Metallocenium incorporated charge-enhanced thiourea catalysts.

Several metallocenium derivatives were prepared including N-ferrocenium-N'-phenylthiourea tetrakis-[3,5-bis(trifluoromethyl)phenyl]borate (BArF4, 4a), N-methylferrocenium-N'-phenylthiourea BArF4 (4b) and N-cobaltocenium-N'-phenylthiourea BArF4 (5). These compounds are competent catalysts for the Friedel-Crafts alkylation of indoles with trans-ß-nitrostyrenes, and are much more active than their reduced non-charged forms. The iron derivatives are less stable than the cobalt analog and were generated and used in situ whereas the cobalt-containing thiourea was isolated and characterized by X-ray crystallography. All three of these metallocenium salts have Lewis and Brønsted acidic sites which were exploited in tandem to afford charge-activated catalysts.

Electrostatically Enhanced 3- and 4-Pyridyl Borate Salt Nucleophiles and Bases.

A variety of electrostatically enhanced 3- and 4-pyridylborate salt catalysts are reported and show significant improvement over an activated noncharged neutral control compound. Their nucleophilicity in a stoichiometric SN2 reaction and catalytic performance in a urethane synthesis are evaluated along with three methods for rapidly evaluating the basicity of these species. That is, qualitative titrations in CH2Cl2 and CHCl3 were carried out, two separate solution-state IR studies in CCl4 and CDCl3 are reported, and the proton affinities of the anionic components of the salts were computed. Charge differences between the anion and its protonated zwitterionic conjugate acid are evaluated along with the highest occupied molecular orbitals of the anions in relationship to some of the surprising reactivity findings that were observed in the two kinetic studies.

Anion-Activated Bases and Nucleophiles Characterized by Photoelectron Spectroscopy.

Negative ion photoelectron spectra at 20 K along with ab initio [CCSD(T)] and M06-2X density functional theory calculations are reported for a series of six basic and nucleophilic pyridine derivatives with an anionic substituent [i.e., 3- and 4-PyrBX3-, where X = F, 4-t-BuC6H4, 4-MeOC6H4, and 3,5-(MeO)2C6H3]. Vertical detachment energies (VDEs) of these charge-activated reagents span from 4.50-5.85 eV and are well reproduced by M06-2X/aug-cc-pVTZ and CCSD(T)/maug-cc-pVTZ computations. Surprisingly, the VDEs are found to correlate with the SN2 reactivity of the PPh4+ salts of the substituted pyridine anions with 1-iodooctane in dichloromethane. This provides an experimental measure of the nucleophilicity of these charge-activated anions, which represent a new class of chemical reagent.

How generic is iodide-tagging photoelectron spectroscopy: An extended investigation on the Gly·X- (Gly = glycine, X = Cl or Br) complexes.

We report a joint negative ion photoelectron spectroscopy (NIPES) and quantum chemical computational study on glycine-chloride/bromide complexes (denoted Gly·X-, X = Cl/Br) in close comparison to the previously studied Gly·I- cluster ion. Combining experimental NIPE spectra and theoretical calculations, various Gly·X- complexes were found to adopt the same types of low-lying isomers, albeit with different relative energies. Despite more congested spectral profiles for Gly·Cl- and Gly·Br-, spectral assignments were accomplished with the guidance of the knowledge learned from Gly·I-, where a larger spin-orbit splitting of iodine afforded well-resolved, recognizable spectral peaks. Three canonical plus one zwitterionic isomer for Gly·Cl- and four canonical conformers for Gly·Br- were experimentally identified and characterized in contrast to the five canonical ones observed for Gly·I- under similar experimental conditions. Taken together, this study investigates both genericity and variations in binding patterns for the complexes composed of glycine and various halides, demonstrating that iodide-tagging is an effective spectroscopic means to unravel diverse ion-molecule binding motifs for cluster anions with congested spectral bands by substituting the respective ion with iodide.

Liberating the Anion: Evaluating Weakly Coordinating Cations.

A series of commonly used weakly coordinating cations (WCCs) including tetraalkylammonium, bis(triphenylphosphine)iminium (PPN), P2 and P5 phosphazenium, and tetraphenylphosphonium ions were investigated along with five additional tetraarylphosphonium ions [Ar = 4-Me, 4-t-Bu, 3,5-Me2, 4-Me2N, and 3,5-(MeO)2 phenyl derivatives]. Dissociation enthalpies of their chloride complexes were computed in the gas phase and in dichloromethane. These results are compared to infrared spectra of these salts in chloroform-d which provide free and bound C-D stretches, 19F NMR spectra of the corresponding tetrafluoroborate salts, ion-pair equilibrium constants, and reaction rates of the chlorides and acetates with 1-iodooctane. The latter transformation was also carried out under catalytic conditions. Substituted tetraphenylphosphonium ion derivatives are found to be surprisingly good WCCs that function as well or better than the P2 and P5 phosphazenium ions, the current WCC gold standard.

N-Vinyl and N-Aryl Hydroxypyridinium Ions: Charge-Activated Catalysts with Electron-Withdrawing Groups.

Charge-enhanced Brønsted acid organocatalysts with electron-withdrawing substituents were synthesized, and their relative acidities were characterized by computations, 1:1 binding equilibrium constants (K1:1) with a UV-vis active sensor, 31P NMR shifts upon coordination with triethylphosphine oxide, and in one case by infrared spectroscopy. Pseudo-first-order rate constants were determined for the Friedel-Crafts alkylations of N-methylindole with trans-ß-nitrostyrene and 2,2,2-trifluoroacetophenone and the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone. These results along with kinetic isotope effect determinations revealed that the rate-determining step in the Friedel-Crafts transformations can shift from carbon-carbon bond formation to proton transfer to the catalyst's conjugate base. This leads to an inverted parabolic reaction rate profile and slower reactions with more acidic catalysts in some cases. Electron-withdrawing groups placed on the N-vinyl and N-aryl substituents of hydroxypyridinium ion salts lead to enhanced acidities, more acidic catalysts than trifluoroacetic acid, and a linear correlation between the logarithms of the Diels-Alder rate constants and measured K1:1 values.

Electrostatically Enhanced Phosphoric Acids and Their Applications in Asymmetric Friedel-Crafts Alkylations.

A series of electrostatically enhanced phosphoric acid catalysts were synthesized and studied. These compounds possess two positively charged N-octylpyridinium or triarylphosphonium ion centers at the 3,3'-positions of the (R)-BINOL backbone to enhance reactivity and provide needed steric bulk for enantioselective transformations. Catalytic activities for Friedel-Crafts alkylations of indoles with trans-ß-nitrostyrenes were studied. Both types of catalysts accelerate reaction conversions relative to noncharged analogues, and good enantioselectivities up to 90% ee are observed with the phosphonium-ion-tagged phosphoric acids. This transformation also can be scaled up to synthetically useful amounts, affording >250 mg of product without losing any reactivity or selectivity.

Ferrocene Acidity and C-H Bond Dissociation Energy via Experiment and Theory.

The gas-phase acidity of ferrocene (ΔH°acid(1) = 391.5 ± 1.3 kcal mol-1) and electron affinity of the ferrocenyl radical (EA(1r) = 1.74 ± 0.08 eV) were measured in a Fourier transform mass spectrometer and combined in a thermodynamic cycle with the known ionization energy of the hydrogen atom to afford the C-H bond dissociation energy of 1 (BDE(1) = 118.0 ± 2.3 kcal mol-1). Companion M06-2X but not B3LYP computations reproduce each of these thermodynamic quantities and are in accord with an unusually strong aromatic C-H BDE. Natural population analysis and atomic polar tensor charges indicate that a covalent description of ferrocene with a neutral iron atom is a better representation of this compound than an ionic one with a doubly charged Fe2+ center. Predicted structural differences upon deprotonation of MCp2, M = Fe and Mg, are also in accord with this view.

Quantification of Catalytic Activity for Electrostatically Enhanced Thioureas via Reaction Kinetics and UV-vis Spectroscopic Measurement.

Charged thiourea derivatives containing one and two methylated or octylated pyridinium ion centers and a tetraarylborate or triflate counteranion are reported. These novel catalysts are much more active in the Friedel-Crafts reactions of trans-ß-nitroalkenes with N-methylindoles than the privileged N, N'-bis(3,5-bis(trifluoromethyl)phenyl)thiourea (i.e., Schreiner's thiourea) by up to 2-3 orders of magnitude. A previously reported UV-vis spectroscopic method by Kozlowski et al. was exploited to rationalize their reactivity order along with noncharged analogues. These results offer a new design strategy for organocatalysts by introducing positively charged centers without adding additional N-H, O-H, or S-H hydrogen bond donor sites.

Synthesis of Cyclic Organic Carbonates Using Atmospheric Pressure CO2 and Charge-Containing Thiourea Catalysts.

Cycloadditions of epoxides with CO2 to synthesize cyclic five-membered ring organic carbonates are of broad interest from a synthetic, environmental, and green chemistry perspective, and the development of effective catalysts for these transformations is an ongoing challenge. A series of eight charge-containing thiourea salts that catalyze these reactions under mild conditions (i.e., 60 °C and atmospheric CO2 pressure) are reported. Substrate scope and mechanistic studies were also carried out, isotope effects were measured, and a reactive intermediate was isolated revealing a surprising pathway in which a thiourea catalyst serves as a nucleophile in the cleavage of the epoxide ring.

Enantioselective Friedel-Crafts Alkylation between Nitroalkenes and Indoles Catalyzed by Charge Activated Thiourea Organocatalysts.

A series of methylated and octylated pyridinium and quinolinium containing thiourea salts with a chiral 2-indanol substituent are reported. These organocatalysts are positively charged analogues of privileged bis(3,5-trifluoromethyl)phenyl substituted thioureas, and are found to be much more active catalysts despite the absence of an additional hydrogen bond donor or acceptor site (i.e., the presence of a heteroatom-hydrogen or heteroatom). Friedel-Crafts reactions of trans-ß-nitorostyrenes with indoles are examined, and good yields and enantioselectivities are obtained. Mechanistic studies indicate that this is a second-order transformation under the employed conditions, and is consistent with the dimer of the thiourea being the active catalyst. Charged organocatalysts, consequently, represent an attractive design strategy for catalyst development.

Phenylcyclopropane Energetics and Characterization of Its Conjugate Base: Phenyl Substituent Effects and the C-H Bond Dissociation Energy of Cyclopropane.

The α-C-H bond dissociation energy (BDE) of phenylcyclopropane (1) was experimentally determined using Hess' law. An equilibrium acidity determination of 1 afforded ΔH°acid = 389.1 ± 0.8 kcal mol-1, and isotopic labeling established that the α-position of the three-membered ring is the favored deprotonation site. Interestingly, the structure of the base proved to be a key factor in correctly determining the proper ionization site (i.e., secondary amide ions are needed, and primary ones and OH- lead to incorrect conclusions since they scramble the deuterium label). An experimental measurement of the electron affinity of 1-phenylcyclopropyl radical (EA = 17.5 ± 2.8 kcal mol-1) was combined with the ionization energy of hydrogen (313.6 kcal mol-1) to afford BDE = 93.0 ± 2.9 kcal mol-1. This enabled the effect of the phenyl substituent to be evaluated and compared to other situations where it is attached to an sp3- or sp2-hybridized carbon center. M06-2X, CCSD(T), G4, and W1BD computations were also carried out, and a revised C-H BDE for cyclopropane of 108.9 ± 1.0 kcal mol-1 is recommended.

Anion Binding of One-, Two-, and Three-Armed Thiourea Receptors Examined via Photoelectron Spectroscopy and Quantum Computations.

Benzene rings substituted with 1-3 thiourea containing arms (1-3) were examined by photoelectron spectroscopy and density functional theory computations. Their conjugate bases and chloride, acetate, and dihydrogen phosphate anion clusters are reported. The resulting vertical and adiabatic detachment energies span 3.93-5.82 eV (VDE) and 3.65-5.10 (ADE) for the deprotonated species and 4.88-5.97 eV (VDE) and 4.45-5.60 eV (ADE) for the anion complexes. These results reveal the stabilizing effects of multiple hydrogen bonds and anionic host-guest interactions in the gas phase. Previously measured equilibrium binding constants in aqueous dimethyl sulfoxide for all three thioureas are compared to the present results, and cooperative binding is uniformly observed in the gas phase but only for one case (i.e., 3·H2PO4-) in solution.

Flexible Acyclic Polyol-Chloride Anion Complexes and Their Characterization by Photoelectron Spectroscopy and Variable Temperature Binding Constant Determinations.

Flexible acyclic alcohols with one to five hydroxyl groups were bound to a chloride anion and these complexes were interrogated by negative ion photoelectron spectroscopy and companion density functional theory computations. The resulting vertical detachment energies are reproduced on average to 0.10 eV by M06-2X/aug-cc-pVTZ predictions and range from 4.45-5.96 eV. These values are 0.84-2.35 eV larger than the adiabatic detachment energy of Cl(-) as a result of the larger hydrogen bond networks in the bigger polyols. Adiabatic detachment energies of the alcohol-Cl(-) clusters are more difficult to determine both experimentally and computationally. This is due to the large geometry changes that occur upon photodetachment and the large bond dissociation energy of H-Cl which enables the resulting chlorine atom to abstract a hydrogen from any of the methylene (CH2) or methine (CH) positions. Both ionic and nonionic hydrogen bonds (i.e., OH···Cl(-) and OH···OH···Cl(-)) form in the larger polyols complexes and are found to be energetically comparable. Subtle structural differences, consequently can lead to the formation of different types of hydrogen bonds, and maximizing the ionic ones is not always preferred. Solution equilibrium binding constants between the alcohols and tetrabutylammonium chloride (TBACl) in acetonitrile at -24.2, +22.0, and +53.6 °C were also determined. The free energies of association are nearly identical for all of the substrates (i.e., ΔG° = -2.8 ± 0.7 kcal mol(-1)). Compensating enthalpy and entropy values reveal, contrary to expectation and the intrinsic gas-phase preferences, that the bigger systems with more hydroxyl groups are entropically favored and enthalpically disfavored relative to the smaller species. This suggests that more solvent molecules are released upon binding TBACl to alcohols with more hydroxyl groups and is consistent with the measured negative heat capacities. These quantities increase with molecular complexity of the substrate, however, contrary to common interpretation of these values.

Charge-enhanced acidity and catalyst activation.

Acidities are commonly measured in polar solvents but catalytic reactions are typically carried out in nonpolar media. IR spectra of a series of phenols in CCl4 and 1% CD3CN/CCl4 provide relative acidities. Nonprotonated charged substituents with an appropriate counterion are found to enhance their Brønsted acidities and improve catalyst performance by orders of magnitude.

Preorganized Hydrogen Bond Donor Catalysts: Acidities and Reactivities.

Measured DMSO pKa values for a series of rigid tricyclic adamantane-like triols containing 0-3 trifluoromethyl groups (i.e., 3(0)-3(3)) are reported. The three compounds with CF3 substituents are similar or more acidic than acetic acid (pKa = 13.5 (3(1)), 9.5 (3(2)), 7.3 (3(3)) vs 12.6 (HOAc)), and the resulting hydrogen bond network enables a remote γ-trifluoromethyl group to enhance the acidity as well as one located at the α-position. Catalytic abilities of 3(0)-3(3) were also examined. In a nonpolar environment a rate enhancement of up to 100-fold over flexible acyclic analogs was observed presumably due to an entropic advantage of the locked-in structure. Gas-phase acidities are found to correlate with the catalytic activity better than DMSO pKa values and appear to be a better measure of acidities in low dielectric constant media. These trends are reduced or reversed in polar solvents highlighting the importance of the reaction environment.

Power of a remote hydrogen bond donor: anion recognition and structural consequences revealed by IR spectroscopy.

Natural and synthetic anion receptors are extensively employed, but the structures of their bound complexes are difficult to determine in the liquid phase. Infrared spectroscopy is used in this work to characterize the solution structures of bound anion receptors for the first time, and surprisingly only two of three hydroxyl groups of the neutral aliphatic triols are found to directly interact with Cl(­). The binding constants of these triols with zero to three CF3 groups were measured in a polar environment, and KCD3CN(Cl(­)) = 1.1 × 10(6) M(­1) for the tris(trifluoromethyl) derivative. This is a remarkably large value, and high selectivity with respect to interfering anions such as, Br(­), NO3(­) and NCS(­) is also displayed. The effects of the third "noninteracting" hydroxyl groups on the structures and binding constants were also explored, and surprisingly they are as large or larger than the OH substituents that hydrogen bond to Cl(­). That is, a remote hydroxyl group can play a larger role in binding than two OH substituents that directly interact with an anionic center.

Synthesis and properties of the strained alkene perfluorobicyclo[2.2.0]hex-1(4)-ene.

The title fluoroalkene has been generated by dehalogenation of dibromide and diiodide precursors and trapped in situ. retro-Diels-Alder reaction of its adduct with N-benzylpyrrole has made the alkene available in high yield and purity. In sharp contrast to its extremely labile hydrocarbon counterpart, the fluoroalkene is very stable yet highly reactive. Its characterization includes its electron affinity, photoelectron spectrum, and the previously reported structure determination by electron diffraction.

Selective binding and extraction of aqueous dihydrogen phosphate solutions via three-armed thiourea receptors.

A series of neutral anion receptors with one to three thiourea arms were synthesized and their binding to tetrabutylammonium chloride, acetate, and dihydrogen phosphate salts in aqueous DMSO mixtures was examined. The three-armed thiourea host was found to strongly and selectively bind H2PO4(-) even in DMSO solutions containing up to 30% water. This enabled the dihydrogen phosphate salt to be extracted from water into chloroform in its dibasic form despite the high heat of the hydration of HPO4(2-).

Stereoelectronic effects: a simple yet powerful tool to manipulate anion affinity.

Different strategies are employed in designing strong and selective anion receptors but stereoelectronic effects have been largely ignored. In this work, the stereo configuration of a non-interacting ether is found to have a large impact of more than two orders of magnitude on the binding of a rigid diol with tetrabutylammonium chloride in acetonitrile-d3. A favorable carbon-oxygen dipole and an intramolecular C-HOH hydrogen bond in an equatorially substituted ether is found to be energetically more important than a stabilizing hydrogen bond in the corresponding axially oriented alcohol. IR spectroscopy is also used to probe the structures of the bound complexes and several binding motifs are identified.