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ABSTRACT: The dimeric structure is characterized for a chiral amide base complex consisting of an (S)-N-isopropyl-O-triisopropylsilyl valinol ligand and lithium. The complex is characterized by a variety of NMR techniques, including multinuclear one- and two-dimensional NMR experiments and diffusion-ordered NMR spectroscopy (DOSY) as well as diffusion coefficient-formula weight (D-fw) correlation analyses. Spartan calculations are presented which support the structural assignment. This structural characterization leads to an explanation of the behavior and the reactivity of these complexes in solution.
Journal of the American Chemical Society 05/2011; 133(17):6596-602. · 9.91 Impact Factor
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ABSTRACT: Formula weight (FW) information is important to characterize the composition, aggregation number, and solvation state of reactive intermediates and organometallic complexes. We describe an internal reference correlated DOSY method for calculating the FW of unknown species in different solvents with different concentrations. Examples for both the small molecule (DIPA) and the organometallic complex (aggregate 1) yield excellent correlations. We also found the relative diffusion rate is inversely proportional to the viscosity change of the solution, which is consistent with the theoretical Stokes-Einstein equation. The accuracy of the least-squares linear prediction r(2) and the percentage difference of FW prediction are directly related to the density change; greater accuracy was observed with decreasing density. We also discuss the guidelines and other factors for successful application of this internal reference correlated DOSY method. This practical method can be conveniently modified and applied to the characterization of other unknown molecules or complexes.
Journal of the American Chemical Society 04/2009; 131(15):5627-34. · 9.91 Impact Factor
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ABSTRACT: Nuclear magnetic resonance (NMR) is the most powerful and widely utilized technique for determining molecular structure. Although traditional NMR data analysis involves the correlation of chemical shift, coupling constant, and NOE interactions to specific structural features, a largely overlooked method introduced more than 40 years ago, pulsed gradient spin-echo (PGSE), measures diffusion coefficients of molecules in solution, thus providing their relative particle sizes. In the early 1990s, the PGSE sequence was incorporated into a two-dimensional experiment, dubbed diffusion-ordered NMR spectroscopy (DOSY), in which one dimension represents chemical shift data while the second dimension resolves species by their diffusion properties. This combination provides a powerful tool for identifying individual species in a multicomponent solution, earning the nickname "chromatography by NMR". In this Account, we describe our efforts to utilize DOSY techniques to characterize organometallic reactive intermediates in solution in order to correlate structural data to solid-state crystal structures determined by X-ray diffraction and to discover the role of aggregate formation and solvation states in reaction mechanisms. In 2000, we reported our initial efforts to employ DOSY techniques in the characterization of reactive intermediates such as organolithium aggregates. Since then, we have explored DOSY experiments with various nuclei beyond (1)H, including (6)Li, (7)Li, (11)B, (13)C, and (29)Si. Additionally, we proposed a diffusion coefficient-formula weight relationship to determine formula weight, aggregation number, and solvation state of reactive intermediates. We also introduced an internal reference system to correlate the diffusion properties of unknown reactive intermediates with known inert molecular standards, such as aromatic compounds, terminal olefins, cycloolefins, and tetraalkylsilanes. Furthermore, we utilized DOSY to interpret the role of aggregation number and solvation state of organometallic intermediates in the reactivity, kinetics, and mechanism of organic reactions. By utilizing multinuclear DOSY methodologies at various temperatures, we also correlated solid-state X-ray structures with those in solution and discovered new reactive complexes, including a monomeric boron enolate, a product-inhibition aggregate, and a series of intermediates in the vinyl lithiation of allyl amines. As highlighted by our efforts, DOSY techniques provide practical and feasible NMR procedures and hold the promise of even more powerful insights when extended to three-dimensional experiments.
Accounts of Chemical Research 01/2009; 42(2):270-80. · 21.64 Impact Factor
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ABSTRACT: A chiral enolate aggregate 1 containing a lithium enolate and a chiral lithium amide was systematically investigated by various NMR techniques. (1)H and (13)C DOSY at 25 and -78 degrees C provide its solution structure, aggregation number, and formula weight. Multiple 2D (6)Li NMR techniques, such as (6)Li-(6)Li EXSY, (6)Li-(1)H HOESY, were utilized to investigate its stereochemical structure. The configuration of the enolate in complex 1 was confirmed by (6)Li-(1)H HOESY and trapping with TMS-Cl. A unique (6)Li-(1)H coupling through the Li-N-C-H network was observed. This scalar coupling was corroborated by (6)Li-(1)H HMQC, deuterium labeling experiments, and selective (1)H decoupling (6)Li NMR. The stereostructure of 1 provides a model for the origin of enantioselectivity of chiral lithium amide-induced enolate addition reactions.
Journal of the American Chemical Society 10/2008; 130(35):11726-36. · 9.91 Impact Factor
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ABSTRACT: A 2:1 lithium amide/ n-butyllithium aggregate 1 is investigated as an asymmetric addition template in hydrocarbon solvents. Several different chiral lithium amides were synthesized from l-valine and tested in the asymmetric addition of n-BuLi to various aldehydes. Enantiomeric excesses up to 83% were obtained in the case of the addition of n-BuLi to pivaldehyde at -116 degrees C in pentane. (1)H and (13)C INEPT DOSY were utilized to characterize a new trimeric complex 12 between 2 equiv of lithium amide and 1 equiv of lithium alkoxide. This mixed aggregate strongly indicates the possibility of product-induced chirality inhibition that is detrimental to the enantioselectivity of asymmetric addition reaction.
The Journal of Organic Chemistry 07/2008; 73(11):4045-52. · 4.45 Impact Factor
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ABSTRACT: 13C INEPT Diffusion-ordered NMR spectroscopy (DOSY) with an internal reference system was developed to study the aggregation state of THF-solvated LDA dimeric complex. Six components are clearly identified in the diffusion dimension, and their DOSY-generated 13C INEPT spectrum slices agree extremely well with their respective INEPT spectra. The correlation between log D and log FW of the linear least-squares fit to reference points of all components is exceptionally high: (r = 0.9985).
Organic Letters 04/2008; 10(5):909-11. · 5.86 Impact Factor
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ABSTRACT: A system consisting of a chiral lithium amide and n-BuLi in tol-d(8) solution was investigated with (1)H and (13)C INEPT DOSY, (6)Li and (15)N NMR, and other 2D NMR techniques. A mixed 2:1 trimeric complex was identified as the major species as the stoichiometry approached 1.5 equiv of n-BuLi to 1 equiv of amine compound. (1)H and (13)C INEPT DOSY spectra confirmed this lithium aggregate in the solution. The formula weight of the aggregate, correlated with diffusion coefficients of internal references, indicated the aggregation number of this complex. Plots of log D(rel) vs log FW are linear (r > 0.9900). (6)Li and (15)N NMR titration experiments also corroborated these results. These NMR experiments indicate that this mixed aggregate is the species that is responsible for asymmetric addition of n-BuLi to aldehydes.
The Journal of Organic Chemistry 03/2008; 73(6):2373-81. · 4.45 Impact Factor
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ABSTRACT: Lithium, sodium, and potassium enolates reacted with bisaminoboron halides to give bisaminoboron enolates 1a−5c. Specifically, the potassium enolate of tert-butyl methyl ketone reacted with bis(diisopropylamino)boron chloride in THF at room temperature within 1 h to give the bis(diisopropylamino)boron enolate of tert-butyl methyl ketone (3b) in 61−84% isolated yields. Under similar conditions, the reactivity is highly dependent on the metal employed to generate enolates (K > Na > Li) as well as the nitrogen substituents in the bisaminoboron halides (iPr > Et > TMS). This latter observation is a compromise between the boron−nitrogen resonance and the steric effect. The structural information of enolate 3b was studied in detail. Unlike the aggregated alkali-metal enolates, this boron enolate exists exclusively as a monomer in both the solid and solution states, as identified by X-ray and diffusion-ordered NMR.
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