Diketonates as NMR Shift Reagents

Immense activity in this area in the early 1970s resulted as the use of LSRs enabled simplification of the spectra of organic molecules without the use of high-frequency spectrometers. The spreading-out of the spectmm and differential nature of the shifts removed degeneracies and overlaps, whilst study of the shifts, particularly when more than one LSR was used, permitted spatial assignment of the protons (or other resonant nucleus) with concomitant structural information about the organic molecule. 

The 100 MHz proton NMR spectrum of benzyl alcohol in the presence of Eu(dpm)3 (0.39 mol) (reproduced by permission of the Royal Society of Chemistry from J.K. M. Sanders and D.H. Williams, Chem. Commun., 1970, 422). 

Eigure 5.18 shows the H NMR spectrum of a mixture of 1 -phenylethylamine and Yb(tfc)3 in CDCI3. The (5 )-(- -) and (R)-(-) isomers here give clearly distinguished peaks (the amine resonances are well downfleld and not displayed). 

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There are many hundreds of published reports on the use of achiral lanthanide tris(/3-diketonates) as NMR shift reagents. Essentially any substrate with an oxygen, nitrogen or sulfur atom is a potential candidate for analysis with lanthanide shift reagents. These include sulfur- and phosphorus-containing functional groups that have oxygen atoms. Carboxylic acids and phenols were observed to decompose lanthanide chelates of dpm, whereas solutions with chelates of fod were stable for several days and suitable for study. 

Recently the use of mixed lanthanide silver complexes as NMR shift reagents has been assessed. In the original experiments232,233 silver(I) carboxylates such as Ag02CCF3 and Ag02CC3F7 were used, although later studies showed that larger shifts could be induced with silver /3-diketonates (see Section 54.1.4.4). 

The p -diketones and Schiff bases containing acidic substituents are ionizable and may be slightly soluble in water. The ft -diketone complexes are used as NMR shift reagents. Their luminescence properties are also useful. 

Metal /3-diketonates are often coordinatively unsaturated see Coordinative Saturation Unsaturation) and will therefore react with Lewis bases to form complexes. For example, the trimer [Ni(acac)2]3 will react with Lewis bases such as water or pyridine to form monomeric trans-[Ni(acac)2L2]. The formation of weak complexes with lanthanide /3-diketonates is critical in their use as NMR shift reagents. 

Several research groups recognized the potential of /3-diketones as extracting and complexing agents for the spectrophotometric determination of metal ions in dilute solutions, and for chromatographic separations. Lanthanide /3-diketonates were also found to be useful as NMR shift-reagents.2... 

Novel lanthanide fi-diketonate complexes have been synthesized, Their properties include thermal, hydrolytic and oxidative stabilities, volatility, Lewis acidity, and unusually high solubility in nonpolar organic solvents. Various combinations of these properties make lanthanide complexes useful as NMR shift reagents and fuel antiknock additives and in other applications. NMR spectral studies revealed that the Pr(III), Yb(III), and Eu(III) complexes of 1,1,1,2,2,3,3,7,7,7- decafluoro-4,6-heptanedione have sufficient Lewis acidity to induce appreciable shifts in the proton resonances of weak Lewis bases such as anisole, acetonitrile, nitromethane, and p-nitrotoluene. Data from single-crystal structure determinations indicate that the NMR shift reagent-substrate complexes are not stereochemically rigid and that effective axial symmetry may exist by virtue of rapid intramolecular rearrangements. 

Perhaps the most widely recognized use of lanthanide )8-diketonates is as NMR shift reagents. This application takes advantage not only of the intrinsic paramagnetic nature of certain of the lanthanide ions, but also of the Lewis acidity, hydrolytic stability, and high solubility in nonpolar organic solvents of their complexes. This paper describes our recent studies of the use of these unusual chelates as NMR shift reagents. 

Further substitution of fluorine atoms in the -diketone side chains has led to the synthesis and characterization of the Ln(dfhd)s complexes as NMR shift reagents. Although the hydrated Ln(fod)3 complexes are more soluble in chloroform than the hydrated Ln(dfhd)3 complexes, the lanthanide dfhd complexes have superior solubility in dioxane and aceto-... 

Diels-Alder reactions are often very much accelerated by the presence of catalytic amounts of a Lewis acid, usually AlCl It was recently observed that some lanthanide tris-3 diketonates used as nmr shift reagents smoothly catalyze various Diels-Alder and hetero Diels-Alder reactions (eq. [38, 39j ). 

Table 1 Lanthanide diketonate chelates used as NMR shift reagents...

Stable metal complexes can be favorably formed when a bidentate metal-binding site is available, such as a- and -diketone moieties which are the tautomeric forms of a- and /3-ketoenols. Some /S-diketonate complexes of paramagnetic lanthanides such as Pr(III), Eu(III) and Yb(III) have been extensively utilized as paramagnetic shift reagents for structural assignment of molecules with complicated stereochemistry prior to 2D techniques in NMR spectroscopy. Their syntheses and application are discussed in separate chapters in this volume. The examples below provide some dynamic and structural basis for better understanding of metal enolates in biomolecules and biochemical processes. 

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