[14024-18-1]  · C15H21FeO6  · Tris(acetylacetonato)iron(III)  · (MW 353.21)

(organotransition metal catalyst used in the cross coupling of acid halides or vinyl bromides with Grignard reagents, the stereoselective epoxidation of steroidal alkenes, and the reductive decyanation of alkyl nitriles)

Alternate Names: ferric acetylacetonate; ferric triacetylacetonate; iron acetylacetonate.

Physical Data: mp 182-185 °C (191 °C by differential thermal analysis1).

Solubility: sol alcohols, chlorinated solvents.

Form Supplied in: deep red powder.

Analysis of Reagent Purity: CH analysis (calc 57.51% C, 5.96% H).1

Purification: recrystallization from ethanol2 or methanol/H2O.1

Handling, Storage, and Precautions: severe eye irritant and possible teratogen. Poor thermal stability in molten state.1

Preparation of Ketones from Acyl Chlorides and Grignard Reagents.3

The inclusion of a catalytic amount of Fe(acac)3 in the coupling reaction of acid chlorides and Grignard reagents gives the desired ketones without the significant formation of carbinols which accompanies the reaction in its absence (eq 1).4 The use of other organometallic reagents5 in place of Grignard reagents has also effected the formation of ketones without the accompanying formation of secondary and/or tertiary alcohols; however, these reagents lack the generality and convenience shown with the Fe(acac)3 catalyzed reaction (Table 1). The reaction was also extended to aromatic acid chlorides and thiophenyl acid chlorides, which were coupled with long-chain di-Grignard reagents to produce symmetrical 1,n-diketones (n &egt; 8) and long-chain dicarboxylic thiol esters in moderate to good yield.6

Preparation of Alkenes: Cross Coupling of Vinyl Bromides,7 Vinyl Sulfones,8 and Vinyl Sulfoximines9 with Grignard Reagents.

FeIII complexes containing b-diketonate ligands, such as Fe(acac)3, are useful catalysts for the cross coupling of vinyl bromides with Grignard reagents (eq 2).7 The coupling reactions with vinyl bromides proceed with primary, secondary, and tertiary Grignard reagents. It is proposed that Fe(acac)3 is initially reduced by the Grignard reagent to form an active FeI or Fe0 catalyst,10 which has been shown to undergo an irreversible deactivation during the course of the cross-coupling reaction. A similar reagent, Tris(dibenzoylmethide)iron(III), has been shown to be more resistant to this deactivation and is the preferred iron catalyst for this reaction.7

The cross coupling of Grignard reagents with vinyl sulfones in the presence of Fe(acac)3 or Nickel(II) Acetylacetonate proceeds with some stereoselectivity; however, the reaction is complicated by reduction byproducts.8 The stereoselective construction of exocyclic alkenes from the cross-coupling reaction of alkenylsulfoximines, prepared stereoselectively from the corresponding ketone, with Grignard reagents in the presence of stoichiometric amounts of Fe(acac)3 and NiCl2(dppp) has also been reported (eq 3).9 This serves as a useful alternative to standard Wittig-type alkenations for the construction of exocyclic alkenes.11

Epoxidation of Steroidal Alkenes.12

Fe(acac)3 is used to catalyze the stereoselective b-epoxidation of cholesterol derivatives (allylic alcohols) with excess Hydrogen Peroxide in acetonitrile under mild conditions (eq 4). This shows opposite stereoselectivity to epoxidation reactions using conventional organic peracids, where shielding by the angular methyl groups prevents epoxidation on the b-face. This method offers similar stereoselectivity to halohydrin methodology,13 but the reaction is effected in a single step. The observed stereoselectivity is independent of R, unlike other methodologies.

Preparation of N-Acylpiperidines: Ene Carbocyclization of Trienes.

The in situ generation of a (bipy)Fe0Ln catalyst by the reaction of Fe(acac)3 and Triethylaluminum is used to prepare cyclopentyl, cyclohexyl, and tetrahydropyranyl rings, as well as N-acylpiperidines by the formal [4 + 4] ene carbocyclization of trienes, triene ethers, and azatrienes (eq 5).14

Miscellaneous Reactions.

Hydrocarbons are produced in good to excellent yield from alkyl nitriles upon treatment with Fe(acac)3 and Sodium sand in benzene.15 The best results for this reductive decyanation were obtained with saturated alkyl nitriles. Nontransition metal promoted cleavage of primary nitriles in liquid ammonia gives inferior results.16 The Michael addition of ethyl acetoacetates to cyclic enones was catalyzed by Fe(acac)3 and an electrophilic cocatalyst.17 Other M(acac)n compounds were also examined.

1. Yoshida, I.; Kobayashi, H.; Ueno, K. BCJ 1974, 47, 2203.
2. Chaudhuri, M. K.; Ghosh, S. K. JCS(D) 1983, 839.
3. (a) Fiandanese, V.; Marchese, G.; Marina, V.; Ronzini, L. TL 1984, 25, 4805. (b) Ritter, K.; Hanack, M. TL 1985, 26, 1285.
4. Shirley, D. A. OR 1954, 8, 28.
5. (a) Posner, G. H. OR 1975, 22, 253. (b) Bergbreiter, D. E.; Killough, J. M. JOC 1976, 41, 2750. (c) Friour, G.; Alexakis, A.; Cahiez, G.; Normant, J. T 1984, 40, 683.
6. Babudri, F.; D'Ettole, A.; Fiandanese, V.; Marchese, G.; Naso, F. JOM 1991, 405, 53.
7. Neumann, S. M.; Kochi, J. K. JOC 1975, 40, 599.
8. Fabre, J.-L.; Julia, M.; Verpeaux, J.-N. TL 1982, 23, 2469.
9. Erdelmeier, I.; Gais, H.-J. JACS 1989, 111, 1125.
10. Yubo, Y.; Yamamoto, A.; Ikeda, S. JOM 1972, 46, C50.
11. (a) Hanessian, S.; Delorme, D.; Beaudoin, S.; Leblanc, Y. JACS 1984, 106, 5754. (b) Gais, H.-J.; Schmiedl, G.; Ball, W. A.; Bund, J.; Hellmann, G.; Erdelmeier, I. TL 1988, 29, 1773. (c) Rehwinkel, H.; Skupsch, J.; Vorbruggen, H. TL 1988, 29, 1775.
12. (a) Tohma, M.; Tomita, T.; Kimura, M. TL 1973, 4359. (b) Sheng, M. N.; Zajacek, J. G. JOC 1970, 35, 1839. (c) Slevens, H. C.; Kaman, A. J. JACS 1965, 87, 734.
13. Kirk, D. N.; Hargshorn, M. P. Steroid Reaction Mechanisms; Elsevier: Amsterdam, 1968; p 71.
14. Takacs, B. E.; Takacs, J. M. TL 1990, 31, 2865 and references therein.
15. van Tamelen, E. E.; Rudler, H.; Bjorklund, C. JACS 1971, 93, 7113.
16. Arapakos, P. G. JACS 1967, 89, 6794.
17. Kecovsky, P.; Dvorak, D. TL 1986, 27, 5015.

Mark W. Zettler

The Dow Chemical Company, Midland, MI, USA

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