Lanthanide Shift Reagents


[17631-68-4]  · C30H30EuF21O6  · Eu(fod)3  · (MW 1037.50) (Yb(fod)3)

[18323-96-1]  · C30H30F21O6Yb  · Yb(fod)3  · (MW 1058.58) (Eu(hfc)3)

[34788-82-4]  · C42H42EuF21O6  · Eu(hfc)3  · (MW 1193.73) (Eu(tfc)3)

[34830-11-1]  · C36H42EuF9O6  · Eu(tfc)3  · (MW 893.72)

(mild Lewis acids capable of catalyzing a variety of synthetic transformations)

Alternate Names: Eu(fod)3 = tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium; Yb(fod)3 = tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)ytterbium; Eu(hfc)3 = tris[3-(heptafluoropropylhydroxymethylene)-(+ or -)-camphorato]europium; Eu(tfc)3 = tris[3-(trifluoromethylhydroxymethylene)-(+ or -)-camphorato]europium.

Physical Data: Eu(fod)3: mp 203-207 °C; Yb(fod)3: mp 108-111 °C; Eu(hfc)2: mp 156-158 °C; Eu(tfc)3: mp 195-198 °C.

Solubility: generally sol in a wide variety of organic solvents; commonly used in chlorinated solvents such as CH2Cl2 and CHCl3.

Form Supplied in: hygroscopic solids; commercially available. Drying: if necessary, they can be dried and stored over P2O5.

Purification: can generally be used directly without purification. Occasionally contain insoluble material which can be removed by filtration of a solution of the reagent through a millipore filter or a plug of cotton or glass wool. Insoluble material can also be separated and removed by centrifugation.

Handling, Storage, and Precautions: though hygroscopic, they can be handled for short periods of time in the presence of air without deleterious effect. In general, the use of glove bags or dry boxes is not required.

Fluorinated lanthanide dionato complexes are commonly employed as NMR shift reagents.1 The Lewis acidity of these reagents has allowed them to be exploited as catalysts for a variety of synthetic transformations. In general, they are easy to use and handle and are mild enough to tolerate a variety of acid labile functionality. A wide array of these complexes is commercially available. They have an octahedral geometry with the general structure (1) but are capable of expanding their coordination environment in order to accommodate additional Lewis bases. Generally they are believed to function by coordination at a single site, though chelation to two sites has also been suggested to occur.2-4 Achiral versions generally employ the heptafluorooctanedionato (fod) ligand while complexes of optically active camphor derived ligands, 3-(trifluoromethylhydroxymethylene)camphorato (tfc) or 3-(heptafluoropropylhydroxymethylene)camphorato (hfc), have been investigated in connection with enantioselective synthesis. Both the (+)- and (-)-isomers of Eu(hfc)3 and Eu(tfc)3 are commercially available. Most commonly employed is the europium derivative, Eu(fod)3. In several cases, Yb(fod)3 has been reported to be a stronger Lewis acid than Eu(fod)3 and a more effective catalyst for certain transformations.

The first report of their use as catalysts involved the Eu(fod)3 induced rearrangement of oxaspiropentanes to cyclobutanones (eq 1).5 The lanthanide complex is more effective at catalyzing this reaction than other more conventional Lewis acid catalysts.

During a study of its shift reagent properties, Eu(tfn)3 (tris(1,1,1,2,2,3,3,7,7,8,8,9,9,9-tetradecafluoro-4,6-nonanedionato)europium) was found to smoothly catalyze the Diels-Alder dimerization of (2) (eq 2).6 More recently, it has been demonstrated that Yb(fod)3 will catalyze the cycloaddition of a variety of dienes with acrolein (eqs 3-5).7 Several of these reactions cannot be readily accomplished with other catalysts or reaction conditions because of problems associated with the polymerization of acrolein.

The lanthanide shift reagent catalyzed Diels-Alder cycloaddition reaction of oxygenated dienes with aldehydes has been extensively investigated. Eu(fod)3 effectively catalyzes this reaction at room temperature and, in many cases, allows the relatively unstable silyl enol ether intermediates to be isolated (eqs 6-11).3,8-10

Enol ethers undergo [4 + 2] cycloaddition with a,b-unsaturated aldehydes in the presence of catalytic amounts of lanthanide shift reagents to give dihydropyran derivatives (eqs 12 and 13).11

Lanthanide shift reagents catalyze the addition of silyl enol ethers to aldehydes.4,12 The yield and diastereoselectivity obtained with lanthanide shift reagents are often better than those observed with more conventional catalysts (eq 14).

Shift reagents also catalyze the [2 + 2] cycloaddition of ketenimines with aldehydes to produce 2-iminooxetanes (eq 15).13 Again, the acid labile product is not stable to other catalysts.

The ene reaction of aldehydes with alkyl enol ethers is effectively catalyzed by Yb(fod)3 (eq 16).14

The optically active camphor derivative Eu(hfc)3 has been used as an enantioselective catalyst. Though the enantioselectivity with this catalyst alone is often modest (eq 17),8,15 when used in concert with additional chiral auxiliaries, high levels of enantioselectivity have been obtained in the hetero-Diels-Alder cycloaddition reaction (eq 18).15 The reduction of methyl phenylglyoxylate by the NADH mimic N-benzyldihydronicotinamide is catalyzed by lanthanide shift reagents with a modest level of asymmetric induction (eq 19).16

1. Nuclear Magnetic Resonance Shift Reagents; Sievers, R. E., Ed.; Academic: New York, 1973.
2. Dunkelblum, E.; Hart, H. JOC 1977, 42, 3958.
3. Midland, M. M.; Graham, R. S. JACS 1984, 106, 4294.
4. Mikami, K.; Terada, M.; Nakai, T. CC 1993, 343.
5. Trost, B. M.; Bogdanowicz, M. J. JACS 1973, 95, 2038.
6. Morrill, T. C.; Clark, R. A.; Bilobran, D.; Youngs, D. S. TL 1975, 397.
7. Danishefsky, S.; Bednarski, M. TL 1985, 26, 2507.
8. Bednarski, M.; Danishefsky, S. JACS 1983, 105, 3716.
9. Danishefsky, S.; Harvey, D. F.; Quallich, G.; Uang, B. J. JOC 1984, 49, 392.
10. Castellino, S.; Simms, J. J. TL 1984, 25, 2307.
11. Danishefsky, S.; Bednarski, M. TL 1984, 25, 721.
12. Takai, K.; Heathcock, C. H. JOC 1985, 50, 3247.
13. (a) Barbaro, G.; Battaglia, A.; Giorgianni, P. TL 1987, 28, 2995. (b) Barbaro, G.; Battaglia, A.; Giorgianni, P. JOC 1988, 53, 5501.
14. Deaton, M. V.; Ciufolini, M. A. TL 1993, 34, 2409.
15. Bednarski, M.; Danishefsky, S. JACS 1983, 105, 6968.
16. Zekhani, S.; Gelbard, G. CC 1985, 1162.

Daniel F. Harvey

University of California, San Diego, CA, USA

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