Fluorine in a C−F Bond as the Key to Cage Formation

Cage molecules have long been employed to trap reactive or transient species, as their rigid nature allows them to enforce situations that otherwise would not persist. In this Minireview, we discuss our use of rigid cage structures to investigate the close noncovalent interactions of fluorine with other functional groups and determine how mutual proximity affects both physical properties and reactivity. Unusual covalent interactions of fluorine are also explored: the cage can close to form the first solution‐phase C‐F‐C fluoronium ion.     

Initial Carbon−Carbon Bond Formation during the Early Stages of Methane Dehydroaromatization

Methane dehydroaromatization (MDA) is among the most challenging processes in catalysis science owing to the inherent harsh reaction conditions and fast catalyst deactivation. To improve this process, understanding the mechanism of the initial C?C bond formation is essential. However, consensus about the actual reaction mechanism is still to be achieved. In this work, using advanced magic‐angle spinning (MAS) solid‐state NMR spectroscopy, we study in detail the early stages of the reaction over a well‐dispersed Mo/H‐ZSM‐5 catalyst. Simultaneous detection of acetylene (i.e., presumably the direct C?C bond‐forming product from methane), methylidene, allenes, acetal, and surface‐formate species, along with the typical olefinic/aromatic species, allow us to conclude the existence of at least two independent C?H activation pathways. Moreover, this study emphasizes the significance of mobility‐dependent host–guest chemistry between an inorganic zeolite and its trapped organic species during heterogeneous catalysis.     

Late‐Stage Formation of Carbon–Fluorine Bonds

In this account, we review work from our lab on the development of methods for carbon–fluorine bond formation, with an emphasis on late‐stage fluorination of functionalized small molecules and synthesis of ¹⁸F‐labeled molecules for potential use as tracers in positron emission tomography (PET). We attempt to highlight reactions that we feel are of particular practical relevance, as well as areas of research where there is still significant room for advancement.     

Palladium‐Catalyzed Carbon–Fluorine and Carbon–Hydrogen Bond Alumination of Fluoroarenes and Heteroarenes

Through serendipitous discovery, a palladium bis(phosphine) complex was identified as a catalyst for the selective transformation of sp²C−F and sp²C−H bonds of fluoroarenes and heteroarenes to sp²C−Al bonds (19 examples, 1 mol % Pd loading). The carbon–fluorine bond functionalization reaction is highly selective for the formation of organoaluminium products in preference to hydrodefluorination products (selectivity=4.4:1 to 27:1). Evidence is presented for a tandem catalytic process in which hydrodefluorination is followed by sp²C−H alumination.     

Ruthenium(II)‐Catalyzed Traceless C−H Functionalization Using an N−N Bond as an Internal Oxidant

A previously elusive Ru^II‐catalyzed N?N bond‐based traceless C?H functionalization strategy is reported. An N‐amino (i.e., hydrazine) group is used for the directed C?H functionalization with either an alkyne or an alkene, affording an indole derivative or olefination product. The synthesis features a broad substrate scope, superior atom and step economy, as well as mild reaction conditions.     

Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group

A ruthenium(II)‐catalyzed asymmetric intramolecular hydroarylation assisted by a chiral transient directing group has been developed. A series of 2,3‐dihydrobenzofurans bearing chiral all‐carbon quaternary stereocenters have been prepared in remarkably high yields (up to 98 %) and enantioselectivities (up to >99 % ee). By this methodology, a novel asymmetric total synthesis of CB2 receptor agonist MDA7 has been successfully developed.     

Oxidative P−P Bond Addition to Cobalt(−I): Formation of a Low‐Spin Cobalt(III) Phosphanido Complex

The first homoleptic cobalt phosphanido complex [K(thf)₄][Co{1,2‐(Pt Bu₂)₂C₂B₁₀H₁₂}₂] ( 1 ) was prepared by an unprecedented oxidative P−P bond addition of an ortho ‐carborane‐substituted 1,2‐diphosphetane to cobalt(−I) in [K(thf)_0.2][Co(η⁴‐cod)₂)] (cod=1,5‐cycloctadiene). Compound 1 is a rare distorted tetrahedral 3d⁶ complex with a low‐spin ground state configuration. Magnetic measurements revealed that the complex is diamagnetic between 2 to 270 K in the solid state and at 298 K in [D₈]THF solution. Based on DFT calculations, the unusual singlet ground state is caused by the strong σ‐donor and moderate π‐donor properties of the bis(phosphanido) ligand.     

N−H Bond Formation at a Diiron Bridging Nitride

Despite their connection to ammonia synthesis, little is known about the ability of iron‐bound, bridging nitrides to form N?H bonds. Herein we report a linear diiron bridging nitride complex supported by a redox‐active macrocycle. The unique ability of the ligand scaffold to adapt to the geometric preference of the bridging species was found to facilitate the formation of N?H bonds via proton‐coupled electron transfer to generate a μ‐amide product. The structurally analogous μ‐silyl‐ and μ‐borylamide complexes were shown to form from the net insertion of the nitride into the E?H bonds (E=B, Si). Protonation of the parent bridging amide produced ammonia in high yield, and treatment of the nitride with PhSH was found to liberate NH₃ in high yield through a reaction that engages the redox‐activity of the ligand during PCET.     

Activating a Peroxo Ligand for C−O Bond Formation

Dioxygen activation for effective C?O bond formation in the coordination sphere of a metal is a long‐standing challenge in chemistry for which the design of catalysts for oxygenations is slowed down by the complicated, and sometimes poorly understood, mechanistic panorama. In this context, olefin–peroxide complexes could be valuable models for the study of such reactions. Herein, we showcase the isolation of rare “Ir(cod)(peroxide)” complexes (cod=1,5‐cyclooctadiene) from reactions with oxygen, and then the activation of the peroxide ligand for O?O bond cleavage and C?O bond formation by transfer of a hydrogen atom through proton transfer/electron transfer reactions to give 2‐iradaoxetane complexes and water. 2,4,6‐Trimethylphenol, 1,4‐hydroquinone, and 1,4‐cyclohexadiene were used as hydrogen atom donors. These reactions can be key steps in the oxy‐functionalization of olefins with oxygen, and they constitute a novel mechanistic pathway for iridium, whose full reaction profile is supported by DFT calculations.     

Carbon–Nitrogen Bond Cleavage by a Thorium‐NHC‐bpy Complex

Actinide complexes demonstrate unparalleled reactivity towards small molecules. However, utilizing these powerful transformations in a predictable and deliberate manner remains challenging. Therefore, developing actinide systems that not only perform noteworthy chemistry but also demonstrate controllable reactivity is a key goal. We describe a bis(NHC)borate thorium‐bpy complex ( 1 ) that is capable of reductively cleaving the R?NC bond in a series of organic isocyanides. In contrast to most actinide‐mediated bond activations, the dealkylation event mediated by 1 is remarkably general and yields very well‐defined products that assist in mechanistic elucidation. Synthesis of the rearranged but‐3‐enyl product from the reaction of 1 and cyclopropylmethyl isocyanide supports the notion of a radical‐based mechanism.     

Silver‐Catalyzed Oxidative C(sp3)−P Bond Formation through C−C and P−H Bond Cleavage

The silver‐catalyzed oxidative C(sp³)−H/P−H cross‐coupling of 1,3‐dicarbonyl compounds with H‐phosphonates, followed by a chemo‐ and regioselective C(sp³)−C(CO) bond‐cleavage step, provided heavily functionalized β‐ketophosphonates. This novel method based on a readily available reaction system exhibits wide scope, high functional‐group tolerance, and exclusive selectivity.     

Carbon Monoxide Activation by a Molecular Aluminium Imide: C−O Bond Cleavage and C−C Bond Formation

Anionic molecular imide complexes of aluminium are accessible via a rational synthetic approach involving the reactions of organo azides with a potassium aluminyl reagent. In the case of K₂[( NON )Al(NDipp)]₂ ( NON =4,5‐bis(2,6‐diisopropylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethyl‐xanthene; Dipp=2,6‐diisopropylphenyl) structural characterization by X‐ray crystallography reveals a short Al?N distance, which is thought primarily to be due to the low coordinate nature of the nitrogen centre. The Al?N unit is highly polar, and capable of the activation of relatively inert chemical bonds, such as those found in dihydrogen and carbon monoxide. In the case of CO, uptake of two molecules of the substrate leads to C?C coupling and C≡O bond cleavage. Thermodynamically, this is driven, at least in part, by Al?O bond formation. Mechanistically, a combination of quantum chemical and experimental observations suggests that the reaction proceeds via exchange of the NR and O substituents through intermediates featuring an aluminium‐bound isocyanate fragment.     

Benzonitrile Hydrolysis Catalyzed by a Ruthenium(II) Complex

The rate constant for the basic hydrolysis of benzonitrile (PhCN) to benzamide (PhCONH₂) in the [Ru^II(tpy)(bpy)] moiety (tpy = 2,2' : 6',2"-terpyridine, bpy = 2,2'-bipyridine) (k_OH = 3.7 2 10^-2 M^-1s^-1) is 5 2 10³ times higher than that of the free ligand and two times higher than that corresponding to the analogous acetonitrile complex. This effect is unusual for a transition metal in the (II) oxidation state, and can be attributed to the π-electron acceptor properties of both the polypyridyl ligands and the phenyl group. Since amides, being poor π-acceptor ligands, are rapidly released from the coordination sphere of ruthenium(II), the final product of this process is the [Ru(tpy)(bpy)(OH)]⁺ complex. The activation parameters for this nitrile hydrolysis have been determined and compare reasonably well with other values for similar reactions.