Shift reagents lanthanide-induced shifts

A study195 based on the NMR lanthanide-induced shifts (LIS) for a series of cis- and trans-3-substituted, and 3,3-disubstituted thietane oxides concluded that all cis-substituted oxides (5c R = CH3, t-Bu and aryl) exist exclusively in the diequatorial conformation. The trans-3-substituted isomers (185) prefer the equatorial oxygen conformation (R = CH3,86% t-Bu, 65-75% aryl, 75%), which means an axial preference for the substituents (e.g. 185d), at least when they are bound to a shift reagent (equation 75). 

R and S diastereomers (AA5 = 10 ppm) and experience a large lanthanide induced shift with the CH3 resonating at +21 and +31 ppm respectively for (It)- and (5)-lactate respectively (c.f. +1.3 ppm in the free form). The large shifts exhibited by this unique chiral derivatising agent may be compared to the much smaller AA8 values reported for shift reagents which are generally of the order 1 ppm, and often <0.1 ppm. 

The site of Ai-alkylation in pyrazolotropones 143a,b (72TL1925) and imidazotropones 185 and 186 (92JHC1219) was elucidated by the lanthanide-induced shift reagents Eu (dpm)3 and Eu (fod)3, respectively. Likewise, Pr (dpm)3 was used [93JCS(P1)1617]. 

Achiral binuclear reagents have been added to mixtures of a chiral crown ether (74) and chloroform-soluble amino acid ester hydrochlorides to enhance the chiral discrimination in the NMR spectrum. The [Ln(fod)4] preferentially associated with the enantiomer in the bulk solution such that the enantiomer with lower association with 74 showed the larger lanthanide-induced shifts. The system also enhanced the chiral discrimination in acetonitrile-fifs, although [Pr(fod)4] was needed because it causes larger shifts than the... 

This method of resolution of polyolefins has been extensively studied for cyclooctatetraene systems where excellent enantiomeric excesses are normally observed. Lanthanide-induced shifting can be used to determine the diastereoisomeric composition of the urazoles. Alternate means for the resolution of polyenes based on kinetic resolution using (+)-tetra-2-pinany Iborane have been described, but this reagent consumes valuable substrate. Chiral platinum complexes can also be used but at prohibitive cost on a large scale and with poor regioselec-tivity when several coordination sites are present. 

Alternatively, the sulfites can be oxidized to the sulfates 85 in 45 min at 0°C by employing a 350 ppm RUO4 solution in water, but in only 30% yield <1992NJC107>. Diastereotopically labeled 0-sulfates 84 and 85, obtained by oxidation of diastereoisomeric cyclic sulfites with Ru 04, were shown by application of lanthanide-induced shift reagents on the NMR signals to be formed with retention of configuration at sulfur <1983CC1392>. 

Barriers for interconversion between BC-3 and its enantiomer, BC-7, have been calculated. Passage through either a BC-5 or a BC-1 conformation, are calculated to be 5.0 kcal mol and 6.7 kcal mol , respectively. The small barriers allow for a rapid pseudorotation between BC-3 and BC-7, even at low temperatures, and account for the symmetric spectra. NMR results on oxocane-2,2,7,7-d4 have allowed a definitive assignment for the H and C chemical shifts. Lanthanide-induced shift reagents provide compelling proof, that the lowest energy conformations are BC-3 and BC-7. 

The silver ion coordinates with the soft Lewis base and the lanthanide induces the shifts. Chiral binuclear reagents have been applied to chiral olefins and aromatics. Binuclear reagents formed using the dcm ligand are not effective for chiral resolution, presumably because this ligand is too sterically hindered to permit formation of the tetrakis chelate anion. Experimentation is often needed to find the correct combination of lanthanide and silver P-diketonate to cause enantiomeric resolution. 

Confirmation that cw-addition of alkyl copper complexes occurs in these reactions has been obtained by studies of lanthanide-induced shift H n.m.r. spectra of the products. Corey has now introduced (3-methyl-3-methoxybut-l-ynyl)copper in THF as a relatively inexpensive reagent for the generation of mixed cuprates (Gilman s reagents), which enable coupling reactions to occur in high yield with alkyl-lithium reagents. ... 

Lanthanide Shift Reagents.—New theoretical treatments of the origin of the paramagnetic shifts induced in the n.m.r. spectra of substrates bound to... 

Europium(III), and particularly ytterbium(III) shift reagents, induce downfield proton resonance shifts while the praseodymium(III) analogs cause upfield shifts. Lanthanide chelates of fluorinated /3-diketonates are more soluble in organic solvents, and they form more stable association complexes with donor molecules, than do LSRs with nonfluorinated ligands. Thus Eu(fod)3 is the preferred achiral LSR for weak nucleophiles89. 

The determination of ee with chiral lanthanide shift reagents is normally performed in organic solvents. However, the development of chiral reagents capable of inducing shift nonequivalence in water, which is the appropriate solvent for many natural products, is of great importance. The europium(III) (R)-propylenediaminetetraacetate ion (Table 1) has been proposed as a chiral reagent suitable for use in aqueous solution90. 

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