Lithium Diisopropylamide Solvated by Monodentate and Bidentate Ligands:  Solution Structures and Ligand Binding Constants

Abstract

6Li and 15N NMR spectroscopic studies of lithium diisopropylamide ([6Li]LDA and [6Li,15N]LDA) in toluene/pentane solutions containing a variety of mono- and polydentate ligands are reported. LDA forms exclusively dimers in the presence of n-BuOMe, Et2O, t-BuOMe, THF, 2-methyltetrahydrofuran, 2,2-dimethyltetrahydrofuran, tetrahydropyran, dimethoxyethane, N,N,N‘,N‘-tetramethylethylenediamine, and MeOCH2CH2NR2 (NR2 = NMe2, NEt2, pyrrolidino). Addition of 1,2-dipyrrolidinoethane and (2-pyrrolidinoethyl)dimethylamine provides monomer−dimer mixtures. Treatment of LDA with trans-N,N,N‘,N‘-tetramethylcyclohexanediamine (TMCDA) or trans-1-(dimethylamino)-2-isopropoxycyclohexane in hydrocarbons afford exclusively monomers. Sparteine binds only reluctantly, giving a mixture of unsolvated oligomers and monomer. Competitions of the ethereal ligands vs TMCDA afford binding constants and associated free energies for dimer solvation which are correlated with those obtained previously for lithium hexamethyldisilazide.

Regioselective Lithium Diisopropylamide-Mediated Ortholithiation of 1-Chloro-3-(trifluoromethyl)benzene: Role of Autocatalysis, Lithium Chloride Catalysis, and Reversibility

“…23 A plot of initial rates versus THF concentration using hexanes as cosolvent (Figure 15) shows a high (1.6 ± 0.3) order in THF. The curvature—a departure from a linear first-order dependence—was traced to medium effects using a now-routine protocol 38 in which the hydrocarbon is replaced with the polar 39 yet weakly coordinating 40 cosolvent, 2,5-dimethyltetrahydrofuran (Me 2 THF). Holding the polarity of the medium approximately constant afforded a THF order slightly above unity (1.1 ± 0.1 order).…”

Lithium Diisopropylamide: Solution Kinetics and Implications for Organic Synthesis

“…THF is a strongly coordinating solvent that will displace most ligands from lithium, dictating both structure and reactivity 7. 8b, 35a Specialized ligands (such as sparteine) often cannot compete with neat THF 8b. 56 Therefore, hydrocarbon cosolvents maximize the probability that added ligands will participate in the reaction coordinates.…”

“…It exists as a single observable structural form—disolvated dimer 1 —in all monofunctional solvents 7–12. Chelating ligands afford isostructural disolvated dimers 2 8b, 10 with the notable exception of TMCDA‐solvated monomer 3 8b. 13 The structural control is tactically important because rate studies based on either uncharacterized reagents or well‐characterized mixtures are of limited value.…”

Nucleophilicity of Neutral versus Cationic Magnesium Silyl Compounds

“…Benzene, toluene, pentane, and tetrahydrofuran were degassed by sparging with nitrogen, filtered through activated alumina columns, and stored under N 2 . Benzene-d 6 and THF-d 8 36 and dpe 37 were prepared according to literature procedures, and 3.0 M MeMgBr in diethyl ether was purchased from Aldrich and used as received. 1 …”