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The 2,7‐fluorenone‐linked bis(6‐imidazo[1,5‐a]pyridinium) salt H2‐1(PF6)2 reacts with Ag2O in CH3CN to yield the [2]catenane [Ag4(1)4](PF6)4. The [2]catenane rearranges in DMF to yield two metallamacrocycles [Ag2(1)2](PF6)2. 2,7‐Fluorenone‐bridged bis‐(imidazolium) salts H2‐L(PF6)2 (L=2 a, 2 b) react with Ag2O in CH3CN to yield metallamacrocycles [Ag2(L)2](PF6)2 with interplanar distances between the fluorenone rings too small for [2]catenane formation. Intra‐ and intermolecular π⋅⋅⋅π interactions between the fluorenone groups were observed by X‐ray crystallography. The strongly kinked 2,7‐fluorenone bridged bis(5‐imidazo[1,5‐a]pyridinium) salt H2‐4(PF6)2 reacts with Ag2O to yield [Ag2(4)(CN)](PF6), while the tetranuclear assembly [Ag4(4)2(CO3)](PF6)2 was obtained in the presence of K2CO3. [ABSTRACT FROM AUTHOR]

Design of metal cofactor ligands is essential for controlling the reactivity of metalloenzymes. We investigated a carbene transfer reaction catalyzed by myoglobins containing iron porphyrin cofactors with one and two trifluoromethyl groups at peripheral sites (FePorCF3 and FePor(CF3)2, respectively), native heme and iron porphycene (FePc). These four myoglobins show a wide range of Fe(II)/Fe(III) redox potentials in the protein of +147 mV, +87 mV, +42 mV and −198 mV vs. NHE, respectively. Myoglobin reconstituted with FePor(CF3)2 has a more positive potential, which enhances the reactivity of a carbene intermediate with alkenes, and demonstrates superior cyclopropanation of inert alkenes, such as aliphatic and internal alkenes. In contrast, engineered myoglobin reconstituted with FePc has a more negative redox potential, which accelerates the formation of the intermediate, but has low reactivity for inert alkenes. Mechanistic studies indicate that myoglobin with FePor(CF3)2 generates an undetectable active intermediate with a radical character. In contrast, this reaction catalyzed by myoglobin with FePc includes a detectable iron–carbene species with electrophilic character. This finding highlights the importance of redox‐focused design of the iron porphyrinoid cofactor in hemoproteins to tune the reactivity of the carbene transfer reaction. [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed carbene transfer reactions have a century‐old history in organic chemistry and are a primary method for the synthesis of cyclopropanes. Much of the work in this field has focused on the use of diazo compounds and related precursors, which can transfer a carbene fragment to a catalyst with concomitant loss of a stable byproduct. Despite the utility of this approach, there are persistent limitations in the scope of viable carbenes, most notably those lacking stabilizing substituents. By coupling carbene transfer chemistry with two‐electron redox cycles, it is possible to expand the available starting materials that can be used as carbene precursors. In this Minireview, we discuss emerging catalytic reductive cyclopropanation reactions using either gem‐dihaloalkanes or carbonyl compounds. This strategy is inspired by classic stoichiometric transformations, such as the Simmons–Smith cyclopropanation and the Clemmensen reduction, but instead entails the formation of a catalytically generated transition metal carbene or carbenoid. We also present recent efforts to generate carbenes directly from methylene (CR2H2) groups via a formal 1,1‐dehydrogenation. These reactions are currently restricted to substrates containing electron‐withdrawing substituents, which serve to facilitate deprotonation and subsequent oxidation of the anion. [ABSTRACT FROM AUTHOR]

Singlet carbenes are not always isolable and often even elude direct detection. When they escape observation, their formation can sometimes be evidenced by in situ trapping experiments. However, is carbene‐like reactivity genuine evidence of carbene formation? Herein, using the first example of a spectroscopically characterized cyclic (amino)(aryl)carbene (CAArC), we cast doubt on the most common carbene trapping reactions as sufficient proof of carbene formation. [ABSTRACT FROM AUTHOR]

Trifluoromethyl-substituted cyclopropanes (CF3 -CPAs) constitute an important class of compounds for drug discovery. While several methods have been developed for synthesis of trans-CF3 -CPAs, stereoselective production of corresponding cis-diastereomers remains a formidable challenge. We report a biocatalyst for diastereo- and enantio-selective synthesis of cis-CF3 -CPAs with activity on a variety of alkenes. We found that an engineered protoglobin from Aeropyrnum pernix (ApePgb) can catalyze this unusual reaction at preparative scale with low-to-excellent yield (6-55 %) and enantioselectivity (17-99 % ee), depending on the substrate. Computational studies revealed that the steric environment in the active site of the protoglobin forced iron-carbenoid and substrates to adopt a pro-cis near-attack conformation. This work demonstrates the capability of enzyme catalysts to tackle challenging chemistry problems and provides a powerful means to expand the structural diversity of CF3 -CPAs for drug discovery.

Azetidines, being four‐membered N‐heterocycles, possess significant potential in contemporary medicinal chemistry owing to their favorable pharmacokinetic properties. Regrettably, the incorporation of functionalized azetidines into pharmaceutical lead structures has been impeded by the absence of efficient synthetic methods for their synthesis. In this study, a Rh‐catalyzed one‐carbon ring expansion of aziridines with vinyl‐N‐triftosylhydrazones is presented, which facilitates the synthesis of high value‐added 2‐alkenyl azetidine products. This research represents the first example of ring expansion of aziridines enabled by vinyl carbenes. Additionally, a one‐pot two‐step protocol, initiated from cinnamaldehyde, was successfully achieved, offering a step‐economical and facile approach for the synthesis of these compounds. The pivotal aspect of this successful transformation lies in the in situ formation of an alkenyl aziridinium ylide intermediate. Experimental investigations, coupled with computational studies, suggest that a diradical pathway is involved in the reaction mechanism. [ABSTRACT FROM AUTHOR]

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−CH2Ar 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 β‐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. [ABSTRACT FROM AUTHOR]

Luminescent metal complexes based on earth abundant elements are a valuable target to substitute 4d/5d transition metal complexes as triplet emitters in advanced photonic applications. Whereas CuI complexes have been thoroughly investigated in the last two decades for this purpose, no structure‐property‐relationships for efficient luminescence involving triplet excited states from ZnII complexes are established. Herein, we report on the design of monomeric carbene zinc(II) dithiolates (CZT) featuring a donor‐acceptor‐motif that leads to highly efficient thermally activated delayed fluorescence (TADF) with for ZnII compounds unprecedented radiative rate constants kTADF=1.2×106 s−1 at 297 K. Our high‐level DFT/MRCI calculations revealed that the relative orientation of the ligands involved in the ligand‐to‐ligand charge transfer (1/3LLCT) states is paramount to control the TADF process. Specifically, a dihedral angle of 36–40° leads to very efficient reverse intersystem‐crossing (rISC) on the order of 109 s−1 due to spin‐orbit coupling (SOC) mediated by the sulfur atoms in combination with a small ΔES1‐T1 of ca. 56 meV. [ABSTRACT FROM AUTHOR]

The skeletal ring expansion of heteroarenes through carbene insertion is gaining popularity in synthetic chemistry. Efficient strategies for heterocyclic ring expansion to access heterocycles containing a fluoroalkyl quaternary carbon center through fluoroalkyl carbene insertion are highly desirable because of their broad applications in medicinal chemistry. Herein, we report a general strategy for the dearomative one‐carbon insertion of azoles using fluoroalkyl N‐triftosylhydrazones as fluoroalkyl carbene precursors, resulting in ring‐expanded heterocycles in excellent yields with good functional‐group compatibility. The broad generality of this methodology in the late‐stage diversification of pharmaceutically interesting bioactive molecules and versatile transformations of the products has been demonstrated. [ABSTRACT FROM AUTHOR]

An enantioselective carbene‐catalyzed radical‐radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N‐heterocyclic carbene‐derived ketyl radical and a secondary sp3‐carbon radical and allows access to chiral α‐aryl aliphatic ketones in moderate‐to‐good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late‐stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N‐heterocyclic carbene controls the double‐facial selectivity of the ketyl radical and the alkyl radicals, respectively. [ABSTRACT FROM AUTHOR]

We have developed a photoinduced protocol for the synthesis of pharmaceutically important oxazole molecules using diazo‐ and nitrile‐containing reactants. The process involves the initial photolysis of the diazo compound to afford singlet carbenes, which are tapped by nitriles in a [3+2] cycloaddition fashion to give substituted oxazoles. With di‐nitrile compounds, useful bis‐oxazoles were obtained. The applicability of the transformation is showcased through the expedient synthesis of small‐molecule drugs and biologically relevant molecules such as felbinac, pimprinine, texamine, ugnenenazole etc. The protocol is also useful for the generation of 2H and 13C isotope labelled oxazoles. Merging photolysis with continuous‐flow chemistry was demonstrated for scaling up the reaction. The non‐requirement of metal catalysis or photosensitizers to harness the light energy with blue light sufficing the execution of the reaction makes it a versatile and general protocol for the synthesis of structurally diverse oxazoles [ABSTRACT FROM AUTHOR]

α‐Trifluoromethylated ketones have attracted significant attention as valuable building blocks in organic synthesis. Such compounds are generally accessed through trifluoromethylation of ketones. Here we report an alternative disconnection approach for the construction of α‐CF3 carbonyl compounds by using aroyl fluorides as bifunctional reagents for fluoroaroylation of gem‐difluoroalkenes through cooperative photoredox and N‐heterocyclic carbene (NHC) catalysis. This strategy bypasses the use of expensive or sensitive trifluoromethylation reagents and/or the requirement for ketone pre‐functionalization, thus enabling an efficient and general synthetic method to access α‐CF3‐substituted ketones. A wide variety of gem‐difluoroalkenes and aroyl fluorides bearing a diverse set of functional groups are eligible substrates. Notably, the developed methodology also provides rapid access to mono‐ or difluoroalkyl ketones. Mechanistic studies reveal that merging photoredox catalysis with NHC catalysis is essential for the reaction. [ABSTRACT FROM AUTHOR]

Azomethine ylides are typically in situ generated synthons for making N‐heterocycles through cycloaddition reactions. But an offbeat aspect about them is the isomeric nature of aldiminium‐based azomethine ylides and (alkyl/aryl)(amino)carbenes, interconvertible by a formal 1,3‐H+ transfer. Herein, two thermally robust azomethine ylides with a N‐appended picolyl sidearm are isolated, which cyclize to pyaziridines at 80 °C but unprecedentedly result N−picoCAAC‐CuCl (CAAC=cyclic(alkyl)(amino)carbene) complexes when heated with CuCl at merely 60 °C. The pendant Npy, as revealed by computational analysis, plays a crucial role in this unusual 1,3‐H+ shift using a deprotonation‐protonation sequence, as well as in placing the CuCl at the carbenic site in tandem. The softer nature of Cu(I) is also critical. Chelating CAACs are rare and one with a N‐tethered additional donor is priorly unknown. Both N‐picoCAAC and pyaziridine are bidentate chelators giving highly active cationic Rh(I) catalysts for hydrosilylating unactivated olefins by Et3SiH. Notably, the pyaziridine‐Rh(I) is superior than the N‐picoCAAC‐Rh(I) catalyst. [ABSTRACT FROM AUTHOR]

Nickel PyBox catalysts promote nucleophilic cyclopropanation reactions using CH2Cl2 as a methylene source and Mn as a stoichiometric reductant. The substrate scope includes a broad range of alkenes bearing electron‐withdrawing substituents, including esters, amides, ketones, nitriles, sulfones, phosphonate esters, trifluoromethyl groups, and electron‐deficient arenes. Enantioselective cyclopropanations of α,β‐unsaturated esters have been developed using chiral PyBox ligands. Mechanistic studies suggest the intermediacy of a (PyBox)Ni=CH2 species, which adds to the alkene by a stepwise [2+2]‐cycloaddition/C−C reductive elimination mechanism. DFT models provide a rationale for the nucleophilic character of the nickel carbene and the sense of enantioinduction. [ABSTRACT FROM AUTHOR]

The control of the reactivity of diazo compounds is commonly achieved by the choice of a suitable catalyst, e.g. via stabilization of singlet carbenes or radical intermediates. Herein, we report on the light‐promoted reactivity of cyclic diazo imides with thiols, where the choice of solvent results in two fundamentally different reaction pathways. In dichloromethane (DCM), a carbene is formed initially and engages in a cascade C−H functionalization/thiolation reaction to deliver indane‐fused pyrrolidines in good to excellent yields. When switching to acetonitrile solvent, the carbene pathway is shut down and an unusual reduction of the diazo compound occurs under otherwise identical reaction conditions, where the aryl thiol acts as reductant. A combined set of experimental and computational studies was carried out to obtain mechanistic understanding and to support that indane formation proceeds via the insertion of a triplet carbene, while the reduction of diazo imides proceeds via an electron transfer process. [ABSTRACT FROM AUTHOR]

Chiral Au nanoclusters have promising application prospects in chiral sensing, asymmetric catalysis, and chiroptics. However, enantiopure superatomic homogold clusters with crystallographic structures emitting bright circularly polarized luminescence (CPL) remain challenging. In this study, we designed chiral N‐heterocyclic carbenes (NHCs), and for the first time enantioselectively synthesized a pair of monovalent cationic superatomic Au13 clusters. This new enantiomeric pair of clusters has a quasi‐C2 symmetric core and exhibited CPL with an unprecedent solution‐state quantum yield (QY) of 61 % among those of the atomically precise Au nanoclusters. DFT calculations provided insights into the circular dichroism behavior, and revealed the origin of CPL from superatomic Au clusters. This work opens a new avenue for developing novel homochiral nanoclusters using chiral NHC ligands and provides fundamental understanding of the origin of the chiroptics of metal clusters. [ABSTRACT FROM AUTHOR]

An oxidative strategy is reported to access α‐oxo BMIDA gold carbenes directly from BMIDA‐terminated alkynes. Besides offering expedient access to seldom studied boryl metal carbenes, these BMIDA gold carbene species undergo facile insertions into methyl, methylene, methine, and benzylic C−H bonds in the absence of the Thorpe–Ingold effect. They also undergo efficient OH insertion, cyclopropanation, and F−C alkylations. This chemistry provides rapid access to structurally diverse α‐BMIDA ketones, which are scarcely documented. In combination with DFT studies, the role of BMIDA is established to be an electron‐donating group that attenuates the high electrophilicity of the gold carbene center. [ABSTRACT FROM AUTHOR]

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high‐pKa Brønsted acid catalysts that enable free carbene insertion into N−H bonds of amines to prepare chiral α‐amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high‐energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high‐pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton‐transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol. [ABSTRACT FROM AUTHOR]

[2,3]‐Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle–Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp3)−S and C−C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper‐catalyzed enantioselective Doyle–Kirmse reaction via azide‐ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2‐b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities. Importantly, this protocol represents a unique catalytic asymmetric Doyle–Kirmse reaction via a non‐diazo approach and an unprecedented asymmetric [2,3]‐sigmatropic rearrangement via α‐imino metal carbenes. [ABSTRACT FROM AUTHOR]

Trifluoromethyl‐bearing 5‐membered rings are prevalent in bioactive molecules, but modular approaches to these compounds by functionalization of robust C(sp3)−H bonds in a direct and selective manner are extremely challenging. Herein we report the rhodium‐catalyzed α‐CF3‐α‐alkyl carbene insertion into C(sp3)−H bonds of a broad range of substrates to access 7 types of CF3‐bearing saturated 5‐membered carbo‐ and heterocycles. The reaction is particularly effective for benzylic C−H insertion exerting good site‐, diastereo‐ and enantiocontrol, and applicable to the synthesis of chiral CF3 analogues of bioactive molecules. Ruthenium α‐CF3‐α‐alkyl carbene complexes underwent stoichiometric reactions to give C−H insertion products, lending evidence for the involvement of metal α‐CF3‐α‐alkyl carbene species in the catalytic cycle. DFT calculations revealed that the π⋅⋅⋅π attraction and intra‐carbene C−H⋅⋅⋅F hydrogen bond elucidate the origin of selectivity of the benzylic C−H insertion reactions. [ABSTRACT FROM AUTHOR]

Phenyl azides substituted by an (alkylphenyl)ethynyl group facilitate benzylic sp3(C−H) functionalization in the presence of a JohnPhosAu catalyst, resulting in indole‐fused tetra‐ and pentacycles via divergent N‐ or C‐cyclization. The chemoselectivity is influenced depending on the counter‐anion, the electron density of the α‐imino gold(I) carbene, and the alkyl groups stabilizing the benzylic carbocation originating from a 1,5‐hydride shift. An isotopic labeling experiment demonstrates the involvement of an indolylgold(I) species resulting from a tautomerization that is much faster than the deauration. The formation of a benzylic sp3(C−H) functionalization leading to an indole‐fused seven‐membered ring is also demonstrated. [ABSTRACT FROM AUTHOR]

Though [60]fullerene is an achiral molecular nanocarbon with Ih symmetry, it could attain an inherent chirality depending upon a functionalization pattern. The conventional chiral induction of C60 relies mainly upon a multiple addition affording a mixture of achiral and chiral isomers while their chiral function would be largely offset by the existence of pseudo‐mirror plane(s). These are major obstacles to proceed further study on fullerene chirality and yet leave its understanding elusive. Herein, we showcase a carbene‐mediated synthesis of C1‐symmetric chiral open [60]fullerenes showing an intense far‐red to near‐infrared absorption. The large dissymmetry factor of |gabs|=0.12 was achieved at λ=820 nm for circular dichroism in benzonitrile. This is, in general, unachievable by other small chiral organic molecules, demonstrating the potential usage of open [60]fullerenes as novel types of chiral chromophores. [ABSTRACT FROM AUTHOR]

An extended class of stable mesoionic N‐heterocyclic imines (mNHIs), containing a highly polarized exocyclic imine moiety, were synthesized. The calculated proton affinities (PA) and experimentally determined Tolman electronic parameters (TEPs) reveal that these synthesized mNHIs have the highest basicity and donor ability among NHIs reported so far. The superior nucleophilicity of newly designed mNHIs was utilized in devising a strategy to incorporate CO2 as a bridging unit under reductive conditions to couple inert primary amides. This strategy was further extended to hetero‐couplings between amide and amine using CO2. These hitherto unknown catalytic transformations were introduced in the diversification of various biologically active drug molecules under metal‐free conditions. The underlying mechanism was explored by performing a series of control experiments, characterizing key intermediates using spectroscopic and crystallographic techniques. [ABSTRACT FROM AUTHOR]

An extended class of stable mesoionic N‐heterocyclic imines (mNHIs), containing a highly polarized exocyclic imine moiety, were synthesized. The calculated proton affinities (PA) and experimentally determined Tolman electronic parameters (TEPs) reveal that these synthesized mNHIs have the highest basicity and donor ability among NHIs reported so far. The superior nucleophilicity of newly designed mNHIs was utilized in devising a strategy to incorporate CO2 as a bridging unit under reductive conditions to couple inert primary amides. This strategy was further extended to hetero‐couplings between amide and amine using CO2. These hitherto unknown catalytic transformations were introduced in the diversification of various biologically active drug molecules under metal‐free conditions. The underlying mechanism was explored by performing a series of control experiments, characterizing key intermediates using spectroscopic and crystallographic techniques. [ABSTRACT FROM AUTHOR]

Ru‐porphyrins act as convenient pedestals for the assembly of N‐heterocyclic carbenes (NHCs) on solid surfaces. Upon deposition of a simple NHC ligand on a close packed Ru‐porphyrin monolayer, an extraordinary phenomenon can be observed: Ru‐porphyrin molecules are transferred from the silver surface to the next molecular layer. We have investigated the structural features and dynamics of this portering process and analysed the associated binding strengths and work function changes. A rearrangement of the molecular layer is induced by the NHC uptake: the NHC selective binding to the Ru causes the ejection of whole porphyrin molecules from the molecular layer on silver to the layer on top. This reorganisation can be reversed by thermally induced desorption of the NHC ligand. We anticipate that the understanding of such mass transport processes will have crucial implications for the functionalisation of surfaces with carbenes. [ABSTRACT FROM AUTHOR]

A combined synthetic and theoretical investigation of N‐heterocyclic carbene (NHC) adducts of magnesium amidoboranes is presented, which involves a rare example of reversible migratory insertion within a normal valent s‐block element. The reaction of (NHC)Mg(N(SiMe3)2)2 (1) and dimethylamine borane yields the tris(amide) adduct (NHC−BN)Mg(NMe2BH3)(N(SiMe3)2) (2; NHC−BN = NHC−BH2NMe2). In addition to Me2N=BH2 capture at the NHCC−Mg bond, mechanistic investigations suggest the likelihood of aminoborane migratory insertion from an RMg(NMe2BH2NMe2BH3) intermediate. To elucidate these processes, the carbene complexes (NHC)Mg(NMe2BH3)2 (8) and (NHC)Mg(NMe2BH2NMe2BH3)2 (9) were synthesized, and a dynamic migration of Me2N=BH2 between Mg−N and NHCC−Mg bonds was observed in 9. This unusual reversible migratory insertion is presumably induced by dissimilar charge localization in the −{NMe2BH2NMe2BH3} anion, as well as the capacity of NHCs to reversibly capture Me2N=BH2 in the presence of Lewis acidic magnesium species. [ABSTRACT FROM AUTHOR]

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O‐heterocycles, and the formation of carbonyl ylides by the reaction of metal carbenes with carbonyls has attracted increasing attention over the past decades. However, a catalyst‐controlled highly enantioselective reaction of carbonyl ylides from metal carbenes is extremely challenging. Herein, we report a novel copper‐catalyzed asymmetric formal [2+1] and [4+1] annulations of diynes with ketones via carbonyl ylides. Importantly, this protocol not only represents the first example of successful asymmetric epoxidation via carbonyl ylides, but also constitutes the first reaction of vinyl cations with carbonyl compounds. This method leads to the divergent, practical and atom‐economical synthesis of a range of chiral oxiranes and dihydrofurans in moderate to excellent yields with generally excellent enantioselectivities and diastereoselectivities via remote‐stereocontrol strategy. [ABSTRACT FROM AUTHOR]

Chiral quinacridines react up to four times, step‐by‐step, with α‐diazomalonates under RuII and RhII catalysis. By selecting the catalyst, [CpRu(CH3CN)3][PF6] (Cp=cyclopentadienyl) or Rh2(oct)4, chemo and regioselective insertions of derived metal carbenes are achieved in favor of mono‐ or bis‐functionalized malonate derivatives, respectively, (r.r.>49 : 1, up to 77 % yield, 12 examples). This multi‐introduction of malonate groups is particularly useful to tune optical and chemical properties such as absorption, emission or Brønsted acidity but also cellular bioimaging. Density‐functional theory further elucidates the origin of the carbene insertion selectivity and also showcases the importance of conformations in the optical response. [ABSTRACT FROM AUTHOR]

Carbenes, including N‐heterocyclic carbene (NHC) ligands, are used extensively to stabilize open‐shell transition metal complexes and organic radicals. Yet, it remains unknown, which carbene stabilizes a radical well and, thus, how to design radical‐stabilizing C‐donor ligands. With the large variety of C‐donor ligands experimentally investigated and their electronic properties established, we report herein their radical‐stabilizing effect. We show that radical stabilization can be understood by a captodative frontier orbital description involving π‐donation to‐ and π‐donation from the carbenes. This picture sheds a new perspective on NHC chemistry, where π‐donor effects usually are assumed to be negligible. Further, it allows for the intuitive prediction of the thermodynamic stability of covalent radicals of main group‐ and transition metal carbene complexes, and the quantification of redox non‐innocence. [ABSTRACT FROM AUTHOR]

With the discovery of late transition metal platforms that support clean photoreductive halogen eliminations, we now describe an indazol‐3‐ylidene gold trichloride complex ([7]+) decorated at the 4‐position by a xanthylium unit. This orange complex features a low energy band in the visible part of the spectrum, assigned to the charge transfer excitation of the indazol‐3‐ylidene/xanthylium donor/acceptor dyad. Green‐light irradiation of this complex in the presence of a chlorine trap elicits the clean photoelimination of chlorine radicals, producing the corresponding gold(I) complex. This visible‐light‐induced photoreduction is very efficient, reaching quantum yields close to 10 %. A neutral analog of [7]+ featuring an anthryl group rather than a xanthylium unit proved to be perfectly photostable, supporting the importance of the xanthylium‐based photoredox unit present in [7]+. [ABSTRACT FROM AUTHOR]

We report here "sandwich" diimine‐copper(I) catalysts for C(sp3)−H bond functionalization. Reactions of alkanes and ethers with trimethylsilyldiazomethane, ethyl diazoacetate, and trifluoromethyl‐diazomethane have been demonstrated. We also report C(sp3)−H bond methylation, benzylation, and diphenylmethylation by diazomethane, aryldiazomethanes, and diphenyldiazomethane. These reactions are rare examples of base‐metal catalyzed, intermolecular C(sp3)−H functionalizations by employing unactivated diazo compounds. Electrophilicity and unique steric environment of "sandwich"‐copper catalysts are likely reasons for their catalytic efficiency. [ABSTRACT FROM AUTHOR]

Herein we report secondary pyrrolidin‐2‐ols as a source of cyclic (alkyl)(amino)carbenes (CAAC) for the synthesis of CAAC‐CuI‐complexes and cyclic thiones when reacted with CuI‐salts and elemental sulfur, respectively, under reductive elimination of water from the carbon(IV)‐center. This result demonstrates a convenient and facile access to CAAC‐based CuI‐salts, which are well known catalysts for different organic transformations. It further establishes secondary alcohols to be a viable source of carbenes—realizing after 185 years Dumas' dream who tried to prepare the parent carbene (CH2) by 1,1‐dehydration of methanol. Addressed is also the reactivity of water towards CAACs, which proceeds through an oxidative addition of the O−H bond to the carbon(II)‐center. This emphasizes the ability of carbon‐compounds to mimic the reactivity of transition‐metal complexes: reversible oxidative addition and reductive elimination of the O−H bond to/from the C(II)/C(IV)‐centre. [ABSTRACT FROM AUTHOR]

Herein, we report the development of a method for highly regio‐, stereo‐, and enantioselective B−H bond insertion reactions of α‐silylcarbenes generated from 1‐silylcyclopropenes in the presence of a chiral copper(I)/bisoxazoline catalyst for the construction of chiral γ,γ‐disubstituted allylic gem‐silylboranes, which cannot be prepared by any other known methods. This reaction is the first highly enantioselective carbene insertion reaction of α‐silylcarbenes ever to be reported. The method shows general applicability for various 3,3‐disubstituted silylcyclopropenes and exclusively affords E‐products. The novel chiral γ,γ‐disubstituted allylic gem‐silylborane products are versatile allylic bimetallic reagents with high stability and have great synthetic potential, especially for the construction of complex molecules with continuous chiral centers. [ABSTRACT FROM AUTHOR]

Panowamycins are a group of isochroman‐based natural products first isolated from Streptomyces sp. K07‐0010 in 2012 by Satoshi Ōmura and co‐workers that exhibit modest anti‐trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium‐catalyzed C−H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond‐forming step. The syntheses are completed without the use of protecting groups and feature a late‐stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co‐workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM‐135, and veramycin F. [ABSTRACT FROM AUTHOR]

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet‐metal‐carbene intermediates. However, previous transition‐metal‐catalyzed cyclopropanation of alkenes with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible‐light‐induced transition‐metal‐free cyclopropanation reaction of terminal alkenes with trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic and aliphatic alkenes as well as electron‐deficient alkenes are suitable substrates for the highly cis‐selective [2+1] cyclization reaction. A combination of experimental and computational studies identified triplet carbenes as being key intermediates in this transformation. The gram scale reaction and late‐stage functionalization demonstrated the synthetic potential of this strategy. [ABSTRACT FROM AUTHOR]

Carbones are divalent carbon(0) species that contain two lone pairs of electrons. Herein, we have prepared the first known stable and isolable free bis‐(carbone) pincer framework with a well‐defined solid‐state structure. This bis‐(carbone) ligand is an effective scaffold for forming monometallic (Ni and Pd) and trinuclear heterometallic complexes with Au−Pd−Au, Au−Ni−Au, and Cu−Ni−Cu configurations. Sophisticated quantum‐theoretical analyses found that the metal–metal interactions are too weak to play a significant role in upholding these multi‐metallic configurations; rather, the four lone pairs of electrons within the bis‐(carbone) framework are the main contributors to the stability of the complexes. [ABSTRACT FROM AUTHOR]

Borepin, a 7‐membered boron‐containing heterocycle, has become an emerging molecular platform for the development of new materials and optoelectronics. While electron‐deficient borepins are well‐established, reduced electron‐rich species have remained elusive. Herein we report the first isolable, crystalline borepin radical (2 a, 2 b) and anion (3 a, 3 b) complexes, which have been synthesized by potassium graphite (KC8) reduction of cyclic(alkyl)(amino) carbene‐dibenzo[b,d]borepin precursors. Borepin radicals and anions have been characterized by EPR or NMR, elemental analysis, X‐ray crystallography, and cyclic voltammetry. In addition, the bonding features have been investigated computationally using density functional theory. [ABSTRACT FROM AUTHOR]

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α‐diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N′‐dioxide/cobalt(ΙΙ) complexes (2–5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins. Density functional theory calculations reveal that the reaction initiates from a doublet state cobalt(ΙΙ) carbenoid, which is followed by a quartet cobalt(ΙΙ)‐bound thiocarbonyl ylide pathway. This work provides a route for the selective construction of tetrasubstituted thiiranes and olefins that are otherwise difficult to access. [ABSTRACT FROM AUTHOR]

Umpolung N‐heterocyclic carbene (NHC) catalysis of non‐aldehyde substrates offers new pathways for C−C bond formation, but has proven challenging to develop in terms of viable substrate classes. Here, we demonstrate that pyridinium ions can undergo NHC addition and subsequent intramolecular C−C bond formation through a deoxy‐Breslow intermediate. The alkylation demonstrates, for the first time, that deoxy‐Breslow intermediates are viable for catalytic umpolung of areniums. [ABSTRACT FROM AUTHOR]

Although the synthesis of common cyclopropenes has been well studied, the access to cyclopropenols is rather limited. Herein, we report the first synthesis of α‐trifluoromethylated cyclopropenols via 2+1 cycloaddition reactions between alkynes and trifluoroacylsilanes, enabled by visible‐light‐induced organocatalysis. The novel ambiphilic donor–acceptor carbenes derived from trifluoroacetylsilanes reacted efficiently with both activated and non‐activated alkynes. The reaction features simple operation, mild conditions, broad substrate scope and good functional group tolerance. The synthetic potential of the reaction is highlighted by the gram‐scale reactions and first synthesis of α‐trifluoromethylated cyclopropanols through the combination of the 2+1 cyclization and high diastereoselective hydrogenation reaction in one pot. [ABSTRACT FROM AUTHOR]

gem‐Hydrogenation of propargyl alcohol derivatives with [CpXRu(MeCN)3]PF6 (CpX=substituted cyclopentadienyl) as catalysts affords cationic pianostool ruthenium carbene complexes which are so electrophilic that they attack a tethered olefin to furnish cyclopentene products; cyclopropanation or metathesis do not compete with this novel transformation. If the transient carbenes carry appropriate propargylic substituents, however, they engage in ([2,3]‐sigmatropic) rearrangements to give enol esters (carbonates, carbamates, sulfonates) or alkenyl halides. Both pathways are unprecedented in the vast hydrogenation literature. The proposed mechanistic scenarios are in line with labeling experiments and spectroscopic data; most notably, PHIP NMR spectroscopy (PHIP=parahydrogen induced polarization) provides compelling evidence that the reactions are indeed triggered by highly unorthodox gem‐hydrogenation events. [ABSTRACT FROM AUTHOR]

A simple experimental procedure for scaling carbene Brønsted basicity is described. The results highlight the strong basicity of pyrazol‐4‐ylidenes, a type of mesoionic carbene, also named cyclic‐bentallenes (CBA). They are more basic (pKaH >42.7 in acetonitrile) than the popular proazaphosphatrane Verkade bases, and even the Schwesinger phosphazene superbase P4(tBu). The basicity of these compounds can readily be tuned, and they are accessible in multigram quantities. These results open new avenues for carbon centered superbases. [ABSTRACT FROM AUTHOR]

We report the synthesis of acyl azolium salts stemming from thiazolylidenes CNS, triazolylidenes CTN, mesoionic carbenes CMIC and the generation of their corresponding radicals and enolates, covering about 60 Breslow‐type derivatives. This study highlights the role of additives in the redox behavior of these compounds and unveils several critical misconceptions about radical transformations of aldehyde derivatives under N‐heterocyclic carbene catalysis. In particular, the reducing ability of enolates has been dramatically underestimated in the case of biomimetic CNS. In contrast with previous electrochemical studies, we show that these catalytic intermediates can transfer electrons to iodobenzene within minutes at room temperature. Enols derived from CMIC are not the previously claimed super electron donors, although enolate derivatives of CNS and CMIC are powerful reducing agents. [ABSTRACT FROM AUTHOR]

Nickelacyclobutanes are mostly invoked as reactive intermediates in the reaction of nickel carbenes and olefins to yield cyclopropanes. Nevertheless, early work suggested that other decomposition routes such as β‐hydride elimination and even metathesis could be accessible. Herein, we report the isolation and characterization of a stable pentacoordinated nickelacyclobutane incorporated in a pincer complex. The coordination of different coligands to the nickelacyclobutane determines its selective decomposition along cyclopropanation, metathesis or apparent β‐hydride elimination pathways. DFT calculations shed light on the mechanism of these different pathways. [ABSTRACT FROM AUTHOR]

The reaction of propargyl esters with alkynylsilanes under gold catalysis provides vinylallene derivatives through consecutive [1,2]‐acyloxy/[1,2]‐silyl rearrangements. Good yields, full atom‐economy, broad substrate scope, easy scale‐up and low catalyst loadings are salient features of this novel transformation. Density Functional Theory (DFT) calculations suggest a reaction mechanism involving initial [1,2]‐acyloxy rearrangement to generate a gold vinylcarbene intermediate which upon regioselective attack of the alkynylsilane affords a vinyl cation which undergoes a type II‐dyotropic rearrangement involving the silyl group and the metal fragment. Preliminary results on the enantioselective version of this transformation are also disclosed. [ABSTRACT FROM AUTHOR]

The scarcity of reliable methods for synthesizing chiral gem‐diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium‐catalyzed B−H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem‐diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B−H bond was most likely the rate‐determining step. [ABSTRACT FROM AUTHOR]

A series of reactions between Lewis bases and an imidazole‐based dithione dimer (1) has been investigated. Both cyclic(alkyl)(amino)carbene (CAAC) (2) and N‐heterocyclic carbene (NHC) (4), in addition to N‐heterocyclic silylene (NHSi) (6), demonstrate the capability to cleave the sulphur–sulphur bonds in 1, giving carbene‐stabilized dithiolene (L0) zwitterions (3 and 5) and a spirocyclic silicon–dithiolene compound (7), respectively. The bonding nature of 3, 5, and 7 are probed by both experimental and theoretical methods. [ABSTRACT FROM AUTHOR]

Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or reagents, with general solutions lacking. Herein, we describe a selective copper‐catalyzed Markovnikov hydrofunctionalization of terminal alkynes that is facilitated by strongly donating cyclic (alkyl)(amino)carbene (CAAC) ligands. Using this method, both alkyl‐ and aryl‐substituted alkynes are coupled with a variety of boryl and silyl reagents with high α‐selectivity. The reaction is scalable, and the products are versatile intermediates that can participate in various downstream transformations. Preliminary mechanistic experiments shed light on the role of CAAC ligands in this process. [ABSTRACT FROM AUTHOR]

We report the discovery that simple carboxylic acids, such as benzoic acid, boost the activity of N‐heterocyclic carbene (NHC) catalysts in the oxidative esterification of aldehydes. A simple and efficient protocol for the transformation of a wide range of sterically hindered α‐ and β‐substituted aliphatic aldehydes/enals, catalyzed by a novel and readily accessible N‐Mes‐/N‐2,4,6‐trichlorophenyl 1,2,4‐triazolium salt, and benzoic acid as co‐catalyst, was developed. A whole series of α/β‐substituted aliphatic aldehydes/enals hitherto not amenable to NHC‐catalyzed esterification could be reacted at typical catalyst loadings of 0.02–1.0 mol %. For benzaldehyde, even 0.005 mol % of NHC catalyst proved sufficient: the lowest value ever achieved in NHC catalysis. Preliminary studies point to carboxylic acid‐induced acceleration of acyl transfer from azolium enolate intermediates as the mechanistic basis of the observed effect. [ABSTRACT FROM AUTHOR]

Single‐electron N‐heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C−C bonds. Guided by density functional theory and mechanistic analyses, we report the light‐driven synthesis of aliphatic and α‐amino ketones using single‐electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate‐dependent and can be modulated through steric and electronic parameters of the NHC. Catalyst potential is harnessed in the visible‐light driven generation of an acyl azolium radical species that undergoes selective coupling with various radical partners to afford diverse ketone products. This methodology is showcased in the direct late‐stage functionalization of amino acids and pharmaceutical compounds, highlighting the utility of single‐electron NHC operators. [ABSTRACT FROM AUTHOR]