Carbon-Based Weakly Coordinating Anions: Molecular Design, Synthesis and Applications.

Although carbanions, which are usually regarded as reactive species and powerful metalation reagents, can be stabilized through choice of the substitution pattern, they have rarely been considered for the design of weakly coordinating anions (WCA).  Here, we report on an evaluation of the potential of a series of differently substituted carbanions to serve as WCA by computational methods. This led us to the synthesize the water- and air-stable allyl anion 1 with triflyl and 3,5-bis(trifluoromethyl)phenyl (ArF) moieties, which can be isolated in high yields even on a gram-scale. Single crystal X-ray crystallography and NMR studies confirmed the weak coordination ability of the anion by showing negligible or only weak interactions with different cations. This property enabled the application of 1 in the stabilization of reactive group 14 and 15 cations. In addition to the crystallization of a phosphenium cation, the first all-carbon salt with a non-aromatic carbanion is reported, which revealed to be a convenient reagent for hydride abstraction such as from silanes. Overall, this work demonstrates the so far untapped potential of carbanions as WCA, that are accessible with a variety of different cations for various applications.

Reactivity of Superbasic Carbanions Generated via Reductive Radical-Polar Crossover in the Context of Photoredox Catalysis.

Photocatalytic reactions involving a reductive radical-polar crossover (RRPCO) generate intermediates with carbanionic reactivity. Many of these proposed intermediates resemble highly reactive organometallic compounds. However, conditions of their formation are generally not tolerated by their isolated organometallic versions and often a different reactivity is observed. Our investigations on their nature and reactivity under commonly used photocatalytic conditions demonstrate that these intermediates are indeed best described as free, superbasic carbanions capable of deprotonating common polar solvents usually assumed to be inert such as acetonitrile, dimethylformamide, and dimethylsulfoxide. Their basicity not only towards solvents but also towards electrophiles, such as aldehydes, ketones, and esters, is comparable to the reactivity of isolated carbanions in the gas-phase. Previously unsuccessful transformations thought to result from a lack of reactivity are explained by their high reactivity towards the solvent and weakly acidic protons of reaction partners. An intuitive explanation for the mode of action of photocatalytically generated carbanions is provided, which enables methods to verify reaction mechanisms proposed to involve an RRPCO step and to identify the reasons for the limitations of current methods.

Photoredox-Catalyzed Generation of Tertiary Anions from Primary Amines via a Radical Polar Crossover.

A method for the generation of tertiary carbanions via a deaminative radical-polar crossover is reported using redox active imines from α-tertiary primary amines. A variety of benzylic amines and amino esters can be used in this approach, with the latter engaging in a novel "aza-Reformatsky" reaction. Electronic trends correlate the stability of the resulting carbanion with reaction efficiency. The anions can be trapped with different electrophiles including aldehydes, ketones, imines, Michael acceptors, and H2 O/D2 O. Selective anion formation can be achieved in the presence of another equivalent or more acidic C-H bond in both an inter- and intramolecular fashion. Mechanistic studies suggest the intermediacy of a discrete carbanion intermediate.

C versus O Protonation in Zincate Anions: A Simple Gas-Phase Model for the Surprising Kinetic Stability of Organometallics.

For better understanding the intrinsic reactivity of organozinc reagents, we have examined the protolysis of the isolated zincate ions Et3 Zn- , Et2 Zn(OH)- , and Et2 Zn(OH)2 Li- by 2,2,2-trifluoroethanol in the gas phase. The protonation of the hydroxy groups and the release of water proceed much more efficiently than the protonation of the ethyl groups and the liberation of ethane. Quantum-chemical computations and statistical-rate theory calculations fully reproduce the experimental findings and attribute the lower reactivity of the more basic ethyl moiety to higher intrinsic barriers, which override the thermodynamic preference for its protonation. Thus, our minimalistic gas-phase model provides evidence for the intrinsically low reactivity of organozinc reagents toward proton donors and helps to explain their remarkable kinetic stability against moisture and even protic media.

Live Monitoring of Anionic Living Polymerizations by Electrospray-Ionization Mass Spectrometry.

Anionic polymerizations are of exceptional practical importance, but difficult to analyze due to the high reactivity of the growing polymer chains. Here, we demonstrate that electrospray-ionization mass spectrometry (ESI-MS) permits direct observation of the active carbanionic intermediates formed in the anionic ring-opening polymerization of 1-cyanocyclopropanecarboxylate in tetrahydrofuran. This includes the identification of a side product, as well as real-time analysis of the polymerization reaction. From the mass spectra obtained, we can derive not only the mean molar mass and the polydispersity, but also the rate constants for the initiation and the individual propagation steps. The initiation proceeds significantly faster than the propagation steps. Accordingly, the examined reaction corresponds to a living polymerization, as we also confirmed by additional control experiments. Besides giving detailed insight into the reaction system probed here, we also expect the presented methodology to make possible the in-situ analysis of further anionic polymerizations.

Crystalline Anions Based on Classical N-Heterocyclic Carbenes.

Herein, the first stable anions K[SIPrBp ] (4 a-K) and K[IPrBp ] (4 b-K) (SIPrBp =BpC{N(Dipp)CH2 }2 , IPrBp =BpC{N(Dipp)CH}2 ; Bp=4-PhC6 H4 ; Dipp=2,6-iPr2 C6 H3 ) derived from classical N-heterocyclic carbenes (NHCs) (i.e. SIPr and IPr) have been isolated as violet crystalline solids. 4 a-K and 4 b-K are prepared by KC8 reduction of the neutral radicals [SIPrBp ] (3 a) and [IPrBp ] (3 b), respectively. The radicals 3 a and 3 b as well as [Me-IPrBp ] 3 c (Me-IPrBp =BpC{N(Dipp)CMe}2 ) are accessible as crystalline solids on treatment of the respective 1,3-imidazoli(ni)um bromides (SIPrBp )Br (2 a), (IPrBp )Br (2 b), and (Me-IPrBp )Br (2 c) with KC8 . The cyclic voltammograms of 2 a-2 c exhibit two one-electron reversible redox processes in -0.5 to -2.5 V region that correspond to the radicals 3 a-3 c and the anions (4 a-4 c)- . Computational calculations suggest a closed-shell singlet ground state for (4 a-4 c)- with the singlet-triplet energy gap of 17-24 kcal mol-1 .

Probing Reactivity with External Forces: The Case of Nitroacetamides in Water.

Many computational methods have been applied to interpret and predict changes in reactivity by slight modifications of a given molecular scaffold. We describe a novel and simple method based on approximate density-functional theory of valence electrons that can be applied within a large high-performance computational infrastructure to probe such changes using a statistical sample of molecular configurations, including the solvent. All the used computational tools are fully open-source. Following our previous application, we are able to explain the high acidity of C-H bond at α position in nitro compounds when the amide linkage an ammonium group is inserted into the α substituent.

From Stable PH-Ylides to α-Carbanionic Phosphines as Ligands for Zwitterionic Catalysts.

Although ylides are commonly used reagents in organic synthesis, the parent methylphosphine MePH2 only exists in its phosphine form in the condensed phase. Its ylide tautomer H3 P+ -CH2 - is considerably higher in energy. Here, we report on the formation of bis(sulfonyl)methyl-substituted phosphines of the type (RO2 S)2 C(H)-PR2, which form stable PH ylides under ambient conditions, amongst the first examples of an acyclic phosphine which only exists in its PH ylide form. Depending on the exact substitution pattern the phosphines form an equilibrium between the PH ylide and the phosphine form or exist as one of both extremes. These phosphines were found to be ideal starting systems for the facile formation of α-carbanionic phosphines. The carbanion-functionalization leads to a switch from electron-poor to highly electron-rich phosphines with strong donor abilities and high basicities. Thus, the phosphines readily react with different electrophiles exclusively at the phosphorus atom and not at the carbanionic center. Furthermore, the anionic nature of the phosphines allows the formation of zwitterionic complexes as demonstrated by the isolation of a gold(I) complex with a cationic metal center. The cationic gold center allows for catalytic activity in the hydroamination of alkyne without requiring a further activation step.

Alkylation of Nitroarenes via Vicarious Nucleophilic Substitution - Experimental and DFT Mechanistic Studies.

Alkylation of nitroarenes via Vicarious Nucleophilic Substitution (VNS) was tested experimentally and modelled with DFT calculations. Mechanistic studies reveal intrinsic differences between reactions of archetypal carbanion precursor PhSO2 CH2 Cl, and alkyl phenyl sulfones, in which benzenesulfinate acts as a leaving group. Accordingly, for the latter precursors steric hindrance develops at the ß-elimination step, that raises energy barrier and results in the formation of byproducts.

THF-solvated Heavy Alkali Metal Benzyl Compounds (Na, Rb, Cs): Defined Deprotonation Reagents for Alkali Metal Mediation Chemistry.

The incorporation of heavy alkali metals into substrates is both challenging and essential for many reactions. Here, we report the formation of THF-solvated alkali metal benzyl compounds [PhCH2 M ⋅ (thf)n ] (M=Na, Rb, Cs). The synthesis was carried out by deprotonation of toluene with the bimetallic mixture n-butyllithium/alkali metal tert-butoxide and selective crystallization from THF of the defined benzyl compounds. Insights into the molecular structure in the solid as well as in solution state are gained by single crystal X-ray experiments and NMR spectroscopic studies. The compounds could be successfully used as alkali metal mediating reagents. The example of caesium showed the convenient use by deprotonating acidic C-H as well as N-H compounds to gain insight into the aminometalation using these reagents.

Synthesis of Polycyclic Aromatic Hydrocarbons Decorated by Fluorinated Carbon Acids/Carbanions.

The carboarylation reaction of biphenyl-alkynes was successfully triggered by electrophilic attack of 1,1-bis(triflyl)ethylene on the alkyne moiety to give polycyclic aromatic hydrocarbons (PAHs) decorated by superacidic carbon acid functionality. Neutralisation of thus obtained acids with NaHCO3 yielded the corresponding sodium salts, which showed improved solubility in both aqueous and organic solvents.

"Snapshot" Trapping of Multiple Transient Azolyllithiums in Batch.

Recent developments in flow microreactor technology have allowed the use of transient organolithium compounds that cannot be realized in a batch reactor. However, trapping the transient aryllithiums in a "halogen dance" is still challenging. Herein is reported the trapping of such short-lived azolyllithiums in a batch reactor by developing a finely tuned in situ zincation using zinc halide diamine complexes. The reaction rate is controlled by the appropriate choice of diamine ligand. The reaction is operationally simple and can be performed at 0 °C with high reproducibility on a multigram scale. This method was applicable to a wide range of brominated azoles allowing deprotonative functionalization, which was used for the concise divergent syntheses of both constitutional isomers of biologically active azoles.

Catalytic Generation of Carbanions through Carbonyl Umpolung.

Carbonyl Umpolung is a powerful strategy in organic chemistry to construct complex molecules. Over the last few years, versatile catalytic approaches for the generation of acyl anion equivalents from carbonyl compounds have been developed, but methods to obtain alkyl carbanions from carbonyl compounds in a catalytic fashion are still at an early stage. This Minireview summarizes recent progress in the generation of alkyl carbanions through catalytic carbonyl Umpolung. Two different catalytic approaches can be utilized to enable the generation of alkyl carbanions from carbonyl compounds: the catalytic Wolff-Kishner reaction and the catalytic single-electron reduction of carbonyl compounds and imines. We discuss the reaction scope, mechanistic insights, and synthetic applications of the methods as well as potential future developments.

A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes.

Installation of a carbanionic substituent, that is strongly stabilized by two (trifluoromethyl)sulfonyl (Tf=SO2 CF3 ) groups, into several fluorescence dyes including boron-dipyrromethenes (BODIPYs), fluoresceins, and aminocoumarins has been achieved by the 2,2-bis(triflyl)ethylation reaction of the dye frameworks with highly electrophilic Tf2 C=CH2 , followed by neutralization with NaHCO3 . Despite the contradiction between water solubility and lipophilicity, the carbanion-decorated dyes thus obtained showed significant enhancement of not only water solubility but also lipophilicity. This work clearly demonstrates that the fluorinated, highly stabilized carbanionic substituent is a new option for controlling the macroscopic property of chemical materials.

A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects.

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s reaction time), efficiently, and chemoselectively with a broad substrate scope in the environmentally responsible cyclopentyl methyl ether, at ambient temperature and under air, to provide ketones in up to 93 % yield with an effective suppression of the notorious over-addition reaction. Detailed DFT calculations and NMR investigations support the experimental results. The described methodology was proven to be amenable to scale-up and recyclability protocols. Contrasting classical procedures carried out under inert atmospheres, this work lays the foundation for a profound paradigm shift of the reactivity of carboxylic acid amides with organolithiums, with ketones being straightforwardly obtained by simply combining the reagents under aerobic conditions and with no need of using previously modified or pre-activated amides, as recommended.

Electrophilic and Nucleophilic Aromatic Substitutions are Mechanistically Similar with Opposite Polarity.

Confrontation of the recently formulated general mechanism of nucleophilic substitution in electron-deficient arenes with the well-known mechanism of electrophilic substitution revealed that these fundamental processes are mechanistically identical but proceed according to opposite polarity-an Umpolung relation. In this viewpoint this apparently controversial concept is supported by discussion of a variety of experimental results.

Aminopotassiation by Mixed Potassium/Lithium Amides: A Synthetic Path to Difficult to Access Phenethylamine Derivates.

Insights gained from a comparison of aminometalation reactions with lithium amides, potassium amides and mixed lithium/potassium amides are presented. A combination of structural characterization, DFT calculations and electrophile reactions of aminometalated intermediates has shown the advantages of using a mixed metal strategy. While potassium amides fail to add, the lithium amides are uncontrollable and eliminated, yet the mixed K/Li amides deliver the best of both systems. Aminopotassiation proceeds to form the alkylpotassium species which has enhanced stability over its lithium counterpart allowing for its isolation and thereby its further characterization.

Synthesis, Isolation and Crystal Structures of the Metalated Ylides [Cy3P-C-SO2Tol]M (M = Li, Na, K).

The preparation and isolation of the metalated ylides [Cy3PCSO2Tol]M ( Cy1-M) (with M = Li, Na, K) are reported. In contrast to its triphenylphosphonium analogue the synthesis of Cy1-M revealed to be less straight forward. Synthetic routes to the phosphonium salt precursor Cy1-H2 via different methods revealed to be unsuccessful or low-yielding. However, nucleophilic attack of the ylide Cy3P = CH2 at toluenesulfonyl fluoride under basic conditions proved to be a high-yielding method directly leading to the ylide Cy1-H. Metalation to the yldiides was finally achieved with strong bases such as nBuLi, NaNH2, or BnK. In the solid state, the lithium compound forms a tetrameric structure consisting of a (C-S-O-Li)4 macrocycle, which incorporates an additional molecule of lithium iodide. The potassium compound forms a C 4-symmetric structure with a (K4O4)2 octahedral prism as central structural motif. Upon deprotonation the P-C-S linkage undergoes a remarkable contraction typical for metalated ylides.

Building up Strain in One Step: Synthesis of an Edge-Fused Double Silacyclobutene from an Extensively Trichlorosilylated Butadiene Dianion.

The exhaustive trichlorosilylation of hexachloro-1,3-butadiene was achieved in one step by using a mixture of Si2 Cl6 and [nBu4 N]Cl (7:2 equiv) as the silylation reagent. The corresponding butadiene dianion salt [nBu4 N]2 [1] was isolated in 36 % yield after recrystallization. The negative charges of [1]2- are mainly delocalized across its two carbanionic (Cl3 Si)2 C termini (α-effect of silicon) such that the central bond possesses largely C=C double-bond character. Upon treatment with 4 equiv of HCl, [1]2- is converted into neutral 1,2,3,4-tetrakis(trichlorosilyl)but-2-ene, 3. The Cl- acceptor AlCl3 , induces a twofold ring-closure reaction of [1]2- to form a six-membered bicycle 4 in which two silacyclobutene rings are fused along a shared C=C double bond (84 %). Compound 4, which was structurally characterized by X-ray crystallography, undergoes partial ring opening to a monocyclic silacyclobutene 2 in the presence of HCl, but is thermally stable up to at least 180 °C.

Ligand effects on coordination properties of organolithium compounds: insights from computational experiments on a "weakened" Li.

A simple numerical experiment is presented which allows tuning the lithium electrophilicity, a parameter strongly affected by the solvent and additives coordination. A series of coordination of Li+ to carbanions or polydentate nucleophiles is examined showing the potential and the limits of this approach. The results suggest that such a simple trick can be remarkably helpful to model and decipher the effects of solvation on the structure and properties of lithiated organometallic species.