A computational study of oxiranyllithium

[reaction: see text] Computational methods were used to determine the structure, bonding, and aggregation states of oxiranyllithium in the gas phase and in THF solution, at 200 and 298 K. THF solvation was modeled by microsolvation with explicit THF ligands, forming a supermolecule that includes the oxiranyllithium aggregate and its first solvation shell. Because oxiranyllithium has a chiral center, two diastereomeric dimers were formed, the RR and the RS, along with their enantiomers. Similarly, three diastereomers of the tetramer were formed, the RRRR, RRRS, and RRSS and their enantiomers. Oxiranyllithium was found to exist predominantly as the tetramer in the gas phase, while the dimer was the dominant species in THF solution. The relative concentrations of the different stereoisomers were calculated from equilibrium constants.     

Introducing a Hydrogen‐Bond Donor into a Weakly Nucleophilic Brønsted Base: Alkali Metal Hexamethyldisilazides (MHMDS,M=Li,Na, K,Rb and Cs) with Ammonia

Alkali metal 1,1,1,3,3,3‐hexamethyldisilazide (MHMDSs) are one of the most utilised weakly nucleophilic Brønsted bases in synthetic chemistry and especially in natural product synthesis. Like lithium organics, they aggregate depending on the employed donor solvents. Thus, they show different reactivity and selectivity as a function of their aggregation and solvation state. To date, monomeric LiHMDS with monodentate donor bases was only characterised in solution. Since the first preparation of LiHMDS in 1959 by Wannagat and Niederprüm, all efforts to crystallise monomeric LiHMDS in the absence of chelating ligands failed. Herein, we present ammonia adducts of LiHMDS, NaHMDS, KHMDS, RbHMDS and CsHMDS with unprecedented aggregation motifs: 1) The hitherto missing monomeric key compound in the LiHMDS aggregation architectures. Monomeric crystal structures of trisolvated LiHMDS ( 1 ) and NaHMDS ( 2 ), showing unique intermolecular hydrogen bonds, 2) the unprecedented tetrasolvated KHMDS ( 3 ) and RbHMDS ( 4 ) dimers and 3) the disolvated CsHMDS ( 5 ) dimer with very close intermolecular Si?CH₃???Cs s‐block “agostic” interactions have been prepared and characterised by single‐crystal X‐ray structure analysis.     

Solvent effects on the aggregation state of lithium dialkylaminoborohydrides

DFT calculations were performed to determine the effects of ethereal solvents on the aggregation state of lithium dialkylaminoborohydrides (LABs). The calculations included dimerization energies in the gas phase, with continuum solvation only, microsolvation with coordinating ethereal ligands, and a combination of the microsolvation and continuum models. The continuum model alone overestimates the stability of the dimers, apparently due to the lack of steric effects from the coordinating ethereal ligands. The use of the combined microsolvation and continuum solvation models predicts lithium dimethylaminoborohydride to be a mixture of monomer and dimer in THF, and more sterically hindered lithium aminoborohydrides to exist primarily as monomers. The kinetics of amination of 1-chlorodecane by lithium dimethylaminoborohydride showed no detectable change in reaction rate with time, suggesting that the LAB reagent may exist primarily as a monomer in THF.     

7Li, 31P, and 1H pulsed gradient spin-echo (PGSE) diffusion NMR spectroscopy and ion pairing: on the temperature dependence of the ion pairing in Li(CPh3), fluorenyllithium, and Li[N(SiMe3)2] amongst other salts

7Li, 31P, and 1H variable-temperature pulsed gradient spin-echo (PGSE) diffusion methods have been used to study ion pairing and aggregation states for a range of lithium salts such as lithium halides, lithium carbanions, and a lithium amide in THF solutions. For trityllithium (2) and fluorenyllithium (9), it is shown that ion pairing is favored at 299 K but the ions are well separated at 155 K. For 2-lithio-1,3-dithiane (13) and lithium hexamethyldisilazane (LiHMDS 16), low-temperature data show that the ions remain together. For the dithio anion 13, a mononuclear species has been established, whereas for the lithium amide 16, the PGSE results allow two different aggregation states to be readily recognized. For the lithium halides LiX (X = Br, Cl, I) in THF, the 7Li PGSE data show that all three salts can be described as well-separated ions at ambient temperature. The solid state structure of trityllithium (2) is described and reveals a solvent-separated ion pair formed by a [Li(thf)4]+ ion and a bare triphenylmethide anion.     

A computational study of lithium enolate mixed aggregates

Ab initio calculations were performed to examine the formation of mixed dimer and trimer aggregates between the lithium enolate of acetaldehyde (lithium vinyloxide, LiOV) and lithium chloride, lithium bromide, and lithium amides. Gas-phase calculations showed that in the absence of solvation effects, the mixed trimer 2LiOV.LiX is the most favored species. Solvation in ethereal solvents was modeled by a combination of specific coordination of dimethyl ether ligands on each lithium and "dielectric solvation" (DSE, dielectric solvation energies), immersion of each molecule in a cavity within a continuous dielectric having the dielectric constant of THF at room temperature. DSE is less important for aggregates (reduced dipoles or quadrupoles) than monomers (dipoles) and is also reduced for the coordinatively solvated species. Both solvation terms reduce the exothermicity of aggregation. In many cases, lithium salts that are three- rather than four-coordinate have significant populations at room temperature. The strongly basic lithium amides prefer mixed aggregates with weaker bases than homoaggregates. The computational results are consistent with the limited experimental data available.     

Ketone enolization by lithium hexamethyldisilazide: structural and rate studies of the accelerating effects of trialkylamines

Mechanistic studies of the enolization of 2-methylcyclohexanone mediated by lithium hexamethyldisilazide (LiHMDS; TMS2NLi) in toluene and toluene/amine mixtures are described. NMR spectroscopic studies of LiHMDS/ketone mixtures in toluene reveal the ketone-complexed cyclic dimer (TMS2NLi)2(ketone). Rate studies using in situ IR spectroscopy show the enolization proceeds via a dimer-based transition structure, [(TMS2NLi)2(ketone)]++. NMR spectroscopic studies of LiHMDS/ketone mixtures in the presence of relatively unhindered trialkylamines such as Me2NEt reveal the quantitative formation of cyclic dimers of general structure (TMS2NLi)2(R3N)(ketone). Rate studies trace a >200-fold rate acceleration to a dimer-based transition structure, [(TMS2NLi)2(R3N)(ketone)]++. Amines of intermediate steric demand, such as Et3N, are characterized by recalcitrant solvation, saturation kinetics, and exceptional (>3000-fold) accelerations traced to the aforementioned dimer-based pathway. Amines of high steric demand, such as i-Pr2NEt, do not observably solvate (TMS2NLi)2(ketone) but mediate enolization via [(TMS2NLi)2(R3N)(ketone)]++ with muted accelerations. The most highly hindered amines, such as i-Bu3N, do not influence the LiHMDS structure or the enolization rate. Overall, surprisingly complex dependencies of the enolization rates on the structures and concentrations of the amines derive from unexpectedly simple steric effects. The consequences of aggregation, mixed aggregation, and substrate-base precomplexation are discussed.     

Reaction of ketones with lithium hexamethyldisilazide: competitive enolizations and 1,2-additions

Reaction of 2-methylcyclohexanone with lithium hexamethyldisilazide (LiHMDS, TMS(2)NLi) displays highly solvent-dependent chemoselectivity. LiHMDS in THF/toluene effect enolization. Rate studies using in situ IR spectroscopy are consistent with a THF concentration-dependent monomer-based pathway. LiHMDS in pyrrolidine/toluene affords exclusively 1,2-addition of the pyrrolidine fragment to form an alpha-amino alkoxide-LiHMDS mixed dimer shown to be a pair of conformers by using (6)Li, (15)N, and (13)C NMR spectroscopies. Rate studies are consistent with a monomer-based transition structure [(TMS(2)NLi)(ketone)(pyrrolidine)(3)](). The partitioning between enolization and 1,2-addition is kinetically controlled.     

Structure, bonding, and solvation of lithium vinylcarbenoids

[reaction: see text] Molecular modeling was used to determine the structure of lithium vinylcarbenoids in the gas phase and in THF solution. Solvent effects were modeled by microsolvation with explicit THF ligands on each of the lithium atoms. The carbenoid geometries are dependent on the heteroatom and on solvation. The calculations predict 1-chlorovinyllithium and 1-bromovinyllithium to be a mixture of monomer and dimer at 200 K and mostly monomer at higher temperatures, whereas the 1-fluoro-, 1-methoxy-, and 1-dimethylaminovinyllithium are predicted to be dimeric in solution.     

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.     

Equilibrium constants and alkylation kinetics of two lithium enolates/LiHMDS mixed aggregates in THF

[reaction: see text] Mixed aggregates between lithium enolates and lithium hexamethyldisilazide (LiHMDS) have been studied in THF using UV-vis spectroscopy. The equilibrium constants (K(agg)) between monomeric LiEn and monomeric LiHMDS are 760 and 560 M(-1) when LiEn are LiSIBP and LiBnPAT, respectively. The alkylation kinetics of the reactions with benzyl bromide were studied at 25 degrees C. The rate constants for the mixed aggregates, k(Mixed), are substantially smaller than those of the monomeric enolates.     

Amine- and ether-chelated aryllithium reagents-structure and dynamics

Chelation and aggregation in phenyllithium reagents with potential 6- and 7-ring chelating amine (2, 3) and 5-, 6-, and 7-ring chelating ether (4, 5, 6) ortho substituents have been examined utilizing variable temperature (6)Li and (13)C NMR spectroscopy, (6)Li and (15)N isotope labeling, and the effects of solvent additives. The 5- and 6-ring ether chelates (4, 5) compete well with THF, but the 6-ring amine chelate (2) barely does, and 7-ring amine chelate (3) does not. Compared to model compounds (e.g., 2-ethylphenyllithium 7), which are largely monomeric in THF, the chelated compounds all show enhanced dimerization (as measured by K = [D]/[M](2)) by factors ranging from 40 (for 6) to more than 200 000 (for 4 and 5). Chelation isomers are seen for the dimers of 5 and 6, but a chelate structure could be assigned only for 2-(2-dimethylaminoethyl)phenyllithium (2), which has an A-type structure (both amino groups chelated to the same lithium in the dimer) based on NMR coupling in the (15)N, (6)Li labeled compound. Unlike the dimer, the monomer of 2 is not detectably chelated. With the exception of 2-(methoxymethyl)phenyllithium (4), which forms an open dimer (12) and a pentacoordinate monomer (13), the lithium reagents all form monomeric nonchelated adducts with PMDTA.     

DFT study of the effect of sigma-ligands on the structure of ester enolates in THF, as models of the active center in the anionic polymerization of methyl methacrylate.

A Density Functional Theory (DFT) study was carried out on structures of the lithium ester enolate of methyl isobutyrate (MIB-Li) in THF solution, in the presence of TMEDA, dimethoxyethane (DME), crown ether 12-crown-4, and cryptand-2,1,1, as electron donor ligands (sigma-ligands). Both specific solvation with THF and/or ligand molecules and nonspecific solvation by the solvent continuum were taken into account. The possibility of ligand-separated ion pair formation was analyzed for each of the ligands, including THF alone. In most cases peripherally solvated dimers are the most stable species. Only in the presence of cryptand-2,1,1 was a ligand-separated triple ion pair, (MIB-Li-MIB)(-)(THF)(2),Li(2,1,1)(1)(+), shown to be comparable in stability to the THF-solvated dimer, (MIB-Li)(2)(THF)(4). These results are in agreement with experimental NMR data on the structure of MIB-Li in the presence of DME, 12-crown-4, and cryptand-2,1,1. An upfield shift of the (13)C NMR signal of the alpha-carbon of MIB-Li observed in the presence of cryptand-2,1,1, originally attributed to a ligand-separated monomer, MIB(-),Li(2,1,1)(+), was well reproduced by Hartree--Fock calculated NMR shifts for the predicted ligand-separated triple ion pair.     

Reversible enolization of beta-amino carboxamides by lithium hexamethyldisilazide

The enolization of beta-amino carboxamides by lithium hexamethyldisilazide (LiHMDS) in THF/toluene and subsequent diastereoselective alkylation with CH(3)I are reported. In situ IR spectroscopic studies reveal that beta-amino carboxamides coordinate to LiHMDS at -78 degrees C before enolization. Comparison with structurally similar carboxamides suggests that the beta-amino group promotes the enolization. IR spectroscopic studies also show that the enolization is reversible. Efficient trapping of the enolate by CH(3)I affords full conversion to products. (6)Li and (15)N NMR spectroscopic studies reveal that lithium enolate-LiHMDS mixed dimers and trimers as well as a homoaggregated enolate are formed during the reaction. At ambient temperature, racemization of the beta-position through a putative reversible Michael addition was observed.     

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.     

Lithium diisopropylamide-mediated reactions of imines, unsaturated esters, epoxides, and aryl carbamates: influence of hexamethylphosphoramide and ethereal cosolvents on reaction mechanisms

Several reactions mediated by lithium diisopropylamide (LDA) with added hexamethylphosphoramide (HMPA) are described. The N-isopropylimine of cyclohexanone lithiates via an ensemble of monomer-based pathways. Conjugate addition of LDA/HMPA to an unsaturated ester proceeds via di- and tetra-HMPA-solvated dimers. Deprotonation of norbornene epoxide by LDA/HMPA proceeds via an intermediate metalated epoxide as a mixed dimer with LDA. Ortholithiation of an aryl carbamate proceeds via a mono-HMPA-solvated monomer-based pathway. Dependencies on THF and other ethereal cosolvents suggest that secondary-shell solvation effects are important in some instances. The origins of the inordinate mechanistic complexity are discussed.     

Ion pair first and second acidities of some beta-diketones and aggregation of their lithium and cesium enediolates in THF

Ion pair pK values were measured for three beta-diketones in THF, 1-3, with lithium and cesium counterions. The results showed variations with concentration indicative of aggregation of the metal enolates to dimers. Similarly, ion pair pK values could be determined for some of these metal enolates going to the corresponding dimetal dienediolates which were also found to form dimers. These equilibria are more complicated to analyze because aggregation affects both sides of the proton transfer equilibria. The results show that all of the species measured exist mostly as dimers at concentrations >0.01 M typical of most organic synthesis reactions and physical measurements. NMR measurements show that the enols of 1 and 2, which can undergo intramolecular hydrogen bonding, predominate in both THF and DMSO solutions, whereas 3, whose enols cannot be so stabilized, is mostly keto in THF but approximately equimolar enol and keto in DMSO. Dimerization of the monolithium salts is rapid on the NMR time scale but that of the dilithium salts is slow.     

Effect of solvent on aggregation and reactivity of two lithium enolates(1)

Studies with two lithium enolates show that aggregation varies from comparable to lower in dimethoxyethane (DME) compared to tetrahydrofuran (THF) but that aggregation is much higher in methyl tert-butyl ether (MTBE). Alkylation reactions, which occur dominantly with the enolate monomers, are exceptionally slow in MTBE, but even acylation reactions that can occur with aggregates are orders of magnitude slower in MTBE. These reactions apparently require additional solvation of the lithium cation, and MTBE is ineffective at such solvation.     

Molecular structures of THF-solvated alkali-metal 2,2,6,6-tetramethylpiperidides finally revealed: X-ray crystallographic, DFT, and NMR (including DOSY) spectroscopic studies

The often studied THF solvates of the utility alkali-metal amides lithium and sodium 2,2,6,6-tetramethylpiperidide are shown to exist in the solid state as asymmetric cyclic dimers containing a central M(2)N(2) ring and one molecule of donor per metal to give a distorted trigonal planar metal coordination. DFT studies support these structures and confirm the asymmetry in the ring. In C(6)D(12) solution, the lithium amide displays a concentration-dependent equilibrium between a solvated and unsolvated species which have been shown by diffusion-ordered NMR spectroscopy (DOSY) to be a dimer and larger oligomer, respectively. A third species, a solvated monomer, is also present in very low concentration, as proven by spiking the NMR sample with THF. In contrast, the sodium amide displays a far simpler C(6)D(12) solution chemistry, consistent with the solid-state dimeric arrangement but with labile THF ligands.     

Solution and solid-state structures of lithiated cyclic phosphonates

Spectroscopic analysis of lithiated cyclic phospho-nates belonging to the 1,3,2-dioxaphosphorinane 2-oxide class have been examined by NMR spectroscopy in THF and by single-crystal X-ray crystallography. Lithio P-benzyl-1,3,2-dioxaphosphorinane 2-oxide (Li⁺7⁻) and lithio P-isopropyl-1,3,2-dioxaphosphorinane 2-oxide (Li⁺8⁻) are characterized by freely rotating, sp²-hybridized anions devoid of lithium–carbon contacts. The anions are most likely dimers linked through oxygen-lithium bridges. The P-isopropyl compound crystallized from TMEDA/THF as a C-lithiated dimer in which each lithium bridges a carbon and an oxygen and is solvated by one TMEDA molecule. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:209–218, 1998