Iron(III) Chloride-Dimethylformamide1


[36654-49-6]  · C9H21Cl6Fe2N3O3  · Iron(III) Chloride-Dimethylformamide  · (MW 543.73)

(mild oxidant; oxidative coupling2 of phenols, ketone enolates,3 and allylic sulfones;4 ring expansion of silyloxybicyclo[n.1.0]alkanes;5 oxidative decomplexation of chromium carbonyl complexes6)

Alternate Name: ferric chloride-DMF.

Physical Data: mp 220 °C.

Preparative Method: N,N-Dimethylformamide (1.5 mol) is added with stirring to a solution of Iron(III) Chloride (1 mol) in dry ether (1.6 L) to yield a precipitate which is filtered and dried in vacuo to yield a yellowish green powder (95%) which is sufficiently pure to use for oxidation reactions.2

Purification: recrystallize from dichloromethane and ethanol to give needles.

Handling, Storage, and Precautions: stable to air and moisture; FeCl3 is hygroscopic and corrosive; inhalation or ingestion may be fatal; DMF is mildly toxic by skin contact and inhalation; it is a skin and eye irritant. Use in a fume hood.

Oxidative Coupling of Phenols.2

Oxidative aryl-aryl coupling represents a challenging synthetic transformation. Iron(III) chloride in DMF or [Fe(DMF)3Cl2][FeCl4] is a good reagent for intramolecular (eq 1) and intermolecular (eq 2) phenol coupling reactions.1,2 As the redox potential of substrates differ, many alternate reagents exist for this transformation (intiated by one-electron abstraction from the substrate by the oxidant). Alternative reagents used are Vanadyl Trichloride,7 Thallium(III) Trifluoroacetate,8 manganese(II) acetylacetonate,9 Potassium Ferricyanide,10 copper(II) amine complexes,11 photolysis,12 (Diacetoxyiodo)benzene,13 electrochemical anodic oxidation,1a and FeCl3 in the solid state.14

Oxidative Coupling of Ketone Enolates.

Addition of anhydrous FeCl3 in DMF to an enolate in THF yields the 1,4-ketone (eq 3).3 This reaction has also been applied in an intramolecular fashion (eq 4).15

Oxidative Dimerization of Allylic Sulfones.

Lithium salts of allylic sulfones are oxidized by addition of [Fe(DMF)3Cl2][FeCl4] at 0 °C (eq 5) to give 1,6-disulfones by 3-3 coupling.4 These products can undergo Cope rearrangement to 1,2-disulfones.

Ring Expansion of Cyclic Ketones.

Trimethylsilyloxybicyclo[n.1.0]alkanes (available by Simmons-Smith reaction of enolates of cycloalkanones) can be oxidized by FeCl3 in DMF at 0 °C to afford the one-carbon ring homologation product (eq 6).5 This method has been utilized to synthesize 3-methoxycycloheptatrienones (eq 7).16

Oxidative Demetallation of Chromium Carbonyl Complexes.

[Fe(DMF)3Cl2][FeCl4] is an excellent reagent for oxidative workup of chromium tricarbonyl complexes to obtain the arene ligand or aryl product.6 Cerium(IV) Ammonium Nitrate represents a viable alternative.17

1. (a) Tobinaga, S. Bioorg. Chem. 1975, 4, 110. (b) Murase, M.; Kotani, E.; Okazaki, K.; Tobinaga, S. CPB 1986, 34, 3159. (c) Krauss, A. S.; Taylor, W. C. AJC 1991, 44, 1307.
2. Tobinaga, S.; Kotani, E. JACS 1972, 94, 309.
3. Frazier, R. H., Jr.; Harlow, R. L. JOC 1980, 45, 5408.
4. Buchi, G.; Freidinger, R. M. TL 1985, 26, 5923.
5. Ito, Y.; Fujii, S.; Saegusa, T. JOC 1976, 41, 2073.
6. (a) Semmelhack, M. F.; Hall, H. T., Jr.; Farina, R.; Yoshifuji, M.; Clark, G.; Bargar, T.; Hirotsu, K.; Clardy, J. JACS 1979, 101, 3535. (b) Wulff, W. D.; Tang, P.-C. JACS 1984, 106, 434.
7. Schwartz, M. A.; Holton, R. A.; Scott, S. W. JACS 1969 91, 2800.
8. Schwartz, M. A.; Rose, B. F.; Vishnuvajjala, B. JACS 1973, 95, 612.
9. Dewar, M. J. S.; Nakaya, T. JACS 1968 90, 7134.
10. Barrett, A. G. M.; Barton, D. H. R.; Franckowiak, G.; Papaioannou, D.; Widdowson, D. A. JCS(P1) 1979, 662.
11. Feringa, B.; Wynberg, H. TL 1977, 18, 4447.
12. Chatterjee, S.; Ghosal, P. K. TL 1977, 18, 1451.
13. Krishna, K. V. R.; Sujatha, K.; Kapil, R. S. TL 1990, 31, 1351.
14. Toda, F.; Tanaka, K.; Iwata, S. JOC 1989, 54, 3007.
15. Poupart, M.-A., Paquette, L. A. TL 1988, 29, 269.
16. Roberts, V. A.; Garst, M. E.; Torres, N. E. JOC 1984, 49, 1136.
17. Wulff, W. D.; Tang, P.-C.; McCallum, J. S. JACS 1981, 103, 7677.

Andrew D. White

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

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.