Copper Nitrene Research Articles

Chiral bis(pyrazolyl)methane copper(I) complexes and their application in nitrene transfer reactions

Abstract In this study, chiral bis(pyrazolyl)methane copper(I) acetonitrile complexes were applied to generate two novel terminal copper tosyl nitrene complexes with the nitrene generating agent SPhINTs in dichloromethane at low temperatures. The syntheses of the chiral bis(pyrazolyl)methane ligands are based on pulegone and camphor, members of the natural chiral pool. The chiral copper(I) acetonitrile complexes were applied as catalysts in the copper nitrene mediated aziridination reaction of different styrene derivatives and the C–H amination of various substrates. The reactions afforded good yields, but low enantiomeric excess under mild conditions. The nitrene species have been characterized with UV/Vis and EPR spectroscopy and the products of the decay by ESI mass spectrometry.

Stable, but still reactive – investigations on the effects of Lewis acid binding on copper nitrene intermediates

AbstractCopper nitrenes are proposed as reactive intermediates in a number of copper mediated aziridination and amination reactions. However, the isolation and characterization of such intermediates have proved challenging because of their transient nature. One successful approach for the stabilization of the copper‐nitrene cores is the employment of a redox innocent Lewis acid (LA) like Sc3+. We herein report the stabilization of two transient copper nitrene species 3 and 4 in the absence of LAs by employing electronegative −CF3 and −NO2 groups in the nitrene substituent. Detailed investigations of the spectroscopic properties of 3 and 4 by theoretical and experimental methods, and a comparison of their reactivities in presence and absence of LAs provide some vital insights into the effect of LAs on the geometric and electronic structures of the copper nitrenes.

A new generation of terminal copper nitrenes and their application in aromatic C-H amination reactions.

Copper nitrene complexes are highly reactive species and are known as intermediates in the copper catalyzed C-H amination. In this study, three novel copper tosyl nitrene complexes were synthesized at low temperatures, stabilized with heteroscorpionate ligands of the bis(pyrazolyl)methane family. The copper nitrenes were obtained by the reaction of a copper(i) acetonitrile complex with SPhINTs in dichloromethane. We show that the ligand design has a major influence on the catalytic activity and the thermal stability of the copper nitrene complex. Not only the choice of the third N donor, but also the substituent in the 5-position of the pyrazolyl moiety, have an impact on the stability. Furthermore, the novel copper nitrene complexes were used for catalytic aziridination of styrenes and C-H amination reactions of aromatic and aliphatic substrates under mild reaction conditions. Even challenging substrates like benzene and cyclohexane were aminated with good yields. The copper nitrene complexes were characterized using UV/Vis spectroscopy, low temperature Evans NMR spectroscopy, density functional theory, domain-based local pair natural orbital coupled cluster calculations (DLPNO-CCSD(T)) and cryo-UHR mass spectrometry.

Copper arylnitrene intermediates: formation, structure and reactivity.

The mechanism of oxidation of arylamines by copper enzymes is not clarified yet. Here, we explored a reaction between a possible high-valent copper(ii)-oxyl intermediate and arylamine. We have employed a TPA ligand (TPA = tris(2-pyridylmethyl)amine) with the NH2 group in position 2 of one of the pyridine rings (TPANH2). This model system allows generation of [(TPANH2)Cu(O)]+ in the gas phase, which immediately undergoes a reaction between the arylamino group and the copper oxyl moiety. The reaction leads to elimination of H2O and formation of a copper-nitrene complex. The structure of the resulting copper-nitrene complex was confirmed by infrared spectroscopy in the gas phase. We show that the copper-nitrene complex reacts by hydrogen atom transfer with 1,4-cyclohexadiene and by an order of magnitude faster by a double hydrogen atom transfer with ethanethiol and methanol. DFT calculations explain the formation of the copper nitrene as well as its reactivity in agreement with the experimental findings.

Synthesis of a copper-supported triplet nitrene complex pertinent to copper-catalyzed amination.

Terminal copper-nitrenoid complexes have inspired interest in their fundamental bonding structures as well as their putative intermediacy in catalytic nitrene-transfer reactions. Here, we report that aryl azides react with a copper(I) dinitrogen complex bearing a sterically encumbered dipyrrin ligand to produce terminal copper nitrene complexes with near-linear, short copper-nitrenoid bonds [1.745(2) to 1.759(2) angstroms]. X-ray absorption spectroscopy and quantum chemistry calculations reveal a predominantly triplet nitrene adduct bound to copper(I), as opposed to copper(II) or copper(III) assignments, indicating the absence of a copper-nitrogen multiple-bond character. Employing electron-deficient aryl azides renders the copper nitrene species competent for alkane amination and alkene aziridination, lending further credence to the intermediacy of this species in proposed nitrene-transfer mechanisms.

Catching a copper nitrene

Inorganic Chemistry Nitrogen typically forms three bonds in its stable compounds. If only one bond is available, the resultant electron-deficient nitrene can react rapidly with hydrocarbons to fill out its valence shell. Metal-stabilized nitrenes have been widely implicated in carbon-nitrogen bond-forming reactions, but the putative intermediates have rarely been synthesized directly. Carsch et al. now report preparation of a copper nitrene complex from an azide precursor. X-ray absorption and diffraction studies support a triplet electronic state that does not engage in multiple bonding with the copper center. Science , this issue p. [1138][1] [1]: /lookup/doi/10.1126/science.aax4423

Designed To React: Terminal Copper Nitrenes and Their Application in Catalytic C-H Aminations.

Heteroscorpionate ligands of the bis(pyrazolyl)methane family have been applied in the stabilisation of terminal copper tosyl nitrenes. These species are highly active intermediates in the copper-catalysed direct C-H amination and nitrene transfer. Novel perfluoroalkyl-pyrazolyl- and pyridinyl-containing ligands were synthesized to coordinate to a reactive copper nitrene centre. Four distinct copper tosyl nitrenes were prepared at low temperatures by the reaction with SO2 tBuPhINTs and copper(I) acetonitrile complexes. Their stoichiometric reactivity has been elucidated regarding the imination of phosphines and the aziridination of styrenes. The formation and thermal decay of the copper nitrenes were investigated by UV/Vis spectroscopy of the highly coloured species. Additionally, the compounds were studied by cryo-UHR-ESI mass spectrometry and DFT calculations. In addition, a mild catalytic procedure has been developed where the copper nitrene precursors enable the C-H amination of cyclohexane and toluene and the aziridination of styrenes.

Characterization and Reactivity Studies of a Terminal Copper–Nitrene Species

AbstractHigh‐valent terminal copper–nitrene species have been postulated as key intermediates in copper‐catalyzed aziridination and amination reactions. The high reactivity of these intermediates has prevented their characterization for decades, thereby making the mechanisms ambiguous. Very recently, the Lewis acid adduct of a copper–nitrene intermediate was trapped at −90 °C and shown to be active in various oxidation reactions. Herein, we describe for the first time the synthesis and spectroscopic characterization of a terminal copper(II)–nitrene radical species that is stable at room temperature in the absence of any Lewis acid. The azide derivative of a triazamacrocyclic ligand that had previously been utilized in the stabilization of aryl–CuIII intermediates was employed as an ancillary ligand in the study. The terminal copper(II)–nitrene radical species is able to transfer a nitrene moiety to phosphines and abstract a hydrogen atom from weak C−H bonds, leading to the formation of oxidized products in modest yields.

Characterization and Reactivity Studies of a Terminal Copper-Nitrene Species.

High-valent terminal copper-nitrene species have been postulated as key intermediates in copper-catalyzed aziridination and amination reactions. The high reactivity of these intermediates has prevented their characterization for decades, thereby making the mechanisms ambiguous. Very recently, the Lewis acid adduct of a copper-nitrene intermediate was trapped at -90 °C and shown to be active in various oxidation reactions. Herein, we describe for the first time the synthesis and spectroscopic characterization of a terminal copper(II)-nitrene radical species that is stable at room temperature in the absence of any Lewis acid. The azide derivative of a triazamacrocyclic ligand that had previously been utilized in the stabilization of aryl-CuIII intermediates was employed as an ancillary ligand in the study. The terminal copper(II)-nitrene radical species is able to transfer a nitrene moiety to phosphines and abstract a hydrogen atom from weak C-H bonds, leading to the formation of oxidized products in modest yields.

Copper catalysis in organic synthesis.

Copper is a very versatile transition metal that has been used as a building material by human civilizations for over 6000 years. Copper is also an essential element, responsible for important biological processes. The title of this Thematic Series published in the Beilstein Journal of Organic Chemistry is “Copper catalysis in organic synthesis”. A web of scienceTM topic search of “copper-catalyzed synthesis” indicated over 500 papers had been published in 2014. In point of fact, there has been a steady increase in publications on this topic since 1988. In the late 1980’s and early 1990’s, the topics centered on copper nitrene reactivity (e.g., aziridination), copper carbene chemistry, conjugate additions and cross-coupling reactions. Some of the most highly cited papers of all time on this topic are reviews on conjugate addition, cross-coupling, and [3 + 2] “Click” reaction applied to bioconjugation. The growth in copper-catalyzed organic reactions may be driven by a couple of factors. First, copper chemistry is incredibly diverse. Depending on its oxidation state, this metal can efficiently catalyze reactions involving both one and two-electron (radical and polar) mechanisms, or both. Copper coordinates easily to heteroatoms and to π-bonds and is well-known to activate terminal alkynes. The Ullman and Goldberg C–C and C–N cross-coupling reactions were discovered over a century ago and their development has really blossomed over the past twenty years. Second, copper is an earth-abundant metal, making its use more cost effective and more sustainable than precious transition metal catalysts. Over 25 contributions from leaders in the field of copper-catalysis from 7 countries make up this Thematic Series, “Copper catalysis in organic synthesis”. Contributions include authoritative reviews on the latest developments in copper-catalyzed Click applications, C–N cross-coupling, C–H functionalization, trifluoromethylations, asymmetric Ullmann and Goldberg couplings, asymmetric acetylide additions to carbonyl groups, radical alkylations and asymmetric conjugate additions as well as original contributions in the area of copper-catalyzed C–C cross-coupling, conjugate additions, allylic alkylations, alkene difunctionalizations, heterocycle synthesis, amide bond formation and photochemical Click reaction development. I am grateful to the contributors and the reviewers who participated in the production of this Thematic Series. It is clear from the impact copper catalysis has had on organic synthesis that copper should be considered a first line catalyst for many organic reactions. I anticipate further growth in the field in the years to come. Sherry R. Chemler Buffalo, November 2015

An Open‐Shell Spin Singlet Copper‐Nitrene Intermediate Binding Redox‐innocent Metal Ions: Influence of the Lewis Acidity of the Metal Ions on Spectroscopic and Reactivity Properties

AbstractThe yield of the Lewis acid adducts of a copper‐tosylnitrene intermediate and their decay are dependent on the Lewis acidity of the redox innocent metal ions. Surprisingly, however, their spectroscopic properties and reactivity in nitrene transfer reaction with PPh3 are independent of the nature of the Lewis acid used. The result provides some new insights into the structure and reactivity of the Lewis‐acid bound copper nitrene complexes.

Reaction of Alkynes and Azides: Not Triazoles Through Copper–Acetylides but Oxazoles Through Copper–Nitrene Intermediates

Well-defined copper(I) complexes of composition [Tpm*(,Br) Cu(NCMe)]BF4 (Tpm*(,Br) =tris(3,5-dimethyl-4-bromo-pyrazolyl)methane) or [Tpa(*) Cu]PF6 (Tpa(*) =tris(3,5-dimethyl-pyrazolylmethyl)amine) catalyze the formation of 2,5-disubstituted oxazoles from carbonyl azides and terminal alkynes in a direct manner. This process represents a novel procedure for the synthesis of this valuable heterocycle from readily available starting materials, leading exclusively to the 2,5-isomer, attesting to a completely regioselective transformation. Experimental evidence and computational studies have allowed the proposal of a reaction mechanism based on the initial formation of a copper-acyl nitrene species, in contrast to the well-known mechanism for the copper-catalyzed alkyne and azide cycloaddition reactions (CuAAC) that is triggered by the formation of a copper-acetylide complex.

Evidence of two-state reactivity in alkane hydroxylation by Lewis-acid bound copper-nitrene complexes.

The behavior of the Lewis-acid adducts of two copper-nitrene [Cu(NR)](+) complexes in nitrene-transfer and H-atom abstraction reactions have been demonstrated to depend on the nature of the nitrene substituents. Two-state reactivity, in which a singlet ground state and a nearby triplet excited-state both contribute, provides a useful model for interpreting reactivity trends of the two compounds.

Copper(ii) complexes incorporating poly/perfluorinated alkoxyaluminate-type weakly coordinating anions: Syntheses, characterization and catalytic application in stereoselective olefin aziridination

The synthesis and characterization of a series of cationic copper(II) complexes of the type [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) (R = CH(3), Ph; R' = CF(3), Ph, PhCH(3)), incorporating poly/perfluoronated alkoxyaluminates as weakly coordinating anions (WCAs) is presented. Aziridination of various olefins, such as the unreactive olefins e.g. ethylhex-2-enoate and 1-decene, with N-tosyliminophenyliodinane catalyzed by [Cu(NCR)(6)][Al(OC(CF(3))(2)R')(4)](2) affords very good yields (up to 96%) and high TOFs (up to 5000 h(-1)) under mild conditions. Using disubstituted olefins as substrates, high stereoselectivities are obtained at room temperature. The to date highest cis : trans ratio (98 : 2) of the obtained aziridines is achieved for cis-stilbene in good yield (85%) as well as promising TOF (> 2000 h(-1)). The investigation of the solvent effect on yield and selectivity reveals that for certain oleophilic substrates (1-decene), less polar solvents, such as dichloromethane are a better choice than acetonitrile, which is commonly considered as the best solvent for olefin aziridination. Accordingly, a mechanism involving a paramagnetic copper nitrene intermediate with both concerted and stepwise pathways is proposed.

Copper–Nitrene Complexes in Catalytic CH Amination

Copper–Nitrene Complexes in Catalytic CH Amination

Copper–Nitrene Complexes in Catalytic CH Amination

Copper–Nitrene Complexes in Catalytic CH Amination

Bonding and Structure of Copper Nitrenes

Copper nitrenes are of interest as intermediates in the catalytic aziridination of olefins and the amination of C-H bonds. However, despite advances in the isolation and study of late-transition-metal multiply bonded complexes, a bona fide structurally characterized example of a terminal copper nitrene has, to our knowledge, not been reported. In anticipation of such a report, terminal copper nitrenes are studied from a computational perspective. The nitrene complexes studied here are of the form (beta-diketiminate)Cu(NPh). Density functional theory (DFT), complete active space self-consistent-field (CASSCF) electronic structure techniques, and hybrid quantum mechanical/molecular mechanical (QM/MM) methods are employed to study such species. While DFT methods indicate that a triplet (S = 1) is the ground state, CASSCF calculations indicate that a singlet (S = 0) is the ground state, with only a small energy gap between the singlet and triplet. Moreover, the ground-state (open-shell) singlet copper nitrene is found to be highly multiconfigurational (i.e., biradical) and to possess a bent geometry about the nitrene nitrogen, contrasting with the linear nitrene geometry of the triplet copper nitrenes. CASSCF calculations also reveal the existence of a closed-shell singlet state with some degree of multiple bonding character for the copper-nitrene bond.

The Mechanism of the (Bispidine)copper(II)-Catalyzed Aziridination of Styrene: A Combined Experimental and Theoretical Study

Experimental and DFT-based computational results on the aziridination mechanism and the catalytic activity of (bispidine)copper(I) and -copper(II) complexes are reported and discussed (bispidine=tetra- or pentadentate 3,7-diazabicyclo[3.1.1]nonane derivative with two or three aromatic N donors in addition to the two tertiary amines). There is a correlation between the redox potential of the copper(II/I) couple and the activity of the catalyst. The most active catalyst studied, which has the most positive redox potential among all (bispidine)copper(II) complexes, performs 180 turnovers in 30 min. A detailed hybrid density functional theory (DFT) study provides insight into the structure, spin state, and stability of reactive intermediates and transition states, the oxidation state of the copper center, and the denticity of the nitrene source. Among the possible pathways for the formation of the aziridine product, the stepwise formation of the two N-C bonds is shown to be preferred, which also follows from experimental results. Although the triplet state of the catalytically active copper nitrene is lowest in energy, the two possible spin states of the radical intermediate are practically degenerate, and there is a spin crossover at this stage because the triplet energy barrier to the singlet product is exceedingly high.

Theoretical insights of copper(I)–nitrene complexes

Density functional theory has been used to study the geometries and character of the copper–nitrene complexes L n Cu N R ( 1, R = Me; 2, R = CO 2Me; 3, R = SO 2Me; 4, R = SO 2ph). Calculation results confirm that the copper–nitrene nitrogen bonds of the copper–nitrene complexes A2, B2, C2, and D2 (R=CO 2Me) show strong double-bonded character, and thus those of the copper–nitrene complexes A1, A3, A4, B1, B3, B4, C1, C3, C4, D1, D3, D4, E1, E2, E3, E4, F1, F2, F3, and F4 show single-bonded character. The copper–nitrene nitrogen bonds and the copper and nitrogen atoms of the bonds are the reactive center for the copper–nitrene complexes. The geometry, electronic structure, frontier orbitals (HOMO and LUMO), and molecular electrostatic potential (MEP) are discussed in detail.

Oxidation‐Resistant, Sterically Demanding Phenanthrolines as Supporting Ligands for Copper(I) Nitrene Transfer Catalysts.

AbstractFor Abstract see ChemInform Abstract in Full Text.