Iron(III) Chloride-Alumina1


[7705-08-0]  · Cl3Fe  · Iron(III) Chloride-Alumina  · (MW 162.20) (Al2O3)

[1344-28-1]  · Al2O3  · Iron(III) Chloride-Alumina  · (MW 101.96)

(proton scavenger; mild Lewis acid catalyst for ene reactions1,2)

Alternate Name: ferric chloride-alumina.

Form Supplied in: the individual reagents are commercially available.

Preparative Method: anhydrous Iron(III) Chloride (62 mmol) is added to anhydrous CH2Cl2 (160 mL) under argon. The mixture is stirred vigorously while 50 g chromatography grade basic Alumina is added in small portions under argon. Stirring is continued for 1 h to obtain homogeneous adsorbtion and the solvent is then removed under reduced pressure. The basic alumina supported FeCl3 obtained can be stored under argon for several months without loss of catalytic activity.

Handling, Storage, and Precautions: should be stored and manipulated in an inert, dry atmosphere; FeCl3 is hygroscopic and corrosive, inhalation or ingestion may be fatal; basic alumina is an irritant. Use in a fume hood.

Lewis Acid Catalyzed Intramolecular Ene Reactions.1

Anhydrous iron(III) chloride on basic alumina proved to be the best Lewis acid catalyst for the intramolecular ene reaction of the Knoevenagel adduct from citronellal and dimethyl malonate. The trans-1,2-disubstituted cyclohexane was obtained as the major product in a 98.8:1.2 ratio in 92% yield in dichloromethane at -78 °C (eq 1).1,2 The thermal ene reaction3 yields a 9:1 ratio in 75% yield.1

Strong Lewis acid catalysts, (e.g. Aluminum Chloride and Titanium(IV) Chloride) yield complex mixtures.1 Anhydrous Zinc Chloride4 and alkyl aluminum halides5 yield product but the overall yields and ratios are not quite as good.1 FeCl3 also works well; however, competing reactions attributable to traces of water were sometimes observed. The supported catalyst avoids this problem presumably because the catalyst acts as a proton scavenger similar to alkylaluminum halides.2,6 The FeCl3-Al2O3 mediated cyclization can be utilized for 1,6-dienes additionally to yield trans-1,2-substituted cyclopentanes. The allylsilane moiety on the ene component is necessary otherwise the reaction is limited to trisubstituted alkenes (eq 2).7 Silica gel at high pressure (15 kbar) (see Iron(III) Chloride-Silica Gel) may provide an alternative8 as a mild acid catalyst for highly sensitive functionality, although the yield (73%) and selectivity (9.4:1) for eq 1 does not compare with FeCl3-Al2O3 and is only equivalent to the best thermal ene reaction conditions.1

Electrophilic Cyclizations.

Intramolecular electrophilic cyclization of doubly activated imines using FeCl3-Al2O3 yields an annulated piperidine lactone (eq 3). However, better chemoselectivities but lower yields are obtained with gallium trichloride or Trifluoroacetic Acid.9 Trialkylsilyl triflates yield the substituted piperidine predominantly. In the corresponding cyclizations to pyrrolidines, FeCl3-Al2O3 was inferior to GaCl3.10

1. Tietze, L. F.; Beifuss, U. S 1988, 359.
2. Tietze, L. F.; Beifuss, U.; Antel, J.; Sheldrick, G. M. AG(E) 1988, 27, 703.
3. (a) Hoffman, H. M. R. AG 1969, 81, 597. (b) Hoffman, H. M. R. AG(E) 1969, 8, 556. (c) Oppolzer, W.; Snieckus, V. AG 1978, 90, 506. (d) Oppolzer, W.; Snieckus, V. AG(E) 1978, 17, 476. (e) Taber, D. F. Intramolecular Diels-Alder and Alder-Ene Reactions; Springer: Berlin, 1984; p 61. (f) Mikami, K.; Shimizu, M. CRV 1992, 92, 1021.
4. Marshall, J. A., Wuts, P. G. M. JOC 1977, 42, 1794.
5. Snider, B. B.; Rodini, D. J.; Karras, M.; Kirk, T. C.; Deutsch, E. A.; Cordova, R.; Price, R. T. T 1981, 37, 3927.
6. Snider, B. B.; Rodini, D. J.; Kirk, T. C.; Cordova, R. JACS 1982, 104, 555.
7. Tietze, L. F.; Ruther, M. CB 1990, 123, 1387.
8. Dauben, W. G.; Hendricks, R. T. TL 1992, 33, 603.
9. Tietze, L. F.; Bratz, M. CB 1989, 122, 997.
10. Tietze, L. F.; Bratz, M. LA 1989, 559.

Andrew D. White

Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA

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