Lewis acids, lanthanide shift-reagents

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

Cycloaddition with aldehydes 2-iminooxetanes.2 Lewis acids are not useful for this cycloaddition, but traces of lanthanide shift reagents, Yt(fod)3, Yt(hfc)3, or Eu(hfc)3 are very efficient catalysts for cycloaddition to a mixture of (cis)- and (fra/w)-2-iminooxetanes (2) in the case of both aliphatic and aromatic aldehydes. 

Lanthanide shift reagents are hard Lewis acids and normally do not react with alkenes. But Eu(fod)3 in combination with silver heptafluorobutyrate [46] alters the spectrum of alkenes by a type of interaction shown in Fig. 10.19. 

Diels-Alder reaction of aldehydes with activated dienes. This lanthanide shift reagent can function as a Lewis acid catalyst in the cyclocondensation of l-methoxy-3-trimethylsilyloxy-1,3-diene (2) with aromatic aldehydes, and permits isolation of the initial... 

An important discovery in the area of carbonyl cycloadditions is that highly oxygenated 1,3-dienes are excellent 4ir components. These reactions occur at low temperatures with a wide range of aldehydes provided Lewis acid catalysts are used. " " This general type of reaction is shown by the example in equation (81). It was also found by Danishefsky and coworkers that lanthanide shift reagents are elective catalysts for the cycloaddition.An example of one of these cycloadditions is outlined in equation (82). 2 <>... 

In the nineteen-eighties stoichiometric amounts of conventional Lewis acids such as TiCl4, AICI3, SnCU, BFs-Olt,., Mgl r, and ZnCU were frequently used for HDA reactions of siloxy-substituted dienes with heterodienophiles [286, 287]. Danishefsky et al., however, found that a lanthanide shift reagent such as Eu(fod)3 can promote the cycloaddition catalytically [294]. Several Bronsted and Lewis acids have recently been shown to have high catalytic activity in the DA reaction of siloxy-substituted dienes in non-aqueous or aqueous media, and elaboration of Lewis acids has achieved unique chemo- and regioselectivity. 

The rate of this interconversion is fast on the n.m.r. time-scale, and hence, the actual n.m.r. spectrum observed for the substrate will be the weighted time-average of the spectra of the free and bound substrate. Insofar as there is a substantial change between the shifts of the free and bound substrate (up to - 40 p.p.m. ), it is only necessary for a small proportion of the substrate to bind with the lanthanide in order to produce a substantial change in the shifts observed. Nevertheless, it is mandatory that the substrate shall associate with the lanthanide, and hence, it is necessary for the substrate to have some suitable donor-site as lanthanide shift-reagents are hard Lewis acids, this means that the donor atom must be a hard Lewis base. Fortunately, many functional groups commonly found in carbohydrate systems, such as the hydroxyl, acetoxyl, amino, and acetamido groups, form donor bonds with lanthanides. 

In one of the first examples of a specific synthetic application of a lanthanide shift reagent, Eu(fod)3 acted as a mild Lewis acid catalyst in hetero-Diels-Alder reactions (Bednarski and Danishefsky, 1983a). 

Recently, some efficient asymmetric Diels-Alder reactions catalyzed by chiral Lewis acids have been reported [67]. The chiral Lewis acids employed in these reactions are generally based on traditional acids such as titanium, boron, or aluminum reagents, and they are well modified to realize high enantioselectivi-ties. Although lanthanide compounds were expected to be Lewis acid reagents, only a few asymmetric reactions catalyzed by chiral lanthanide Lewis acids were reported. Pioneering work by Danishefsky et al. demonstrated that Eu(hfc)3 (an NMR shift reagent) catalyzed hetero-Diels-Alder reactions of aldehydes with si-loxydienes, but enantiomeric excesses were moderate [68]. 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

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. 

L ligands, list, 176 Lagrangian multipliers, 227, 228 Lanthanide chemical shift reagents, 13 LCAO, 229 Lewis acid, xiii... 

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 ). 

Diels-Alder reactions constitute one of the most important methodologies for the constructuction of a cyclic molecular framework. Lanthanide Lewis acid catalyzed Diels-Alder reaction was pioneered by Danishefsky et al., who revealed that NMR shift reagent Eu(hfc)3 served as chiral catalyst in hetero Diels-Alder reaction of silyloxydiene and aldehydes [32]. Later, although Yb(OTf)3 was first introduced for Diels-Alder reactions as an effective catalyst among lanthanide triflates, scandium triflates (Sc(OTf)3), classified as rare earth metal triflate, has gained popularity as a superior catalyst for Diels-Alder reactions [11, 33]. This section highlights several examples of the reactions where lanthanide triflates displayed preferable performance over scandium triflates. 

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