Disolvated Dimer Research Articles

Sodium Hexamethyldisilazide: Using 15N-29Si Scalar Coupling to Determine Aggregation and Solvation States.

29Si NMR spectroscopy, the method of continuous variations, and density functional theory computations show that sodium hexamethyldisilazide (NaHMDS) is a disolvated dimer in toluene, a mixture of disolvated dimer and tetrasolvated monomer in THF/toluene, and exclusively monomer in neat THF. The dioxane-solvated NaHMDS only partially deaggregates to monomer even in neat dioxane. 15N-29Si coupling constants and 29Si chemical shifts show a high and dependable correlation with the aggregation state. Monitoring either chemical shift or coupling constant versus THF concentration even in the high-temperature, rapid-exchange limit affords the solvation numbers consistent with DFT computations. The preparation of 15N-labeled NaHMDS has been improved.

A Combined 1 H/6 Li NMR DOSY Strategy Finally Uncovers the Structure of Isopropyllithium in THF.

Despite its common use in synthesis, the structure of isopropylliyhium in THF has never been determined, a dimer being generally proposed but not supported. This paper fills this data gap through a sophisticated NMR study that shows that, in THF at low-temperature, isopropyllithium is in the form of a 1:2 mixture of a trisolvated monomer and a disolvated dimer in equilibrium. The presence of the monomer, never evoked before, together with a hypo-solvation of the dimer hinted by DFT calculations, provides a rational explanation to the remarkable reactivity of this organolithium reagent in ethereal solvents.

Doubly Diastereoconvergent Preparation and Microsolvation-Controlled Properties of (Z)- and (E)-1'-Lithio-1'-(2,6-dimethylphenyl)propenes.

A doubly diastereoconvergent reaction can ad libitum generate either one or the other of two diastereomeric products with complete consumption of the diastereomeric precorsors or their mixtures. Thus, the preparation of configurationally pure (Z)-1'-lithio-1'-(2,6-dimethylphenyl)propene [(Z)-1] from any Z,E mixture of the corresponding bromoalkenes with n-butyllithium succeeded by means of a user-friendly (E)-1 → (Z)-1 configurational interconversion. The subsequent treatment of (Z)-1 with a minimum amount of THF afforded exclusively (E)-1 as the other diastereomeric product and was mediated by a beneficial (Z)-1 → (E)-1 interconversion. This behavior provided microsolvation-controlled choices of highly diastereoselective derivatizations of 1. Low-temperature 13C NMR spectra established that (Z)-1 was dissolved as a trisolvated monomer in THF but as a disolvated dimer in monodentate, ethereal, non-THF solvents, whereas (E)-1 was always monomeric. Backed by such knowledge, kinetic experiments indicated that the electrophiles 1-bromobutane or ClSiMe3 in Et2O reacted at 32 °C with the tiny (NMR-invisible) population of monomeric (Z)-1 that was formed in a mobile equilibrium from the inactive, predominantly dimeric (Z)-1. The equilibration of monomeric (Z)-1 and (E)-1 in THF as the solvent was fast (seconds on the 1H NMR time scale), whereas the corresponding stereoinversion of both solvated and unsolvated (E)-1 → (Z)-1 in non-THF solvents occurred on the laboratory time scale (minutes at ambient temperatures). Dicyclopropyl ketone added rapidly to the monomers (Z)-1&3THF and (E)-1&3THF with a rate ratio of at least 14:1 in THF at -78 °C. Di-tert-butyl ketone added less rapidly to the less shielded (Z)-1 [but never to (E)-1]; this singly diastereoconvergent process was much more slowly reversible in THF.

Kinetics of α-(2,6-Dimethylphenl)vinyllithium: How To Control Errors Caused by Inefficient Mixing with Pairs of Rapidly Competing Ketones.

Kinetic studies are a suitable tool to disclose the role of tiny reagent fractions. The title compound 2 reacted in a kinetic reaction order of 0.5 (square root of its concentration) with an excess of the electrophiles ClSiMe3, 1-bromobutane (n-BuBr), or 1-iodobutane (n-BuI) at 32 °C in Et2O or in hydrocarbon solvents. This revealed that the tiny (NMR-invisible) amount of a deaggregated equilibrium component (presumably monomeric 2) was the reactive species, whereas the disolvated dimer 2 was only indirectly involved as a supply depot. Selectivity data (relative rate constants κobs) were collected from competition experiments with the faster reactions of 2 in THF and the addition reactions of 2 to carbonyl compounds. This provided the rate sequences of Et2C═O > dicyclopropyl ketone > t-Bu-C(═O)-Ph > diisopropyl ketone ≫ t-Bu2C═O > ClSiMe3 > n-BuI > n-BuBr ≈ (bromomethyl)cyclopropane (but t-Bu2C═O < ClSiMe3 in THF only) and also of cyclopropanecarbaldehyde > acetone ≥ t-Bu-CH═O. It is suggested that a deceivingly depressed selectivity (1 < κobs < kA/kB), caused by inefficient microscopic mixing of a reagent X with two competing substrates A and B, may become evident toward zero deviation from the correlation line of the usual inverse (1/T) linear temperature dependence of ln κobs.

What can 13C and 1H NMR lithiation shifts tell us about the charge distribution in α-arylvinyllithium compounds?

The energetically stabilizing delocalization of negative electric charge from the LiC(α) bond into the aryl π system of α-arylvinyllithiums, ArC(Li)CH2, is most efficient with an orthogonal relationship of the aryl ring plane and the CC double-bond plane. This aryl conformation remains favored with at least one ortho-substituent in the α-aryl group. The lithiation NMR shifts, Δδ = δ(R–Li) − δ(R–H), of the remote, para-positioned 13C and 1H nuclei appear to be dominated by the delocalized π charge (quasi-benzyllithium), as judged through comparison of the C-para/para-H lithiation shift quotients with that of benzyllithium. The magnitudes ∣Δδ(C-para)∣ observed with two α-(2-alkylphenyl)vinyllithiums are highest for the trisolvated monomers in THF and decrease with decreasing solvation and increasing aggregation. In 3-lithio-1,1-dimethylindene, on the other hand, the α-aryl group is conformationally fixed in a coplanar relationship with the CC double bond; this prevents a direct π charge delocalization from the LiC(α) bond into the adjacent aryl ring with the expected result of Δδ(C-para) ≈ 0 in the absence of electron donor ligands. However, the disolvated dimer of this conformationally flattened α-arylvinyllithium exhibited a Δδ(C-para) value whose magnitude was reduced by only 51% from that of the disolvated dimer of the above α-(2-methylphenyl)vinyllithium with its orthogonal orientation.

Microsolvation, Dimerization, and sp2-Stereoinversion of Monomeric α-(2,6-Diisopropylphenyl)vinyllithium

The title compound is entirely monomeric in THF as the solvent, but its two ortho-diisopropyl substituents (in contrast to two tert-butyl groups) do not suffice to prevent its dimerization in Et2O: At −107 °C, the disolvated dimer (43% of the total material in monomeric formula units) was accompanied by the disolvated (15%) and the trisolvated monomers (42%). Increasing temperatures reduced trisolvation by Et2O to disolvation and diminished also the combined monomer portions (10% at +25 °C); hence, dimerization in Et2O is endothermic (+3.1 kcal mol–1) but favored by a strongly positive entropy. Microsolvation by only one tert-butyl methyl ether (t-BuOMe) ligand per Li cation of the dimer in t-BuOMe solution was discovered through NMR integration; this disolvated dimer was also observed in cyclopentane as the solvent from −85 to at least +25 °C (hence, no monomer, no higher aggregate). Aryl rotations about the (partial) single bond to the carbanionic center C-α were assessed from the temperatures of NMR signal coalescences of the diastereotopic methyls in an isopropyl group: they are slowest in THF as the solvent because the monomer is then always trisolvated, and delocalization of the negative charge from C-α into the aromatic π-system is therefore most efficient (hence, more rotation-resistant). Microsolvation controls also the cis/trans sp2-stereoinversion, which is faster in THF than in the other three solvents because only one additional THF ligand must temporarily be immobilized (performing THF catalysis) on the way to the tetrasolvated, ionic transition state that involves rehybridization (close to sp) of C-α (pseudoactivation entropy ΔSψ⧧ = −23.6 cal mol–1 K–1). Most of the pertaining microsolvation numbers became available through their empirical relationship with the measured one-bond 13C–6Li NMR coupling constants.

Microsolvation, aggregation, and pseudomonomolecular, ionic sp2-stereoinversion mechanism of two exocyclic β,β-di-tert-alkyl-α-arylvinyllithiums

A THF-solvated, crystalline, exocyclic alkenyllithium, (tert-alkyl)2CC(Li)–Ph, was synthesized and shown to be a disolvated dimer in the solid state and in toluene as the solvent; increasing amounts of the monomeric species emerged on cooling the toluene solution. In THF as the solvent, only the trisolvated monomer was present and identified as a contact ion pair (CIP) through its scalar 13C,6Li NMR coupling. This ground-state needs only one further THF ligand as a catalyst for breaking the C–Li bond with formation of a tetrasolvated, solvent-separated ion pair (SSIP) on the way to the transition state of cis/trans sp2-stereoinversion. The ensuing pseudomonomolecular, ionic mechanism is confirmed by low pseudoactivation parameters: enthalpy ΔHψ‡ = 6.9(3) kcal mol−1; entropy ΔSψ‡ = −23.3(9) cal mol−1 K−1. Similar parameters were found with 2,6-dimethylphenyl in place of Ph.

Structures of Lithium N-Monosubstituted Anilides: Trisolvated Monomer to Tetrasolvated Dimer

Crystal structure determination of lithiated N-methylaniline with a variety of ligands, including tetrahydrofuran, methyltetrahydrofuran, trans-2,5-dimethyltetrahydrofuran, dimethoxyethane, tetrahydropyran and N,N-diethylpropionamide, reveals a common Li–N–Li–N four-membered-ring dimeric structure motif. A progression of solvation from tetrasolvated dimer (PhNMeLi·S2)2 through trisolvated dimer to disolvated dimer (PhNMeLi·S)2 was observed by increasing the steric hindrance of the ligand. Solid-state structures of several other lithium N-alkylanilides solvated by tetrahydrofuan are also reported. When the methyl group of N-methylaniline is replaced by an isopropyl or a phenyl group, trisolvated monomers are formed instead of dimers. Interestingly, the solid-state structure of lithiated N-isobutylaniline in tetrahydrofuran is a trisolvated dimer while that of lithium N-neopentylanilide is a disolvated dimer.

Mechanism of Lithium Diisopropylamide-Mediated Ester Deprotonation: The Role of Disolvated Monomers

Lithium diisopropylamide (LDA) is one of the most important Bronsted bases in organic synthesis.1 While LDA structure determinations2-4 have progressed quickly, rate studies have also established rate laws for several LDA-mediated reactions.5,6 However, the most important reaction of LDAsenolizationshas remained mechanistically opaque to date. We now report rate studies of an LDA-mediated ester enolization that constitutes the first detailed view of the key solvation and deaggregation events. LDA was generated from diisopropylamine using n-BuLi and was multiply recrystallized from hexane.3b Previous structural investigations have shown LDA to be a disolvated dimer (1) over a range of THF and LDA concentrations.3f,5 Pseudo-first-order conditions were established with LDA at normal concentrations (typically 0.10 M) by restricting the ester concentration to 0.004 M. The THF was maintained at high, yet adjustable, concentrations in toluene to determine the reaction order in THF. IR spectra were recorded with a ReactIR 1000 fitted with an immersible SiComp ATR probe.7 The disappearance of ester 2 (1727 cm-1) and the appearance of enolate 3 (1646-1664 cm-1) was readily monitored. An esterLDA complex is not observable under these conditions.8

ChemInform Abstract: Structure and Reactivity of Lithium Diisopropylamide (LDA). The Consequences of Aggregation and Solvation During the Metalation of an N,N‐Dimethylhydrazone.

Abstract6Li and 15N NMR spectroscopic studies are consistent with the assignment of LDA as the disolvated dimer (I).