A computational study of mixed aggregates of chloromethyllithium with lithium dialkylamides

DFT calculations were performed to examine the possible formation of mixed aggregates between chloromethyllithium carbenoids and lithium dimethylamide (LiDMA). In the gas phase mixed aggregates were readily formed and consisted of mixed dimers, mixed trimers, and mixed tetramers. THF solvation disfavored the formation of mixed tetramers and resulted in less exergonic free energies of mixed dimer and mixed trimer formation.     

Ketone enolization with lithium dialkylamides: the effects of structure,solvation, and mixed aggregates with excess butyllithium

The effects of lithium dialkylamide structure, mixed aggregate formation, and solvation on the stereoselectivity of ketone enolization were examined. Of the lithium dialkylamides examined, lithium tetramethylpiperidide (LiTMP) in THF resulted in the best enolization selectivity. The stereoselectivity was further improved in the presence of a LiTMP-butyllithium mixed aggregate. The use of less polar solvents reduced the enolization stereoselectivity. Ab initio calculations predict LDA and LiTMP to form mixed cyclic dimers in ethereal solvents. The calculations also predict LiTMP-alkyllithium mixed aggregates to competitively inhibit the formation of less stereoselective LiTMP-lithium enolate mixed aggregates.     

Structure, bonding, and aggregation of selenium-containing organolithium species

1,3-Dioxo compounds can be prepared from selenium-mediated carbonylation of lithium enolates in the presence of carbon monoxide. Intermediates in this reaction include several organic species that contain both selenium and lithium. The first step in understanding the detailed reaction mechanism is to understand the structure of these intermediates. Like most organolithium compounds, these species can exist as aggregates in solution. The B3LYP density functional theory (DFT) method was used to examine the gas phase and THF solvated structures of these compounds. The calculations showed that each of the compounds forms dimers or higher aggregates in the gas phase. Aggregates are also formed in THF solution, although solvation favors lower aggregates as compared to the gas phase.     

A NMR and theoretical study of the aggregates between alkyllithium and chiral lithium amides: control of the topology through a single asymmetric center

The complexes between methyllithium and chiral 3-aminopyrrolidine (3-AP) lithium amides bearing a second asymmetric center on their lateral amino group were studied using multinuclear ((1)H, (6)Li, (13)C, (15)N) low-temperature NMR spectroscopies in tetrahydrofuran-d(8). The results indicate that lithium chelation forces the pyrrolidine ring of the 3-AP to adopt a norbornyl-like conformation and that robust 1:1 noncovalent complexes between methyllithium and 3-AP lithium amides form in the medium. A set of (1)H-(1)H and (1)H-(6)Li NMR cross-coupling correlations shows that the binding of methyllithium can take place along the "exo" or the "endo" face of this puckered structure, depending on the relative configuration of the lateral chiral group. This aggregation step renders the nitrogen of the 3-amino group chiral, the "exo" and "endo" topologies corresponding to the (S) and (R) configurations, respectively, of this atom. Density functional theory calculations show that the "exo" and "endo" arrangements are, for both diastereomers, almost isoenergetic even when solvent is taken into account. This result suggests that the formation of the mixed aggregates is under strict kinetic control. A relationship between the topology of these complexes and the sense of induction in the enantioselective alkylation of aromatic aldehydes by alkyllithiums is proposed.     

Origin of the detrimental effect of lithium halides on an enantioselective nucleophilic alkylation of aldehydes

The effect of lithium halides on the enantioselectivity of the addition of methyllithium on o-tolualdehyde, in the presence of chiral lithium amides derived from chiral 3-aminopyrrolidines (3APLi), has been investigated. The enantiomeric excess of the resulting 1-o-tolylethanol was found to drop upon addition of significant amounts of LiCl, introduced before the aldehyde. The competitive affinity between the lithium amide, the methyllithium, and the lithium halides in THF was examined by multinuclear NMR spectroscopy and DFT calculations. The results showed that the original mixed aggregate of the chiral lithium amide and methyllithium is rapidly, totally, and irreversibly replaced by a similar 1:1 complex involving one lithium chloride or bromide and one lithium amide. While the MeLi/LiX substitution occurs with some degree of epimerization at the nitrogen for the endo-MeLi:3APLi complex, it is mostly stereospecific for the exo-type arrangements of the aggregate. The thermodynamic preference for mixed aggregates between 3APLi and LiX was confirmed by static DFT calculations: the data show that the LiCl and LiBr aggregates are more stable than their MeLi counterparts by more than 10 kcal.mol(-1) provided THF is explicitly taken into account. These results suggest that a sequestration of the source of chirality by the lithium halides is at the origin of the detrimental effect of these additives on the ee of the model reaction.     

Mixed Aggregates of 1-Methoxyallenyllithium with Lithium Chloride

A combined computational and ¹³C NMR study was used to investigate the formation of mixed aggregates of 1-methoxyallenyllithium and lithium chloride in tetrahydrofuran (THF) solution. The observed and calculated chemical shifts, as well as the calculated free energies of mixed aggregate formation (MP2/6-31+G(d)), are consistent with the formation of a mixed dimer as the major species in solution. Free energies of mixed dimer, trimer, and tetramer formation were calculated by using the B3LYP and MP2 methods and the 6-31+G(d) basis set. The two methods generated different predictions of which mixed aggregates will be formed, with B3LYP/6-31+G(d) favoring mixed trimers and tetramers in THF solution, and MP2/6-31+G(d) favoring mixed dimers. Formation of the sterically unhindered mixed dimers is also consistent with the enhanced reactivity of these compounds in the presence of lithium chloride. The spectra are also consistent with some residual 1-methoxyallenyllithium tetramer, as well as small amounts of higher mixed aggregates. Although neither computational method is perfect, for this particular system, the calculated free energies derived using the MP2 method are in better agreement with experimental data than those derived using the B3LYP method.     

A computational study of halomethyllithium carbenoid mixed aggregates with lithium halides and lithium methoxide

Density functional theory calculations were used to examine the formation of lithium halide and lithium alkoxide mixed aggregates with halomethyllithium carbenoids. These mixed aggregates may be the important intermediates in carbenoid reactions where lithium halides are formed as byproducts, or when the mixture has been exposed to small amounts of air. The calculations showed that in the gas phase and in THF solution, mixed dimers, trimers, and tetramers may coexist with free lithium carbenoids, depending on the lithium salt. The calculations also indicated that mixed aggregates may influence the activation free energies of cyclopropanation reactions of lithium carbenoids.     

Absolute solvation free energy of Li+ and Na+ ions in dimethyl sulfoxide solution: a theoretical ab initio and cluster-continuum model study

The solvation of the lithium and sodium ions in dimethyl sulfoxide solution was theoretically investigated using ab initio calculations coupled with the hybrid cluster-continuum model, a quasichemical theory of solvation. We have investigated clusters of ions with up to five dimethyl sulfoxide (DMSO) molecules, and the bulk solvent was described by a dielectric continuum model. Our results show that the lithium and sodium ions have four and five DMSO molecules into the first coordination shell, and the calculated solvation free energies are -135.5 and -108.6 kcal mol(-1), respectively. These data suggest a solvation free energy value of -273.2 kcal mol(-1) for the proton in dimethyl sulfoxide solution, a value that is more negative than the present uncertain experimental value. This and previous studies on the solvation of ions in water solution indicate that the tetraphenylarsonium tetraphenylborate assumption is flawed and the absolute value of the free energy of transfer of ions from water to DMSO solution is higher than the present experimental values.     

Re-weighted random series path integral simulations of molecular clusters: Applications to lithium solvated by a mixed Stockmayer cluster

Nuclear quantum effects in finite temperature simulations of molecular clusters are determined by taking advantage of a recently developed method based on the Feynman Path Integral. The structural and thermodynamic properties, including the nuclear quantum effects are determined for three Stockmayer clusters. The ionic system contain a lithium ion solvated by six strong dipoles and 12 weaker ones. The presence of the ion in the mixed Stockmayer cluster drastically enhances the fluxional nature of the less polar components which occupy the second solvation layer, whereas the neutral counterpart has the effect of reducing it. The nuclear quantum effects are significant at room temperature and above for the solvated ionic system. These are attributable to two factors: (a) the lightness of the lithium ion and (b) the stiffness of the ion-dipole interactions. At 300 K, the difference between the fully converged quantum and the classical heat capacities is about 1.3 K_B for the ionic cluster. This difference is about 10 SDs obtained from 95% confidence estimates of the statistical fluctuations. Cubic convergence is confirmed for temperatures as low as 50 K by regression analysis. The nuclear quantum effects do not change the peak melting temperature of the cluster.     

Supramolecular structure and physicochemical properties of the trichloromethane–ethanol mixtures

The excess thermodynamic functions (Gibbs energy, enthalpy, and entropy) and the dielectric permittivity of the trichloromethane–ethanol solutions have been analyzed in the entire range of compositions and in a wide temperature range in the framework of the quasichemical model of nonideal associated solution (QCNAS). The model of supramolecular structure, taking into account the chain-like and cyclic association of alcohol molecules and complexation of alcohol aggregates with trichloromethane, is able to reproduce the physicochemical properties of the mixtures with good accuracy. The equilibrium constants, enthalpies and entropies of aggregation, and structural parameters of supramolecular aggregates have been determined. Distribution functions of aggregates over size and structure have been calculated. Supramolecular ethanol aggregates with long-range molecular correlations, which extend beyond the nearest coordination shells have been revealed. Specific interactions are shown to give the main contribution to the positive deviations from the ideal solution behavior. Positive deviation of the dipole correlation factor from unity is due to predominantly parallel orientation of the dipoles in the ethanol aggregates and in the complexes with trichloromethane. The influence of ethanol association (linear and cyclic) as well as solvation on the physicochemical properties of the mixtures is discussed.     

Density functional study of lithium hexamethyldisilazide (LiHMDS) complexes: effects of solvation and aggregation

The title compound, lithium hexamethyldisilazide (LiHMDS), has been studied using modern quantum-chemical methods in the form of the B3LYP approach. Monomers, dimers, trimers, and tetramers, microsolvated with up to four THF molecules have been considered. The choice of model complex is seen to be important-for instance, the simpler water molecule is shown to be an inappropriate substitute for the THF solvent. Calculated lithium NMR shieldings are reported, but by themselves, they seem to be insufficient for unequivocal assignments of the different species. The energetics of aggregation and solvation have been studied. Temperature effects are seen to be important, and the degrees of solvation and aggregation are higher at 0 K than at 298 K. The highest degree of THF solvation for the monomer and dimer is found to be three (0 K) and two (298 K), respectively. The highest possible degree of aggregation for unsolvated LiHMDS is four. However, in nonpolar solvents, formation of the LiHDMS dimer from the trimer is thermodynamically preferred. The pathway is likely to involve an intermediate tetramer. In THF solution, di-solvated monomers and dimers are the most likely species.     

Enthalpy Characteristics and State of N,N-Disubstituted Amides of Formic and Acetic Acids in Water-Formamide Mixtures

The enthalpies of solution of N,N-disubstituted amides of formic and acetic acids at 298.15 K throughout the entire range of compositions of the water-formamide mixed solvent were measured. The enthalpies of solvation and transfer of the amides from water into the mixed solvent were calculated. The effects of the structure and properties of the solutes and also of the composition of the mixed solvent on their thermochemical characteristics were considered. The monotonous weakening of solvation of the alkylamides throughout the entire range of mixture compositions results from reduced exothermicity of their nonspecific and specific solvation. Analysis of the deviations of the enthalpies of transfer from additivity in composition showed that the hydrocarbon radicals of the amides are slightly more solvated by formamide, while the polar functional groups, by water.     

Ring opening reactions of quinoline substituted epoxides

6-Oxiranyl- and 3-oxiranyl-2-phenylquinoline-4-carboxylic acid diisopropylamides react with secondary amines and lithium amides to give (aminohydroxyethyl)quinolines but with opposite regioselectivities. Upon epoxidation of 3-formylquinoline 2 a 5:1 mixture of atropisomers is formed. This ratio is maintained upon epoxide ring-opening with amines in ethanol at reflux, but with lithium amides at room temperature a 1.3:1 ratio of isomers is obtained.     

Computational SN2‐Type Mechanism for the Difluoromethylation of Lithium Enolate with Fluoroform through Bimetallic C−F Bond Dual Activation

The reaction mechanism for difluoromethylation of lithium enolates with fluoroform was analyzed computationally (DFT calculations with the artificial force induced reaction (AFIR) method and solvation model based on density (SMD) solvation model (THF)), showing an S_N2‐type carbon–carbon bond formation; the “bimetallic” lithium enolate and lithium trifluoromethyl carbenoid exert the C?F bond “dual” activation, in contrast to the monometallic butterfly‐shaped carbenoid in the Simmons–Smith reaction. Lithium enolates, generated by the reaction of 2 equiv. of lithium hexamethyldisilazide (rather than 1 or 3 equiv.) with the cheap difluoromethylating species fluoroform, are the most useful alkali metal intermediates for the synthesis of pharmaceutically important α‐difluoromethylated carbonyl products.     

Free energy of solvation of simple ions: molecular-dynamics study of solvation of Cl- and Na+ in the ice/water interface

Molecular-dynamics simulations of Cl(-) and Na(+) ions are performed to calculate ionic solvation free energies in both bulk simple point-charge/extended water and ice 1 h at several different temperatures, and at the basal ice 1 h/water interface. For the interface we calculate the free energy of "transfer" of the ions across the ice/water interface. For the ions in bulk water in the NPT ensemble at 298 K and 1 atm, results are found to be in good agreement with experiments, and with other simulation results. Simulations performed in the NVT ensemble are shown to give equivalent solvation free energies, and this ensemble is used for the interfacial simulations. Solvation free energies of Cl(-) and Na(+) ions in ice at 150 K are found to be approximately 30 and approximately 20 kcal mol(-1), respectively, less favorable than for water at room temperature. Near the melting point of the model the solvation of the ions in water is the same (within statistical error) as that measured at room temperature, and in the ice is equivalent and approximately 10 kcal mol(-1) less favorable than the liquid. The free energy of transfer for each ion across ice/water interface is calculated and is in good agreement with the bulk observations for the Cl(-) ion. However, for the model of Na(+) the long-range electrostatic contribution to the free energy was more negative in the ice than the liquid, in contrast with the results observed in the bulk calculations.     

On the influence of nonlocal molecular vibrations and charge transfer on the spectra of aggregated push-pull chromophores

Through their fluorescence spectrum, aggregates of push-pull chromophores are good reporters of their microenvironment temperature and polarity. The understanding of the fluorescence and charge-separation dynamics in arrays composed of this type of species is consequently of considerable interest. In this article, we study the effect of charge fluctuations induced by molecular nonlocal vibrations on the electronic coupling between a pair of linear push-pull chromophores, for side-to-side or head-to-tail orientations, using a valence-bond charge-transfer (VB-CT) model and the Redfield equation. The results show that the exciton-vibrational dynamics along the bond length alternation coordinate can significantly modify the inter-molecular electronic coupling, which determines the fluorescence spectral band redshift due to aggregation. Numerical results for the electronic and exciton-vibrational contributions to the Coulombic coupling between two of these chromophores are obtained using experimentally based parameters for polyene linker species. The exciton-vibrational contribution is significant relative to the electronic contribution at room temperature in some ranges of the energy gap between the VB and CT states, and it is more important for the side-to-side than for the head-to-tail configuration. Our calculations also show that, even without including solvation effects, the spectral band associated with an S(0) → S(1) transition is redshifted with increasing temperature.     

Reaction field effects on the electronic structure of carbon radical and ionic centers

We examine solvent effects on carbon radical and ionic centers of HCXY by including a self-consistent reaction-field into the AM 1 and MNDO electronic structure models to mimic dielectric effects. We find that such concepts as merostability are principally solvent effects, and that, as expected, molecules with large dipoles or with charge assymmetry are stabilized more by solvent than those with atoms that are more electrically neutral. Of some importance in this study is the finding that conformation is also dependent on solvation and that change in geometry must be considered if an accurate estimate is to be made of energy differences such as those examined in the calculations of merostabilization.     

Theory of solvation in polar nematics

We develop a linear response theory of solvation of ionic and dipolar solutes in anisotropic, axially symmetric polar solvents. The theory is applied to solvation in polar nematic liquid crystals. The formal theory constructs the solvation response function from projections of the solvent dipolar susceptibility on rotational invariants. These projections are obtained from Monte Carlo simulations of a fluid of dipolar spherocylinders which can exist both in the isotropic and nematic phases. Based on the properties of the solvent susceptibility from simulations and the formal solution, we have obtained a formula for the solvation free energy which incorporates the experimentally available properties of nematics and the length of correlation between the dipoles in the liquid crystal. The theory provides a quantitative framework for analyzing the steady-state and time-resolved optical spectra and makes several experimentally testable predictions. The equilibrium free energy of solvation, anisotropic in the nematic phase, is given by a quadratic function of cosine of the angle between the solute dipole and the solvent nematic director. The sign of solvation anisotropy is determined by the sign of dielectric anisotropy of the solvent: solvation anisotropy is negative in solvents with positive dielectric anisotropy and vice versa. The solvation free energy is discontinuous at the point of isotropic-nematic phase transition. The amplitude of this discontinuity is strongly affected by the size of the solute becoming less pronounced for larger solutes. The discontinuity itself and the magnitude of the splitting of the solvation free energy in the nematic phase are mostly affected by microscopic dipolar correlations in the nematic solvent. Illustrative calculations are presented for the equilibrium Stokes shift and the Stokes shift time correlation function of coumarin-153 in 4-n-pentyl-4'-cyanobiphenyl and 4,4-n-heptyl-cyanopiphenyl solvents as a function of temperature in both the nematic and isotropic phases.     

Temperature effect on the absorption spectrum of the hydrated electron paired with a lithium cation in deuterated water

The absorption spectra of the hydrated electron in 1.0 to 4.0 M LiCl or LiClO4 deuterated water solutions were measured by pulse radiolysis techniques from room temperature to 300 degrees C at a constant pressure of 25 MPa. The results show that when the temperature is increased and the density is decreased, the absorption spectrum of the electron in the presence of a lithium cation is shifted to lower energies. Quantum classical molecular dynamics (QCMD) simulations of an excess electron in bulk water and in the presence of a lithium cation have been performed to compare with the experimental results. According to the QCMD simulations, the change in the shape of the spectrum is due to one of the three p-like excited states of the solvated electron destabilized by core repulsion. The study of s --> p transition energies for the three p-excited states reveals that for temperatures higher than room temperature, there is a broadening of each individual s --> p absorption band due to a less structured water solvation shell.