Rare‐Earth‐ and Uranium‐Mesoionic Carbenes: A New Class of f‐Block Carbene Complex Derived from an N‐Heterocyclic Olefin

Neutral mesoionic carbenes (MICs) have emerged as an important class of carbene, however they are found in the free form or ligated to only a few d‐block ions. Unprecedented f‐block MIC complexes [M(N′′)₃{CN(Me)C(Me)N(Me)CH}] (M=U, Y, La, Nd; N′′=N(SiMe₃)₂) are reported. These complexes were prepared by a formal 1,4‐proton migration reaction when the metal triamides [M(N′′)₃] were treated with the N‐heterocyclic olefin H₂C=C(NMeCH)₂, which constitutes a new, general way to prepare MIC complexes. Quantum chemical calculations on the 5f³ uranium(III) complex suggest the presence of a U=C donor‐acceptor bond, composed of a MIC→U σ‐component and a U(5f)→MIC(2p) π‐back‐bond, but for the d⁰f⁰ Y and La and 4f³ Nd congeners only MIC→M σ‐bonding is found. Considering the generally negligible π‐acidity of MICs, this is surprising and highlights that greater consideration should possibly be given to recognizing MICs as potential π‐acid ligands when coordinated to strongly reducing metals.     

Enantioselective N‐Heterocyclic Carbene Catalysis that Exploits Imine Umpolung

The catalytic umpolung of imines remains an underdeveloped approach to reaction discovery. Herein we report an enantioselective aza‐Stetter reaction that proceeds via imine umpolung using N‐heterocyclic carbene catalysis. The reaction proceeds with high levels of enantioselectivity (all ≥96:4 er) and good generality (21 examples). Mechanistic studies are reported and are consistent with turnover‐limiting addition of the NHC to the imine.     

Enantio‐ and Diastereoselective Hydrofluorination of Enals by N‐Heterocyclic Carbene Catalysis

In contrast to well‐established asymmetric hydrogenation reactions, enantioselective protonation is an orthogonal approach for creating highly valuable methine chiral centers under redox‐neutral conditions. Reported here is the highly enantio‐ and diastereoselective hydrofluorination of enals by an asymmetric β‐protonation/α‐fluorination cascade catalyzed by N‐heterocyclic carbenes (NHCs). The two nucleophilic sites of a homoenolate intermediate, generated from enals and an NHC, are sequentially protonated and fluorinated. The results show that controlling the relative rates of protonation, fluorination, and esterification is crucial for this transformation, and can be accomplished using a dual shuttling strategy. Structurally diverse carboxylic acid derivatives with two contiguous chiral centers are prepared in a single step with excellent d.r. and ee values.     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .     

C−F Bond Activation by a Saturated N‐Heterocyclic Carbene: Mesoionic Compound Formation and Adduct Formation with B(C6F5)3

The reaction of SIPr, [1,3‐bis(2,6‐diisopropylphenyl)‐imidazolin‐2‐ylidene] ( 1 ), with C₆F₆ led to the formation of an unprecedented mesoionic compound ( 2 ). The formation of 2 is made accessible by deprotonation of the SIPr backbone with simultaneous elimination of HF. The C?F bond para to the imidazolium ring in 2 is only of 1.258(4) Å, which is the one of the shortest structurally authenticated C?F bonds known to date. The liberation of HF during the reaction is unequivocally proved by the addition of one more equivalent of SIPr, which leads to the imidazolium salt with the HF₂^? anion. To functionalize 2 , the latter reacted with B(C₆F₅)₃ to give an unusual donor–acceptor compound, where the fluoride atom from the C₆F₅ moiety coordinates to B(C₆F₅)₃ and the carbanion moiety remains unaffected. Such coordination susceptibility of the fluoride atom of a nonmetallic system to a main‐group Lewis acid (F_non‐metal→BR₃) is quite unprecedented.     

Accessing Difluoromethylated and Trifluoromethylated cis‐Cycloalkanes and Saturated Heterocycles: Preferential Hydrogen Addition to the Substitution Sites for Dearomatization

Reported here is a straightforward process in which a cyclic (alkyl)(amino)carbene/Rh catalyst system facilitates the preferential addition of hydrogen to the substitution sites of difluoromethylated and trifluoromethylated arenes and heteroarenes, leading to dearomative reduction. This strategy enables the diastereoselective synthesis of cis‐difluoromethylated and cis‐trifluoromethylated cycloalkanes and saturated heterocycles, and even allows formation of all‐cis multi‐trifluoromethylated cyclic products with a defined equatorial orientation of the di‐ and trifluoromethyl groups. Deuterium‐labeling studies indicate that hydrogen preferentially attacks the substitution sites of planar arenes, resulting in dearomatization, possibly with heterogeneous Rh as the reactive species, followed by either reversible or irreversible hydrogen addition to the nonsubstitution sites.     

Visible‐Light‐Driven N‐Heterocyclic Carbene Catalyzed γ‐ and ϵ‐Alkylation with Alkyl Radicals

The merging of photoredox catalysis and N‐heterocyclic carbene (NHC) catalysis for γ‐ and ?‐alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ‐oxidized enals with alkyl halides worked well for the synthesis γ‐multisubstituted‐α,β‐unsaturated esters, including those with challenging vicinal all‐carbon quaternary centers. The synthesis of ?‐multisubstituted‐α,β‐γ,δ‐diunsaturated esters by an unprecedented NHC‐catalyzed ?‐functionalization was also established.     

Cyclometalated Gold(III) Complexes Containing N‐Heterocyclic Carbene Ligands Engage Multiple Anti‐Cancer Molecular Targets

Metal N‐heterocyclic carbene (NHC) complexes are a promising class of anti‐cancer agents displaying potent in vitro and in vivo activities. Taking a multi‐faceted approach employing two clickable photoaffinity probes, herein we report the identification of multiple molecular targets for anti‐cancer active pincer gold(III) NHC complexes. These complexes display potent and selective cytotoxicity against cultured cancer cells and in vivo anti‐tumor activities in mice bearing xenografts of human cervical and lung cancers. Our experiments revealed the specific engagement of the gold(III) complexes with multiple cellular targets, including HSP60, vimentin, nucleophosmin, and YB‐1, accompanied by expected downstream mechanisms of action. Additionally, Pt^II and Pd^II analogues can also bind the cellular proteins targeted by the gold(III) complexes, uncovering a distinct pincer cyclometalated metal–NHC scaffold in the design of anti‐cancer metal medicines with multiple molecular targets.     

Redox‐Active Ligands in Catalysis

Nature’s use of redox‐active moieties combined with 3d transition‐metal ions is a powerful strategy to promote multi‐electron catalytic reactions. The ability of these moieties to store redox equivalents aids metalloenzymes in promoting multi‐electron reactions, avoiding high‐energy intermediates. In a biomimetic spirit, chemists have recently developed approaches relying on redox‐active moieties in the vicinity of metal centers to catalyze challenging transformations. This approach enables chemists to impart noble‐metal character to less toxic, and cost effective 3d transitional metals, such as Fe or Cu, in multi‐electron catalytic reactions.     

N‐Heterocyclic Carbene/Copper Cooperative Catalysis for the Asymmetric Synthesis of Spirooxindoles

Highly enantioselective [3+3] and [3+4] annulations of isatin‐derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones are enabled by NHC/cooper cooperative catalysis, leading to a big library of spirooxindole derivatives in high structural diversity and enantioselectivity (up to 99 % ee). Both reactions represent a nicely synergistic integration of NHC and copper catalysis, in which both catalysts activate the substrates and the chiral NHC perfectly controls the stereochemistry.     

A Benchtop Method for Appending Protic Functional Groups to N-Heterocyclic Carbene Protected Gold Nanoparticles

The remarkable resilience of N-heterocyclic carbene (NHC) gold bonds has quickly made NHCs the ligand of choice when functionalizing gold surfaces. Despite rapid progress using deposition from free or CO₂-protected NHCs, synthetic challenges hinder the functionalization of NHC surfaces with protic functional groups, such as alcohols and amines, particularly on larger nanoparticles. Here, we synthesize NHC-functionalized gold surfaces from gold(I) NHC complexes and aqueous nanoparticles without the need for additional reagents, enabling otherwise difficult functional groups to be appended to the carbene. The resilience of the NHC−Au bond allows for multi-step post-synthetic modification. Beginning with the nitro-NHC, we form an amine-NHC terminated surface, which further undergoes amide coupling with carboxylic acids. The simplicity of this approach, its compatibility with aqueous nanoparticle solutions, and its ability to yield protic functionality, greatly expands the potential of NHC-functionalized noble metal surfaces.     

Knight Shift in 13C NMR Resonances Confirms the Coordination of N‐Heterocyclic Carbene Ligands to Water‐Soluble Palladium Nanoparticles

The coordination of N‐heterocyclic carbene (NHC) ligands to the surface of 3.7 nm palladium nanoparticles (PdNPs) can be unambiguously established by observation of Knight shift (KS) in the ¹³C resonance of the carbenic carbon. In order to validate this coordination, PdNPs with sizes ranging from 1.3 to 4.8 nm were prepared by thermal decomposition or reduction with CO of a dimethyl NHC Pd^II complex. NMR studies after ¹³CO adsorption established that the KS shifts the ¹³C resonances of the chemisorbed molecules several hundreds of ppm to high frequencies only when the particle exceeds a critical size of around 2 nm. Finally, the resonance of a carbenic carbon is reported to be Knight‐shifted to 600 ppm for ¹³C‐labelled NHCs bound to PdNPs of 3.7 nm. The observation of these very broad KS resonances was facilitated by using Car–Purcell–Meiboom–Gill (CPMG) echo train acquisition NMR experiments.     

Enantioselective N‐Heterocyclic Carbene Catalyzed Bis(enoate) Rauhut–Currier Reaction

While the enantioselective Rauhut–Currier reaction is established with bis(enone) substrates, it is yet to be reported with less electrophilic bis(enoate) substrates. By exploiting high‐nucleophilicity N‐heterocyclic carbenes, it is possible to achieve Rauhut–Currier reactions with these substrates. The reaction is demonstrated with a range of intramolecular reactions (20 examples) and six esterification/RC reaction cascades, which all proceed with high enantioselectivity (most >93:7 er).