IPr# Complexes-Highly-Hindered, Sterically-Bulky Cu(I) and Ag(I) N-Heterocyclic Carbenes: Synthesis, Characterization, and Reactivity.

Metal-N-heterocyclic carbene (M-NHC) complexes are well-known as an important class of organometallic compounds widely used in transition-metal catalysis. Taking into account that the steric hindrance around the metal center is one of the major effects in M-NHC catalysis, the development of new, sterically hindered M-NHC complexes is an ongoing interest in this field of research. Herein, we report the synthesis and characterization of exceedingly sterically hindered, well-defined, air- and moisture-stable Cu(I) and Ag(I) complexes, [Cu(NHC)Cl] and [Ag(NHC)Cl], in the recently discovered IPr# family of ligands that hinge upon modular peralkylation of anilines. The complexes in both the BIAN and IPr families of ligands are reported. X-ray crystallographic analyses and computational studies were conducted to determine steric effects, Frontier molecular orbitals, and bond orders. The complexes were evaluated in the model hydroboration of the alkynes. We identified [Cu(BIAN-IPr#)Cl] and [Ag(BIAN-IPr#)Cl] as highly reactive catalysts with the reactivity outperforming the classical IPr and IPr*. Considering the attractive features of well-defined Cu(I)-NHC and Ag(I)-NHC complexes, this class of sterically bulky yet wingtip-flexible complexes will be of interest for catalytic processes in various areas of organic synthesis and catalysis.

IPr*F - Highly Hindered, Fluorinated N-Heterocyclic Carbenes.

The introduction of fluorine atom has attracted considerable interest in molecular design owing to the high electronegativity and the resulting polarization of carbon-fluorine bonds. Simultaneously, sterically-hindered N-heterocyclic carbenes (NHCs) have received major interest due to high stabilization of the reactive metal centers, which has paved the way for the synthesis of stable and reactive organometallic compounds with broad applications in main group chemistry, inorganic synthesis and transition-metal-catalysis. Herein, we report the first class of sterically-hindered, fluorinated N-heterocyclic carbenes. These ligands feature variable fluorine substitution at the N-aromatic wingtip, permitting to rationally vary steric and electronic characteristics of the carbene center imparted by the fluorine atom. An efficient, one-pot synthesis of fluorinated IPr*F ligands is presented, enabling broad access of academic and industrial researchers to the fluorinated ligands. The evaluation of steric, electron-donating and π-accepting properties as well as coordination chemistry to Au(I), Rh(I) and Se is presented. Considering the unique properties of carbon-fluorine bonds, we anticipate that this novel class of fluorinated carbene ligands will find widespread application in stabilizing reactive metal centers.

Gold-catalysed amine synthesis by reductive hydroamination of alkynes with nitroarenes.

Amines are the most pivotal class of organic motifs in pharmaceutical compounds. Here we provide a blueprint for a general synthesis of amines by catalyst differentiation enabled by triple Au-H/Au+/Au-H relay catalysis. The parent catalyst is differentiated into a set of catalytically active species to enable triple cascade catalysis, where each catalytic species is specifically tuned for one catalytic cycle. This strategy enables the synthesis of biorelevant amine motifs by reductive hydroamination of alkynes with nitroarenes. Using this triple cascade approach, we have achieved exceptional functional group tolerance, enabling the use of bulk chemical feedstocks as coupling partners for the amination of both simple and complex alkynes (>100 examples), including those derived from pharmaceuticals, peptides and natural products (>30 examples). The isolation and full crystallographic characterization of gold hydride and hydride-bridged gold complexes has garnered insights into the catalyst differentiation process of fundamental organometallic gold hydride complexes.

Near-IR Emissive B-N Lewis Pair-Functionalized Anthracenes via Selective LUMO Extension in Conjugated Dimer and Polymer.

Acenes are attractive as building blocks for low gap organic materials with applications, for example, in organic light emitting diodes, solar cells, bioimaging and diagnostics. Previously, we have shown that modification of dipyridylanthracene via B-N Lewis pair fusion (BDPA) strongly redshifts the emission, while facilitating self-sensitized reactivity toward O2 to reversibly generate the corresponding endoperoxides. Herein, we report on the further expansion of the π-system of BDPA to a vinyl-substituted monomer, vinylene-bridged dimer, and a polymer with an average of 20 chromophores. The extension of π-conjugation results in largely reduced band gaps of 1.8 eV for the dimer and 1.7 eV for the polymer, the latter giving rise to NIR emission with a maximum at 731 nm and an appreciable quantum yield of 7 %. Electrochemical and computational studies reveal efficient delocalization of the lowest unoccupied molecular orbital (LUMO) along the pyridyl-anthracene-pyridyl axis, which results in effective electronic communication between BDPA units, selectively lowers the LUMO, and ultimately narrows the band gap. Time-resolved emission and transient absorption (TA) measurements offer insights into the pertinent photophysical processes. Extension of π-conjugation also slows down the self-sensitized formation of endoperoxides, while significantly accelerating the thermal release of singlet oxygen to regenerate the parent acenes.

Pushing the Limits of Organometallic Redox Chemistry with an Isolable Mn(-I) Dianion.

We report an incredibly reducing and redox-active Mn-I dianion, [Mn(CO)3(Ph2B(tBuNHC)2)]2- (NHC = N-heterocyclic carbene), furnished via 2e- reduction of the parent 16e- MnI complex with Na0 or K0. Cyclic voltammograms show a Mn0/-I redox couple at -3.13 V vs Fc+/0 in tetrahydrofuran (THF), -3.06 V in 1,2-dimethoxyethane, and -2.85 V in acetonitrile. The diamagnetic Mn-I dianion is stable in solution and solid-state at room temperature, tolerating a wide range of countercations ([M(2.2.2)crypt]+, [M(18-crown-6)]+, [nBu4N]+; M = Na, K). Countercation identity does not significantly alter 13C NMR spectral signatures with [nBu4N]+ and Na+, suggesting minimal ion pairing in solution. IR spectroscopy reveals a significant decrease in CO stretching frequencies from MnI to Mn-I (ca. 240 cm-1), consistent with a drastic increase in electron density at Mn. State-of-the-art DFT calculations are in excellent agreement with the observed IR spectral data. Moreover, the Mn-I dianion behaves as a chemical reductant, smoothly releasing 1e- or 2e- to regenerate the oxidized Mn0 or MnI species in solution. The reducing potential of [Mn(CO)3(Ph2B(tBuNHC)2)]2- surpasses the naphthalenide anion in THF (-3.09 V) and represents one of the strongest isolable chemical redox agents.

"Catch and release" of the CpN3 ligand using cobalt: dissociation, protonation, and C-H bond thermochemistry.

The coordination chemistry of an amine-rich CpN3 ligand has been explored with cobalt. We demonstrate that in the presence of NaCo(CO)4, the cationic precursor [CpN3]+ yields the complex CpN3CoI(CO)2. While 2e- oxidation generates new CoIII complexes such as [CpN3Co(NCMe)3]2+ and CpN3CoI2(CO), subsequent ligand loss is facile, generating free [CpN3]+ or the protonated dication [CpN3H]2+. We have structurally characterized both these ligand release products via single crystal X-ray diffraction and obtained thermochemical C-H bond strengths via experiment and density functional theory (DFT). Upon reversible 1e- reduction, the radical cation [CpN3H]˙+ has a weak C-H BDFE of 52 kcal mol-1 in acetonitrile. Mechanistic analysis shows that [CpN3H]˙+ undergoes radical-radical disproportionation in the absence of exogenous H-atom acceptors, which is supported by deuterium isotope labelling experiments. Structural comparison of these organic molecules shows a high degree of iminium-like electron delocalization over the C-N bonds connected to the central five-membered ring.

Organocatalytic Enantioselective [1,2]-Stevens Rearrangement of Azetidinium Salts.

The first organocatalyzed enantioselective [1,2]-Stevens rearrangement is reported. 4-Alkylideneproline derivatives are produced in up to 86% yield and in up to 90:10 er, with recrystallization enhancing er up to >99.5:0.5. Product configuration was opposite that predicted by existing stereochemical models for this organocatalyst class, and DFT calculations revealed a novel mode of asymmetric induction. The adaptability of this catalytic strategy for asymmetric [1,2]-Stevens rearrangements of other heterocyclic amines was demonstrated.

Crystal structure and analytical profile of 1,2-diphenyl-2-pyrrolidin-1-ylethanone hydrochloride or `α-D2PV': a synthetic cathinone seized by law enforcement, along with its diluent sugar, myo-inositol.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT-IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl-·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π-π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π-π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.

Accessing Ni(0) to Ni(IV) via nickel-carbon-phosphorus bond reorganization.

Two-electron oxidation of a NiIIPh(PCP) pincer complex initiates phosphine ligand insertion, generating an η6-arylphosphonium moiety coordinated to NiII. The reaction is fully reversible under reducing conditions. X-ray crystallography, NMR/EPR spectroscopy, electrochemistry, and DFT calculations support the proposed Ni-C-P bond reorganization mechanisms, which access oxidation states from Ni0 to NiIV.

Wingtip-Flexible N-Heterocyclic Carbenes: Unsymmetrical Connection between IMes and IPr.

IMes (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) and IPr (IPr=1,3- bis(2,6-diisopropylphenyl)imidazol-2-ylidene) represent by far the most frequently used N-heterocyclic carbene ligands in homogeneous catalysis, however, despite numerous advantages, these ligands are limited by the lack of steric flexibility of catalytic pockets. We report a new class of unique unsymmetrical N-heterocyclic carbene ligands that are characterized by freely-rotatable N-aromatic wingtips in the imidazol-2-ylidene architecture. The combination of rotatable N-CH2 Ar bond with conformationally-fixed N-Ar linkage results in a highly modular ligand topology, entering the range of geometries inaccessible to IMes and IPr. These ligands are highly reactive in Cu(I)-catalyzed ß-hydroboration, an archetypal borylcupration process that has had a transformative impact on the synthesis of boron-containing compounds. The most reactive Cu(I)-NHC in this class has been commercialized in collaboration with MilliporeSigma to enable broad access of the synthetic chemistry community. The ligands gradually cover %Vbur geometries ranging from 37.3 % to 52.7 %, with the latter representing the largest %Vbur described for an IPr analogue, while retaining full flexibility of N-wingtip. Considering the modular access to novel geometrical space in N-heterocyclic carbene catalysis, we anticipate that this concept will enable new opportunities in organic synthesis, drug discovery and stabilization of reactive metal centers.

[IPr#-PEPPSI]: A Well-Defined, Highly Hindered and Broadly Applicable Pd(II)-NHC (NHC = N-Heterocyclic Carbene) Precatalyst for Cross-Coupling Reactions.

In this Special Issue, "Featured Papers in Organometallic Chemistry", we report on the synthesis and characterization of [IPr#-PEPPSI], a new, well-defined, highly hindered Pd(II)-NHC precatalyst for cross-coupling reactions. This catalyst was commercialized in collaboration with MilliporeSigma, Burlington, ON, Canada (no. 925489) to provide academic and industrial researchers with broad access to reaction screening and optimization. The broad activity of [IPr#-PEPPSI] in cross-coupling reactions in a range of bond activations with C-N, C-O, C-Cl, C-Br, C-S and C-H cleavage is presented. A comprehensive evaluation of the steric and electronic properties is provided. Easy access to the [IPr#-PEPPSI] class of precatalysts based on modular pyridine ligands, together with the steric impact of the IPr# peralkylation framework, will facilitate the implementation of well-defined, air- and moisture-stable Pd(II)-NHC precatalysts in chemistry research.

ItOct (ItOctyl) - pushing the limits of ItBu: highly hindered electron-rich N-aliphatic N-heterocyclic carbenes.

ItBu (ItBu = 1,3-di-tert-butylimidazol-2-ylidene) represents the most important and most versatile N-alkyl N-heterocyclic carbene available in organic synthesis and catalysis. Herein, we report the synthesis, structural characterization and catalytic activity of ItOct (ItOctyl), C2-symmetric, higher homologues of ItBu. The new ligand class, including saturated imidazolin-2-ylidene analogues has been commercialized in collaboration with MilliporeSigma: ItOct, 929 298; SItOct, 929 492 to enable broad access of the academic and industrial researchers within the field of organic and inorganic synthesis. We demonstrate that replacement of the t-Bu side chain with t-Oct results in the highest steric volume of N-alkyl N-heterocyclic carbenes reported to date, while retaining the electronic properties inherent to N-aliphatic ligands, such as extremely strong σ-donation crucial to the reactivity of N-alkyl N-heterocyclic carbenes. An efficient large-scale synthesis of imidazolium ItOct and imidazolinium SItOct carbene precursors is presented. Coordination chemistry to Au(i), Cu(i), Ag(i) and Pd(ii) as well as beneficial effects on catalysis using Au(i), Cu(i), Ag(i) and Pd(ii) complexes are described. Considering the tremendous importance of ItBu in catalysis, synthesis and metal stabilization, we anticipate that the new class of ItOct ligands will find wide application in pushing the boundaries of new and existing approaches in organic and inorganic synthesis.

L-Shaped Heterobidentate Imidazo[1,5-a]pyridin-3-ylidene (N,C)-Ligands for Oxidant-Free AuI /AuIII Catalysis.

In the last decade, major advances have been made in homogeneous gold catalysis. However, AuI /AuIII catalytic cycle remains much less explored due to the reluctance of AuI to undergo oxidative addition and the stability of the AuIII intermediate. Herein, we report activation of aryl halides at gold(I) enabled by NHC (NHC=N-heterocyclic carbene) ligands through the development of a new class of L-shaped heterobidentate ImPy (ImPy=imidazo[1,5-a]pyridin-3-ylidene) N,C ligands that feature hemilabile character of the amino group in combination with strong σ-donation of the carbene center in a rigid conformation, imposed by the ligand architecture. Detailed characterization and control studies reveal key ligand features for AuI /AuIII redox cycle, wherein the hemilabile nitrogen is placed at the coordinating position of a rigid framework. Given the tremendous significance of homogeneous gold catalysis, we anticipate that this ligand platform will find widespread application.

Synthesis and Structure-Property Relationships in Regioisomeric Alternating Borane-Terthiophene Polymers.

Main-chain boron-containing π-conjugated polymers are attractive for organic electronic, sensing, and imaging applications. Alternating terthiophene-borane polymers were prepared and the effects of regioisomeric attachment of the conjugated linker and variations in the electronic effect of the pendent aryl groups (2,4,6-tri-tert-butylphenyl, Mes*; 2,4,6-tris(trifluoromethyl)phenyl, FMes) examined. Pd2 dba3 /P(t-Bu)3 -catalyzed Stille polymerization of arylbis(2-thienyl)borane and arylbis(3-thienylborane) with 2,5-bis(trimethylstannyl)thiophene at 120 °C gave polymers with appreciable molecular weight but MALDI-TOF MS analyses showed evidence of unusually prominent homocoupling. These defects could be suppressed by using brominated rather than iodinated monomers, more hindered 2,5-bis(tri-n-butylstannyl)thiophene as comonomer, and Pd2 dba3 /P(o-tol)3 as the catalyst at 100 °C. Under these conditions, macrocyclic species with n=3-10 repeating units formed preferentially according to MALDI-TOF MS analyses. Photophysical studies revealed a prominent effect of the regiochemistry and the nature of the pendent aryl groups on the absorption and emission, giving rise to orange, yellow-green, blue-green, and blue emissive materials respectively. The electronic effects were rationalized through DFT calculations on bis(terthiophene) model systems.

[Au(Np#)Cl]: Highly Reactive and Broadly Applicable Au(I)─NHC Catalysts for Alkyne π-Activation Reactions.

Cationic Au(I)─NHC (NHC = N-heterocyclic carbene) complexes have become an important class of catalysts for alkyne π-activation reactions in organic synthesis. In particular, these complexes are characterized by high stability of catalytic species engendered by strong σ-donation and metal backbonding. Herein, we report the synthesis and characterization of well-defined [Au(NHC)Cl] complexes featuring recently discovered IPr# family of ligands that hinge upon modular peralkylation of aniline. These ligands have been commercialized in collaboration with MilliporeSigma (IPr#: 915653; Np#: 915912; BIAN-IPr#: 916420). Evaluation of the [Au(NHC)Cl] complexes in a series of Au(I)─NHC-catalyzed π-functionalizations of alkynes, such as hydrocarboxylation, hydroamination and hydration, resulted in the identification of wingtip-flexible [Au(Np#)Cl] as a highly reactive and broadly applicable catalyst with the re-activity outperforming the classical [Au(IPr)Cl] and [Au(IPr*)Cl] complexes. The utility of this catalyst has been demonstrated in the direct late-stage derivatization of complex pharmaceuticals. Structural and computational studies were conducted to determine steric effects, frontier molecular orbitals and bond orders of this class of catalysts. Considering the attractive features of well-defined Au(I)─NHC complexes, we anticipate that this class of bulky and wingtip-flexible Au(I)─NHCs based on the modular peralkylated naphthylamine scaffold will find broad application in π-functionalization of alkynes in various areas of organic synthesis and catalysis.

A redox-active Mn(0) dicarbene metalloradical.

We report a rare redox-active Mn0 metalloradical [Mn(CO)3(Ph2B(tBuNHC)2)]- (NHC = N-heterocyclic carbene) with countercations [K(2.2.2)crypt]+, [Na(2.2.2)crypt]+, or [Li(DME)(12-crown-4)]+ (DME = 1,2-dimethoxyethane), all characterized via single crystal X-ray diffraction. Cyclic voltammograms reveal solvation-dependent MnI/0 redox potentials that are modeled using the Born equation.

CAAC-IPr*: easily accessible, highly sterically-hindered cyclic (alkyl)(amino)carbenes.

IPr* (IPr* = 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene) has emerged as a powerful highly hindered and sterically-flexible ligand platform for transition-metal catalysis. CAACs (CAAC = cyclic (al-kyl)(amino)carbenes) have gained major attention as strongly electron-rich carbon analogues of NHCs (NHC = N-heterocyclic carbene) with broad applications in both industry and academia. Herein, we report a merger of CAAC ligands with highly-hindered IPr*. The efficient synthesis, electronic characterization and application in model Cu-catalyzed hydroboration of alkynes is described. The ligands are strongly electron-rich, bulky and flexible around the N-Ar wingtip. The availability of various IPr* and CAAC templates offers a significant potential to expand the existing arsenal of NHC ligands to electron-rich bulky architectures with critical applications in metal stabilization and catalysis.

N-Heterocyclic Carbene Complexes of Nickel(II) from Caffeine and Theophylline: Sustainable Alternative to Imidazol-2-ylidenes.

Xanthines, such as caffeine and theophylline, are abundant natural products that are often present in foods. Leveraging renewable and benign resources for ligand design in organometallic chemistry and catalysis is one of the major missions of green and sustainable chemistry. In this Special Issue on Sustainable Organometallic Chemistry, we report the first nickel-N-heterocyclic carbene complexes derived from Xanthines. Well-defined, air- and moisture-stable, half-sandwich, cyclopentadienyl [CpNi(NHC)I] nickel-NHC complexes are prepared from the natural products caffeine and theophylline. The model complex has been characterized by x-ray crystallography. The evaluation of steric, electron-donating and π-accepting properties is presented. High activity in the model Suzuki-Miyaura cross-coupling is demonstrated. The data show that nickel-N-heterocyclic carbenes derived from both Earth abundant 3d transition metal and renewable natural products represent a sustainable alternative to the classical imidazol-2-ylidenes.

Near-Infrared-Absorbing B-N Lewis Pair-Functionalized Anthracenes: Electronic Structure Tuning, Conformational Isomerism, and Applications in Photothermal Cancer Therapy.

B-N-fused dianthracenylpyrazine derivatives are synthesized to generate new low gap chromophores. Photophysical and electrochemical, crystal packing, and theoretical studies have been performed. Two energetically similar conformers are identified by density functional theory calculations, showing that the core unit adopts a curved saddle-like shape (x-isomer) or a zig-zag conformation (z-isomer). In the solid state, the z-isomer is prevalent according to an X-ray crystal structure of a C6F5-substituted derivative (4-Pf), but variable-temperature nuclear magnetic resonance studies suggest a dynamic behavior in solution. B-N fusion results in a large decrease of the HOMO-LUMO gap and dramatically lowers the LUMO energy compared to the all-carbon analogues. 4-Pf in particular shows significant absorbance at greater than 700 nm while being almost transparent throughout the visible region. After encapsulation in the biodegradable polymer DSPE-mPEG2000, 4-Pf nanoparticles (4-Pf-NPs) exhibit good water solubility, high photostability, and an excellent photothermal conversion efficiency of ∼41.8%. 4-Pf-NPs are evaluated both in vitro and in vivo as photothermal therapeutic agents. These results uncover B-N Lewis pair functionalization of PAHs as a promising strategy toward new NIR-absorbing materials for photothermal applications.

Structures of the Most Twisted Thioamide and Selenoamide: Effect of Higher Chalcogens of Twisted Amides on N-C(X) Resonance.

Amide bond replacement with planar isosteric chalcogen analogues has an important implication for the properties of the N-C(X) linkage in structural chemistry, biochemistry and organic synthesis. Herein, we report the first higher chalcogen derivatives of non-planar twisted amides. The synthesis of twisted thioamide in a versatile system has been accomplished by direct thionation without cleavage of the σ N-C bond. The synthesis of twisted selenoamide has been accomplished by selenation with Woollins' reagent. The structures of higher chalcogen analogues of non-planar amides were unambiguously confirmed by X-ray crystallography. Reactivity studies were conducted to determine the effect of isologous N-C(O) to N-C(X) replacement on the properties of the amide linkage. Computational studies were employed to evaluate structural and energetic parameters of amide bond alteration in higher chalcogen amides. The study provides the first experimental evidence on the effect of chalcogen isologues on the structural and electronic properties of the non-planar amide N-C(X) linkage.