Diphosphorus Tetraiodide1,2

P2I4

[13455-00-0]  · I4P2  · Diphosphorus Tetraiodide  · (MW 569.54)

(exhibits a high affinity for oxygen and acts as a unique reagent able to promote substitution, dehydration, and reduction reactions)

Physical Data: mp 124 °C (from CS2);3 X-ray;4 31P NMR.5

Solubility: sol CS2; partly sol CH2Cl2.

Form Supplied in: bright orange solid; commercially available.

Handling, Storage, and Precautions: can be weighed out rapidly in air into vials flushed with nitrogen. Store under nitrogen in the absence of moisture. This reagent should be handled in a fume hood.

Introduction.

Diphosphorus tetraiodide is a bright orange solid which fumes in air, probably due to the presence of trace amounts of white phosphorus. It is most conveniently prepared by mixing, at rt, stoichiometric amounts of white phosphorus and iodine in CS2,3 or by reaction of phosphorus trichloride with potassium iodide in ether (3 equiv KI, reflux, 12 h, 75%).6 Diphosphorus tetraiodide often exhibits similar reactivity to Phosphorus(III) Iodide. P2I4 exhibits a high affinity for oxygen and acts as a unique reagent able to promote substitution and dehydration, as well as reduction, reactions. In the last case, a mixture of phosphorus acids (including hypophosphorous acid) and iodine is formed. The characteristic reactivity of P2I4 was disclosed very early by Berthelot in 1855, when he described the synthesis of allyl iodide from glycerol and P2I4.7 In this transformation, H2O2 is formally removed and one hydroxy group is substituted by an iodide ion.

P2I4 was first used in the early 1920s by Kuhn8,9 and later by Inhoffen10 for the reduction of unsaturated diols to trans-polyenes or enepolyynes (eq 1).

Reactions of P2I4 Involving Substitutions with Iodide Ion.

P2I4 reacts with alcohols (CS2, 20 °C, 0.5-24 h) to form alkyl iodides in good to very good yields (eq 2).3 The reaction is quite general and occurs with primary, secondary, and tertiary alcohols,3,11 as well as with benzyl3 and allyl alcohols.12 The reaction is very fast (<0.5 h) with t-alkyl, benzyl, and allyl alcohols, but quite slow (24 h for completion) with primary and secondary alcohols, especially with neopentyl derivatives (144 h). It has also been successfully carried out in special cases (i.e. for the preparation of [11C]methyl iodide (99.5% purity, 3.4 Ci mmol-1)13 and [11C]allyl iodide3), under vacuum (10-2 mmHg), in the gas phase, and on solid supports (VGSR).

Rearrangement does not usually occur3 except with allyl alcohols12 and only in rare cases are elimination reactions observed (for example from cis-4-t-butyl-1-cyclohexanol and a little from its trans stereoisomer).3 The reaction is stereoselective with secondary alkyl halides and occurs by net inversion of configuration.3 The reaction takes another course (i) when carried out on primary and secondary alcohols if it is rapidly quenched by water (after 0.1 h instead of 24 h), where it mainly produces dialkyl phosphites (eq 2),3 and (ii) when carried out on benzyl alcohols bearing electron-withdrawing groups (or whose benzylic carbon is quite hindered by a t-butyl group or by two methyl groups in 2,6-positions on the aromatic ring), which undergo reduction in refluxing benzene to form the parent hydrocarbons in good to moderate yields.14 Under the same conditions, but in the presence of disulfides, benzyl alcohols afford the corresponding benzyl sulfides (0.5 equiv P2I4, benzene, reflux 4-10 h, 6-90% yield).15

a,o-Diols, with the exception of 1,2-glycols (see below), produce the corresponding diiodides on reaction with 0.5 equiv of P2I43 and form monoiodides if half the amount of P2I4 is used instead.16 Selective transformation of primary over secondary carbinols has been achieved. Cyclopropyl carbinols which do not bear a fully alkyl substituted carbinol carbon produce the corresponding iodides in good yield (70%), in addition to trace amounts of 3-alkenyl iodides resulting from cyclopropane ring opening (eq 3).17 However, these cleavage products are formed as predominant products17 (i) from alcohols where the carbinol carbon is fully alkyl substituted, (ii) from cyclopropyl carbinols bearing a silyl substituent on the cyclopropane ring (eq 3), and (iii) from seleno analogs which possess hydroxy groups at an allylic position.17

b-Aminoalkyl carbinols are cyclized to aziridines (P2I4, benzene, 20 °C, 24 h, 45-75% yield).18

The high oxygenophilicity of the phosphorus atom of P2I4 coupled with the high nucleophilicity of iodide ion allows the ring opening of cyclopropyl ketones to g-iodo ketones,17 oxetanes,19 tetrahydrofurans,19 and tetrahydropyrans19 to the corresponding o-diiodides (60, 50, and 15% yield, respectively, reaction carried out at 20 °C) and of g-butyrolactone (90 °C, 24 h) to 4-iodobutyric acid or to methyl butyrate, depending upon the reagent (H2O or methanol) used to quench the reaction.1)

P2I4 can be employed for the deprotection of a,a-bis(methoxy)- and a,a-bis(ethoxy)alkanes, leading to the corresponding aldehydes or ketones together with methyl or ethyl iodide. The reaction is particularly easy with a,a-bis(methoxy)alkanes (20 °C, 0.2 h), but does not occur with dioxolanes even under drastic conditions.20 This reaction has been successfully used21 for the cleavage of alkoxymethyl aryl ethers to give hydroxyarenes and has been applied to the synthesis of the antibiotic ascofuranone.21

P2I4 also reacts with thioacetals, orthothioesters, and their seleno analogs to produce vinyl sulfides, ketene thioacetals, vinyl selenides, and ketene selenoacetals, respectively.22

Reactions of P2I4 Involving Reduction.

P2I4 reacts differently with glycols (eq 1) or related a,d-diols whose b,g-carbons are both sp2, sp, or part of a cyclopropane ring. These substrates lose two hydroxy groups and are converted to alkenes,8 -10 1,3-dienes,10 1,2,3-trienes,6 or 1,4-dienes,23 respectively. b-Thioalkyl carbinols24 and b-selenoalkyl carbinols1,17 also behave differently from b-aminoalkyl carbinols (see above) and afford alkenes. The reaction is best achieved in the presence of Triethylamine, occurs in a few hours at rt, is more efficient with methylseleno than with methylthio, phenylseleno, or phenylthio derivatives (which are the least reactive), and allows the regioselective synthesis of terminal, di-, tri-, and tetrasubstituted alkenes. The synthesis of alkylidenecyclopropanes17 and allenes25 via this approach can only be achieved from b-hydroxyalkyl methyl selenides. The elimination is in general antistereospecific,1,17 except with b-hydroxyalkyl phenyl sulfides24 which are the least reactive compounds and probably react via the intermediate formation of a thiiranium or a seleniranium ion (eq 4). Since b-hydroxyalkyl selenides can be synthesized from a-selenoalkyllithiums and carbonyl compounds, even hindered and/or enolizable ones such as 2,2,6-trimethylcyclohexanone or deoxybenzoin,26 this set of reactions allows the synthesis of the corresponding alkenes which are not available via the Wittig reaction (eq 5).27-29

P2I4 also reduces epoxides (eq 6)1,19,30 and thiiranes31 to alkenes. The reduction of epoxides takes place at rt in methylene chloride in the presence of a base such as triethylamine or pyridine.19 The reduction of thiiranes requires more drastic conditions (DMF, 80 °C).31 Both reactions are regioselective and highly stereoselective, allowing the synthesis of a variety of alkenes (terminal, di-, tri-, and tetrasubstituted)19,30,31 whose stereochemistry is derived from that of the starting epoxides or thiiranes (eq 6).19,30,31

This reaction allows the synthesis of polyfunctionalized alkenes such as enones,19,30 diphenylvinylphosphine oxides,32 vinylcyclopropanes,30 and 1,3-dienes19,30 from the corresponding epoxides. The ethylidene derivative shown in eq 6 is produced in modest yield as the pure (E) stereoisomer.33 Other reagents able to deoxygenate epoxides, such as Tungsten(VI) Chloride-n-Butyllithium and [n-Bu3SnAlMe]Li, result in considerable scrambling of alkene stereochemistry.33

P2I4 is a valuable reducing agent, able to reduce under mild conditions iodo,34 bromo,34 and seleno ketones,17 including cyclic ones (0.5 equiv, 25 °C, 1-7 h, 54-97% yield; eq 7). Sequential reaction of terminal epoxides with Iodotrimethylsilane, Jones reagent, and P2I4 allows the one-pot chemoselective synthesis of the corresponding methyl ketone resulting from the reduction of the iodomethyl ketone intermediate (eq 7).34

P2I4 also reduces, under mild conditions, aminoxides,35 sulfoxides,36,37 and selenoxides36 to amines, sulfides, and selenides, respectively (eq 8). These conditions are sufficiently mild so that the very easy selenoxide elimination leading to alkenes does not compete.

P2I4 reduces ozonides very rapidly at -78 °C;17 promotes, under unusually mild conditions, the reduction of nitroalkanes to nitriles (eq 9);36 and transforms, in boiling acetonitrile, arenesulfonic acids, their salts, their chlorides, and their esters to diaryl disulfides.38 Arenesulfonamides are stable towards P2I4 in boiling acetonitrile, but are successfully reduced at much higher temperature and under neat conditions to give diaryl disulfides as the sole products.38

Reactions of P2I4 Involving Dehydration or Related Reactions.

P2I4 has proved to be a valuable dehydrating agent. Thus 2-amino alcohols are transformed to aziridines (see above);18 aldoximes30,39 and amides40 are smoothly transformed to nitriles, and thioamides behave similarly.41 P2I4 also allows the dehydrative condensation of carboxylic acids with amines.42 The latter reaction seems to be attractive for converting weak or hindered amines into amides and has been used for the synthesis of a few peptides.42

Related Reagents.

Lithium Aluminum Hydride-Diphosphorus Tetraiodide.


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5. Carroll, R. L.; Carter, R. P. IC 1967, 6, 401.
6. Newkome, G. R.; Sauer, J. D.; Erbland, M. L. CC 1975, 885.
7. Berthelot, M. Ann. Chim. Phys. 1855, 93, 257.
8. Kuhn, R.; Winterstein, A. HCA 1928, 11, 87.
9. Kuhn, R.; Wallenfels, K. CB 1938, 71, 1889.
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26. Krief, A. T 1980, 36, 2531.
27. Krief, A. In The Chemistry of Organic Selenium and Tellurium Compounds; Patai, S. Ed.; Wiley: New York, 1987; Vol. 2, Chapter 17, p 675.
28. Krief, A. COS 1991, 1, 629.
29. Krief, A. Top. Curr. Chem. 1987, 135, 1.
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32. Yamashita, M.; Tsunekawa, K.; Sugiura, M.; Oshikawa, T. S 1985, 65.
33. Shull, B. K.; Koreeda, M. JOC 1990, 55, 99.
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35. Suzuki, H.; Sato, N.; Osuka, A. CL 1980, 459.
36. Denis, J. N.; Krief, A. TL 1979, 3995.
37. Suzuki, H.; Sato, N.; Osuka, A. CL 1980, 143.
38. Suzuki, H.; Tani, H.; Osuka, A. CL 1984, 139.
39. Suzuki, H.; Fuchita, T. NKK 1977, 1679.
40. Suzuki, H.; Fuchita, T.; Iwasa, A.; Mishina, T. S. NKK 1979, 91.
41. Suzuki, H.; Tani, H.; Takeuchi, S. BCJ 1985, 58, 2421.
42. Suzuki, H.; Tsuji, J.; Hiroi, Y.; Sato, N.; Osuka, A. CL 1983, 449.

Alain Krief

Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium



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