Copper(II) Acetate-Iron(II) Sulfate


[142-71-2]  · C4H6CuO4  · Copper(II) Acetate-Iron(II) Sulfate  · (MW 181.64) (Cu(OAc)2.H2O)

[6046-93-1]  · C4H8CuO5  · Copper(II) Acetate-Iron(II) Sulfate  · (MW 199.65) (FeSO4.7H2O)

[7782-63-0]  · FeO4S  · Copper(II) Acetate-Iron(II) Sulfate  · (MW 278.02)

(hydroperoxide reduction; alkoxy radical formation and b-fragmentation; carbon radical oxidation and alkene formation; stereocontrolled macrolide synthesis)

Alternate Name: cupric acetate-ferrous sulfate.

Physical Data: Cu(OAc)2.H2O: mp 115 °C (dec 240 °C); d 1.882 g cm-3. FeSO4.7H2O: forms tetrahydrate at 56.6 °C, monohydrate at 65 °C, loses last H2O at about 300 °C and dec at higher temperatures; d 1.897 g cm-3.

Solubility: Cu(OAc)2.H2O: sol H2O and alcohol; slightly sol ether and glycerol. FeSO4.7H2O: sol H2O; very slightly sol alcohol.

Form Supplied in: Cu(OAc)2.H2O: dark green solid; widely available. FeSO4.7H2O: blue-green solid; widely available.

Preparative Methods: the reagents are prepared individually as saturated solutions in methanol and used directly. Generally, the substrate is mixed with methanolic copper acetate and to this is added a methanolic solution of iron sulfate.

Handling, Storage, and Precautions: aqueous solutions of FeSO4 are oxidized by air. Use in a fume hood.

Alkoxy Radical Generation by Iron(II) Sulfate.

One-electron reduction of peroxide bonds by FeSO4 generates alkoxy radicals1-4 which are valuable intermediates in organic synthesis.5 Alkoxy radicals rearrange to more stable alkyl radicals via d-hydrogen abstraction,6-8 b-fragmentation9-17 or, in the presence of a suitably disposed pendant alkene, cyclization18 pathways. In most cases the generated alkyl radical is oxidatively trapped giving, for example, alkene or alkyl halide products; copper(II) acetate plays the role of alkyl radical oxidant in the reagent pair.

Alkyl Radical Oxidation by Copper(II) Acetate.

One-electron oxidation of secondary carbon radicals by Cu(OAc)2 efficiently generates alkene products. Oxidation of simple alkyl radicals, such as 3-pentyl and 2-butyl, gives a mixture of alkene isomers.2,19 In more complex systems, however, alkene formation often proceeds regio- and stereoselectively.1,20-23 In some cases, heteroatom coordination to a CuIII alkyl intermediate has been invoked to explain product selectivity.1,22,24

Macrolide Synthesis from a-Alkoxy Hydroperoxides.

Schreiber has used the fragmentation of a-alkoxy hydroperoxides with copper(II) acetate-iron(II) sulfate to prepare macrolides (eqs 1-3).20-22 Requisite a-alkoxy hydroperoxides can be prepared by direct peroxyacetalization of carbonyl precursors or by trapping carbonyl oxide intermediates generated by ozonolysis. In eq 1 an alkoxy radical is produced from the hydroperoxide by the transfer of an electron from Fe2+; the alkoxy radical then spontaneously transforms into a carbon-centered radical which is then oxidized by the Cu2+ ion to give an alkylcopper intermediate which undergoes a b-elimination to furnish the product recifeiolide.2 The exclusive trans geometry observed in the product is explained by means of internal coordination of the intermediate alkylcopper with transannular oxygen lone pairs.22

This method has been used to prepare substrates for use in studies directed towards preparation of ionophore subunits (eq 2)27 and for the preparation of 14-membered macrocycles from octalins (eq 3).21 Ozonolysis of (1) (eq 3) selectively gives hydroperoxide (2) with the allylic methoxy group of (1) directing breakdown of the primary ozonide.25 The sequence of hydroperoxide reduction, followed by b-fragmentation and alkene oxidation, results in overall dehydration of the molecule. Similar fragmentations have been achieved by treatment of a-alkoxy hydroperoxides with Methanesulfonyl Chloride/Sulfur Dioxide.26

The redox reagents were also used in a new synthesis of racemic syn-4,8-dimethyldecanal, the aggregation pheromone of the confused and red flour beetles, respectively.32

Other b-Fragmentation Reactions.

The isopropenyl group of carvone derivatives can be removed by ozonolysis in methanol, followed by treatment of the intermediate a-methoxy hydroperoxide with the reagents (eqs 5 and 6).13,22 The (+)-6-methylcyclohex-2-enone produced in eq 5 is a useful synthetic intermediate.22 A similar reaction occurs with ozonolysis products from cycloalkenes (eqs 4 and 7).28,32

Copper(II) acetate-iron(II) sulfate was used to convert allyl hydroperoxide (4) to cyclic ether (5) (eq 8), which is an important fragrance chemical.12 Here the oxidized alkyl radical is trapped by an internal nucleophile before it can form the normal alkene product. Other methods to reduce the hydroperoxide (4) were ineffective.

Iron(II) will promote homolysis of the O-O bond in cyclic peroxides.29,30 Treatment of tetracyclic secondary ozonide (6) with the reagents gives cyclopentene derivative (7) (eq 9).31

1. Cekovic, Z.; Dimitrijevic, L.; Djokic, G.; Srnic, T. TL 1979, 35, 2021.
2. Kochi, J. K. Free Radicals; Wiley: New York, 1973; Vol. 1.
3. Sheldon, R. A. In The Chemistry of Peroxides; Patai, S., Ed.; Wiley: New York, 1983.
4. Sosnovsky, G.; Rawlinson, D. J. In Organic Peroxides; Swern, D., Ed.; Wiley: New York, 1971; Vol. 2.
5. For recent reviews of radical reactions in organic synthesis, see: (a) Curran, D. P. S 1988, 417. (b) Curran, D. P. S 1988, 489. (c) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. CRV 1991, 91, 1237.
6. Barton, D. H. R. PAC 1968, 16, 1.
7. Burke, S. D.; Silks, L. A., III; Strickland, S. M. S. TL 1988, 29, 2761.
8. Wincott, F. E.; Danishefsky, S. J.; Schulte, G. TL 1987, 28, 4951.
9. Ellwood, C. W.; Pattenden, G. TL 1991, 32, 1591.
10. Arencibia, M. T.; Freire, R.; Perales, A.; Rodriguez, M. S.; Suárez, E. JCS(P1) 1991, 3349.
11. O'Dell, D. E.; Loper, J. T.; Macdonald, T. L. JOC 1988, 53, 5225.
12. Decorzant, R.; Vial, C.; Näf, F.; Whitesides, G. M. T 1987, 43, 1871.
13. Jansen, B. J. M.; Kreuger, J. A.; de Groot, A. T 1989, 45, 1447.
14. Suginome, H.; Senboku, H.; Yamada, S. TL 1988, 29, 79.
15. Beckwith, A. L. J.; Hay, B. P. JACS 1989, 111, 230.
16. Beckwith, A. L. J.; Hay, B. P. JACS 1989, 111, 2674.
17. Ramaiah, M. T 1987, 43, 3541.
18. Kraus, G. A.; Thurston, J. TL 1987, 28, 4011.
19. Jenkins, C. L.; Kochi, J. K. JACS 1972, 94, 843.
20. Schreiber, S. L.; Hulin, B.; Liew, W. F. T 1986, 42, 2945.
21. Schreiber, S. L.; Liew, W. JACS 1985, 107, 2980.
22. Schreiber, S. L. JACS 1980, 102, 6163.
23. Snider, B. B.; Kwon, T. JOC 1990, 55, 1965.
24. Breuilles, P.; Uguen, D. BSF(2) 1988, 705.
25. Bunnelle, W. H. CRV 1991, 91, 335.
26. Grant, P. K.; Lai, C. K.; Prasad, J. S.; Yap, T. M. AJC 1988, 41, 711.
27. Schreiber, S. L.; Sammakia, T.; Hulin, B.; Schulte, G. E. JACS 1986, 108, 2106.
28. Schreiber, S. L.; Liew, W.-F. TL 1983, 24, 2363.
29. Bascetta, E.; Gunstone, F. D.; Scrimgeour, C. M. JCS(P1) 1984, 2199.
30. Yoshida, M.; Miura, M.; Nojima, M.; Kusabayashi, S. JACS 1983, 105, 6279.
31. Paquette, L. A.; Reagan, J.; Schreiber, S. L.; Teleha, C. A. JACS 1989, 111, 2331.
32. Schreiber, S. L.; Hulin, B. TL 1986, 27, 4561.

William Crowe

Emory University, Atlanta, GA, USA

Joseph Sweeney

University of Bristol, UK

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