Photochemical Synthesis of Acyl Fluorides Using Copper-Catalyzed Fluorocarbonylation of Alkyl Iodides.

Acyl fluorides are important reagents due to their unique balance between reactivity and stability. Here, we report a copper-catalyzed carbonylative coupling strategy for synthesizing acyl fluorides under photoirradiation. Alkyl iodides were transformed in high yields into acyl fluorides by using a commercially available copper precatalyst (CuBr·SMe2) and a readily available fluoride salt (KF) at ambient temperature and mild CO pressure (6 atm) under blue light irradiation.

Coordination-induced O-H/N-H bond weakening by a redox non-innocent, aluminum-containing radical.

Several renewable energy schemes aim to use the chemical bonds in abundant molecules like water and ammonia as energy reservoirs. Because the O-H and N-H bonds are quite strong (>100 kcal/mol), it is necessary to identify substances that dramatically weaken these bonds to facilitate proton-coupled electron transfer processes required for energy conversion. Usually this is accomplished through coordination-induced bond weakening by redox-active metals. However, coordination-induced bond weakening is difficult with earth's most abundant metal, aluminum, because of its redox inertness under mild conditions. Here, we report a system that uses aluminum with a redox non-innocent ligand to achieve significant levels of coordination-induced bond weakening of O-H and N-H bonds. The multisite proton-coupled electron transfer manifold described here points to redox non-innocent ligands as a design element to open coordination-induced bond weakening chemistry to more elements in the periodic table.

Triazenide-supported [Cu4S] structural mimics of CuZ that mediate N2O disproportionation rather than reduction.

As part of the nitrogen cycle, environmental nitrous oxide (N2O) undergoes the N2O reduction reaction (N2ORR) catalyzed by nitrous oxide reductase, a metalloenzyme whose catalytic active site is a tetranuclear copper-sulfide cluster (CuZ). On the other hand, heterogeneous Cu catalysts on oxide supports are known to mediate decomposition of N2O (deN2O) by disproportionation. In this study, a CuZ model system supported by triazenide ligands is characterized by X-ray crystallography, NMR and EPR spectroscopies, and electronic structure calculations. Although the triazenide-ligated Cu4(µ4-S) clusters are closely related to previous formamidinate derivatives, which differ only in replacement of a remote N atom for a CH group, divergent reactivity with N2O is observed. Whereas the formamidinate-ligated clusters were previously shown to mediate single-turnover N2ORR, the triazenide-ligated clusters are found to mediate deN2O, behavior that was previously unknown to natural or synthetic copper-sulfide clusters. The reaction pathway for deN2O by this model system, including previously unidentified transition state models for N2O activation in N-O cleavage and O-O coupling steps, are included. The divergent reactivity of these two related but subtly different systems point to key factors influencing behavior of Cu-based catalysts for N2ORR (i.e., CuZ) and deN2O (e.g., CuO/CeO2).

Uncovering a CF3 Effect on X-ray Absorption Energies of [Cu(CF3 )4 ]- and Related Copper Compounds by Using Resonant Diffraction Anomalous Fine Structure (DAFS) Measurements.

Understanding the electronic structures of high-valent metal complexes aids the advancement of metal-catalyzed cross coupling methodologies. A prototypical complex with formally high valency is [Cu(CF3 )4 ]- (1), which has a formal Cu(III) oxidation state but whose physical analysis has led some to a Cu(I) assignment in an inverted ligand field model. Recent examinations of 1 by X-ray spectroscopies have led previous authors to contradictory conclusions, motivating the re-examination of its X-ray absorption profile here by a complementary method, resonant diffraction anomalous fine structure (DAFS). From analysis of DAFS measurements for a series of seven mononuclear Cu complexes including 1, here it is shown that there is a systematic trifluoromethyl effect on X-ray absorption that blue shifts the resonant Cu K-edge energy by 2-3 eV per CF3 , completely accounting for observed changes in DAFS profiles between formally Cu(III) complexes like 1 and formally Cu(I) complexes like (Ph3 P)3 CuCF3 (3). Thus, in agreement with the inverted ligand field model, the data presented herein imply that 1 is best described as containing a Cu(I) ion with dn count approaching 10.

Activation of robust bonds by carbonyl complexes of Mn, Fe and Co.

Metal carbonyl complexes possess among the most storied histories of any compound class in organometallic chemistry. Nonetheless, these old dogs continue to be taught new tricks. In this Feature, we review the historic discoveries and recent advances in cleaving robust bonds (e.g., C-H, C-O, C-F) using carbonyl complexes of three metals: Mn, Fe, and Co. The use of Mn, Fe, and Co carbonyl catalysts in controlling selectivity during hydrofunctionalization reactions is also discussed. The chemistry of these earth-abundant metals in the field of robust bond functionalization is particularly relevant in the context of sustainability. We expect that an up-to-date perspective on these seemingly simple organometallic species will emphasize the wellspring of reactivity that continues to be available for discovery.

Metal Site-Specific Electrostatic Field Effects on a Tricopper(I) Cluster Probed by Resonant Diffraction Anomalous Fine Structure (DAFS).

Studies of multinuclear metal complexes are greatly enhanced by resonant diffraction measurements, which probe X-ray absorption profiles of crystallographically independent metal sites within a cluster. In particular, X-ray diffraction anomalous fine structure (DAFS) analysis provides data that can be interpreted akin to site-specific XANES, allowing for differences in metal K-edge resonances to be deconvoluted even for different metal sites within a homometallic system. Despite the prevalence of Cu-containing clusters in biology and energy science, DAFS has yet to be used to analyze multicopper complexes of any type until now. Here, we report an evaluation of trends using a series of strategically chosen Cu(I) and Cu(II) complexes to determine how energy dependencies of anomalous scattering factors are impacted by coordination geometry, ligand shell, cluster nuclearity, and oxidation state. This calibration data is used to analyze a formally tricopper(I) complex that was found by DAFS to be site-differentiated due to the unsymmetrical influence on different Cu sites of the electrostatic field from a proximal K+ cation.

Reactivity of a Dithiocarbamate-Ligated [WVI≡S] Complex with Hydride Donors: Toward a Synthetic Mimic of Formate Dehydrogenase.

Formate dehydrogenase (FDH) enzymes catalyze redox interconversion of CO2 and HCO2-, with a key mechanistic step being the transfer of H- from HCO2- to an oxidized active site featuring a [MVI≡S] group in a sulfur-rich environment (M = Mo or W). Here, we report reactivity studies with HCO2- and other reducing agents of a synthetic [WVI≡S] model complex ligated by dithiocarbamate (dtc) ligands. Reactions of [WVIS(dtc)3][BF4] (1) conducted in MeOH solvent generated [WVIS(S2)(dtc)2] (2) and [WVS(µ-S)(dtc)]2 (3) products by a solvolysis pathway that was accelerated by the presence of [Me4N][HCO2] but did not require it. Under MeOH-free conditions, the reaction of 1 with [Et4N][HCO2] produced some [WIV(µ-S)(µ-dtc)(dtc)]2 (4), but predominantly [WV(dtc)4]+ (5), along with stoichiometric CO2 detected by headspace gas chromatography (GC) analysis. Stronger hydride sources such as K-selectride generated the more reduced analogue, 4, exclusively. The reaction of 1 with the electron donor, CoCp2, also produced 4 and 5 in varying amounts depending on reaction conditions. These results indicate that formates and borohydrides act as electron donors rather than hydride donors toward 1, an outcome that diverges from the behavior of FDHs. The difference is ascribed to the more oxidizing potential of [WVI≡S] complex 1 when supported by monoanionic dtc ligands that allows electron transfer to outcompete hydride transfer, as compared to the more reduced [MVI≡S] active sites supported by dianionic pyranopterindithiolate ligands in FDHs.

Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides.

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on a bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to generate a heterogeneous Cu0 photocatalyst in situ, maintains high efficiency and selectivity upon scale-up, and operates by a radical mechanism with several beneficial features. This discovery will enable the engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.

Recent advances in cooperative activation of CO2 and N2O by bimetallic coordination complexes or binuclear reaction pathways.

The gaseous small molecules, CO2 and N2O, play important roles in climate change and ozone layer depletion, and they hold promise as underutilized reagents and chemical feedstocks. However, productive transformations of these heteroallenes are difficult to achieve because of their inertness. In nature, these gases are cycled through ecological systems by metalloenzymes featuring multimetallic active sites that employ cooperative mechanisms. Thus, cooperative bimetallic chemistry is an important strategy for synthetic systems, as well. In this Perspective, recent advances (since 2010) in cooperative activation of CO2 and N2O are reviewed, including examples involving s-block, p-block, d-block, and f-block metals and different combinations thereof.

Cooperative Activation of CO2 and Epoxide by a Heterobinuclear Al-Fe Complex via Radical Pair Mechanisms.

Activation of inert molecules like CO2 is often mediated by cooperative chemistry between two reactive sites within a catalytic assembly, the most common form of which is Lewis acid/base bifunctionality observed in both natural metalloenzymes and synthetic systems. Here, we disclose a heterobinuclear complex with an Al-Fe bond that instead activates CO2 and other substrates through cooperative behavior of two radical intermediates. The complex Ldipp(Me)AlFp (2, Ldipp = HC{(CMe)(2,6-iPr2C6H3N)}2, Fp = FeCp(CO)2, Cp = η5-C5H5) was found to insert CO2 and cyclohexene oxide, producing LdippAl(Me)(µ:κ2-O2C)Fp (3) and LdippAl(Me)(µ-OC6H10)Fp (4), respectively. Detailed mechanistic studies indicate unusual pathways in which (i) the Al-Fe bond dissociates homolytically to generate formally AlII and FeI metalloradicals, then (ii) the metalloradicals add to substrate in a pairwise fashion initiated by O-coordination to Al. The accessibility of this unusual mechanism is aided, in part, by the redox noninnocent nature of Ldipp that stabilizes the formally AlII intermediates, instead giving them predominantly AlIII-like physical character. The redox noninnocent nature of the radical intermediates was elucidated through direct observation of LdippAl(Me)(OCPh2) (22), a metalloradical species generated by addition of benzophenone to 2. Complex 22 was characterized by X-band EPR, Q-band EPR, and ENDOR spectroscopies as well as computational modeling. The "radical pair" pathway represents an unprecedented mechanism for CO2 activation.

Preparation of Potassium Acyltrifluoroborates (KATs) from Carboxylic Acids by Copper-Catalyzed Borylation of Mixed Anhydrides.

We report the preparation of potassium acyltrifluoroborates (KATs) from widely available carboxylic acids. Mixed anhydrides of carboxylic acids were prepared using isobutyl chloroformate and transformed to the corresponding KATs using a commercial copper catalyst, B2 (pin)2 , and aqueous KHF2 . This method allows for the facile preparation of aliphatic, aromatic, and amino acid-derived KATs and is compatible with a variety of functional groups including alkenes, esters, halides, nitriles, and protected amines.

Copper-Catalyzed Carbonylative Coupling of Alkyl Halides.

Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to introduce oxygen functionality into organic compounds, with CO acting as an inexpensive and readily available C1 feedstock. Despite the long history of carbonylation catalysis, including many processes that have been industrialized at bulk scale, there remain several challenges to tackle. For example, noble metals such as Pd, Rh, and Ir are typically used as catalysts for carbonylation reactions, rather than earth-abundant alternatives. Additionally, while carbonylation of C(sp2)-hybridized substrates (e.g., aryl halides) is well-known, carbonylation of unactivated alkyl electrophiles, especially where ß-hydride elimination can compete with desired CO migratory insertion at the catalyst site, remains challenging for many systems. Recently, base metal catalysis based on Mn, Co, and other metals has enabled advances in carbonylative coupling of alkyl electrophiles, though the nucleophiles are often limited to alcohols or amines to generate esters or amides as products. Thus, we have targeted base metal-catalyzed carbonylative C-C and C-E (E = N, H, Si, B) coupling reactions as a method for approaching diverse carbonyl compounds of synthetic importance.Initially, we designed a heterobimetallic catalyst platform for carbonylative C-C coupling of alkyl halides with arylboronic esters (i.e., carbonylative Suzuki-Miyaura coupling) to generate aryl alkyl ketones. Subsequently, we developed multicomponent carbonylation reactions of alkyl halides using NHC-Cu catalysts (NHC = N-heterocyclic carbene). These reactions operate by radical mechanisms, converting alkyl halides into either acyl radical or acyl halide intermediates that undergo subsequent C-C or C-E coupling at the Cu site. This mechanistic paradigm is relatively novel in the metal-catalyzed carbonylation area, allowing us to discover a previously unexplored chemical space in carbonylative coupling catalysis. We have successfully developed the following reactions: (a) hydrocarbonylative coupling of alkynes with alkyl halides; (b) borocarbonylative coupling of alkynes with alkyl halides; (c) reductive aminocarbonylation of alkyl halides with nitroarenes; (d) reductive carbonylation of alkyl halides; (e) carbonylative silylation of alkyl halides; (f) carbonylative borylation of alkyl halides. These reactions provide a broad range of valuable products including ketones, allylic alcohols, ß-borylenones, amides, alcohols, acylsilanes, and acylborons in an efficient manner. Notably, the preparation of some of these products has previously required multistep syntheses, harsh conditions, or specialized reagents. By contrast, the multicomponent coupling platform that we have developed requires only readily available building blocks and rapidly increases molecular complexity in a single synthetic manipulation.

Cobalt-Catalyzed (E)-ß-Selective Hydrogermylation of Terminal Alkynes.

A cobalt-catalyzed method for the hydrogermylation of alkynes is reported, providing a selective and accessible route to (E)-ß-vinyl(trialkyl)germanes from terminal alkynes and HGeBu3. As shown in multiple examples, the developed method demonstrates a broad functional group tolerance an practical utility for late-stage hydrogermylation of natural products. The method is compatible with alkynes bearing both aryl and alkyl substituents, providing unrivaled selectivity for previously challenging 1° alkyl-substituted alkynes. Moreover, the catalyst used in this method, Co2(CO)8, is a cheap and commercially available reagent. Conducted mechanistic studies supported the syn-addition of Bu3GeH to an alkyne π-complex.

Coordination chemistry of the CuZ site in nitrous oxide reductase and its synthetic mimics.

Atmospheric nitrous oxide (N2O) has garnered significant attention recently due to its dual roles as an ozone depletion agent and a potent greenhouse gas. Anthropogenic N2O emissions occur primarily through agricultural disruption of nitrogen homeostasis causing N2O to build up in the atmosphere. The enzyme responsible for N2O fixation within the geochemical nitrogen cycle is nitrous oxide reductase (N2OR), which catalyzes 2H+/2e- reduction of N2O to N2 and H2O at a tetranuclear active site, CuZ. In this review, the coordination chemistry of CuZ is reviewed. Recent advances in the understanding of biological CuZ coordination chemistry is discussed, as are significant breakthroughs in synthetic modeling of CuZ that have emerged in recent years. The latter topic includes both structurally faithful, synthetic [Cu4(µ4-S)] clusters that are able to reduce N2O, as well as dicopper motifs that shed light on reaction pathways available to the critical CuI-CuIV cluster edge of CuZ. Collectively, these advances in metalloenzyme studies and synthetic model systems provide meaningful knowledge about the physiologically relevant coordination chemistry of CuZ but also open new questions that will pose challenges in the near future.

Synthesis and characterization of heteromultinuclear Ni/M clusters (M = Fe, Ru, W) including a paramagnetic (NHC)Ni-WCp*(CO)3 heterobinuclear complex.

A diverse range of heteromultinuclear NiI/[MCO] clusters (MCO = CpFe(CO)2, CpRu(CO)2, Cp*W(CO)3) supported by a N-heterocyclic carbene ligand have been synthesized by reacting the NiI precursor, [IPrNi(µ-Cl)]2, with [MCO]- reagents under various conditions. Clusters with Ni2Fe2, NiFe2, Ni2Ru, Ni2Ru2, NiRu2, and Ni2W, and NiW cores were all characterized using NMR and IR spectroscopies and X-ray crystallography. The NiI-containing paramagnetic heterobinuclear species, IPrNi-Wp* (7), was further characterized by EPR spectroscopy and DFT calculations. Notably, unlike previously studied (NHC)CuI-[MCO] derivatives, complex 7 was found to coordinate Lewis bases like 3-chloropyridine to produce (IPr)(3-Clpy)NiWp* (9). Complex 9 further underwent thermolytic C-Cl activation, proposed to involve NHC-free [(3-Clpy)Ni(µ-Wp*)]2 (10), to provide the C-arylated N-heterocyclic carbene product, [IPr(py-3-yl)]+[Cp*WCl2(CO)2]- (11).

One-Step Synthesis of Acylboron Compounds via Copper-Catalyzed Carbonylative Borylation of Alkyl Halides*.

A copper-catalyzed carbonylative borylation of unactivated alkyl halides has been developed, enabling efficient synthesis of aliphatic potassium acyltrifluoroborates (KATs) in high yields by treating the in situ formed tetracoordinated acylboron intermediates with aqueous KHF2 . A variety of functional groups are tolerated under the mild reaction conditions, and primary, secondary, and tertiary alkyl halides are all applicable. In addition, this method also provides facile access to N-methyliminodiacetyl (MIDA) acylboronates as well as α-methylated potassium acyltrifluoroborates in a one-pot manner. Mechanistic studies indicate a radical atom transfer carbonylation (ATC) mechanism to form acyl halide intermediates that are subsequently borylated by (NHC)CuBpin.

A W/Cu Synthetic Model for the Mo/Cu Cofactor of Aerobic CODH Indicates That Biochemical CO Oxidation Requires a Frustrated Lewis Acid/Base Pair.

Constructing synthetic models of the Mo/Cu active site of aerobic carbon monoxide dehydrogenase (CODH) has been a long-standing synthetic challenge thought to be crucial for understanding how atmospheric concentrations of CO and CO2 are regulated in the global carbon cycle by chemolithoautotrophic bacteria and archaea. Here we report a W/Cu complex that is among the closest synthetic mimics constructed to date, enabled by a silyl protection/deprotection strategy that provided access to a kinetically stabilized complex with mixed O2-/S2- ligation between (bdt)(O)WVI and CuI(NHC) (bdt = benzene dithiolate, NHC = N-heterocyclic carbene) sites. Differences between the inorganic core's structural and electronic features outside the protein environment relative to the native CODH cofactor point to a biochemical CO oxidation mechanism that requires a strained active site geometry, with Lewis acid/base frustration enforced by the protein secondary structure. This new mechanistic insight has the potential to inform synthetic design strategies for multimetallic energy storage catalysts.

C-C and C-X coupling reactions of unactivated alkyl electrophiles using copper catalysis.

Transition metal-catalysed cross-coupling reactions are widely used for construction of carbon-carbon and carbon-heteroatom bonds. However, compared to aryl or alkenyl electrophiles, the cross-coupling of unactivated alkyl electrophiles containing ß hydrogens remains a challenge. Over the past few years, the use of suitable ligands such as bulky phosphines or N-heterocyclic carbenes (NHCs) has enabled reactions of unactivated alkyl electrophiles not only limited to the traditional cross-coupling with Grignard reagents, but also including a diverse range of organic transformations via either SN2 or radical pathways. This review provides a comprehensive overview of the recent development in copper-catalysed C-C, C-N, C-B, C-Si and C-F bond-forming reactions using unactivated alkyl electrophiles.

Impact of Electronic and Steric Changes of Ligands on the Assembly, Stability, and Redox Activity of Cu4(µ4-S) Model Compounds of the CuZ Active Site of Nitrous Oxide Reductase (N2OR).

Model compounds have been widely utilized in understanding the structure and function of the unusual Cu4(µ4-S) active site (CuZ) of nitrous oxide reductase (N2OR). However, only a limited number of model compounds that mimic both structural and functional features of CuZ are available, limiting insights about CuZ that can be gained from model studies. Our aim has been to construct Cu4(µ4-S) clusters with tailored redox activity and chemical reactivity via modulating the ligand environment. Our synthetic approach uses dicopper(I) precursor complexes (Cu2L2) that assemble into a Cu4(µ4-S)L4 cluster with the addition of an appropriate sulfur source. Here, we summarize the features of the ligands L that stabilize precursor and Cu4(µ4-S) clusters, along with the alternative products that form with inappropriate ligands. The precursors are more likely to rearrange to Cu4(µ4-S) clusters when the Cu(I) ions are supported by bidentate ligands with 3-atom bridges, but steric and electronic features of the ligand also play crucial roles. Neutral phosphine donors have been found to stabilize Cu4(µ4-S) clusters in the 4Cu(I) oxidation state, while neutral nitrogen donors could not stabilize Cu4(µ4-S) clusters. Anionic formamidinate ligands have been found to stabilize Cu4(µ4-S) clusters in the 2Cu(I):2Cu(II) and 3Cu(I):1Cu(II) states, with both the formation of the dicopper(I) precursors and subsequent assembly of clusters being governed by the steric factor at the ortho positions of the N-aryl substituents. Phosphaamidinates, which combine a neutral phosphine donor and an anionic nitrogen donor in the same ligand, form multinuclear Cu(I) clusters unless the negative charge is valence-trapped on nitrogen, in which case the resulting dicopper precursor is unable to rearrange to a multinuclear cluster. Taken together, the results presented in this study provide design criteria for successful assembly of synthetic model clusters for the CuZ active site of N2OR, which should enable future insights into the chemical behavior of CuZ.

Probing the electronic and mechanistic roles of the µ4-sulfur atom in a synthetic CuZ model system.

Nitrous oxide (N2O) contributes significantly to ozone layer depletion and is a potent greenhouse agent, motivating interest in the chemical details of biological N2O fixation by nitrous oxide reductase (N2OR) during bacterial denitrification. In this study, we report a combined experimental/computational study of a synthetic [4Cu:1S] cluster supported by N-donor ligands that can be considered the closest structural and functional mimic of the CuZ catalytic site in N2OR reported to date. Quantitative N2 measurements during synthetic N2O reduction were used to determine reaction stoichiometry, which in turn was used as the basis for density functional theory (DFT) modeling of hypothetical reaction intermediates. The mechanism for N2O reduction emerging from this computational modeling involves cooperative activation of N2O across a Cu/S cluster edge. Direct interaction of the µ4-S ligand with the N2O substrate during coordination and N-O bond cleavage represents an unconventional mechanistic paradigm to be considered for the chemistry of CuZ and related metal-sulfur clusters. Consistent with hypothetical participation of the µ4-S unit in two-electron reduction of N2O, Cu K-edge and S K-edge X-ray absorption spectroscopy (XAS) reveal a high degree of participation by the µ4-S in redox changes, with approximately 21% S 3p contribution to the redox-active molecular orbital in the highly covalent [4Cu:1S] core, compared to approximately 14% Cu 3d contribution per copper. The XAS data included in this study represent the first spectroscopic interrogation of multiple redox levels of a [4Cu:1S] cluster and show high fidelity to the biological CuZ site.