Influence of Steric Factors on Chiral Lithium Amide Aggregates

The solution structures of three mixed aggregates dissolved in toluene-<i>d</i>₈ consisting of the lithiated amides derived from (<i>S</i>)-<i>N</i>-isopropyl-1-((triisopropylsilyl)­oxy)­propan-2-amine, (<i>R</i>)-<i>N</i>-(1-phenyl-2-((triisopropylsilyl)­oxy)­ethyl)­propan-2-amine, or (<i>S</i>)-<i>N</i>-isobutyl-3-methyl-1-((triisopropylsilyl)­oxy)­butan-2-amine and <i>n</i>-butyllithium are characterized by various NMR experiments including diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight correlation analyses (D-FW) and other one- and two-dimensional NMR techniques. We report that steric hindrance of R₁ and R₂ groups of the chiral lithium amide controls the aggregation state of the mixed aggregates. With a less hindered R₂ group, lithium (<i>S</i>)-<i>N</i>-isopropyl-1-((triisopropylsilyl)­oxy)­propan-2-amide forms mostly a 2:2 ladder-type mixed aggregate with <i>n</i>-butyllithium. Increase of steric hindrance of the R₁ and R₂ groups suppresses the formation of the 2:2 mixed aggregate and promotes formation of a 2:1 mixed aggregate. We observe that lithium (<i>S</i>)-<i>N</i>-isobutyl-3-methyl-1-((triisopropylsilyl)­oxy)­butan-2-amide forms both a 2:2 mixed aggregate and a 2:1 mixed trimer with <i>n</i>-butyllithium. Further increase in the steric hindrance of R₁ and R₂ groups results in the formation of only 2:1 mixed aggregate as observed with lithium (<i>R</i>)-<i>N</i>-(1-phenyl-2-((triisopropylsilyl)­oxy)­ethyl)­propan-2-amide

Diffusion Coefficient-Formula Weight (D-FW) Analysis of ²H Diffusion-Ordered NMR Spectroscopy (DOSY)

We report extension of the D-FW analysis using referenced ²H DOSY. This technique was developed in response to limitations due to peak overlay in ¹H DOSY spectra. We find a corresponding linear relationship (<i>R</i>² > 0.99) between log <i>D</i> and log FW as the basis of the D-FW analysis. The solution-state structure of THF solvated lithium diisopropyl amide (LDA) in hydrocarbon solvent was chosen to demonstrate the reliability of the methodology. We observe an equilibrium between monosolvated and disolvated dimeric LDA complexes at room temperature. Additionally we demonstrate the application of the ²H D-FW analysis using a compound with an exchangeable proton that is readily labeled with ²H. Hence, the ²H DOSY D-FW analysis is shown to provide results consistent with the ¹H DOSY method, thereby greatly extending the applicability of the D-FW analysis

Characterization of Cyclopentyllithium and Cyclopentyllithium Tetrahydrofuran Complex

The solid-state structures of unsolvated, hexameric cyclopentyllithium and tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single-crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon solvents. Solution-state structural analyses of cyclopentyllithium and cyclopentyllithium–tetrahydrofuran complexes in toluene-<i>d</i>₈ were also carried out by diffusion-ordered NMR spectroscopy with diffusion coefficient–formula weight correlation analyses and other one- and two-dimensional NMR techniques. The solution-state studies suggest that unsolvated cyclopentyllithium exists as hexamer and tetramer equilibrating with each other. Upon solvation with tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran tetrasolvated tetramer

Ligand Binding Constants to Lithium Hexamethyldisilazide Determined by Diffusion-Ordered NMR Spectroscopy

We report the direct measurement of ligand-binding constants of organolithium complexes using a ¹H NMR/diffusion-ordered NMR spectroscopy (DOSY) titration technique. Lithium hexamethyldisilazide complexes with ethereal and ester donor ligands (THF, diethyl ether, MTBE, THP, <i>tert</i>-butyl acetate) are characterized using ¹H NMR and X-ray crystallography. Their aggregation and solvation states are confirmed using diffusion coefficient–formula weight correlation analysis, and the ¹H NMR/DOSY titration technique is applied to obtain their binding constants. Our work suggests that steric hindrance of ethereal ligands plays an important role in the aggregation, solvation, and reactivity of these complexes. It is noteworthy that diffusion methodology is utilized to obtain binding constants

Deoxygenation of Mono-oxo Bis(dithiolene) Mo and W Complexes by Protonation

Protonation-assisted deoxygenation of a mono-oxo molybdenum center has been observed in many oxotransferases when the enzyme removes an oxo group to regenerate a substrate binding site. Such a reaction is reported here with discrete synthetic mono-oxo bis­(dithiolene) molybdenum and tungsten complexes, the chemistry of which had been rarely studied because of the instability of the resulting deoxygenated products. An addition of tosylic acid to an acetonitrile solution of [Mo^IVO­(S₂C₂Ph₂)₂]^2– (<b>1</b>) and [W^IVO­(S₂C₂Ph₂)₂]^2– (<b>2</b>) results in the loss of oxide with a concomitant formation of novel deoxygenated complexes, [M­(MeCN)₂(S₂C₂Ph₂)₂] (M = Mo (<b>3</b>), W (<b>4</b>)), that have been isolated and characterized. Whereas protonation of <b>1</b> exclusively produces <b>3</b>, two different reaction products can be generated from <b>2</b>; an oxidized product, [WO­(S₂C₂Ph₂)₂]⁻, is produced with 1 equiv of acid while a deoxygenated product, [W­(MeCN)₂(S₂C₂Ph₂)₂] (<b>4</b>), is generated with an excess amount of proton. Alternatively, complexes <b>3</b> and <b>4</b> can be obtained from photolysis of [Mo­(CO)₂(S₂C₂Ph₂)₂] (<b>5</b>) and [W­(CO)₂(S₂C₂Ph₂)₂] (<b>6</b>) in acetonitrile. A di- and a monosubstituted adducts of <b>3</b>, [Mo­(CO)₂(S₂C₂Ph₂)₂] (<b>5</b>) and [Mo­(PPh₃)­(MeCN)­(S₂C₂Ph₂)₂] (<b>7</b>) are also reported

Crystal Structure and Solution State Characterization of Lithium (<i>S</i>)‑(1-(Bis(2-methoxyethyl)amino)-3-methylbutan-2-yl)(methyl)amide

The solid state structure of lithiated (<i>S</i>)-<i>N</i>¹,<i>N</i>¹-bis­(2-methoxyethyl)-<i>N</i>²,3-dimethylbutane-1,2-diamine, which is a chiral amide base synthesized from (<i>S</i>)-valine was determined by single-crystal X-ray diffraction. The complex in solution state is also characterized by a variety of NMR experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion coefficient-formula weight correlation analyses and other one- and two-dimensional NMR techniques by dissolving the crystal in toluene-<i>d</i>₈. The crystallography and NMR results suggest that the chiral amide is dimeric in both solid and solution states

Structures of Lithium <i>N</i>‑Monosubstituted Anilides: Trisolvated Monomer to Tetrasolvated Dimer

Crystal structure determination of lithiated <i>N</i>-methylaniline with a variety of ligands, including tetrahydrofuran, methyltetrahydrofuran, <i>trans</i>-2,5-dimethyltetrahydrofuran, dimethoxyethane, tetrahydropyran and <i>N</i>,<i>N</i>-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 <i>N</i>-alkylanilides solvated by tetrahydrofuan are also reported. When the methyl group of <i>N</i>-methylaniline is replaced by an isopropyl or a phenyl group, trisolvated monomers are formed instead of dimers. Interestingly, the solid-state structure of lithiated <i>N</i>-isobutylaniline in tetrahydrofuran is a trisolvated dimer while that of lithium <i>N</i>-neopentylanilide is a disolvated dimer

Characterization of Cyclopentyllithium and Cyclopentyllithium Tetrahydrofuran Complex

The solid-state structures of unsolvated, hexameric cyclopentyllithium and tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single-crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon solvents. Solution-state structural analyses of cyclopentyllithium and cyclopentyllithium–tetrahydrofuran complexes in toluene-<i>d</i>₈ were also carried out by diffusion-ordered NMR spectroscopy with diffusion coefficient–formula weight correlation analyses and other one- and two-dimensional NMR techniques. The solution-state studies suggest that unsolvated cyclopentyllithium exists as hexamer and tetramer equilibrating with each other. Upon solvation with tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran tetrasolvated tetramer

Characterization of Cyclopentyllithium and Cyclopentyllithium Tetrahydrofuran Complex

The solid-state structures of unsolvated, hexameric cyclopentyllithium and tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single-crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon solvents. Solution-state structural analyses of cyclopentyllithium and cyclopentyllithium–tetrahydrofuran complexes in toluene-<i>d</i>₈ were also carried out by diffusion-ordered NMR spectroscopy with diffusion coefficient–formula weight correlation analyses and other one- and two-dimensional NMR techniques. The solution-state studies suggest that unsolvated cyclopentyllithium exists as hexamer and tetramer equilibrating with each other. Upon solvation with tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran tetrasolvated tetramer

Crystal Structure and Solution State Characterization of Lithium (<i>S</i>)‑(1-(Bis(2-methoxyethyl)amino)-3-methylbutan-2-yl)(methyl)amide

The solid state structure of lithiated (<i>S</i>)-<i>N</i>¹,<i>N</i>¹-bis­(2-methoxyethyl)-<i>N</i>²,3-dimethylbutane-1,2-diamine, which is a chiral amide base synthesized from (<i>S</i>)-valine was determined by single-crystal X-ray diffraction. The complex in solution state is also characterized by a variety of NMR experiments including diffusion-ordered NMR spectroscopy (DOSY) with diffusion coefficient-formula weight correlation analyses and other one- and two-dimensional NMR techniques by dissolving the crystal in toluene-<i>d</i>₈. The crystallography and NMR results suggest that the chiral amide is dimeric in both solid and solution states