Cerium(III) Chloride1


[7790-86-5]  · CeCl3  · Cerium(III) Chloride  · (MW 246.47) (.7H2O)

[18618-55-8]  · H14CeCl3O7  · Cerium(III) Chloride  · (MW 372.59)

(mild Lewis acid capable of selective acetalization;2 organocerium reagents have increased oxo-3 and azaphilicity4 and greatly reduced basicity;5 in combination with NaBH4 is a selective 1,2-reducing agent6)

Alternate Name: cerous chloride; cerium trichloride.

Physical Data: mp 848 °C; bp 1727 °C; d 3.92 g cm-3.

Solubility: insol cold H2O; sol alcohol and acetone; slightly sol THF.

Form Supplied in: white solid; widely available. Drying: for some applications the cerium trichloride must be strictly anhydrous. The following procedure has proven most efficacious: a one-necked base-washed flask containing the heptahydrate and a magnetic stirring bar was evacuated to 0.1 Torr and heated slowly to 140 °C over a 2 h period. At 70 and 100 °C, considerable amounts of water are given off, and these critical temperature zones should not be passed through too quickly. The magnetically stirred white solid is heated overnight at 140 °C, cooled, blanketed with nitrogen, treated with dry THF (10 mL g-1), and agitated at rt for 3 h. To guarantee the complete removal of water, t-butyllithium is added dropwise until an orange color persists.

Handling, Storage, and Precautions: anhydrous CeCl3 should be used as prepared for best results. Cerium is reputed to be of low toxicity.

Organocerium Reagents.

Organocerates, most conveniently prepared by the reaction of lithium compounds with anhydrous CeCl3 in THF, are highly oxophilic and significantly less basic than their RLi and RMgBr counterparts. As a consequence, 1,2-addition reactions involving readily enolizable ketones are not adversely affected by competing enolization.3 Well-studied examples of this phenomenon abound.7 Although alkyl and vinyl cerates have most often been used,3,5,7 Cl2CeCH2CN,8 Cl2CeCH2COOR,9 Cl2CeC&tbond;CSiMe3,10 and Cl2CeCH2SiMe311 are known to be equally effective. The last reagent has been utilized for the methylenation of highly enolizable ketones (eq 1)11a and for the conversion of carboxylic acid halides, esters, and lactones into allylsilanes (eq 2).11b-d Amides and nitriles also condense with organocerates with equal suppression of enolization.3,4 In general, high levels of steric hindrance in either reaction partner can be tolerated (eq 3). In select examples, the level of double stereodifferentiation can be impressively high.5,7,12

The discovery has been made that allyl anions produced by the reductive metalation of allyl phenyl sulfides condense cleanly with a,b-unsaturated aldehydes in 1,2-fashion at the more substituted allyl terminus in the presence of Titanium Tetraisopropoxide.13 Use of the allylcerium reagent instead reverses the regioselectivity. Further, the stereochemical preference is cis at -78 °C (kinetic control) and trans when warmed to -40 °C (eq 4).14 Grignard addition reactions to vinylogous esters are improved if promoted by CeCl3 (eq 5).15

Stereodivergent pathways relative to other organometallics have surfaced in the addition of organocerium(III) reagents to chiral a-keto amides (eq 6)16 and 2-acyloxazolidines (eq 7).17 Applications of this type hold considerable synthetic potential not only in additions to carbonyl compounds,18 but also to oxime ethers,19 oxiranes,20 and oxazolidines.21

The uniquely high reactivity of cerium reagents toward the often poorly electrophilic azomethine or C=N double bond of hydrazones has been extensively investigated. Smooth 1,2-addition occurs in good yield (67-81%) provided the air-sensitive hydrazones are acylated; when a chiral auxiliary is present, excellent diastereofacial control operates and enantiomerically enriched a-branched amines result (eq 8).22 There appears to be a fundamental difference between warmed reagents (-78 °C -> 0 °C -> -78 °C) and those generated and used at -78 °C. Sonication appears to facilitate conversion to the organocerate.23 For SAMP hydrazones and related compounds the condensation is accommodating of a wide range of substitution both in the hydrazone and in the nucleophile. Subsequent reductive cleavage of the N-N bond with preservation of configuration can be performed by hydrogenolysis over W-2 Raney Nickel at 60 °C (free hydrazones; less preferred because of competing saturation of aromatic substituents if present) or by treatment with Lithium in liquid ammonia (acylated hydrazines).22c

The preparation of (±)-1,3-diphenyl-1,3-propanediamine illustrates an alternative way in which this chemistry can be utilized (eq 9).24 In all of the 1,2-addition reactions, the preferred reagent stoichiometry appears to be RLi:CeCl3:hydrazone = 2:2:1. A detailed study of the consequences of varying the relative proportions of these constituents has indicated the optimal ratios of RLi:CeCl3 to be 1:1, notwithstanding the fact that not all of the CeCl3 is consumed in the transmetalation step.25 The proposal has been made that the empirical formula of the cerate best approximates R3CeCl3Li3.

Cerium enolates, available by transmetalation of the lithium salts with CeCl3 at -78 °C26 or by reduction of a-bromo ketones with Cerium(III) Chloride-Tin(II) Chloride,27 give higher yields of crossed aldol products without altering the stereoselectivity. The CeCl3-SnCl2 reagent combination also acts on a,a-dibromo ketones to give oxylallyl cations that can be captured in the usual way.28

Selective Reductions.

Equimolar amounts of Sodium Borohydride4 and CeCl3.7H2O in methanol act on a,b-unsaturated ketones at rt or below to deliver allylic alcohols cleanly by 1,2-addition.29 This widely used reducing agent30 is not renowned for its diastereoselectivity31 and asymmetric induction capabilities,32 although exceptions are known.33 Sometimes a stereofacial preference opposite that realized with other hydrides is encountered (eqs 10 and 11).34

Allylic alcohol products that are especially sensitive are known to undergo ionization and solvent capture under these mildly acidic conditions (eq 12).35 The Lewis acidic character of CeCl3 has also been used to advantage in the selective acetalization6 of saturated aldehydes under the Luche conditions, thereby preventing their reduction.2 Since ketones and conjugated aldehydes are less responsive, these functionalities are not transiently protected and suffer reduction (eq 13).36 NaBH4-CeCl3 in MeCN transforms cinnamoyl chlorides into cinnamyl alcohols,37 while Lithium Aluminum Hydride-Cerium(III) Chloride in hot DME or THF can effectively reduce alkyl halides and phosphine oxides.5

1. (a) Kagan, H. B.; Namy, J. L. T 1986, 42, 6573. (b) Molander, G. A. CRV 1992, 92, 29.
2. Gemal, A. L.; Luche, J.-L. JOC 1979, 44, 4187.
3. Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. JACS 1989, 111, 4392.
4. Ciganek, E. JOC 1992, 57, 4521.
5. (a) Imamoto, T.; Takeyama, T.; Kusumoto, T. CL 1985, 1491. (b) Paquette, L. A.; Learn, K. S.; Romine, J. L.; Lin, H.-S. JACS 1988, 110, 879.
6. Luche, J.-L.; Gemal, A. L. CC 1978, 976.
7. (a) Paquette, L. A.; DeRussy, D. T.; Cottrell, C. E. JACS 1988, 110, 890. (b) Paquette, L. A.; He, W.; Rogers, R. D. JOC 1989, 54, 2291.
8. Liu, H.-J.; Al-said, N. H. TL 1991, 32, 5473.
9. (a) Nagasawa, K.; Kanbara, H.; Matsushita, K.; Ito, K. TL 1985, 26, 6477. (b) Imamoto, T.; Kusumoto, T.; Tawarayama, Y.; Sugiura, Y.; Mita, T.; Hatanaka, Y.; Yokoyama, M. JOC 1984, 49, 3904.
10. (a) Suzuki, M.; Kimura, Y.; Terashima, S. CL 1984, 1543. (b) Tamura, Y.; Sasho, M.; Ohe, H.; Akai, S.; Kita, Y. TL 1985, 26, 1549.
11. (a) Johnson, C. R.; Tait, B. D. JOC 1987, 52, 281. (b) Anderson, M. B.; Fuchs, P. L. SC 1987, 17, 621. (c) Narayanan, B. A.; Bunnelle, W. H. TL 1987, 28, 6261. (d) Lee, T. V.; Channon, J. A.; Cregg, C.; Porter, J. R.; Roden, F. S.; Yeoh, H. T.-L. T 1989, 45, 5877.
12. (a) Paquette, L. A.; DeRussy, D. T.; Gallucci, J. C. JOC 1989, 54, 2278. (b) Paquette, L. A.; DeRussy, D. T.; Vandenheste, T.; Rogers, R. D. JACS 1990, 112, 5562.
13. Cohen, T.; Guo, B.-S. T 1986, 42, 2803.
14. Guo, B.-S.; Doubleday, W.; Cohen, T. JACS 1987, 109, 4710.
15. Crimmins, M. T.; Dedopoulou, D. SC 1992, 22, 1953.
16. Fujisawa, T.; Ukaji, Y.; Funabora, M.; Yamashita, M.; Sato, T. BCJ 1990, 63, 1894.
17. Ukaji, Y.; Yamamoto, K.; Fukui, M.; Fujisawa, T. TL 1991, 32, 2919.
18. Kawasaki, M.; Matsuda, F.; Terashima, S. TL 1985, 26, 2693.
19. Ukaji, Y.; Kume, K.; Watai, T.; Fujisawa, T. CL 1991, 173.
20. (a) Vougioukas, A. E.; Kagan, H. B. TL 1987, 28, 6065. (b) Schaumann, E.; Kirschning, A. TL 1988, 29, 4281. (c) Cohen, T.; Jeong, I.-H.; Mudryk, B.; Bhupathy, M.; Awad, M. M. A. JOC 1990, 55, 1528. (d) Marczak, S.; Wicha, J. SC 1990, 20, 1511.
21. Pridgen, L. N.; Mokhallalati, M. K.; Wu, M.-J. JOC 1992, 57, 1237.
22. (a) Denmark, S. E.; Weber, T.; Piotrowski, D. W. JACS 1987, 109, 2224. (b) Weber, T.; Edwards, J. P.; Denmark, S. E. SL 1989, 20. (c) Denmark, S. E.; Nicaise, O.; Edwards, J. P. JOC 1990, 55, 6219.
23. Greeves, N.; Lyford, L. TL 1992, 33, 4759.
24. Denmark, S. E.; Kim, J.-H. S 1992, 229.
25. Denmark, S. E.; Edwards, J. P.; Nicaise, O. JOC 1993, 58, 569.
26. Imamoto, T.; Kusumoto, T.; Yokoyama, M. TL 1983, 24, 5233.
27. Fukuzawa, S.; Tsuruta, T.; Fujinami, T.; Sakai, S. JCS(P1) 1987, 1473.
28. Fukuzawa, S.; Fukushima, M.; Fujinami, T.; Sakai, S. BCJ 1989, 62, 2348.
29. (a) Luche, J.-L. JACS 1978, 100, 2226. (b) Luche, J.-L.; Rodriquez-Hahn, L.; Crabbé, P. CC 1978, 601.
30. Examples: Godleski, S. A.; Valpey, R. S. JOC 1982, 47, 381. Block, E.; Wall, A. JOC 1987, 52, 809. Marchand, A. P.; LaRoe, W. D.; Sharma, G. V. M.; Suri, S. C.; Reddy, D. S. JOC 1986, 51, 1622. Rubin, Y.; Knobler, C. B.; Diederich, F. JACS 1990, 112, 1607.
31. (a) Danishefsky, S. J.; DeNinno, M. P.; Chen, S. JACS 1988, 110, 3929. (b) DeShong, P.; Waltermire, R. E.; Ammon, H. L. JACS 1988, 110, 1901. (c) Abelman, M. M.; Overman, L. E.; Tran, V. D. JACS 1990, 112, 6959.
32. (a) Boutin, R. H.; Rapoport, H. JOC 1986, 51, 5320. (b) Paterson, I.; Laffan, D. D. P.; Rawson, D. J. TL 1988, 29, 1461. (c) Coxon, J. M.; van Eyk, S. J.; Steel, P. J. T 1989, 45, 1029.
33. (a) Nimkar, S.; Menaldino, D.; Merrill, A. H.; Liotta, D. TL 1988, 29, 3037. (b) Rücker, G.; Hörster, H.; Gajewski, W. SC 1980, 10, 623.
34. (a) Krief, A.; Surleraux, D. SL 1991, 273. (b) Kumar, V.; Amann, A.; Ourisson, G.; Luu, B. SC 1987, 17, 1279.
35. Scott, L. T.; Hashemi, M. M. T 1986, 42, 1823.
36. Replacement of MeOH by DMSO reverses this chemoselectivity: Adams, C. SC 1984, 14, 1349.
37. Lakshmy, K. V.; Mehta, P. G.; Sheth, J. P.; Triverdi, G. K. OPP 1985, 17, 251.

Leo A. Paquette

The Ohio State University, Columbus, OH, USA

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