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1.
Lizhu Zhang Cunbo Wei Jiawen Wu Dan Liu Yinchao Yao Zhuo Chen Jianxun Liu Chang-Jiang Yao Dinghua Li Rongjie Yang Zhonghua Xia 《Chemical science》2022,13(25):7475
Alkynes are widely used in chemistry, medicine and materials science. Here we demonstrate a transition-metal and photocatalyst-free inverse Sonogashira coupling reaction between iodoalkynes and (hetero)arenes or alkenes under visible-light irradiation. Mechanistic and computational studies suggest that iodoalkynes can be directly activated by visible light irradiation, and an excited state iodoalkyne acted as an “alkynyl radical synthetic equivalent”, reacting with a series of C(sp2)–H bonds for coupling products. This work should open new windows in radical chemistry and alkynylation method.A transition-metal and photocatalyst-free, photoinduced inverse Sonogashira coupling reaction was developed. Under visible-light irradiation, the excited state iodoalkyne acted as an “alkynyl radical synthetic equivalent”.Alkynes are among the most important class of compounds in organic chemistry. Because of their structural rigidity, special electronic properties and numerous methods available for the functionalization of the triple bond, alkynes are important tools and structural elements both in medicinal chemistry and materials sciences.1 Therefore, the development of a new methodology to introduce carbon–carbon triple bonds is of great importance in organic chemistry. The Sonogashira coupling reaction is typically used for the formation of C(sp)–C(sp2) bonds starting from hetero(aryl) halides and terminal alkynes.2 Recently, “inverse Sonogashira coupling” involving the direct alkynylation of unreactive C(sp2)–H bonds with readily available alkynyl halides has received growing interest in the development of a complementary strategy (Fig. 1a). Various main-group and transition metals have been developed to promote this transformation.3 In addition, a photomediated Sonogashira reaction without a photocatalyst was also developed by several groups (Fig. 1b).4Open in a separate windowFig. 1Models of alkynylation. (a) Conventional inverse Sonogashira reaction. (b) Photomediated Sonogashira reaction. (c) SOMOphilic alkynylation. (d) Photoinduced inverse Sonogashira reaction.In recent years, SOMOphilic alkylnylation (SOMO = singly occupied molecular orbital) has become an excellent method of introducing alkynyl groups (Fig. 1c).5 Based on photoredox and transition metal catalysis, numerous in situ generated radicals undergo α-addition and β-elimination to alkynyl reagents, like the broadly applicable ethynylbenziodoxolone (EBX) reagent. Various radical alkynylations were thus discovered by Li,6 Chen,7 Waser,8 and many other groups.9 However, extending the scope of radical precursors, more atom–economic reactions, and a deeper understanding of the mechanism in these transformations are still highly desirable.After the discovering of trityl radicals by Gomberg in 1900, the “rational” era of radical chemistry has since begun.10 Now, the development of radical reactions, especially those involving C(sp3) and C(sp2) radicals, enables rapid access to drug discovery, agrochemistry, materials science, and other disciplines.11 However, the C(sp) radical remains a baffling species. Due to their very high energy, short life time, and limited and harsh preparation methods, alkynyl radicals remain an elusive species, which just exists in some extreme environments, like outer-space and the petrochemical industry.12 Even though alkynyl radicals have been proposed as intermediates for some alkynylation methods, they were regarded as mysterious species and ignored by organic chemists for a long time.13 Recently, two approaches have been developed to aid the alkynyl radical generation step. In 2015, Hashmi and collaborators reported a [Au2(μ-dppm)2]2+ catalyzed free radical–radical C(sp)–C(sp3) bond coupling reaction between iodoalkynes and aliphatic amines.14 Under irradiation of sunlight, the dimeric gold complex was proposed to reduce the iodine acetylide to an alkynyl radical. In 2017, Li developed a transition-metal-free alkynylation reaction between iodoalkyne and 2-indolinone.15 Iodoalkynes could release alkynyl radicals under high temperature conditions. In 2019, we reported an Au(i) and Ir(iii) catalyzed alkynylative cyclization of o-alkylnylphenols with iodoalkynes, wherein the photosensitized energy transfer promoted the oxidative addition of a gold(i) complex with iodoalkynes.16 Based on our continuous interest in haloalkyne and photo-chemistry, we proposed that an iodoalkyne could be a potential “alkynyl radical precursor” under light irradiation. In this work, we uncovered a novel mode of transition-metal and photocatalyst-free, direct photoexcitation of iodoalkynes for the inverse Sonogashira coupling reaction with arenes, heteroarenes, and alkenes via an “alkynyl-radical type” transfer (Fig. 1d). 相似文献
2.
Natural systems produce various γ-dicarbonyl-bearing compounds that can covalently modify lysine in protein targets via the classic Paal–Knorr reaction. Among them is a unique class of lipid-derived electrophiles – isoketals that exhibit high chemical reactivity and critical biological functions. However, their target selectivity and profiles in complex proteomes remain unknown. Here we report a Paal–Knorr agent, 4-oxonon-8-ynal (herein termed ONAyne), for surveying the reactivity and selectivity of the γ-dicarbonyl warhead in biological systems. Using an unbiased open-search strategy, we demonstrated the lysine specificity of ONAyne on a proteome-wide scale and characterized six probe-derived modifications, including the initial pyrrole adduct and its oxidative products (i.e., lactam and hydroxylactam adducts), an enlactam adduct from dehydration of hydroxylactam, and two chemotypes formed in the presence of endogenous formaldehyde (i.e., fulvene and aldehyde adducts). Furthermore, combined with quantitative chemoproteomics in a competitive format, ONAyne permitted global, in situ, and site-specific profiling of targeted lysine residues of two specific isomers of isoketals, levuglandin (LG) D2 and E2. The functional analyses reveal that LG-derived adduction drives inhibition of malate dehydrogenase MDH2 and exhibits a crosstalk with two epigenetic marks on histone H2B in macrophages. Our approach should be broadly useful for target profiling of bioactive γ-dicarbonyls in diverse biological contexts.Natural systems produce various γ-dicarbonyl-bearing compounds that can covalently modify lysine in protein targets via the classic Paal–Knorr reaction.Synthetic chemistry methods have been increasingly underscored by their potential to be repurposed as biocompatible methods for both chemical biology and drug discovery. The most-known examples of such a repurposing approach include the Staudinger ligation1 and the Huisgen-based click chemistry.2 Moreover, bioconjugation of cysteine and lysine can be built upon facile chemical processes,3 while chemoselective labelling of other polar residues (e.g., histidine,4 methionine,5 tyrosine,6 aspartic and glutamic acids7,8) requires more elaborate chemistry, thereby offering a powerful means to study the structure and function of proteins, even at a proteome-wide scale.The classical Paal–Knorr reaction has been reported for a single-step pyrrole synthesis in 1884.9,10 The reaction involves the condensation of γ-dicarbonyl with a primary amine under mild conditions (e.g., room temperature, mild acid) to give pyrrole through the intermediary hemiaminals followed by rapid dehydration of highly unstable pyrrolidine adducts (Fig. S1†).Interestingly, we and others have recently demonstrated that the Paal–Knorr reaction can also readily take place in native biological systems.11–13 More importantly, the Paal–Knorr precursor γ-dicarbonyl resides on many endogenous metabolites and bioactive natural products.14 Among them of particular interest are isoketals15 (IsoKs, also known as γ-ketoaldehydes) which are a unique class of lipid derived electrophiles (LDEs) formed from lipid peroxidation (Fig. S2†)16 that has emerged as an important mechanism for cells to regulate redox signalling and inflammatory responses,17 and drive ferroptosis,18 and this field has exponentially grown over the past few years. It has been well documented that the γ-dicarbonyl group of IsoKs can rapidly and predominantly react with lysine via the Paal–Knorr reaction to form a pyrrole adduct in vitro (Fig. 1).15 Further, the pyrrole formed by IsoKs can be easily oxidized to yield lactam and hydroxylactam products in the presence of molecular oxygen (Fig. 1). These rapid reactions are essentially irreversible. Hence, IsoKs react with protein approximately two orders of magnitude faster than the most-studied LDE 4-hydoxynonenal (4-HNE) that contains α,β-unsaturated carbonyl to generally adduct protein cysteines by Michael addition (Fig. S3†).15 Due to this unique adduction chemistry and rapid reactivity, IsoKs exhibit intriguing biological activities, including inhibition of the nucleosome complex formation,19 high-density lipoprotein function,20 mitochondrial respiration and calcium homeostasis,21 as well as activation of hepatic stellate cells.22 Furthermore, increases in IsoK-protein adducts have been identified in many major diseases,23 such as atherosclerosis, Alzheimer''s disease, hypertension and so on.Open in a separate windowFig. 1The Paal–Knorr precursor γ-dicarbonyl reacts with the lysine residue on proteins to form diverse chemotypes via two pathways. The red arrow shows the oxidation pathway, while the blue one shows the formaldehyde pathway.Despite the chemical uniqueness, biological significance, and pathophysiological relevance of IsoKs, their residue selectivity and target profiles in complex proteomes remain unknown, hampering the studies of their mechanisms of action (MoAs). Pioneered by the Cravatt group, the competitive ABPP (activity-based protein profiling) has been the method of choice to analyse the molecular interactions between electrophiles (e.g., LDEs,24 oncometabolites,25 natural products,26,27 covalent ligands and drugs28–30) and nucleophilic amino acids across complex proteomes. In this regard, many residue-specific chemistry methods and probes have been developed for such studies. For example, several lysine-specific probes based on the activated ester warheads (e.g., sulfotetrafluorophenyl, STP;31N-hydroxysuccinimide, NHS32) have recently been developed to analyse electrophile–lysine interactions at a proteome-wide scale in human tumour cells, which provides rich resources of ligandable sites for covalent probes and potential therapeutics. Although these approaches can also be presumably leveraged to globally and site-specifically profile lysine-specific targets IsoKs, the reaction kinetics and target preference of activated ester-based probes likely differ from those of γ-dicarbonyls, possibly resulting in misinterpretation of ABPP competition results. Ideally, a lysine profiling probe used for a competitive ABPP analysis of IsoKs should therefore possess the same, or at least a similar, warhead moiety. Furthermore, due to the lack of reactive carbonyl groups on IsoK-derived protein adducts, several recently developed carbonyl-directed ligation probes for studying LDE-adductions are also not suitable for target profiling of IsoKs.33,34Towards this end, we sought to design a “clickable” γ-dicarbonyl probe for profiling lysine residues and, in combination with the competitive ABPP strategy, for analysing IsoK adductions in native proteomes. Considering that the diversity of various regio- and stereo- IsoK isomers15 (a total of 64, Fig. S2†) in chemical reactivity and bioactivities is likely attributed to the substitution of γ-dicarbonyls at positions 2 and 3, the “clickable” alkyne handle needs to be rationally implemented onto the 4-methyl group in order to minimize the biases when competing with IsoKs in target engagement. Interestingly, we reasoned that 4-oxonon-8-ynal, a previously reported Paal–Knorr agent used as an intermediate for synthesizing fatty acid probes35 or oxa-tricyclic compounds,36 could be repurposed for the γ-dicarbonyl-directed ABPP application. With this chemical in hand (herein termed ONAyne, Fig. 2A), we first used western blotting to detect its utility in labelling proteins, allowing visualization of a dose-dependent labelling of the proteome in situ (Fig. S4†). Next, we set up to incorporate this probe into a well-established chemoproteomic workflow for site-specific lysine profiling in situ (Fig. 2A). Specifically, intact cells were labelled with ONAyne in situ (200 μM, 2 h, 37 °C, a condition showing little cytotoxicity, Fig. S5†), and the probe-labelled proteome was harvested and processed into tryptic peptides. The resulting probe-labelled peptides were conjugated with both light and heavy azido-UV-cleavable-biotin reagents (1 : 1) via CuI-catalyzed azide–alkyne cycloaddition reaction (CuAAC, also known as click chemistry). The biotinylated peptides were enriched with streptavidin beads and photoreleased for LC-MS/MS-based proteomics. The ONAyne-labelled peptides covalently conjugated with light and heavy tags would yield an isotopic signature. We considered only those modified peptide assignments whose MS1 data reflected a light/heavy ratio close to 1.0, thereby increasing the accuracy of these peptide identifications. Using this criterium, we applied a targeted database search to profile three expected probe-derived modifications (PDMs), including 13 pyrrole peptide adducts (Δ273.15), 77 lactam peptide adducts (Δ289.14), and 557 hydroxylactam peptide adducts (Δ305.14), comprising 585 lysine residues on 299 proteins (Fig. S6 and S7†). Among them, the hydroxylactam adducts were present predominately, since the pyrrole formed by this probe, the same as IsoKs, can be easily oxidized when being exposed to O2. This finding was in accordance with a previous report where the pyrrole adducts formed by the reaction between IsoK and free lysine could not be detected, but rather their oxidized forms.37 Regardless, all three types of adducts were found in one lysine site of EF1A1 (K387, Fig. S8†), further confirming the intrinsic relationship among those adductions in situ.Open in a separate windowFig. 2Adduct profile and proteome-wide selectivity of the γ-dicarbonyl probe ONAyne. (A) Chemical structure of ONAyne and schematic workflow for identifying ONAyne-adducted sites across the proteome. (B) Bar chart showing the distribution of six types of ONAyne-derived modifications formed in situ and in vitro (note: before probe labelling, small molecules in cell lysates were filtered out through desalting columns).State-of-the-art blind search can offer an opportunity to explore unexpected chemotypes (i.e., modifications) derived from a chemical probe and to unbiasedly assess its proteome-wide residue selectivity.38,39 We therefore sought to use one of such tools termed pChem38 to re-analyse the MS data (see Methods, ESI†). Surprisingly, the pChem search identified three new and abundant PDMs (Fig. 1 and Table S1†), which dramatically expand the ONAyne-profiled lysinome (2305 sites versus 585 sites). Overall, these newly identified PDMs accounted for 74.6% of all identifications (Fig. 2B and Table S2†). Among them, the PDM of Δ287.13 (Fig. 1 and S7†) might be an enlactam product via dehydration of the probe-derived hydroxylactam adduct. The other two might be explained by the plausible mechanism as follows (Fig. 1). The endogenous formaldehyde (FA, produced in substantial quantities in biological systems) reacts with the probe-derived pyrrole adduct via nucleophilic addition to form a carbinol intermediate, followed by rapid dehydration to a fulvene (Δ285.15, Fig. S7†) and immediate oxidation to an aldehyde (Δ301.14, Fig. S7†). In line with this mechanism, the amount of FA-derived PDMs was largely eliminated when the in vitro ONAyne labelling was performed in the FA-less cell lysates (Fig. 2B and Table S3†). Undoubtedly, the detailed mechanisms underlying the formation of these unexpected PDMs require further investigation, and so does the reaction kinetics. Regardless, all main PDMs from ONAyne predominantly target the lysine residue with an average localization probability of 0.77, demonstrating their proteome-wide selectivity (Fig. S9†).Next, we adapted an ABPP approach to globally and site-specifically quantify the reactivity of lysine towards the γ-dicarbonyl warhead through a dose-dependent labelling strategy (Fig. 3A) that has been proved to be successful for other lysine-specific probes (e.g., STP alkyne).31 Specifically, MDA-MB-231 cell lysates were treated with low versus high concentrations of ONAyne (1 mM versus 0.1 mM) for 1 h. Probe-labelled proteomes were digested into tryptic peptides that were then conjugated to isotopically labelled biotin tags via CuAAC for enrichment, identification and quantification. In principle, hyperreactive lysine would saturate labelling at the low probe concentration, whereas less reactive ones would show concentration-dependent increases in labelling. For fair comparison, the STP alkyne-based lysine profiling data were generated by using the same chemoproteomic workflow. Although 77.5% (3207) ONAyne-adducted lysine sites can also be profiled by STP alkyne-based analysis, the former indeed has its distinct target-profile with 930 lysine sites newly identified (Fig. S10 and Table S4†). Interestingly, sequence motif analysis with pLogo40 revealed a significant difference in consensus motifs between ONAyne- and STP alkyne-targeting lysines (Fig. S11†).Open in a separate windowFig. 3ONAyne-based quantitative reactivity profiling of proteomic lysines. (A) Schematic workflow for quantitative profiling of ONAyne–lysine reactions using the dose-dependent ABPP strategy (B) Box plots showing the distribution of R10:1 values quantified in ONAyne- and STP alkyne-based ABPP analyses, respectively. Red lines showing the median values. ***p ≤ 0.001 two-tailed Student''s t-test. (C) Representative extracted ion chromatograms (XICs) showing changes in the EF1A1 peptide bearing K273 that is adducted as indicated, with the profiles for light and heavy-labelled peptides in blue and red, respectively.Moreover, we quantified the ratio (R1 mM:0.1 mM) for a total of 2439 ONAyne-tagged lysines (on 922 proteins) and 17904 STP alkyne-tagged lysines (on 4447 proteins) across three biological replicates (Fig. S12 and Table S5†). Strikingly, only 26.7% (651) of quantified sites exhibited nearly dose-dependent increases (R1 mM:0.1 mM > 5.0) in reactivity with ONAyne, an indicative of dose saturation (Fig. 3B and C). In contrast, such dose-dependent labelling events accounted for >69.1% of all quantified lysine sites in the STP alkyne-based ABPP analysis.31 This finding is in accordance with the extremely fast kinetics of reaction between lysine and γ-dicarbonyls (prone to saturation). Nonetheless, by applying 10-fold lower probe concentrations, overall 1628 (80.2%) detected lysines could be labelled in a fully concentration-dependent manner with the median R10:1 value of 8.1 (Fig. 3B, C, S12 and Table S5†). Next, we asked whether the dose-depending quantitation data (100 μM versus 10 μM) can be harnessed to predict functionality. By retrieving the functional information for all quantified lysines from the UniProt Knowledgebase, we found that those hyper-reactive lysines could not be significantly over-represented with annotation (Fig. S12†). Nonetheless, among all quantified lysines, 509 (25.1%) possess functional annotations, while merely 2.5% of the human lysinome can be annotated. Moreover, 381 (74.8%) ONAyne-labelled sites are known targets of various enzymatic post-translational modifications (PTMs), such as acetylation, succinylation, methylation and so on (Fig. S13†). In contrast, all known PTM sites accounted for only 59.6% of the annotated human lysinome. These findings therefore highlight the intrinsic reactivity of ONAyne towards the ‘hot spots’ of endogenous lysine PTMs.The aforementioned results validate ONAyne as a fit-for-purpose lysine-specific chemoproteomic probe for competitive isoTOP-ABPP application of γ-dicarbonyl target profiling. Inspired by this, we next applied ONAyne-based chemoproteomics in an in situ competitive format (Fig. 4A) to globally profile lysine sites targeted by a mixture of levuglandin (LG) D2 and E2, two specific isomers of IsoKs that can be synthesized conveniently from prostaglandin H2 (ref. 41) (Fig. S2†). Specifically, mouse macrophage RAW264.7 cells (a well-established model cell line to study LDE-induced inflammatory effects) were treated with 2 μM LGs or vehicle (DMSO) for 2 h, followed by ONAyne labelling for an additional 2 h. The probe-labelled proteomes were processed as mentioned above. For each lysine detected in this analysis, we calculated a control/treatment ratio (RC/T). Adduction of a lysine site by LGs would reduce its accessibility to the ONAyne probe, and thus a higher RC/T indicates increased adduction. In total, we quantified 2000 lysine sites on 834 proteins across five biological replicates. Among them, 102 (5.1%) sites exhibited decreases of reactivity towards LGs treatment (P < 0.05, Table S6†), thereby being considered as potential targets of LGs. Notably, we found that different lysines on the same proteins showed varying sensitivity towards LGs (e.g., LGs targeted K3 of thioredoxin but not K8, K85 and K94, Table S6†), an indicative of changes in reactivity, though we could not formally exclude the effects of changes in protein expression on the quantified competition ratios. Regardless, to the best of our knowledge, the proteome-wide identification of potential protein targets by IsoKs/LGs has not been possible until this work.Open in a separate windowFig. 4ONAyne-based in situ competitive ABPP uncovers functional targets of LGs in macrophages. (A) Schematic workflow for profiling LGs–lysine interactions using ONAyne-based in situ competitive ABPP. (B) Volcano plot showing the log2 values of the ratio between the control (heavy) and LGs-treated (light) channels and the −log10(P) of the statistical significance in a two-sample t-test for all quantified lysines. Potential targets of LGs are shown in blue (RC/T>1.2, P < 0.05), with the validated ones in red. (C) Bar chart showing the inhibitory effect of 2 μM LGs on the cellular enzymatic activity of MDH2. Data represent means ± standard deviation (n = 3). Statistical significance was calculated with two-tailed Student''s t-tests. (D) Pretreatment of LGs dose-dependently blocked ONAyne-labelling of MDH2 in RAW264.7 cells, as measured by western blotting-based ABPP. (E and F) LGs dose-dependently decreased the H2BK5 acetylation level in RAW 264.7 cells, as measured either by western blotting (E) or by immunofluorescence imaging (F). n = 3. For G, nuclei were visualized using DAPI (blue).We initially evaluated MDH2 (malate dehydrogenase, mitochondrial, also known as MDHM), an important metabolic enzyme that possesses four previously uncharacterized liganded lysine sites (K157, K239, K301 and K329, Fig. 4B) that are far from the active site (Fig. S14†). We found that LGs dramatically reduced the catalytic activity of MDH2 in RAW264.7 cells (Fig. 4C), suggesting a potentially allosteric effect. We next turned our attention to the targeted sites residing on histone proteins, which happen to be modified by functionally important acetylation, including H2BK5ac (Fig. 4B) that can regulate both stemness and epithelial–mesenchymal transition of trophoblast stem cells.42 We therefore hypothesized that rapid adduction by LGs competes with the enzymatic formation of this epigenetic mark. Immunoblotting-based competitive ABPP confirmed that LGs dose-dependently blocked probe labelling of H2B (Fig. 4D). Further, both western blots and immunofluorescence assays revealed that LG treatment decreased the level of acetylation of H2BK5 (average RC/T = 1.3, P = 0.007) in a concentration-dependent manner (Fig. 4E and F). Likewise, a similar competitive crosstalk was observed between acetylation and LG-adduction on H2BK20 (average RC/T = 1.2, P = 0.01) that is required for chromatin assembly43 and/or gene regulation44 (Fig. 4B and S15†). Notably, these findings, together with several previous reports by us and others about histone lysine ketoamide adduction by another important LDE, 4-oxo-2-noenal,11,45,46 highlight again the potentially important link between lipid peroxidation and epigenetic regulation. In addition to the targets validated as above, many other leads also merit functional studies considering diverse biological or physiologic effects of LGs in macrophages. 相似文献
3.
Brendan J. Graziano Thais R. Scott Matthew V. Vollmer Michael J. Dorantes Victor G. Young Jr Eckhard Bill Laura Gagliardi Connie C. Lu 《Chemical science》2022,13(22):6525
Odd-electron bonds have unique electronic structures and are often encountered as transiently stable, homonuclear species. In this study, a pair of copper complexes supported by Group 13 metalloligands, M[N((o-C6H4)NCH2PiPr2)3] (M = Al or Ga), featuring two-center/one-electron (2c/1e) σ-bonds were synthesized by one-electron reduction of the corresponding Cu(i) ⇢ M(III) counterparts. The copper bimetallic complexes were investigated by X-ray diffraction, cyclic voltammetry, electron paramagnetic spectroscopy, and density functional theory calculations. The combined experimental and theoretical data corroborate that the unpaired spin is delocalized across Cu, M, and ancillary atoms, and the singly occupied molecular orbital (SOMO) corresponds to a σ-(Cu–M) bond involving the Cu 4pz and M ns/npz atomic orbitals. Collectively, the data suggest the covalent nature of these interactions, which represent the first examples of odd-electron σ-bonds for the heavier Group 13 elements Al and Ga.Hanging on by a thread. Formally zerovalent copper complexes with an Al(iii) or Ga(iii) support were investigated. The combined experimental and theoretical data corroborate the presence of an odd-electron σ-bond between Cu and the Group 13 center.Odd-electron σ-bonds, where the electrons are delocalized between two atoms, can occur as two-center/one-electron (2c/1e) or two-center/three-electron (2c/3e) interactions. Proposed by Pauling in 1931,1 odd-electron σ-bonds have garnered attention because of their fundamental importance to chemical bonding and their relationship to radical species generated during oxidative stress in biological systems.2–14 Examples of compounds exhibiting odd-electron bonding are typically homonuclear (like H2+, He2+, and alkali metal dimers) and transiently stable, limiting them to spectroscopic characterization.1,11,15–18The first solid-state structure of a formally one-electron σ-bond was a tetraphosphabenzene species (Fig. 1a) which was formed by the coupling of two diphosphirenyl radicals.19 Following this discovery, the formation of discrete 2c/1e σ-bonds, where the odd-electron is delocalized between two homonuclear main group centers, was reported for B·B and then extended to P·P.8,17,20 Of note, the first solid-state structure of a B·B compound was reported in only 2014 (Fig. 1b).21 Examples of 2c/1e σ-bonds between the heavier Group 13 congeners are even more lacking because of the greater propensity for their unpaired spins to couple, forming larger more stable clusters.8 To our knowledge, there are only three structurally characterized examples of odd-electron bonds for the heavy Group 13 atoms,22 and these examples are all homonuclear π-radicals (Fig. 1c).23–26Open in a separate windowFig. 1Select examples of structurally characterized molecules (a–d) featuring odd-electron bonds.Heteronuclear odd-electron σ-bonds are also rare. The Cu(TPB) complex, where TPB is a trisphosphinoborane, is the single structural example of a 2c/1e bond between heteroatoms (Fig. 1d).27 The authors described the bonding as Cu·B, where the unpaired electron is heavily polarized toward B. A theoretical study predicted that such a bond would also exist between Cu and Al, but no heavier analogues of Cu(TPB) have been synthesized to date.28 Furthermore, the heavier Group 13 elements by virtue of their lower electronegativity compared to B should facilitate greater covalent interactions with the Cu center.Hence, we sought to target formally zerovalent Cu complexes supported by Al(III) or Ga(III) as an extension of the previously reported isoelectronic nickelate species and Cu(TPB).29 Herein, we describe the synthesis, structure, spectroscopic characterization, and DFT calculations of cationic [CuML]+ complexes (L = [N((o-C6H4)NCH2PiPr2)3]3−; M = Al and Ga) as well as their one-electron reduced metalloradical counterparts that feature discrete 2c/1e bonds. 相似文献
4.
Long Yang Becky Bongsuiru Jei Alexej Scheremetjew Binbin Yuan A. Claudia Stückl Lutz Ackermann 《Chemical science》2021,12(39):12971
Copper-catalyzed electrochemical direct chalcogenations of o-carboranes was established at room temperature. Thereby, a series of cage C-sulfenylated and C-selenylated o-carboranes anchored with valuable functional groups was accessed with high levels of position- and chemo-selectivity control. The cupraelectrocatalysis provided efficient means to activate otherwise inert cage C–H bonds for the late-stage diversification of o-carboranes.Copper-catalyzed electrochemical cage C–H chalcogenation of o-carboranes has been realized to enable the synthesis of various cage C-sulfenylated and C-selenylated o-carboranes.Carboranes are polyhedral molecular boron–carbon clusters, which display unique properties, such as a boron enriched content, icosahedron geometry and three-dimensional electronic delocalization.1 These features render carboranes as valuable building blocks for applications to optoelectronics,2 as nanomaterials, in supramolecular design,3 organometallic coordination chemistry,4 and boron neutron capture therapy (BNCT) agents.5 As a consequence, considerable progress has been witnessed in transition metal-catalyzed regioselective cage B–H functionalization of o-carboranes6 and different functional motifs have been incorporated into the cage boron vertices.7–10 However, progress in this research arena continues to be considerably limited by the shortage of robust and efficient methods to access carborane-functionalized molecules. While C–S bonds are important structural motifs in various biologically active molecules and functional materials,11 strategies for the assembly of chalcogen-substituted carboranes continue to be scarce. A major challenge is hence represented by the strong coordination abilities of thiols to most transition metals, which often lead to catalyst deactivation.12 While copper-catalyzed B(4,5)–H disulfenylation of o-carboranes was achieved,7e elevated reaction temperature was required, and 8-aminoquinoline was necessary as bidentate directing group. The bidentate directing group13 needs to be installed and removed, which jeopardizes the overall efficacy. Likewise, an organometallic strategy was recently devised for cysteine borylation with a stoichiometric platinum(ii)-based carboranes.14 Meanwhile, oxidative cage B/C–H functionalizations largely call for noble transition metal catalysts15 and stoichiometric amounts of chemical oxidants, such as expensive silver(i) salts.16In recent years, electricity has been identified as an increasingly viable, sustainable redox equivalent for environmentally-benign molecular synthesis.17,18 While significant advances have been realized by the merger of electrocatalysis with organometallic bond activation,19 electrochemical carborane functionalizations continue unfortunately to be underdevelopment. In sharp contrast, we have now devised a strategy for unprecedented copper-catalyzed electrochemical cage C–H chalcogenations of o-carboranes in a dehydrogenative manner, assembling a variety of C-sulfenylated and C-selenylated o-carboranes (Fig. 1a). It is noteworthy that our electrochemical cage C–S/Se modification approach is devoid of chemical oxidants, and does not need any directing groups, operative at room temperature.Open in a separate windowFig. 1Electrochemical diversification of o-carboranes and optimization of reaction conditions. aReaction conditions: procedure A: 1a (0.10 mmol), 2a (0.3 mmol), CuOAc (15 mol%), 2-PhPy (15 mol%), LiOtBu (0.2 mmol), TBAI (2.0 equiv.), solvent (3 mL), platinum cathode (10 mm × 15 mm × 0.25 mm), graphite felt (GF) anode (10 mm × 15 mm × 6 mm), 2 mA, under air, r.t., 16 h. bYield was determined by 1H NMR with CH2Br2 as the internal standard. cIsolated yields in parenthesis. dKI (1.0 equiv.) as additive. eProcedure B: 2 (0.3 mmol), LiOtBu (0.2 mmol), TBAI (2.0 equiv.), solvent (3.0 mL), 2 mA, r.t., 3 h, then adding 1a (0.10 mmol), 2-PhPy (15 mol%), CuOAc (15 mol%), 2 mA, rt, 16 h. f2b (0.3 mmol), LiOtBu (0.2 mmol), KI (1.0 equiv.), TBAI (2.0 equiv.), solvent (3.0 mL), 2 mA, r.t., 3 h, then adding 1a (0.10 mmol), 2-PhPy (15 mol%), CuOAc (15 mol%), r.t., 16 h. TBAI = tetrabutylammonium iodide, TBAPF6 = tetrabutylammonium hexafluorophosphate. DCE = 1,2-dichloroethane, THF = tetrahydrofuran.We commenced our studies by probing various reaction conditions for the envisioned copper-catalyzed cage C–H thiolation of o-carborane in an operationally simple undivided cell setup equipped with a GF (graphite felt) anode and a Pt cathode (Fig. 1b and Table S1†). After extensive experimentation, we observed that the thiolation of substrate 1 proceeded efficiently with catalytic amounts of CuOAc and 2-phenylpyridine, albeit in the presence of 2 equivalents LiOtBu as the base, and 2 equivalents n-Bu4NI as the electrolyte at room temperature under a constant current of 2 mA (entry 1). The yield was reduced when other copper sources or additives were used (entries 2–5). Surprisingly, n-Bu4NPF6 as the electrolyte failed to facilitate the carborane modification, indicating that n-Bu4NI operates not only as electrolyte, but also as a redox mediator (entry 6). Altering the stoichiometry of the electrolyte or using KI did not improve the performance (entries 7–8). Product formation was not observed, when the reaction was conducted with DCE as the solvent, while CH3CN resulted in a drop of the catalytic performance (entries 9–10). Control experiments confirmed the essential role of the electricity and the catalyst (entries 11–12), while a sequential procedure was found to be beneficial (entries 13–15).With the optimized reaction conditions in hand, we explored the versatility of the cage C–H thiolation of o-carborane 1a with different thiols 2 (Scheme 1). Electron-rich as well as electron-deficient substituents on the arenes were found to be amenable to the electrocatalyzed C–H activation, providing the corresponding thiolation products 3aa–3ao in good to excellent yields. Thereby, a variety of synthetically useful functional groups, such as fluoro (3ae, 3am), chloro (3af, 3ak, 3an) and bromo (3ag, 3al), were fully tolerated, which should prove instrumental for further late-stage manipulations. Various disubstituted aromatic and heterocyclic thiols afforded the corresponding cage C–S modified products 3ap–3as. Notably, aliphatic thiols efficiently underwent the electrochemical transformation to provide the corresponding cage alkylthiolated products 3at–3au. Notably, the halogen-containing thiols (2e–2f, 2k–2n and 2q) reacted selectively with o-carboranes to deliver the desired products without halide coupling byproducts being observed. The connectivity of the products 3aa, 3am and 3ao was unambiguously verified by X-ray single crystal diffraction analysis.22Open in a separate windowScheme 1Electrochemical C–H thiolation of o-carborane 1a. (a) Procedure B. (b) KI (1 equiv.). (c) Cul as the catalyst.Encouraged by the efficiency of the cupraelectro-oxidative cage C–H thiolation, we became intrigued to explore the chalcogenantion of differently-decorated o-carboranes 1 (Scheme 2). Electronically diverse carboranes 1 served as competent coupling partners, giving the corresponding thiolation products 4bo–4do with high levels of efficacy in position-selective manner. The strategy was not restricted to phenyl-substituted o-carboranes. Indeed, substrates bearing benzyl and even alkyl groups also performed well to deliver the desired products 4eo–4ga. It is noteworthy that the C–H activation approach was also compatible with selenols to give the o-carboranes 4av–4fv. The molecular structures of the carborane 4br and 4av were unambiguously verified by single-crystal X-ray diffraction.22Open in a separate windowScheme 2Electrochemical cage C–H chalcogenation of o-carboranes. (a) Procedure B. (b) KI (1 equiv.).Scaffold functionalization of the thus obtained carborane 3ag provided the alkynylated derivative 5a and amine 5b (Scheme 3), giving access to carborane-based host materials of relevant to phosphorescent organic light-emitting diodes.20Open in a separate windowScheme 3Late-stage diversification.Next, we became attracted to delineating the mode of the cupraelectro-catalyzed cage C–H chalcogenation. To this end, control experiments were performed (Scheme 4a). First, electrocatalysis in the presence of TEMPO or Ph2C CH2 gave the desired product 3aa. EPR studies of thiol 2a, LiOtBu and THF under the electrochemical conditions showed a small radical signal, which might be attributed to a thiol radical.21 Second, the cupraelectrocatalysis occurred efficiently in the dark. Third, detailed cyclovoltammetric analysis of the thiol and iodide mediator (Scheme 4b and ESI†)21 revealed an irreversible oxidation of the thiol anion at Ep = −0.62 V vs. Ag/Ag+ and two oxidation events for the iodide, including an irreversible oxidation at Ep = 0.12 V vs. Ag/Ag+ and a reversible oxidation at Ep = 0.44 V vs. Ag/Ag+, which is in good agreement with the literature reported iodide oxidation potentials,18c,d and is suggestive of the preferential oxidation of the iodide as a redox mediator. In this context, the use of n-Bu4NI as a redox mediator to achieve copper-catalyzed electrochemical arene C–H aminations had been documented.18d Furthermore, we calculated the redox potential of complex C by means of DFT calculations at the PW6B95-D4/def2-TZVP + SMD(MeCN)//TPSS-D3BJ/def2-SVP level of theory.21 These studies revealed a calculated oxidation half-wave potential for complex C is Eo,calc1/2 = −0.08 V vs. SCE. Hence, iodide is a competent redox mediator to achieve the transformation from complex C to complex D. Analysis of non-covalent interactions21 in complex C (Fig. 2) show the presence of a weak stabilization interaction between the chalcogen''s anisole group and the 2-phenylpyridine. In contrast, in complex D these interactions were found more relevant between the o-carborane phenyl group and the chalcogen aromatic motif.Open in a separate windowFig. 2Non-covalent interaction plots for the complexes C and D. Strong attractive interactions are shown in blue, weak attractive interactions are given in green, while red corresponds to repulsive interactions. Ar = 4-MeOC6H4.Open in a separate windowScheme 4Control experiments and cyclic voltammograms.On the basis of the aforementioned findings,18 a plausible reaction mechanism is proposed in Scheme 5, which commences with an anodic single electron-transfer (SET) oxidation of the thiol anion E to form the sulfur-centered radical F. Subsequently, the copper(i) species A reacts with the sulfur radical F to deliver copper(ii) complex B, which next reacts with o-carborane 1 in the presence of LiOtBu to generate a copper(ii)-o-carborane complex C. Thereafter, the complex C is oxidized by the anodically generated redox mediator I2 to furnish the copper(iii) species D,18d which subsequently undergoes reductive elimination, affording the final product and regenerating the catalytically active complex A. Alternatively, the direct oxidation of copper(ii) complex C by electricity to generate copper(iii) species D can not be excluded at this stage.18a,bOpen in a separate windowScheme 5Proposed reaction mechanism.In conclusion, a sustainable electrocatalytic C–H chalcogenation of o-carboranes with thiols and selenols was realized at room temperature by earth abundant copper catalysis. The C–H activation was characterized by mild reaction conditions and high functional group tolerance, leading to the facile assembly of various o-carboranes. Thereby, a transformative platform for the design of cage C–S and C–Se o-carboranes was established that avoids chemical oxidants by environmentally-sound electricity in the absence of directing groups. A plausible mechanism of paired electrolysis was established by detailed mechanistic studies. 相似文献
5.
Fei Yu Tingting Huo Quanhua Deng Guoan Wang Yuguo Xia Haiping Li Wanguo Hou 《Chemical science》2022,13(3):754
Expediting the oxygen evolution reaction (OER) is the key to achieving efficient photocatalytic overall water splitting. Herein, single-atom Co–OH modified polymeric carbon nitride (Co-PCN) was synthesized with single-atom loading increased by ∼37 times with the assistance of ball milling that formed ultrathin nanosheets. The single-atom Co-N4OH structure was confirmed experimentally and theoretically and was verified to enhance optical absorption and charge separation and work as the active site for the OER. Co-PCN exhibits the highest OER rate of 37.3 μmol h−1 under visible light irradiation, ∼28-fold higher than that of common PCN/CoOx, with the highest apparent quantum yields reaching 4.69, 2.06, and 0.46% at 400, 420, and 500 nm, respectively, and is among the best OER photocatalysts reported so far. This work provides an effective way to synthesize efficient OER photocatalysts.Single-atom CoII-OH modified polymeric carbon nitride synthesized with increased single-atom loading under the assistance of ball milling exhibits high photocatalytic water oxidation activity with Co-N4OH as the highly active site.Massive fuel energy consumption induced environmental and ecological problems, especially the greenhouse effect, and the resultant extreme climates and rise in sea level are threatening human life.1 As a potential substitution for fuel energy, hydrogen energy conversion from solar energy via photocatalytic water splitting attracts great attention from scientists.2–5 However, the photocatalytic hydrogen evolution efficiency from overall water splitting is still restricted by the sluggish oxygen evolution reaction (OER) that involves energy absorption, four-electron transfer, breakage of O–H bonds, and formation of O–O bonds,6,7 and thus efficient OER photocatalysts become the key to achieving efficient overall water splitting. Though numerous hydrogen evolution photocatalysts have been reported, research on OER photocatalysts is mainly around a few semiconductors including BiVO4, WO3, Ag3PO4, α-Fe2O3, etc.8–11 and their activity is not high enough yet for practical applications. Therefore, exploring high-efficiency OER photocatalysts is still necessary.Polymeric carbon nitride (PCN) was first reported in 2009 (ref. 12) as a photocatalyst with a layered melon-type orthorhombic structure,13 and thereafter quickly became a “star” photocatalyst thanks to its advantages of being visible-light responsive and metal-free, non-toxic, and low cost, and its relatively high chemical stability.14 Because of several self-deficiencies including fast photogenerated charge recombination and a narrow optical absorption spectrum, PCN exhibits relatively low photocatalytic activity.15 Then, a series of strategies were put forward successively to enhance the photoactivity of PCN, such as enhancement of crystallinity,16 morphological control,17 structural modification18 (including extensively researched single atom modification in recent years19,20), exfoliation,21 construction of hetero-(homo-)junctions,22 and loading of noble metals.23 Though photocatalytic water splitting on PCN was extensively researched in the past, the research was mainly around the hydrogen evolution half-reaction used for exploring properties and the catalytic mechanism of photocatalysts, and little research was focused on the industrially useable overall water splitting process owing to the sluggish OER.15 Therefore, enhancing the photocatalytic OER activity of PCN becomes the key to practical applications.To increase OER rates of PCN, several kinds of methods were proposed, such as rational design of compound cocatalysts (e.g., CoOx, IrO2, CoP, CoPi, RhOx, RuOx, PtOx, MnOx, Co(OH)2, Ni(OH)2, and CoAl2O4 (ref. 24–30)), modification of carbon dots and carbon rings,31,32 fabrication of special architectures of PCN (e.g., PCN quantum dot stacked nanowires33), and single-atom (e.g., B, Co, and Mn34–36) modification. For instance, Zhao and coauthors prepared B and N-vacancy comodified PCN that exhibits the highest OER rate of ∼28 μmol h−1 (ref. 36) and recently their group further used these B doped PCN ultrathin nanosheets to fabricate a Z-scheme heterojunction for overall water splitting with a solar-to-hydrogen efficiency reaching ∼1.2%.37 Comparatively, PCN loaded with compound cocatalysts can only enhance OER activity to a limited degree and there are finite methods for carbon modification and special architecture fabrication. Single-atom modification shows a bright prospect, on account of metal atoms capable of being inserted into the framework of PCN and effectively increasing the OER activity. However, reported single metal atom modification routes are all based on direct ion adsorption on PCN or calcination of mixtures of metal salts and PCN feedstocks.34,35,38 New routes need be explored to increase effective loading of single atoms in PCN. Besides, the metal-OH structure is considered efficient for the OER,30,39,40 and a single metal atom-OH structure has never been reported for modification of PCN, though Mn–OH was thought to play a key role in the OER process.34Ball milling is an extensively used versatile and scalable way for preparation of heterogeneous catalysts and even single-atom catalysts,41,42 but was rarely used in synthesis of PCN-based single-atom photocatalysts. In this work, we synthesized single-atom Co–OH modified PCN (Co-PCN) with the single-atom content in PCN highly increased with the assistance of ball milling. The simple synthetic route is shown in Fig. 1a. PCN was ball-milled to obtain BM-PCN that then adsorbed Co2+ till saturation to form BM-PCN/Co which was calcined to obtain BM-PCN/Co-c (Co-PCN). For comparison, PCN was directly used to adsorb Co2+ till saturation to form PCN/Co which was calcined to obtain PCN/Co-c. PCN mainly comprises large blocks with the size of several micrometers (Fig. S1†), while BM-PCN contains massive irregular particles with the size reduced to several hundreds of nanometers (Fig. S2†), indicative of high efficacy of ball milling. BM-PCN/Co-c exhibits a similar morphology as BM-PCN (Fig. 1b and S3†) and PCN/Co-c exhibits a similar morphology to PCN (Fig. S4†), but the surface area and mesopore volume of BM-PCN and BM-PCN/Co-c are not higher than those of PCN and PCN/Co-c (Fig. S5†), manifesting that ball-milling and subsequent calcination did not form massive mesopores, which accords well with the particle size variation from several micrometers (before ball milling) to several hundreds of nanometers (after ball milling). However, the Co content in BM-PCN/Co-c, BM-PCN/Co, PCN/Co-c, and PCN/Co was measured to be 0.75, 0.50, 0.02, and ∼0.02 wt%, respectively, by inductively coupled plasma mass spectrometry (ICP-MS). The ∼37 times higher Co content in BM-PCN/Co-c than in PCN/Co-c suggests the ball-milling enhanced adsorption of Co2+ on surfaces of BM-PCN, which should arise mainly from the ball-milling induced increase of surface energy and adsorption sites.43Open in a separate windowFig. 1(a) Schematic illustration for synthesis of single-atom CoII-OH modified PCN (BM-PCN/Co-c); and (b) SEM, (inset in b) TEM, (c) AFM, (d) EDS elemental mapping, and (e) HAADF-STEM images of BM-PCN/Co-c.The TEM image shows the existence of small and ultrathin nanosheets in BM-PCN/Co-c (inset in Fig. 1b) which can also be observed in the atomic force microscopy (AFM) image with a thickness of ∼7–10 nm and lateral size of <70 nm (Fig. 1c), and formation of these ultrathin nanosheets results from the ball milling of PCN.44 It should be noted that most formed ultrathin nanosheets with high surface energy may stack into compact particles upon ball milling, leading to no increase of the total surface area. Energy dispersive X-ray spectroscopy (EDS) elemental mapping images of BM-PCN/Co-c indicate homogeneous distribution of C, N, O, and Co elements in the sample (Fig. 1d). The high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image of BM-PCN/Co-c shows massive white spots (marked by circles) with a mean size of <1 Å dispersed in the sample (Fig. 1e and S6†), which should correspond to single-atom Co.To further verify the single-atom Co structure in BM-PCN/Co-c, Co K-edge X-ray absorption near-edge structure spectroscopy (XANES) and extended X-ray absorption fine structure (EXAFS) analysis were performed. As shown in Fig. 2a, the absorption-edge position of BM-PCN/Co-c is quite close to that of CoO and their peak positions are similar and far from those of other reference samples, indicating that the valence of Co in BM-PCN/Co-c is about +2. The bonding structure around Co was determined by Fourier transformed (FT) k3-weighted EXAFS analysis. As shown in Fig. 2b, a distinct single Co-ligand peak at ∼1.6 Å for BM-PCN/Co-c is observed, which prominently differs from the Co–Co coordination peak at ∼2.2 Å for Co foil and the CoII–O coordination peak at ∼1.7 Å for CoO. The wavelet transform (WT) contour plot of BM-PCN/Co-c shows only one intensity maximum (Fig. S7†), and the Cl 2p core-level XPS spectrum of BM-PCN/Co-c reveals no residue of Cl (Fig. S8†). These further indicate the single-atom dispersion of Co species. Apparently, the Co-ligand peak is almost consistent with the CoII–N peak for Co porphyrin, suggesting that the single-atom Co in BM-PCN/Co-c mainly coordinates with N. Least-square EXAFS curve fitting was performed to confirm quantitative structural parameters of CoII in BM-PCN/Co-c, as shown in Fig. 2c, S9, and S10 and Table S1.† Simple Co–N single-shell fitting of BM-PCN/Co-c (Fig. S10†) gave a coordination number of 5.6 ± 0.4 (Table S1†), that is, CoII coordinates with five atoms. Considering that the PCN monolayer provides four appropriate N coordination sites at most,45 CoII likely coordinates with four N atoms and one OH atom. Thus, we further performed Co–N4/Co–O double-shell fitting (Fig. 2c) and the obtained R-factor (0.0011) remarkably reduces relative to that from Co–N single-shell fitting (0.0035), indicative of rationality of the proposed CoII–N4OH structure. Confirmed Co–N and Co–O bond lengths are 2.04 and 2.15 Å, respectively (Table S1†).Open in a separate windowFig. 2(a) Co K-edge XANES and (b) EXAFS spectra of Co foil, Co porphyrin (Copr), CoO, Co3O4, Co2O3, and BM-PCN/Co-c; EXAFS (c) R space-fitting and (inset in c) K space-fitting curves of BM-PCN/Co-c; (d) optimized structure of PCN and Co-doped PCN with different doping configurations and calculated formation energies (e) of Co doped PCN; and (e) Co 2p and (f) O 1s core-level XPS spectra of samples.To further confirm rationality of the Co–N4OH coordination structure, density functional theory (DFT) calculations were conducted. As shown in Fig. 2d, three possible CoII coordination structures in the PCN monolayer were explored. The Co–N4OH structure without removal of H from PCN exhibits a much lower formation energy (∼0.15 eV) than Co–N4 and Co–N3 structures with removal of two H atoms from PCN (∼2.51 and 3.55 eV), demonstrating a high probability of existence of the Co–N4OH structure in BM-PCN/Co-c. This structure can also be evidenced by X-ray photoelectron spectroscopy (XPS). As shown in Fig. 2e, the Co 2p core-level XPS spectrum of BM-PCN/Co-c shows two distinct peaks at binding energies of 796.8 and 781.4 eV beside satellite peaks, corresponding to Co 2p1/2 and 2p3/2 of CoII ions.46 The spectrum of BM-PCN/Co also shows two Co 2p peaks but at a binding energy ∼1.1 eV higher, suggesting variation of the Co coordination structure from BM-PCN/Co to BM-PCN/Co-c. PCN/Co-c exhibits no peaks because of its low Co content. Fig. 2f shows O 1s core-level spectra of PCN, BM-PCN, BM-PCN/Co-c, and PCN/Co-c. All the samples exhibit one peak at a binding energy of ∼532.0 eV, ascribed to surface hydroxyl species,47 but an additional peak could be obtained for BM-PCN or BM-PCN/Co-c after deconvolution. The peak at a binding energy of ∼531.3 eV for BM-PCN should be assigned to adsorbed H2O at new active adsorption sites generated by ball milling. This peak can also be observed in the spectrum of BM-PCN/Co, but with a ∼0.1 eV shift to a higher binding energy (Fig. S11†) owing to the influence of adsorbed CoII ions. The peak at ∼531.2 eV for BM-PCN/Co-c should be assigned to Co–OH,48 given that there is only one O 1s peak for BM-PCN-c (synthesized by direct calcination of BM-PCN) (Fig. S11†). The calculated Co/O(–Co) molar ratio, based on the XPS data, is ∼1.07 (Table S2†), close to 1, consistent with the Co–N4OH coordination structure.In C 1s and N 1s core-level XPS spectra, BM-PCN, BM-PCN/Co-c, PCN/Co-c, and BM-PCN/Co exhibit similar peaks to PCN (Fig. S12a–d†), indicative of their similar framework structure which can also be evidenced by their similar N/C molar ratios, 1.53 (Table S3†), but the N–H peak of BM-PCN shifts ∼0.2 eV to a lower binding energy relative to that of PCN, likely arising from the ball-milling induced destruction of intralayer hydrogen bonds (Fig. S13†). The Co content in BM-PCN/Co, BM-PCN/Co-c, and PCN/Co-c is too low to cause detectable variation of C 1s and N 1s peaks. Similar FT-IR absorption bands of the samples (Fig. S14a and b†) also indicate their basic frame structure, but in enlarged spectra (Fig. S14c†), ν(C–N) and ν(C N) absorption bands of BM-PCN shift 16 cm−1 to a higher wavenumber and 19 cm−1 to a lower wavenumber, respectively, relative to those of PCN at 1242 and 1640 cm−1,49 likely resulting from the ball-milling induced hydrogen bond destruction, and the shift of these two absorption bands turns smaller for BM-PCN/Co-c, suggesting calcination-induced reforming of the destroyed hydrogen bonds, which is consistent with the XPS results (Fig. S12c†). Besides, BM-PCN exhibits a wider and relatively stronger ν(N–H)/ν(O–H) absorption band than PCN (Fig. S14a†), probably owing to the hydrogen bond destruction and new adsorbed H2O, while this absorption band for BM-PCN/Co-c becomes much weaker, suggesting hydrogen bond reforming and loss of new adsorbed H2O (Fig. 2f). Zeta potentials of the samples dispersed in water reflect variation of surface adsorbed hydroxyl species. As shown in Fig. S15a,† all the samples exhibit negative zeta potentials because of dissociation of surface hydroxyl species. The zeta potentials, following the order PCN (−24 mV) > BM-PCN (−41 mV) < BM-PCN/Co-c (−30 mV) ≈ PCN/Co-c (−28 mV), suggest the ball milling-induced increase of surface hydroxyls in BM-PCN and calcination-induced decrease in BM-PCN/Co-c, consistent with the FT-IR results.Solid-state 13C magic-angle-spinning nuclear magnetic resonance (NMR) spectra of PCN, BM-PCN, BM-PCN/Co-c, and PCN/Co-c show two similar peaks at chemical shifts of ∼164 and 156 ppm (Fig. S15b†), ascribed to C−NHx and N C–N, respectively,50 indicating their similar molecular framework, but in enlarged spectra, BM-PCN exhibits ∼0.3° movement of the N C–N peak to a lower chemical shift compared with PCN, because of the ball-milling induced hydrogen bond destruction, and the C−NHx peak of BM-PCN/Co-c moves ∼0.2° to a lower chemical shift, likely owing to formation of the C–N–Co structure whose peak lies close to the C−NHx peak.51 The XRD patterns of the samples are shown in Fig. S15c.† PCN and PCN/Co-c exhibit typical diffraction peaks of melon-type carbon nitride with a layered orthorhombic structure and peaks at 13.1° and 27.6° correspond to (210) and (002) facets, respectively,13,52 but BM-PCN reveals remarkably decreased peak intensity and ∼0.2° shift of the (002) peak to a lower 2θ (indicative of the increased interlayer distance) relative to PCN, demonstrating the ball-milling induced hydrogen bond destruction and substantial decrease of crystallinity. The remarkable decrease of crystallinity and almost no change of the surface area of BM-PCN, compared with those of PCN, further suggest that ball milling may form massive thin nanosheets (Fig. 1c) most of which stack into compact particles (Fig. 1b) owing to their high surface energy. In comparison with BM-PCN, BM-PCN/Co-c exhibits a narrower (002) peak, suggesting enhanced crystallinity owing to the calcination-induced hydrogen bond reforming, consistent with the FT-IR results. On the whole, it is likely the ball-milling induced destruction of hydrogen bonds that contributes largely to the increase of surface energy and new active adsorption centers and thus Co2+ adsorption on BM-PCN.Optical absorption capability of samples was investigated by UV-vis diffuse reflectance spectroscopy (DRS). As shown in Fig. 3a, BM-PCN/Co-c, BM-PCN, and PCN/Co-c exhibit considerably higher, lower, and similar optical absorption than/to PCN, respectively. For BM-PCN/Co-c, the optical absorption enhancement at a wavelength of <400 nm may benefit from the electron-rich Co that enhances π–π* transitions in heptazine rings,53 and the Urbach tail absorption should arise from the Co–OH doping.54,55 Bandgaps (Eg) of PCN, BM-PCN, BM-PCN/Co-c, and PCN/Co-c were roughly confirmed as 2.70, 2.81, 2.56, and 2.73 eV, respectively, via the formula Eg/eV = 1240/(λed/nm)56 where λed is the absorption edge determined by solid lines in the spectra. The wider Eg of BM-PCN probably results from the quantum size effect of massive ultrathin crystal nanosheets (Fig. 1c) formed by ball milling, and the narrower Eg of BM-PCN/Co-c arises from the Co–OH doping that was then verified by DFT calculations. As shown in Fig. S16,† the calculated Eg of BM-PCN/Co-c, ∼1.90 eV, is much smaller than that of PCN (2.57 eV), in accordance with the experimental results. For PCN, the conduction band (CB) is contributed by C 2p and N 2p orbitals and the valence band (VB) mainly by N 2p orbitals, while for BM-PCN/Co-c, the CB is contributed by Co 3d, C 2p, and N 2p orbitals and the VB mainly by Co 3d and N 2p orbitals (Fig. S16c and d†), effectively manifesting that the narrowing of Eg of BM-PCN/Co-c results from the Co–OH doping. In addition, there are prominent doping levels (Ed) in the bandgap of BM-PCN/Co-c, mainly contributed by Co 3d and O 2p orbitals (Fig. S16d†), effectively proving the Co–OH doping effect in BM-PCN/Co-c. Similar calculation results have been reported for Pt–OH modified carbon nitride.57 Given that the experimental Co content (0.75 wt%) is much lower than the theoretical (6.71 wt%), practical doping levels in the bandgap may approach more to the VB. CB edges of the samples (ECB) could be roughly determined by using Mott-Schottky plots (Fig. S17†) and their Fermi levels (Ef) were subsequently confirmed based on VB-XPS spectra (Fig. S18†). Energy band levels of the samples are shown in Fig. 3b, and it seems that ball milling causes a slight downshift of the VB edge (EVB) of BM-PCN, favorable for photocatalytic water splitting, but the Co–OH doping causes a slight downshift of ECB and upshift of EVB of BM-PCN/Co-c. It is noteworthy that the Ed close to the VB edge (EVB) can capture photogenerated holes58 and thus the single-atom Co–OH works as the active site for the OER (Fig. 3b).Open in a separate windowFig. 3(a) UV-vis diffuse reflectance spectra of PCN, BM-PCN, BM-PCN/Co-c, and PCN/Co-c; (b) energy band levels of the samples and schematic illustration for water oxidation on BM-PCN/Co-c; (c) photoluminescence spectra, (d) time-resolved fluorescence spectra, and (e) anodic photocurrent (Ja) response of the samples; and (f) EPR spectra of the samples in the dark and under visible light irradiation. Data in (d) are the results of fitting decay curves to a tri-exponential model. Dark Ja in (e) was set as zero for distinct comparison.Spectroscopy and photoelectrochemical tests were conducted to evaluate photogenerated charge separation and transfer performance. As shown in Fig. 3c, photoluminescence (PL) spectra of all the samples show one emission peak, basically corresponding to their bandgap emission. BM-PCN exhibits weaker PL intensity than PCN, revealing a decreased photogenerated charge recombination efficiency, which originates from faster charge transfer from the inside to the surface of ultrathin nanosheets (Fig. S19†) and trapped by surface states.59 BM-PCN/Co-c exhibits the lowest PL intensity and the PL intensity of PCN/Co-c is lower than that of PCN, which arises from the Ed capturing photogenerated holes to reduce their direct recombination with electrons beside the ultrathin nanosheet effect in BM-PCN/Co-c. Fig. 3d shows time-resolved fluorescence spectra of the samples. Decay curves were well fitted to a tri-exponential model (S3) and the obtained results are shown in Fig. 3d. Three lifetimes (τ1–τ3) and their mean lifetime (τm, 89.2 ns) of BM-PCN are all much longer than those of PCN (τm = 17.9 ns), further suggesting the faster charge transfer from the inside to the surface of ultrathin nanosheets in BM-PCN, decreasing the direct charge recombination efficiency, but with subsequent surface radiative recombination.60 Interestingly, the τ1–τ3 and τm (10.8 ns) of BM-PCN/Co-c are much shorter than those of PCN, which should result from faster transfer of holes to Ed that effectively decreases the charge recombination efficiency, with subsequent nonradiative energy transformation.61 The Co–OH doping effect also makes PCN/Co-c exhibit shorter τ1–τ3 and τm (16.5 ns) than PCN. Fig. 3e shows the photocurrent response of the samples. Their anodic photocurrent density follows the order PCN < PCN/Co-c < BM-PCN < BM-PCN/Co-c, indicating gradually increased photogenerated charge separation efficiencies,62 basically consistent with the PL results. The relatively high photocurrent response of BM-PCN benefits from the applied bias that effectively inhibits surface recombination of photogenerated charge carriers.To assess charge mobility of the samples, their electrochemical impedance spectroscopy (EIS) spectra were tested with high-frequency data simply fitted to an equivalent circuit (Fig. S20†). The obtained charge transfer resistance (Rct) follows the order PCN (26 Ω) > BM-PCN (18 Ω) ≈ PCN/Co-c (19 Ω) > BM-PCN/Co-c (13 Ω). Apparently, BM-PCN/Co-c exhibits smaller Rct than BM-PCN and PCN/Co-c, and PCN/Co-c exhibits smaller Rct than PCN, indicating the highest charge transfer performance of BM-PCN/Co-c63 which originates from the single-atom Co modification64 that may increase the electron density to facilitate charge transport. The smaller Rct of BM-PCN than that of PCN indicates the additional favorable effect of ultrathin nanosheets.65Fig. 3f shows electron paramagnetic resonance (EPR) spectra of the samples. All reveal one single Lorentzian line centered at a g of 2.0039, attributed to unpaired electrons in heptazine rings.66 In the dark, the EPR signal intensity follows the order PCN < BM-PCN < PCN/Co-c < BM-PCN/Co-c, and the stronger signal of BM-PCN than that of PCN results from formation of ultrathin nanosheets that enhances delocalization of unpaired electrons, while the stronger signal of BM-PCN/Co-c and PCN/Co-c mainly benefits from the Co doping that increases the delocalized electron density.67 Under visible light irradiation, the samples exhibit remarkable signal enhancement, following the sequence PCN < BM-PCN < PCN/Co-c < BM-PCN/Co-c, similar to that of the signal intensity in the dark, suggesting that the increase in the delocalized electron density facilitates charge photoexcitation. The high delocalized electron density favors charge transport, consistent with the EIS results, and the high photoexcited charge density benefits enhancement of photocatalytic activity.Photocatalytic OER activity of various samples was well evaluated using Ag+ as the sacrificial agent (Fig. S21†). The Co content in BM-PCN/Co-c was optimized according to the photocatalytic OER rates and BM-PCN-c exhibits no detectable OER activity (Fig. S22†), indicating indispensability of the Co–OH structure for the OER. The influence of the calcination temperature (Tc °C) of BM-PCN/Co on OER rates of BM-PCN/Co-c (Tc = 460) and BM-PCN/Co-cTc was investigated and BM-PCN/Co-c exhibits the highest photoactivity (Fig. 4a), manifesting that the optimal calcination temperature is 460 °C. Under both simulated solar light and visible light irradiation (λ ≥ 420 nm), BM-PCN/Co-c exhibits substantially higher OER activity than PCN/Co-c (Fig. 4b), further suggesting the significance of the single-atom Co loading amount, and remarkably higher activity than common PCN/CoOx (with 0.75 wt% Co, obtained via photodeposition) and BM-PCN-c/Co(OH)2 (with 0.75 wt% Co), demonstrating the high efficacy of the single-atom distribution of Co–OH in BM-PCN/Co-c. Besides, urea was used as the feedstock to synthesize carbon nitride (marked as PCN-urea) with a larger surface area (76 m2 g−1 (ref. 68)) than PCN, and PCN-urea was further used to synthesize PCN-urea/Co-c similar to the synthesis of BM-PCN/Co-c. The OER activity of BM-PCN/Co-c is prominently higher than that of PCN-urea/Co-c (with the optimized Co content and Co single atom distribution, Fig. S23†), suggesting the significant role of ball milling in fabricating the single-atom Co–N4OH structure. To quantitively compare photoactivity of the samples, their mean OER rates under visible light illumination for 2 h are shown in Fig. 4c. The OER rate of BM-PCN/Co-c can reach ∼37.3 μmol h−1, about 13.8, 28.7, 2.6, and 2.0 times those of PCN/Co-c, PCN/CoOx, BM-PCN-c/Co(OH)2, and PCN-urea/Co-c, respectively. Comparatively, less N2 was generated for BM-PCN/Co-c (Fig. S24†), further demonstrating the significance of single-atom Co–OH modification.Open in a separate windowFig. 4(a) The influence of the calcination temperature (Tc °C) of BM-PCN/Co on photocatalytic OER activity of BM-PCN/Co-c (Tc = 460) and BM-PCN/Co-cTc, under Xe-lamp illumination, with AgNo3 as the sacrificial agent; (b) photocatalytic oxygen evolution on various samples under Xe-lamp illumination with or without using a 420-nm filter; (c) corresponding OER rates of the samples in 2 h; (d) photocatalytic OER rates of BM-PCN/Co-c under irradiation with various monochromatic light sources for 12 h; (e) apparent quantum yields (AQYs) of BM-PCN/Co-c at different wavelengths and reaction times and the highest AQY at every wavelength, along with the UV-DRS spectrum; and (f) proposed mechanism for photocatalytic water oxidation on the single-atom CoII-OH structure.Photocatalytic oxygen evolution on BM-PCN/Co-c was also tested under monochromatic light irradiation (Fig. S25†). Apparently, BM-PCN/Co-c can exhibit OER activity even at a wavelength of 500 nm. The mean OER rate in 12 h decreases from 1.85 to 0.54 μmol h−1 with increasing wavelengths from 400 to 500 nm (Fig. 4d), independent of light intensity of the Xe lamp and is mainly dependent on optical absorption capability of BM-PCN/Co-c at various wavelengths (Fig. 3a). Fig. 4e shows apparent quantum yields (AQYs) of BM-PCN/Co-c at different reaction times and wavelengths. Basically, there are maxima of AQYs with increasing reaction time at every wavelength, suggesting the adverse effect of excessive photodeposited Ag on surfaces of samples. These maxima are shown in Fig. 4e and accord well with the UV-vis DRS spectrum with increasing wavelengths. The maxima of AQYs at 400, 420, 450, and 500 nm can reach 4.69, 2.06, 1.07, and 0.46%, respectively. Compared with the reported photocatalytic OER results for PCN (Table S4†), BM-PCN/Co-c exhibits the top-class performance.To investigate chemical stability of BM-PCN/Co-c, the cyclic OER experiment was conducted. After five consecutive runs, OER rates of BM-PCN/Co-c decrease less (Fig. S26a†), with the morphology similar to the original (Fig. S26b†). Co single atoms in the sample could still be distinctly observed by HAADF-STEM (Fig. S26c and d†). In addition, N 1s core-level XPS spectra of BM-PCN/Co-c are almost similar before and after the cyclic experiment (Fig. S26e†). These indicate the high stability of the basic framework structure of the sample. However, Co 2p core-level spectra show remarkable differences before and after the experiment, not only the CoII peak shift, probably owing to ion (e.g., IO4−) adsorption, but also formation of a large amount of CoIII (Fig. S26f†). Coexistence of CoII/CoIII may suggest the photocatalytic OER mechanism.The proposed OER mechanism based on the Co–OH structure is shown in Fig. 4f, according to the reported results in Mn doped PCN.34 Four holes are needed to complete four oxidation steps and obtain one O2 molecule. The first step starting with one hole may involve formation of the CoIII O bond. The Co–N4OH structure should facilitate the water oxidation more compared with that of Co–N4 without OH coordination, by leaving out the initial adsorption process of H2O molecules.34 On the whole, the high photocatalytic OER activity of Co-PCN benefits from the Co–N4OH structure that not only effectively enhances optical absorption, and charge separation and transport, but also works as the highly active site for the OER. 相似文献
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Herein, we report for the first time single Au38 nanocluster reaction events of highly efficient electrochemiluminescence (ECL) with tri-n-propylamine radicals as a reductive co-reactant at the surface of an ultramicroelectrode (UME). The statistical analyses of individual reactions confirm stochastic single ones influenced by the applied potential.Herein, we report for the first time single Au38 nanocluster reaction events of highly efficient electrochemiluminescence (ECL) with tri-n-propylamine radicals as a reductive co-reactant at the surface of a Pt ultramicroelectrode (UME).Single entity measurements have been introduced by Bard and Wightman based on the collisions/reactions of individual nanoparticles and molecules at an ultramicroelectrode (UME).1–9 Since then, the field of single entity electrochemistry has gradually attracted several research groups and has become a frontier field of nanoelectrochemistry and electroanalytical chemistry.8,10–14 For instance, it has been shown that the chemistry of the electrode surface plays an important role in the collision/reaction events and the kinetics of reaction processes.15–21 Dasari et al. reported that hydrazine oxidation and proton reduction can be detected using single Pt nanoparticles on the surface of a mercury or bismuth modified Pt UME, and the material of the electrode was found to affect the shape of current–time transients.22,23 Fast scan cyclic voltammetry provides better chemical information about transient electrode–nanoparticle interactions, which is otherwise difficult to obtain with constant-potential techniques.24 There are only a few reports on photoelectrochemical systems including semiconductor nanoparticles designed to detect single nanoparticles in the course of photocatalysis processes.25–28 More importantly, owing to the nature of stochastic processes of single entity reactions, statistical analyses have shown substantial influences on the understanding of the underlying processes.Electrochemiluminescence or electrogenerated chemiluminescence (ECL),29 as a background-free technique,30–32 was also utilized to detect individual chemical reactions and single Pt nanoparticle collisions based on the reaction between the Ru(bpy)32+ complex and tri-n-propylamine (TPrA) radicals on the surface of an ITO electrode.2,33,34 It was found that the size of the nanoparticles, the origin of the interaction between particles and the electrode surface, the concentration of species generation, and the lifetime of individual electrogenerated nanocluster species (i.e., Au382+, Au383+, and Au384+) in conjunction with the reactivity of those oxidized species with co-reactant radical intermediates (i.e., TPrA radical) play crucial roles in the frequency of the ECL reaction events leading to individual ECL responses. More strikingly, a higher ECL reaction frequency is directly proportional to the amount of collected ECL light.21 Chen and co-workers also employed ECL to study stationary single gold-platinum nanoparticle reactivity on the surface of an ITO electrode.35 Lin and co-workers monitored the hydrogen evolution reaction in the course of “ON” and “OFF” ECL signals.36 Recently, we performed a systematic and mechanistic ECL study of a series of gold nanoclusters, with the general formula of Aun(SC2H4Ph)mz (n = 25, 38, 144, m = 18, 24, 60 and z = −1, 0, +1), where near-infrared (NIR) ECL emission was observed.37 There are several enhancement factors, such as catalytic loops38,39 that improve the signal to noise ratio. The Wightman group was able to report single ECL reactions based on the capability of ECL.7 Furthermore, thus far, we have explored ECL mechanisms and reported the ECL efficiency of five different gold nanoclusters i.e., Au25(SR)181−, Au25(SR)180, Au25(SR)181+, Au38(SR)240 and Au144(SR)600, among which the Au38(SR)240/TPrA system revealed outstanding ECL efficiency, ca. 3.5 times higher than that of Ru(bpy)32+/TPrA as a gold standard. Therefore, we decided to focus on the Au38 (SR)240/TPrA system. It was discovered that the ECL emission of these nanomaterials can be tuned through varying the applied potential and local concentration of the desired co-reactant.Herein, for the first time we report on ECL via a single Au38(SC2H4Ph)24 nanocluster (hereafter denoted as Au38 NC) reaction (eq. (1)) in the vicinity of an UME in the presence of TPrA radicals as a reductive co-reactant.1where x is the oxidation number that can be either 0, 1, 2, 3 or 4. Single ECL spikes (Fig. 1A) along with ECL spectroscopy were used for elucidating individual reaction events. Indeed, each single ECL spike demonstrates a single Au38(x−1)* reaction product. Au38 NCs were synthesized according to procedures reported by us and others, and fully characterized using UV-Visible-NIR, photoluminescence, 1HNMR spectroscopy and MALDI mass spectrometry to confirm the Au38 nanocluster synthesis (details are provided in ESI, Sections 1–3, Fig. S1–S4†).38,40,41Fig. 2 (left) shows a differential pulse voltammogram (DPV) in an anodic scan of a 2 mm Pt disc electrode immersed in 0.1 mM Au38 acetonitrile/benzene solution containing 0.1 M TBAPF6 as the supporting electrolyte. There are five discrete electrochemical peaks at which Au380 was oxidized to Au38+ (E°′ = 0.39 V), Au382+ (E°′ = 0.60 V), and Au383+/4+ (E°′ = 0.99 V) and reduced to Au38− (E°′ = −0.76 V) and Au382− (E°′ = −1.01 V).38,40,41Open in a separate windowFig. 1(A) An example of the reaction event transient of 10 μM Au38 in benzene/acetonitrile (1 : 1) containing 0.1 M TBAPF6 in the presence of 20 mM TPrA at 0.9 V vs. SCE, acquired at 15 ms time intervals using a 10 μm Pt UME. The white dashed-line indicates the threshold to identify single ECL spikes. (B) Illustration of a single nanocluster ECL spike. (C) ECL instrumentation with an inset showing ECL spike generation in the vicinity of the Pt UME.Open in a separate windowFig. 2Anodic DPV for Au38 (left), reaction energy diagram of Au382+ and TPrA· (middle) along with the ECL–voltage curve (right) in an anodic potential scan at a 2 mm Pt disk electrode immersed in a solution of 10 μM Au38 with 20 mM TPrA.The rich electrochemistry of Au38 NCs is well-matched with that of co-reactants such as TPrA to generate near infrared-ECL (NIR-ECL), and the ECL emission efficiency of the Au38/TPrA system is 3.5 times larger than that of the Ru(bpy)32+/TPrA co-reactant ECL system.27Thus, it is of utmost interest to investigate the ECL generation of the above co-reactant system in single reactions, which improves the ECL signal detection sensitivity. To perform the ECL experiment a solution of 10 μM Au38 NC with 20 mM TPrA was prepared. We first confirmed the ECL light generation of such solution along with its blank solution containing only TPrA using a typical 2 mm diameter Pt disk electrode (Fig. 2, S5 and S6†).A 10 μm Pt UME electrode, which is electrochemically inert (Fig. S7†), was utilized to investigate the ECL of single NC reactions under potentiostatic conditions, at which a specific positive bias potential was applied to oxidize both Au38 and TPrA. Fig. 1A shows a typical ECL–time transient current curve (ECL intensity versus time) at 0.90 V vs. SCE, which was acquired using a photomultiplier tube (PMT, R928) for a duration of 1800 s at data acquisition time intervals of 15 ms (Fig. 1C and ESI, Section 3†). Fig. 1B represents an exemplary event of a single ECL spike with a sharp increase followed by a decay in the ECL intensity. It is observed from the many spikes in Fig. 1B that this process can reoccur with a high probability in the vicinity of the UME, probably due to an electrocatalytic reaction loop (Fig. 1C). Indeed, ECL intensity was enhanced in this way as an already relaxed species, i.e., Au38z+1*, participates in an oxidation step to regenerate Au38z+1 to react with the TPrA radical (TPrA˙).Once photons resulting from the excited state relaxation in the vicinity of the UME are captured by the PMT, individual reaction events can be observed (Fig. 1A with the instrumentation schematic shown in Fig. 1C). As shown in Fig. 3A, there are many ECL spikes during 1800 s of measurement, each of which represents an individual ECL generation reaction in the vicinity of the UME surface. It is worth noting that there are several spikes with various intensities. This is most likely due to the Brownian motion which is random movement due to the diffusion of individual nanocluster species such as Au380, Au381+, Au382+, etc., electrogenerated at the local applied potentials. Long and co-workers42 proposed that silver nanoparticle collision on the surface of a gold electrode follows Brownian motion, leading to several types of surface-nanoparticle response peak shapes. In fact, the observed ECL spikes, shown in Fig. 1C, with a rise and an exponential decay suggested that Au38 nanocluster species diffuse directly through the electrode double-layer, move towards the tunneling region of the electrode surface, collide42 and become oxidized, react with TPrA radicals thereafter to produce excited states, and emit ECL. It is worth emphasizing that this path could be partially different for each individual nanocluster owing to the angle and direction relative to the electrode surface. The single Au38 NC reaction behaviour at various bias potentials was investigated following the electrochemical energy diagram shown in Fig. 2, middle. For example, at a bias potential of 0.70 V (the green spot on the DPV in Fig. 2), Au380 undergoes two successive oxidation reactions to Au382+ and TPrA oxidation and deprotonation start to generate TPrA·. In fact, at a very close oxidation potential to Au382+, TPrA is also oxidized to its corresponding cation radical (ca. 0.80 V vs. SCE) Fig. S6,† followed by deprotonation to form the TPrA radical.38 The TPrA· with a very high reduction power (E°′ = −1.7 eV)43 injects one electron to the LUMO orbital of the nanocluster and forms excited state Au38+*, as illustrated in the reaction energy diagram in Fig. 2, middle.38 Then, Au38+* emits ECL light while relaxing to the ground state. For another instance, at 1.10 V vs. SCE (the red spot on the DPV in Fig. 2), Au380 is oxidized to Au383/4+ feasibly. At this potential, the TPrA radical is generated massively in the vicinity of the electrode. The efficient electron transfer between the TPrA radical and Au383/4+ generates both Au382+* and Au383+* that emit light at the same wavelength of 930 nm.38 The results of such interactions produced a transient composed of many ECL events (Fig. 3A), which is an indication of bias potential enforcement on the nanocluster light emission.Open in a separate windowFig. 3Single-nanocluster ECL photoelectron spectroscopy of Au38. ECL–time transients (A), statistics of the number of photons (B), histogram of the single reaction time between sequential spikes (C) and accumulated ECL spectrum (D) for a 10 μm Pt UME at 1.1 V immersed in a 10 μM Au38 nanocluster solution in benzene/acetonitrile (1 : 1) containing 0.1 M TBAPF6 in the presence of 20 mM TPrA. (E)–(H) The counterpart plots to (A)–(D) for the UME biased at 0.7 V. # represents the number.We further tried to collect the current–time traces of such events; however, owing to the high background current originating from the high concentration of TPrA relative to that of the nanocluster, no noticeable spikes in the current were observed.In order to study the photochemistry and understand deeply the single nanocluster reactions, ECL–time transients were collected at different applied potentials (i.e., 0.7, 0.8, 0.9 and 1.1 V vs. SCE) as labelled in green, brown, purple, and red on the DPV in Fig. 2, respectively. The transients were further analysed using our home-written MATLAB algorithm adapted from that for nanopore electrochemistry.44 The population of individual events was identified by applying an appropriate threshold to discriminate ECL spikes from the noise as demonstrated in Fig. 1A. In fact, the applied algorithm also assisted us to learn about the raising time and intensity of each spike, as well as photons of individual spikes. For instance, Fig. 3A shows another typical transit for 1800 s at an UME potential bias of 1.1 V for the ECL events. Indeed, the integrated area of each peak, the charge of the photoelectrons at the PMT, is directly proportional to the number of photons emitted from individual reactions (see ESI, Section 5†). Basically, the PMT amplifies the collected single photon emitted in the course of light-to-photoelectron conversion (see ESI, Section 6 and Fig. S8†) and translates a single photon into photoelectrons. The extracted charge of each ECL reaction, QECL, was then converted to the corresponding number of photons by dividing by the gain factor, g, which is 1.55 × 106 (Fig. S8†), following eqn (2):2The histograms of the number of photons show a Gaussian distribution (Fig. 3B) with a reaction frequency of 53.5 ± 2.9 at E = 1.1 V, whereas at a lower potential of 0.7 V the reaction frequency drops to 18.5 ± 1.7 (Fig. 3F). This indicates that there is a three-fold lower reaction occurrence at the lower potential. The integration of the Gaussian fitting at 1.1 V and 0.7 V also reveals a three-fold drop from 3.3 × 105 to 1.2 × 105 photons over 1800 s.To further explore the effect of electrode potential bias on the single Au38 NCs ECL reaction, potentials lower than 1.1 and higher than 0.7 V, ca. 0.8 and 0.9 V (brown and purple labels in Fig. 2), were applied. In fact, the resulting ECL–time transients show a lower population of single spikes (Fig. S12A and ESI,†). The integrated Gaussian curve values support the ECL–time transient observations with ∼4.1 × 104 and ∼6.5 × 104 photons, respectively. In fact, it is unlikely that the PMT would get more than two events in the duration, owing to the following reasons: (i) it has been shown that only 5.5% of incoming photons can be effectively converted to photoelectron signals by our R928 PMT during our absolute efficiency calibration, ESI Section 6 and Fig. S8–S19†;45 (ii) spherical ECL emission is proven to be detected for a substantial small part upon examination of our detection system for the absolute ECL quantum efficiency;45 (iii) Au38 nanocluster ECL emissions occur at 930 nm, which is almost at the wavelength detection limit of our PMT response curve.38,45In addition, we evaluated the stochastic (a series of random events at various probability distributions) nature of the observed events and extracted the reaction time interval (τ) at various potentials. The resulting graph shows an exponential decay (Fig. 3C) as expressed in eqn (3):3where frequency (λ) gives the mean rate of the event and A represents the fitting amplitude. One can expect to obtain the distribution of the number of emitted photons and spatial brightness function. In fact, the exponential decay is a clear indication of random single reaction events as Whiteman and co-workers described for a 9,10-diphenylanthracene (DPA) ECL system in the annihilation pathway.7,46 At a potential of 1.1 V, λ and A are found to be 4.98 ± 0.02 ms−1 and 80.4 ± 3.2, whereas at 0.7 V, λ and A turned out to be 32.9 ± 1.6 ms−1 and 9.5 ± 0.1 (Fig. 3C and G). Indeed, the lower potential of 0.70 V vs. SCE is high enough to generate the TPrA radical along with Au382+, thereby leading to excited Au38+*, Fig. 3E. One can conclude that at the applied potentials of 0.7 V and 1.1 V, Au380 is oxidized to Au382+ and Au384+, resulting in the generation of Au38+* and Au383+* under static conditions. Thus, there are higher populations of ECL spikes with no discrepancy in the number of collected photon distributions. However, at two intermediate potentials, i.e., 0.8 and 0.9 V, a dynamic behaviour which is due to the mixed oxidation of Au38 species, in the vicinity of the UME, is observed. In fact, at these two applied potentials, the local concentration of the corresponding gold nanoclusters (i.e., Au383+ and Au384+) is not sufficient to produce significant ECL spikes. We also attempted to collect the ECL spectrum using a charge-coupled device (CCD) camera, which is relatively more sensitive in the NIR region (e.g., λ > 900 nm, Fig. S16†). Fig. 3D and H display an accumulated spectrum at 1.1 and 0.7 V vs. SCE, which is collected for 30 minutes. The fitted accumulated ECL spectrum indicates an ECL peak emission at 930 nm and supports higher reactivity at 1.1 V than that at 0.7 V.38 To confirm that the observed ECL spikes and accumulated spectra are generated based on the oxidation of Au38 nanoclusters in the presence of TPrA radicals, ECL–time transients were recorded upon holding an applied potential at which no faradaic process occurs. Fig. S11† represents ECL–time curves and accumulated ECL spectra at 0.0 V and 0.4 V. One can notice that no appreciable ECL signal can be observed.In addition, we investigate the Pearson cross-correlation (ρ) between the intensities of ECL spikes with τ as shown in Fig. S14† in which there is a positive correlation at 0.7 and 1.0 V and a negative correlation at 0.8 and 0.9 V. In fact, ρ evaluates whether there is a stationary random process between the two defined parameters (see ESI, Section 6†). Interestingly, the frequency of the reaction at different applied potentials revealed decay from 0.7 to 0.8 V, followed by an upward trend to 0.9 and 1.1 V vs. SCE (Fig. S15†). This could be additional support for the transition stage at 0.8 and 0.9 V, where the applied potential as the major driving force to generate oxidized forms (e.g., Au383+ and Au384+) governs the flux of the nanocluster species that reach the vicinity of the electrode. Furthermore, the effectiveness of electron transfer reaction kinetics between the radical species, i.e., Au38z+1 and TPrA radical, competes with the flow of the incoming nanoclusters. It is worth mentioning that each of the ECL single event experiments was repeated three times, and very similar results were obtained. Moreover, lower (5 μM) and higher (20 μM) concentrations of Au38 in the presence of 20 mM were tested. In fact, the former shows a smaller number of single reactions; however the later revealed a larger number of multiple reactions (Fig. S13†).In summary, in this communication we demonstrated that Au38 NC ECL at the single reaction level can be monitored using a simple photoelectrochemical setup following a straightforward protocol. Indeed, we have rich basic knowledge about the ECL mechanisms of various gold nanoclusters with different charge states (Au25(SR)181+, Au25(SR)180, Au25(SR)181−) and various sizes (Au25(SR)180, Au38(SR)240, Au144(SR)600) in fine detail. Thus, the ECL emission mechanisms of gold clusters, including the contribution of each charge state and influence of various concentrations of co-reactants, are well known. For instance, in our previous studies38,39,47–49 we clearly identified three charge states of an Au25(SR)181−/TPrA system and we discovered that at a high concentration of TPrA the reduction in the bulk solution of gold nanoclusters influences the ECL emission wavelength. We also have learnt that the Au38/TPrA system is a co-reactant independent of co-reactant concentration. Furthermore, an extensively higher concentration of TPrA provides a dominant reaction over any unknown decomposition reaction at higher oxidation states of Au38. It was discovered that the population of ECL reactions is directly governed by the applied bias potential on a Pt UME. This work is a strong indication of the high sensitivity of the ECL technique in detecting single ECL reactions in a simple solution, which complements those reported by the Bard group using rubrene, for instance, embedded in an organic emulsion in the presence of TPrA or oxalate as a co-reactant.50,51 These systems needed a substantial ECL enhancement in the presence of an ionic liquid as the supporting electrolyte and emulsifier. The current approach can be further extended to investigate other molecules and nanomaterials'' electrocatalytic processes at the single reaction level. 相似文献
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Hlne Beucher Johannes Schrgenhumer Estíbaliz Merino Cristina Nevado 《Chemical science》2021,12(45):15084
A chelation-assisted oxidative addition of gold(i) into the C–C bond of biphenylene is reported here. The presence of a coordinating group (pyridine, phosphine) in the biphenylene unit enabled the use of readily available gold(i) halide precursors providing a new, straightforward entry towards cyclometalated (N^C^C)- and (P^C)-gold(iii) complexes. Our study, combining spectroscopic and crystallographic data with DFT calculations, showcases the importance of neighboring, weakly coordinating groups towards the successful activation of strained C–C bonds by gold.Pyridine and phosphine directing groups promote the C–C activation of biphenylene by readily available gold(i) halides rendering a new entry to (N^C^C)- and (P^C)-gold(iii) species.Activation of C–C bonds by transition metals is challenging given their inertness and ubiquitous presence alongside competing C–H bonds.1 Both the intrinsic steric hindrance as well as the highly directional character of the p orbitals involved in the σC–C bond impose a high kinetic barrier for this type of processes.2,3 Biphenylene, a stable antiaromatic system featuring two benzene rings connected via a four-membered cycle, has found widespread application in the study of C–C bond activation. Since the seminal report from Eisch et al. on the oxidative addition of a nickel(0) complex into the C–C bond of biphenylene,4 several other late transition metals have been successfully applied in this context.5 Interestingly, despite the general reluctance of gold(i) to undergo oxidative addition,6 its oxidative insertion into the C–C bond of biphenylene was demonstrated in two consecutive reports by the groups of Toste7a and Bourissou,7b respectively. The high energy barrier associated with the oxidation of gold could be overcome by the utilization of gold(i) precursors bearing ligands that exhibit either a strongly electron-donating character (e.g. IPr = [1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene])7a or small bite angles (e.g. DPCb = diphosphino-carborane).7b,8 In line with these two approaches, more sophisticated bidentate (N^C)- and (P^N)-ligated gold(i) complexes have also been shown to aid the activation of biphenylene at ambient temperature (Scheme 1a).7c,dOpen in a separate windowScheme 1(a) Previous reports on oxidative addition of ligated gold(i) precursors onto biphenylene. (b) This work: pyridine- and phosphine-directed C–C bond activation of biphenylene by commercially available gold(i) halides.In this context, we hypothesized that the oxidative insertion of gold(i) into the C–C bond of biphenylene could be facilitated by the presence of a neighboring chelating group.9 This approach would not only circumvent the need for gold(i) precursors featuring strong σ-donor or highly tailored bidentate ligands but also offer a de novo entry towards interesting, less explored ligand templates. However, recent work by Breher and co-workers showcased the difficulty of achieving such a transformation.10Herein, we report the oxidative insertion of readily available gold(i) halide precursors into the C–C bond of biphenylene. The appendage of both pyridine and phosphine donors in close proximity to the σC–C bond bridging the two aromatic rings provides additional stabilization to the metal center and results in a de novo entry to cyclometalated (N^C^C)- and (P^C)gold(iii) complexes (Scheme 1b).Our study commenced with the preparation of 5-chloro-1-pyridino-biphenylene system 2via Pd-catalyzed Suzuki cross coupling reaction between 2-bromo-3-methylpyridine and 2-(5-chlorobiphenylen-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 1 (Scheme 2).11 To our delight, the reaction of 2 with gold(i) iodide in toluene at 130 °C furnished complex κ3-(N^C^C)Au(iii)–I 3 in 60% yield.12,13 Complex 3 was isolated as yellow plate-type crystals from the reaction mixture and its molecular structure was unambiguously assigned by NMR spectroscopy, high-resolution mass spectrometry (HR-MS) and crystallographic analysis. Complex 3 exhibits the expected square-planar geometry around the metal center, with a Au–I bond length of 2.6558(3) Å.14 The choice of a neutral weakly bound gold(i)-iodide precursor is key for a successful reaction outcome: similar reactions in the presence of [(NHC)AuCl + AgSbF6] failed to deliver the desired biscyclometalation adducts, as reported by Breher et al. in ref. 10. The oxidative insertion of gold(i) iodide into the four-membered ring of pyridino-substituted biphenylene provides a novel and synthetically efficient entry to κ3-(N^C^C)gold(iii) halides. These species have recently found widespread application as precursors for the characterization of highly labile, catalytically relevant gold(iii) intermediates,15a–d as well as for the preparation of highly efficient emitters in OLEDs.15e–g Previous synthetic routes towards these attractive biscyclometalated gold(iii) systems involved microwave-assisted double C–H functionalization reactions that typically proceed with low to moderate yields.15aOpen in a separate windowScheme 2Synthesis of complex 3via oxidative addition of Au(i) into the C–C bond of pyridine-substituted biphenylene. X-ray structures of complex 3 with atoms drawn using 50% probability ellipsoids. Hydrogen atoms have been omitted for clarity. Additional selected bond distances [Å]: N–Au = 2.126(2), C1–Au = 1.973(2), C2–Au = 2.025(2), Au–I = 2.6558(3) and bond angles [deg]: N–Au–I = 99.25(6), N–Au–C1 = 79.82(9), C1–Au–C2 = 81.2(1), C2–Au–I = 99.73(8). For experimental details, see ESI.†Encouraged by the successful results obtained with the pyridine-substituted biphenylene and considering the prominent use of phosphines in gold chemistry,6,16 we wondered whether the same reactivity would be observed for a P-containing system. To this end, both adamantyl- and tert-butyl-substituted phosphines were appended in C1 position of the biphenylene motif. Starting from 5-chlorobiphenylene-1-carbaldehyde 4, phosphine-substituted biphenylenes 5a and 5b could be accessed in 3 steps (aldehyde reduction to the corresponding alcohol, Appel reaction and nucleophilic displacement of the corresponding benzylic halide) in 64 and 57% overall yields, respectively.13 The reactions of 5a and 5b with commercially available gold(i) halides (Me2SAuCl and AuI) furnished the corresponding mononuclear complexes 7a–b and 8a–b, respectively (Scheme 3).13 All these complexes were fully characterized and the structures of 7a, 7b and 8a were unambiguously characterized by X-ray diffraction analysis.13 Interestingly, the nature of the halide has a clear effect on the chemical shift of the phosphine ligand so that a Δδ of ca. 5 ppm can be observed in the 31P NMR spectra of 7a–b (Au–Cl) compared to 8a–b (Au–I), the latter being the more deshielded. The Au–X bond length is also impacted, with a longer Au–I distance (2.5608(1) Å for 8a) compared to that measured in the Au–Cl analogue (2.2941(7) Å for 7a) (Δd = 0.27 Å).13Open in a separate windowScheme 3Synthesis and reactivity of complexes 7a–b, 8a–b, 9 and 10. X-ray structure of complexes 11b, 12 and 14 with atoms drawn using 50% probability ellipsoids. Hydrogen atoms have been omitted for clarity. For experimental details and X-ray structures see ESI.†Despite numerous attempts to promote the C–C activation in these complexes,10,13 all reactions resulted in the formation of highly stable cationic species 11a–b and 12, which could be easily isolated from the reaction media. In the case of cationic mononuclear-gold(i) complexes 11, a ligand scrambling reaction in which the chloride ligand is replaced by a phosphine in the absence of a scavenger, a process previously described for gold(i) species, can be used to justify the reaction outcome.17 The formation of dinuclear gold complex 12 can be ascribed to the combination of a strong aurophilic interaction between the two gold centers (Au–Au = 2.8874(4) Å) and the stabilizing η2-coordination of the metal center to the aromatic ring of biphenylene. Similar η2-coordinated gold(i) complexes have been reported but, to the best of our knowledge, only as mononuclear species.18Taking into consideration the observed geometry of complexes 7a–b in the solid state,13 the facile formation of stable cationic species 11 and 12 and the lack of reactivity of the gold(i) iodides 8a–b, we hypothesized that the free rotation around the C–P bond was probably restricted, placing the gold(i) center away from the biphenylene system and thus preventing the desired oxidative insertion reaction. To overcome this problem, we set out to elongate the arm bearing the phosphine unit with an additional methylene group, introduced via a Wittig reaction from compound 4 to yield ligand 6, prepared in 4 steps in 27% overall yield. Coordination with Me2SAuCl and AuI resulted in gold(i) complexes 9 and 10, respectively (Scheme 3). The structure of 9 was unambiguously assigned by X-ray diffraction analysis and a similar environment around the metal center to that determined for complex 7a was observed for this complex.13With complexes 9 and 10 in hand, we explored their reactivity towards C–C activation of the four-membered ring of biphenylene.19 After chloride abstraction and upon heating at 100 °C for 5 hours, ring opening of the biphenylene system was observed for complex 9. Interestingly, formation of mono-cyclometalated adduct 13 was exclusively observed (the structure of 13 was confirmed by 1H, 13C, 31P, 19F, 11B and 2D NMR spectroscopy and HR-MS).13 The solvent appears to play a major role in this process, as performing the reaction in non-chlorinated solvents resulted in stable cationic complexes similar to 11.13,20,21 The presence of adventitious water is likely responsible for the formation of the monocyclometalated (P^C)gold(iii) complex 13 as when the reaction was carried out in C2H4Cl2 previously treated with D2O, the corresponding deuterated adduct 13-d could be detected in the reaction media. These results showcase the difficulties associated with the biscyclometalation for P-based complexes as well as the labile nature of the expected biscyclometalated adducts. Interestingly though, these processes can be seen as a de novo entry towards relatively underexplored (P^C)gold(iii) species.22The C–C activation was further confirmed by X-ray diffraction analysis of the phosphonium salt 14, which arise from the reductive elimination at the gold(iii) center in 13 upon exchange of the BF4− counter-anion with the weakly coordinating sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF).13,23 The phosphorus atom is four-coordinate, with weak bonding observed to the distant counter-anion and a distorted tetrahedral geometry (C1–P–C2 = 95.05(17), C2–P–C3 = 112.1(1), C3–P–C4 = 116.6(1), C4–P–C1 = 107.4(2) deg). These results represent the third example in which the C(sp2)–P bond reductive elimination at gold(iii) has been reported.24Further, it is important to note that, in contrast to the reactivity observed for the pyridine-substituted biphenylene, neither P-coordinated gold(i) iodo complexes 8a, 8b nor 10 reacted to give cyclometalated products despite prolonged heating, which highlights the need for highly reactive cationized gold(i) species to undergo oxidative addition when phosphine ligands are flanking the C–C bond.13To get a deeper understanding on the observed differences in reactivity for the N- vs. P-based directing groups, ground- and transition-state structures for the oxidative insertion of gold(i) halides in C1-substituted biphenylenes were computed by DFT calculations. The reactions of Py-substituted 2 with AuI to give 3 (I) and those of P-substituted 7a (II) and 9 (III) featuring the cationization of the gold(i) species were chosen as models for comparative purposes with the experimental conditions (Fig. 1 and S1–S10 in the ESI†).25–27 The computed activation energies for the three processes are in good agreement with the experimental data. The pyridine-substituted biphenylene I exhibits the lowest activation barrier for the oxidative insertion process (ΔG‡ = 34.4 kcal mol−1). The reaction on the phosphine-substituted derivatives II and III proved to be, after cationization of the corresponding gold(i) halide complexes (II-BF4, III-BF4) higher in energy (ΔG‡ = 39.6 and 46.3 kcal mol−1 respectively), although the obtained values do not rule out the feasibility of the C–C activation process. The transition state between I and I′ exhibits several interesting geometrical features: (a) the biphenylene is significantly bent, (b) the cleavage of the C–C bond is well advanced (dC–C = 1.898 Å in TSIvs. dC–C = 1.504 Å in I), and (c) the two C and the I atoms form a Y-shape around gold with minimal coordination from the pyridine (dN–Au = 2.742 Å in TSIvs. dN–Au = 2.093 Å in I and 2.157 Å in I′, respectively). The transition-state structures found for the P-based ligands (TSII and TSIII) also show an elongation of the C–C bond and display a bent biphenylene. However, much shorter P–Au distances (dP–Au = 2.330 Å for TSII and 2.314 Å for TSIII) can be observed compared to the pyridine-based system, as expected due to the steric and electronic differences between these two coordinating groups. Analogously, longer C–Au distances were also found for the P-based systems (dC1–Au = 2.152 Å for TSIvs. 2.235 Å and 2.204 Å for TSII and TSIII; dC2–Au = 2.143 Å for TSIvs. 2.219 Å and 2.162 Å for TSII and TSIII), with a larger deviation of square planarity for Au in TSIII compared to TSII.28,29 These results suggest that, provided the appropriate distance to the C–C bond is in place, the strong coordination of phosphorous to the gold(i) center does not prevent the C–C activation of biphenylene but other reactions (i.e. formation of diphosphine gold(i) cationic species, protodemetalation) can outcompete the expected biscyclometalation process. In contrast, a weaker donor such as pyridine offers a suitable balance bringing the gold in close proximity to the C–C bond and enables both the oxidative cleavage as well as the formation of the double metalation product.Open in a separate windowFig. 1Energy profile (ΔG and ΔG‡ in kcal mol−1), optimized structures, transition states computed at the IEFPCM (toluene/1,2-dichloroethane)-B3PW91/DEF2QZVPP(Au,I)/6-31++G(d,p)(other atoms) level of theory for the C–C activation of biphenylene with gold(i) iodide from I and gold(i) cationic from II and III. Computed structures of the transition states (TSI, TSII and TSIII) and table summarizing relevant distances. 相似文献
10.
CF2H groups are unique due to the combination of their lipophilic and hydrogen bonding properties. The strength of H-bonding is determined by the group to which it is appended. Several functional groups have been explored in this context including O, S, SO and SO2 to tune the intermolecular interaction. Difluoromethyl ketones are under-studied in this context, without a broadly accessible method for their preparation. Herein, we describe the development of an electrochemical hydrodefluorination of readily accessible trifluoromethylketones. The single-step reaction at deeply reductive potentials is uniquely amenable to challenging electron-rich substrates and reductively sensitive functionality. Key to this success is the use of non-protic conditions enabled by an ammonium salt that serves as a reductively stable, masked proton source. Analysis of their H-bonding has revealed difluoromethyl ketones to be potentially highly useful dual H-bond donor/acceptor moieties.The electrochemical hydrodefluorination of trifluoromethylketones under non-protic conditions make this single-step reaction at deeply reductive potentials uniquely amenable to challenging electron-rich substrates and reductively sensitive functionalities.The difluoromethyl group (CF2H) has attracted significant recent attention in medicinal chemistry,1,2 which complements the well-documented importance and growing use of fluorine in small molecule pharmaceuticals.3–6 The CF2H group is an H-bond donor7,8 that is also lipophilic,9,10 a unique combination that positions it as an increasingly valuable tool within drug-discovery.11 CF2H has been used as a bioisostere of OH and SH in serine and cystine moieties, respectively, as well as NH2 groups, where greater lipophilicity and rigidity provide advantages to pharmacokinetics and potency.12–14The hydrogen-bond acidity of CF2H groups is exceptionally dependent on the atom or group to which it is appended (Fig. 1A).1,2 The H-bond acidity of alkyl-CF2H groups is half that of O–CF2H and even a quarter of SO2–CF2H groups.1 This mode of control allows the H-bonding strength and, therefore its function, to be finely tuned. While much research has focused on the synthesis, behaviour and use of XCF2H groups, where X = O, S, SO, SO2, Ar, it is surprising that the corresponding carbonyl containing moiety (X = CO) has remained relatively elusive in these contexts. Not only would difluoromethyl ketones (DFMK) be expected to provide a relatively strong H-bond, but the carbonyl unit provides a complementary, yet proximal mode of intermolecular interaction (Fig. 1B). Indeed, the dual action of neighbouring H-bond donor and acceptor functionalities provides the fundamental basis for many biological systems, including in the secondary structure assembly mechanisms for proteins and DNA/RNA nucleobase pairing, as well as in enzyme/substrate complexes. Indeed, the DFMK functionality has demonstrated important utility in biological applications, including anti-malarial and -coronaviral properties.15 Finally, the carbonyl provides a useful synthetic handle for further derivatization.Open in a separate windowFig. 1H-Bonding in DFMKs and their synthesis via hydrodefluorination.While some progress has been made on the synthesis of DFMKs,16 there still remains a need for a general and more broadly accessible route to their preparation. Current strategies for DFMK preparation require multi-step processes, expensive reagents, installation of activating groups, or are inherently low yielding.15a,16–25 The hydrodefluorination of trifluoromethyl ketones (1) potentially represents the most accessible strategy, as the starting materials are most readily prepared through a high-yielding trifluoroacetylation of C–H or C–X bonds.26–29 In 2001, Prakash demonstrated the viability of this approach using 2 equivalents of magnesium metal as stoichiometric reductant to drive the defluorination, with a second hydrolysis step (HCl (3–5 M) or fluoride, overnight stirring) to reveal the product.30 The scope in this 2-step process (6 substrates) reflects the limitations of using a reductant, such as Mg, that has a fixed reduction potential, as well as incompatibilities arising from Mg/halide exchange with aryl halides. Similar limitations with the use of electron-rich substrates were revealed in related contributions from Uneyama.31In order to access more electron-rich and reductively challenging substrates, such as those containing medicinally relevant heterocycles, we postulated that electrochemical reduction could be employed (Fig. 1C). Electrosynthesis is becoming an increasingly valuable enabling technology and has seen a recent resurgence due to the precise control, unique selectivity, and the potential scalability and sustainability benefits that it offers.32–36 This strategy would avoid the undesirable use of stoichiometric metals and the ‘deep-reduction’ potentials required are readily accessed by simply selecting the applied potential. Pioneering early work from Uneyama on the cathodic formation of silylenol ether intermediate 2, suggested this approach could be viable.37,38 The fundamental challenge in designing a practical, single-step process under highly reducing potentials (<−2.0 V vs. Fc/Fc+), is to avoid the reduction of the proton source, which would otherwise compete to generate H2 gas and leave the starting material untouched. Uneyama does not demonstrate hydrodefluorination, presumably due to this problem. Additional challenges posed by ‘deep-reduction’ include a lack of tolerance for reduction-sensitive functionality (alkene, C–X bonds etc.), low mass balance due to substrate decomposition and the undesirable use of sacrificial metal anodes.39 Solving these problems should provide generally applicable, safe and scalable conditions for the hydrodefluorination of readily accessible trifluoromethyl ketones (1).Given the electron-rich nature of indoles, their ubiquity in bioactive compounds, and their ease of functionalisation, we chose indole 1a as the model substrate for optimisation. The highly reductive potentials required will render it a challenging substrate, which should lead to more general conditions suitable for other important substrate classes. Indeed, when we applied the Mg conditions of Prakash to this substrate, no silyl enol ether intermediate (2a) was observed, nor product 3a, and the starting material remained completely untouched ( Entry Conditions different from above Reductant Proton source 1a a/% (2a) 3aa/% 1 Mg 0, THF, no electricity (Prakash conditions for3) Mg0 — 100 (0) n/a 2b Undivided cell, TBAPF6 Sacrificial Mg anode — 100 (0) n/a 3b Pb:C (cath:an), 0 oC, 30 mA (Uneyama conditions for2) TBABr (4 eq.) — 33 (32) 0 4b — TBABr (2 eq.) (a) Acetic acid; (b) oxalic acid. 51; 100 0; 0 5b — TBABr (2 eq.) Dimethylurea 82 0 6b — TBABr (2 eq.) TEAPF6 (4 eq.) 49 45 7 TMSCl (0 eq.) TBABr (2 eq.) TEAPF6 (4 eq.) 83 0 8b TMSCl (6 eq.) TBABr (2 eq.) TEAPF6 (4 eq.) 49 49 9c TMSCl (3 + 3 eq.) TBABr (2 eq.) TEAPF 6 (4 eq.) 0 97 10c Entry 9, but Pt:Gr (cath:An) TBABr (2 eq.) TEAPF6 (4 eq.) 0 94 11c Entry 9, but Ni:Pt (cath:An) TBABr (2 eq.) TEAPF6 (4 eq.) 0 83 12c Entry 9, but Stainless Steel:Pt (cath:An) TBABr (2 eq.) TEAPF6 (4 eq.) 0 85 13c Entry 9, but Gr:Pt (cath:An) TBABr (2 eq.) TEAPF6 (4 eq.) 0 18