Lead(IV) Acetate-Iodine1

Pb(OAc)4-I2
(Pb(OAc)4)

[546-67-8]  · C8H12O8Pb  · Lead(IV) Acetate-Iodine  · (MW 443.37) (I2)

[7553-56-2]  · I2  · Lead(IV) Acetate-Iodine  · (MW 253.80)

(functionalization of nonactivated d-carbon atoms;2 mono- and disubstitution on methyl and methylene groups;3,4 cyanohydrin-cyano ketone rearrangement;5 b-fragmentation reactions;6 iododecarboxylation7)

Physical Data: see Lead(IV) Acetate and Iodine.

Functionalization of Nonactivated d-Carbon Atoms.

The original method for oxidative functionalization of d-carbon atoms by lead tetraacetate (LTA), involving conversion of alcohols to cyclic ethers, is modified by using LTA-I2 as reagent.1 This modification is known as the LTA-hypoiodite reaction.1 The reactions are performed under irradiation conditions (500 W lamp) in nonpolar solvents such as cyclohexane and CCl4.2 The selective introduction of a functional group on the d-carbon atom by oxidative transformation of alcohols is based on the specific reactivity of LTA-I2 for the conversion of alcohols to hypoiodites, and on the facile homopolar decomposition of alkyl hypoiodites, under irradiation, with formation of alkoxy radical intermediates (eq 1).1,2

Alkoxy radicals generated by this method from primary and secondary alcohols undergo intramolecular hydrogen transfer from the d-carbon atom, thus forming intermediary d-carbon radicals (eq 2), which under these experimental conditions are then intercepted by iodine with formation of 1,4-iodohydrins.1,2 Depending on the conformational relationship of the hydroxy group, iodine, and d-carbon atom in the iodohydrin, different products can be obtained (eq 2). In the case of a linear arrangement, the hydroxy group approaches the d-carbon atom from the back side of iodine, whereby oxidative monosubstitution takes place with elimination of HI, resulting in closure of a tetrahydrofuran ring (eq 2, path i).1,8 This reaction has often been applied for the functionalization (with cyclic ether formation) of steroidal 18- and 19-methyl groups, and methyl groups in other rigid molecules (eqs 3 and 4).3,9,10

However, when a linear relationship of iodine, d-carbon atom, and hydroxy group is not possible in the iodohydrin, a second oxidative sequence with double substitution on the d-methyl group takes place (eq 2, path ii),1,8 and acetoxy or iodo cyclic ethers are formed. Such a reaction at the angular 19-methyl group of 4b-hydroxy steroids affords 19-acetoxy- (or iodo-) 4b,19-cyclic ethers (eq 5).8,11

The LTA-I2 oxidation of primary and secondary alcohols possessing a nonactivated d-methylene group proceeds either with monosubstitution, i.e. cyclic ether formation, or double substitution to give unsaturated cyclic ethers (eq 6).4,12

By the LTA-I2 oxidation of steroidal alcohols having a methine group at the d-position, unsaturated cyclic ethers are obtained via alkenic alcohols as intermediates (eq 7).4,13

Cyanohydrin-Cyano Ketone Rearrangement.

A particularly interesting and specific reaction of the LTA-iodine reagent is the oxidative rearrangement of cyanohydrins to d-cyano ketones (eq 8).1,5,14 Other hypoiodite forming reagents do not effect this rearrangement.

The cyanohydrin-cyano ketone rearrangement is successfully realized by the LTA-I2 oxidation of 20-cyano-20-hydroxy steroids, and this reaction offers a good method for the introduction of a functional group, with C-C bond formation, at the nonactivated 18-methyl group in a one-pot reaction.1,5 1,4-Migration of the cyano group involves intramolecular addition of a d-alkyl radical to the cyano group, followed by b-cleavage of the resulting imino radical, to give an a-hydroxy-d-cyano radical and, as final product, the corresponding d-cyano ketone (eq 9).1

It is important to note that all of the described reactions of hydroxy compounds with LTA-I2 can take place only when at least one of the reactive centers, the hydroxy group or the d-carbon atom, are part of a fixed system.1

b-Fragmentation Reaction.

In addition to cyclization, alkoxy radicals generated by means of LTA-I2 can also undergo b-cleavage, this process being favored when stable alkyl radical and oxo-containing fragments are formed.6 In this case, homolytic Ca-Cb bond breaking can be more important than functionalization at Cd (eq 10).6,15,16

The relatively stable tertiary radicals generated by b-fragmentation in the LTA-I2 reaction can be either quenched by iodine to give iodides or oxidized to the corresponding carbocations, which usually undergo proton elimination affording unsaturated products (eqs 10 and 11).1 When cleavage of a bridged Ca-Cb bond is involved, the LTA-I2 b-fragmentation can be usefully applied for the preparation of medium or large carbocyclic and heterocyclic rings (eqs 10 and 12).

Iododecarboxylation.

When treated with I2 and LTA in refluxing CCl4 under irradiation with a tungsten lamp, carboxylic acids undergo iododecarboxylation.17 Good yields of alkyl iodides are obtained from primary and secondary acids (eqs 13 and 14).17,18-20

In the dark, the reaction proceeds more slowly and in lower yield. Decarboxylation of carboxylic acids by LTA-I2 under thermal conditions, i.e. by heating at 150-180 °C in a suitable solvent, gives (particularly with primary acids) esters of these acids in fairly good yield (up to 54%) (eq 15).21


1. (a) Kalvoda, J.; Heusler, K. S 1971, 501. (b) Heusler, K.; Kalvoda, J. AG(E) 1964, 3, 525. (c) Heusler, K.; Kalvoda, J. In Organic Reactions in Steroid Chemistry, Fried, J.; Edwards, J. A., Eds.; Reinhold: New York, 1972; vol. II, pp 237-287.
2. (a) Meystre, Ch.; Heusler, K.; Kalvoda, J.; Wieland, P.; Anner, G.; Wettstein, A. E 1961, 17, 475. (b) Meystre, Ch.; Heusler, K.; Kalvoda, J.; Wieland, P.; Anner, G.; Wettstein, A. HCA 1962, 45, 1317.
3. Heusler, K.; Kalvoda, J.; Meystre, Ch.; Anner, G.; Wettstein, A. HCA 1962, 45, 2161.
4. Hauser, D.; Heusler, K.; Kalvoda, J.; Schaffner, K.; Jeger, O. HCA 1964, 47, 1961.
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6. (a) Fuhrer, H.; Lorenc, Lj.; Pavlović, V.; Rihs, G.; Rist, G.; Kalvoda, J.; Mihailović, M. Lj. HCA 1981, 64, 703. (b) Mihailović, M. Lj.; Lorenc, Lj.; Gašić, M.; Rogić, M.; Melera, A.; Stefanović, M. T 1966, 22, 2345.
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9. (a) Bull, J. R. JCS(C) 1969, 1128. (b) Kalvoda, J.; Heusler, K.; Anner, G.; Wettstein, A. HCA 1963, 46, 1017.
10. (a) Kalvoda, J.; Heusler, K.; Ueberwasser, H.; Anner, G.; Wettstein, A. HCA 1963, 46, 1361. (b) Mousseron-Canet, M.; Lanet, J-C. BSF 1969, 1745.
11. Wenkert, E.; Mylari, B. JACS 1967, 89, 174.
12. Meystre, Ch.; Kalvoda, J.; Anner, G.; Wettstein, A. HCA 1963, 46, 2844.
13. Heusler, K.; Kalvoda, J. HCA 1963, 46, 2020.
14. (a) Kalvoda, J. HCA 1968, 51, 267. (b) Kassal, A.; &CCbreve;erny, V. CCC 1966, 31, 2759. (c) Kassal, A.; &CCbreve;erny, V. CCC 1967, 32, 3733.
15. (a) Mutzenbecher, C.; Cross, A. D. Steroids 1965, 5, 429. (b) Fried, J.; Brown, J. W.; Applebaum, M. TL 1965, 849.
16. (a) Lunn, W. H. W. JCS(C) 1970, 2124. (b) Black, R. M.; Gill, G. B. CC 1970, 972. (c) Black, R. M.; Gill, G. B. CC 1971, 172.
17. (a) Barton, D. H. R.; Serebryakov, E. P. Proc. Chem. Soc. 1962, 309. (b) Barton, D. H. R.; Faro, H. P.; Serebryakov, E. P.; Woolsey, N. F. JCS 1965, 2438.
18. Musso, H.; Naumann, K.; Grychtol, K. CB 1967, 100, 3614.
19. Scheidegger, U.; Baldwin, J. E.; Roberts, J. D. JACS 1967, 89, 894.
20. (a) Odham, G. AK 1965, 23, 431. (b) Sakan, T.; Abe, K. TL 1968, 2471.
21. Bachman, G. B.; Wittmann, J. W. JOC 1963, 28, 65.

&ZZbreve;ivorad &CCbreve;eković & Mihailo Lj. Mihailović

University of Belgrade, Yugoslavia



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