Lanthanide complexes, enantiomeric

In principle, lanthanide complexes of alkyl- (phosphinates) or alkoxy- (phosphonate esters) DOTP derivatives may give rise to 32 stereoisomers, existing as 16 enantiomeric pairs, which are indistinguishable by NMR spectroscopy. The isomers originate from chiral elements inherent in these complexes, including the R or S configuration at each phosphorus and the helicity defined by the pendant arm orientations (AIA). Various Ln3+ complexes of phosphinate and phosphonate ester ligands derived from 1,4,7,10-tetraazacyclododecane (cyclen) have been described in the literature [104-107]. 

The use of aqueous chiral lanthanide complexes in the determination of the enantiomeric purity of chiral a-hydroxy acids has also been assessed by H NMR [21], Large lanthanide induced shifts, chemical shift non-equivalence and an apparent absence of kinetic resolution in complex formation is observed upon addition of racemic lactate to [Yb.3a]3+ (Figure 1). The lactate CH3 resonances are clearly resolved for the... 

Asymmetric lanthanide complexes derived from lanthanide triflates and a chiral bidentate sulfonamide ligand were applied to the Mukaiyama aldol reaction (Scheme 19) [299]. Enantiomeric excesses were moderate and the reaction proceeded best in CH2C12 solvent and with ytterbium as metal center. 

This analysis was made possible by our ability to measure CPL from racemic solutions of lanthanide complexes through use of circularly polarized excitation [12,45-47]. The varied lifetime of the lanthanide (III) ions allow for some insight concerning the lability of complexes of this type. For example, we have shown that although no CPL is detected in the luminescence from tris-terdentate complexes of Tb(III) and Eu(III) with oxydiacetate (ODA), CPL is observed from DytDPA -, indicating that, indeed, this complex is D3 in aqueous solution, but that only for the short lived Dy(III) ion (x = 20 psec) is the photoprepared enantiomerically-enriched excited state maintained throughout the emission lifetime [45]. 

The lanthanide complexes are soluble in ethers like Et20 or THE. They are catalysts for the enantioselective reduction of aldehydes, with best results for the lanthanum complex. Thus the yield is 72% when M = La, but 50% when M = Yb more strikingly, the enantiomeric excess is 69% for the La complex but only 3% when the Yb complex was... 

Bis(P-diketones) ligands, were proved to be efficient motifs or structural elements for selfassembling highly luminescent metallo-supramolecular lanthanide complexes [53-59] and representative examples (H2L" ) are shown in Figure 2.8. Special attention has also been paid to the use of enantiomerically pure bis-P-diketones ofH2L " [58]. H2L ° in Figure 2.8 was shown to have the ability to form d-f-d molecular magnetic materials [60]. 

It is best to ran a series of spectra with increasing concentrations of the chiral shift reagent, as demonstrated by the unusual behavior of the orffio-hydrogen resonance of 2-phenyl-2-butanol with Eu(hfc)3. This resonance showed increasing enantiomeric discrimination up to a lanthanide-substrate ratio of about 0.5. At higher lanthanide-substrate ratios the nonequivalence diminished until the resonances recoalesced and then reversed their order in the spectrum. Such behavior likely reflects the dominance of a 2 1 substrate-lanthanide complex at low lanthanide concentration and a 1 1 complex at higher lanthanide concentrations. The chiral discrimination in the 2 1 and 1 1 complexes is markedly different . A similar behavior was observed for 1-phenylethylamine with Eu(dcm)3 . 

Danishefsky and co-workers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is used as an NMR shift reagent, promoted hetero Diels-Alder reactions [30] of aldehydes with siloxydienes and induced enantiomeric enrichment (Sch. 1) [31]. Suitable substituents on the dienes were introduced to improve the extent of asymmetric induction. The best result was obtained in the reaction of benzaldehyde with l-methoxy-2-methyl-3-(trimethyl-siloxy)- , 3-butadiene using 1 mol % Eu(hfc)3 the enantiomerie excess was, however, moderate (58%). The authors maintained that the major advantage of lanthanide catalysis lay in the survival of otherwise labile systems used as adducts. 

Mukaiyama aldol reactions are useful means of constructing complex molecules for the total synthesis of natural products. Although catalytic asymmetric Mukaiyama aldol reactions have been achieved by use of a variety of chiral Lewis acids [42], no report of the use of chiral lanthanide catalysts was available until recently, despite the potency of these catalysts. Shibasaki and co-workers reported the first examples of chiral induction with chiral lanthanide complexes (Sch. 7) [43]. Catalysts prepared from lanthanide triflates and a chiral sulfonamide ligand afforded the corresponding aldol products in moderate enantiomeric excess (up to 49% ee). 

CSR (Chiral shift reagent) A paramagnetic lanthanide complex of known enantiomeric purity used to induce anisochrony in enantiomers of a racemate for NMR analysis. See Section 2.3.3. 

A chiral lanthanide complex catalyzes asymmetric Mukaiyama aldol reactions in aqueous media (Scheme 24). The changes in the water-coordination number is key to the mechanism of die catalytic reaction. The precatalysts yielded -hydroxy carbonyl compounds from aliphatic and aryl substrates widi high diastereomeric ratios and enantiomeric excesses of up to 49 1 and 97%, respectively. 

Stable, weU-defined chiral ytterbium complexes catalyze the asymmetric reduction of a-keto acids in aqueous solution (Scheme 33). Although the enantiomeric excesses are modest (40 50%), this is the first example of asymmetric reduction by a chiral lanthanide complex in water. 

Danishefsky and coworkers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is known as a NMR shift reagent, promoted hetero Diels-Alder reactions of aldehydes with siloxydienes and induced enantiomeric enrichment (Scheme 13.19). The best result was obtained... 

Recently we reported H and C NMR studies of the diamagnetic and paramagnetic lanthanide complexes derived from 1,4,7,10-tetrakis(A(A -diethylacetamido)-1,4,7,10-tetraazacyclododecane (fig. 12 referred to as 3 below) in deuterated acetonitrile (Forsbeig et al. 1995). The complexes demonstrate dynamic behavior that is similar to the analogous dota complexes, with slow interconversion between the two enantiomeric conformers of each ethylenediamine chelate ring of the macrocycle (cf. sect. 4.2.1). 

Alternatively, complexation with lanthanide shift reagents allow the signals of the MTPA ester to be resolved and used to determine enantiomeric... 

Similar differentiation between enantiomers by means of NMR can also be achieved by the use of chiral lanthanide shift reagents (243). Tris-[3-(heptafluoropropylhydroxymethylene)-d-camphorato] -europium was used for the first time (244) for determining the enantiomeric content of benzyl methyl sulfoxide 34. The enantiomeric composition of the partially resolved methyl p-tolyl sulfoxide 41 was estimated using tris-[3-(r-butylhydroxymethylene)-c -camphorato]-europium (245). Another complex of europium, tris-[3-(trifluoro-methylhydroxymethylene)-c -camphorato] europium (TFMC), in contrast to those mentioned above, was effective in the differentiation of various enantiomeric mixtures of chiral sulfinates (107), thiosul-finates (35), and sulfinamides (246). 

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