II) alkoxides [Cu]-OBu and B(CF). Crystallographic, spectroscopic, and DFT studies reveal geometric and electronic structures of these Cu(II) organometallic complexes.

Elusive Terminal Copper Arylnitrene Intermediates.

We report herein three new modes of reactivity between arylazides N Ar with a bulky copper(I) β-diketiminate. Addition of N Ar (Ar =2,4,6-X C H ; X=Cl or Me) to [ Pr NN]Cu(NCMe) results in triazenido complexes from azide attack on the β-diketiminato backbone. Reaction of [ Pr NN]Cu(NCMe) with bulkier azides N Ar leads to terminal nitrenes [ Pr NN]Cu]=NAr that dimerize via formation of a C-C bond at the arylnitrene p-position to give the dicopper(II) diketimide 4 (Ar=2,6- Pr C H ) or undergo nitrile insertion to give diazametallocyclobutene 8 (Ar=4-Ph-2,6-iPr C H ).

Nitric oxide release via oxygen atom transfer from nitrite at copper(ii).

Nitric oxide is a vital signaling molecule that controls blood flow and oxygenation and nitrite serves as an important reservoir for nitric oxide in biology. While copper containing enzymes are known to reduce nitrite to nitric oxide, herein we report a new pathway to release nitric oxide via oxygen atom transfer from nitrite at a copper(ii) site.

Copper Catalyzed sp C-H Etherification with Acyl Protected Phenols.

A variety of acyl protected phenols AcOAr participate in sp C-H etherification of substrates R-H to give alkyl aryl ethers R-OAr employing BuOOBu as oxidant with copper(I) β-diketiminato catalysts [Cu]. Although 1°, 2°, and 3° C-H bonds may be functionalized, selectivity studies reveal a preference for the construction of hindered, 3° C-OAr bonds. Mechanistic studies indicate that β-diketiminato copper(II) phenolates [Cu]-OAr play a key role in this C-O bond forming reaction, formed via transesterification of AcOAr with [Cu]-OBu intermediates generated upon reaction of [Cu] with BuOOBu.

Copper(II) Activation of Nitrite: Nitrosation of Nucleophiles and Generation of NO by Thiols.

Nitrite (NO) and nitroso compounds (E-NO, E = RS, RO, and RN) in mammalian plasma and cells serve important roles in nitric oxide (NO) dependent as well as NO independent signaling. Employing an electron deficient β-diketiminato copper(II) nitrito complex [ClNN]Cu(κ-ON)·THF, thiols mediate reduction of nitrite to NO. In contrast to NO generation upon reaction of thiols at iron nitrite species, at copper this conversion proceeds through nucleophilic attack of thiol RSH on the bound nitrite in [Cu](κ-ON) that leads to S-nitrosation to give the S-nitrosothiol RSNO and copper(II) hydroxide [Cu]-OH.

The Chemistry of a Non-Interacting Vicinal Frustrated Phosphane/Borane Lewis Pair.

The dimesitylphosphinocyclopentene/HB(C F ) -derived vicinal trans-1,2-P/B frustrated Lewis pair (FLP) 4 shows no direct phosphane-borane interaction. Toward some reagents it behaves similar to an intermolecular FLP; it cleaves dihydrogen, deprotonates terminal alkynes, and adds to organic carbonyl compounds including CO . It shows typical intramolecular FLP reaction modes (cooperative 1,1-additions) to mesityl azide, to carbon monoxide, and to NO.

A Frustrated and Confused Lewis Pair.

We report a new class of frustrated Lewis pairs (FLPs) by the hydroboration of bulky isocyanates ArNCO ( Ar=2,6-iPr C H ) and ArNCO ( Ar=2,6-Ph -4-tBuC H ) with Piers' borane (HB(C F ) ). While hydroboration of smaller isocyanates such as ArNCO leads to isocyanate-N/B FLP adducts, hydroboration of the bulkier ArNCO allows isolation of the substrate-free aminoborane with a short, covalent N-B bond. This confused FLP reversibly binds unsaturated substrates such as isocyanates and isocyanides, suggesting the intermediacy of a "normal" FLP along the reaction pathway, supported by high-level DFT studies and variable-temperature NMR spectroscopy.