Mercury(II) Oxide-Iodine

HgO-I2
(HgO)

[21908-53-2]  · HgO  · Mercury(II) Oxide-Iodine  · (MW 216.59) (I2)

[7553-56-2]  · I2  · Mercury(II) Oxide-Iodine  · (MW 253.80)

(hypoiodite formation; generation of alkoxyl radicals)

Physical Data: see Mercury(II) Oxide and Iodine.

Solubility: I2: sol organic solvents (g I2/100 g solvent, 25 °C): benzene (14.09), CS2 (16.47), EtOH (21.43), Et2O (25.20), cyclohexane (2.72), CCl4 (2.60, 35 °C); sol CHCl3, AcOH, glycerol.

Form Supplied in: both reagents are widely available. HgO: bright red or orange-red solid; yellow when finely powdered. I2: violet crystals.

Handling, Storage, and Precautions: protect from light. Avoid contact with skin and eyes.

Introduction.

The HgO-I2 combination is widely used for the conversion of an alcohol to a hypoiodite.1 A nonpolar solvent is generally used for the reaction. Due to the weak RO-I bond (~56 kcal mol-1), hypohalites are generally not isolable but are generated and used in situ. Their subsequent decomposition under thermal or photochemical conditions yields alkoxyl radicals, which are highly reactive and undergo a variety of reactions including H&bdot; abstraction, cleavage of the adjacent C-C bond (b-fragmentation), and addition to unsaturated compounds.

Hydrogen Abstraction.

Intramolecular hydrogen abstraction by an alkoxyl radical is most favored through a six-membered ring transition state (1,5-abstraction) and enables the functionalization of remote unactivated carbons.2 Interception of the intermediate radical by iodine is then followed by cyclization to give tetrahydrofurans (eq 1).2a This Barton-type reaction has been applied extensively in steroid chemistry.1 Other oxidants, such as Lead(IV) Acetate-Iodine can also be used, although the HgO-I2 combination has been reported to give a cleaner and higher yielding reaction.2 An analogous reaction with N-nitro amines gives, by way of hydrogen abstraction by a nitrogen-centered radical, N-nitropyrrolidines.3 Although 1,5-hydrogen abstraction is preferred, 1,6-abstraction is possible, particularly in cases where the former is not feasible (eq 2)2c or when it leads to stabilized radicals (eq 3).4 The title reagents have also been used for functionalization at more remote positions,5 in analogy with the work of Breslow.6

b-Fragmentation.

An important reaction of alkoxyl radicals is the homolytic cleavage of the adjacent C-C bond to yield a carbonyl and (generally) the more stable of the two possible carbon-centered radicals. In an early example, Barton found that irradiation of a mixture of cyclopentanol, HgO, and I2 gives d-iodovaleraldehyde.2a These fragmentation conditions are quite mild, as evidenced by the degradation of a highly functionalized steroidal alcohol to an aldehyde, presumably through an iodo intermediate (eq 4).7 The b-fragmentation is particularly advantageous when the hydroxy group is located on a ring junction, since medium or large ring ketones can be formed, sometimes with elimination of the expected iodide (eq 5).8 The factors that determine whether the central or the side-ring bond is broken are not well understood, although the stability of the resulting radical and relief of ring strain appear to be important (eq 6).9

An analogous fragmentation process, involving the reaction of lactol-derived hypoiodites, provides a general route to medium and large ring lactones (eq 7).10 The HgO-I2 mediated fragmentation of hydroxy groups on nonbridging carbons gives iodoformates, via oxidative fragmentation of a lactol intermediate. Treatment of adamantan-2-ol under these conditions gives oxaadamantane directly, presumably by way of the lactol (eq 8).11 Related fragmentations have been studied extensively and offer a general route to cyclic ethers (eq 9).12 Vicinal diols have been cleaved to the corresponding aldehydes using this reagent system.2b

Additions to Unsaturated Compounds.

The title reagent system effects the addition of alkoxy-iodide to an alkene in an inter- or intramolecular sense (eq 10).13 Interestingly, the intramolecular addition is possible even for allylic alcohols and yields a-iodo epoxides (eq 11),14 which are synthetically useful intermediates.15 The yield of the iodo epoxide is significantly higher in the presence of a small amount of pyridine.

Miscellaneous Reactions.

Advantage has been taken of HgO-I2 as a source of electrophilic iodide. Thianaphthene can be iodinated using this reagent system (eq 12).16 Similarly, anisole is iodinated at the para position in high yield. The ethylene acetal of p-benzoquinone can be made through a two-step sequence in which both steps utilize HgO-I2, first for electrophilic aromatic iodination and then for the formation of an alkoxyl radical from a hypoiodite intermediate (eq 13).17


1. Reviews: (a) Heusler, K.; Kalvoda, J. AG(E) 1964, 3, 525. (b) Kalvoda, J.; Heusler, K. S 1971, 501. (c) Brun, P.; Waegell, B. In Reactive Intermediates; Abramovitch, R. A., Ed.; Plenum: New York, 1982; Vol. 3, Chapter 6, p 367.
2. (a) Akhtar, M.; Barton, D. H. R. JACS 1964, 86, 1528. (b) Goosen, A.; Laue, H. A. H. JCS(C) 1969, 383. (c) Fisch, M.; Smallcombe, S.; Gramain, J. C.; McKervey, M. A.; Anderson, J. E. JOC 1970, 35, 1886. (d) Mihailovic, M. Lj.; Gojkovic, S.; Konstantinovic, S. T 1973, 29, 3675.
3. Hernandez, R.; Rivera, A.; Salazar, J. A.; Suarez, E. CC 1980, 958.
4. Kay, I. T.; Bartholomew, D. TL 1984, 25, 2035.
5. Orito, K.; Ohto, M.; Suginome, H. CC 1990, 1074, 1076.
6. White, P.; Breslow, R. JACS 1990, 112, 6842, and references cited therein.
7. (a) Suginome, H.; Umeda, H.; Masamune, T. TL 1970, 4571. (b) Suginome, H.; Ono, H.; Kuramoto, M.; Masamune, T. TL 1973, 4147.
8. (a) Akhtar, M.; Marsh, S. JCS(C) 1966, 937. (b) Mihailovic, M. Lj.; Lorenc, Lj.; Pavlovic, V.; Kalvoda, J. T 1977, 33, 441.
9. (a) Macdonald, T. L.; O'Dell, D. E. JOC 1981, 46, 1501. (b) O'Dell, D. E.; Loper, J. T.; Macdonald, T. L. JOC 1988, 53, 5225. (c) Beckwith, A. L. J.; Kazlauskas, R.; Syner-Lyons, M. R. JOC 1983, 48, 4718. (d) Suginome, H.; Yamada, S. TL 1987, 28, 3963. (e) Suginome, H.; Liu, C. F.; Tokuda, M.; Furusaki, A. JCS(P1) 1985, 327. (f) Kobayashi, K.; Suzuki, M.; Suginome, H. JOC 1992, 57, 599 and references cited therein.
10. (a) Suginome, H.; Yamada, S. T 1987, 43, 3371. (b) Suginome, H.; Yamada, S. CL 1988, 245, and references cited therein. (c) Freire, R.; Hernandez, R. Rodriguez, M. S.; Suarez, E. TL 1987, 28, 981.
11. Black, R. M.; Gill, G. B.; Hands, D. CC 1972, 311.
12. (a) Suginome, H.; Yamada, S. TL 1984, 25, 3995. (b) Suginome, H.; Yamada, S. JOC 1984, 49, 3753, and references cited therein.
13. (a) Wiberg, K. B.; Rowland, B. I. JACS 1955, 77, 1159. (b) Kraus, G. A.; Thurston, J. TL 1987, 28, 4011.
14. (a) Suginome, H.; Wang, J. B. CC 1990, 1629. (b) Lee, T.-J.; Hoffman, W. F.; Holtz, W. J.; Smith, R. L. JOC 1992, 57, 1966.
15. Rawal, V. H.; Iwasa, S. TL 1992, 33, 4687.
16. Gaertner, R. JACS 1952, 74, 4950.
17. Goosen, A.; McCleland, C. W. CC 1975, 655.

Seiji Iwasa & Viresh H. Rawal

The Ohio State University, Columbus, OH, USA



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