[603-35-0]  · C18H15P  · Triphenylphosphine-Iodine  · (MW 262.30) (I2)

[7553-56-2]  · I2  · Triphenylphosphine-Iodine  · (MW 253.80) (Ph3P.I2)

[80800-01-2]  · C18H15I2P  · Triphenylphosphine-Iodine  · (MW 516.10)

(conversion of alcohols,6,7 thiols,11c and enols9 into iodides; reduction of various sulfur derivatives to sulfides or thiols;11c reduction of epoxides,13 iodohydrins,16 and vicinal diols17a to alkenes; production of iodohydrins from epoxides;14 esterification of carboxylic acids;18 acetalizations of carbonyl groups19)

Alternate Names: triphenylphosphine diiodide; iodotriphenylphosphonium iodide; diiodotriphenylphosphorane.

Physical Data: adduct:2,4 bright yellow solid (from ether). Ph3P: mp 80.5 °C; bp 377 °C (in inert gas); d254 1.194 g cm-3; d804 (liq) 1.075 g cm-3; n80D 1.6358. I2: mp 113.6 °C; bp 184.3 °C; d 4.93 g cm-3.

Solubility: Ph3P: sol ether, PhH, CHCl3, AcOH; less sol alcohol; practically insol H2O. I2: sol ether (25.2 g/100 mL), PhH (14.1 g/100 mL), alcohol (21.4 g/100 mL), MeOH (23 g/100 mL), CHCl3, CCl4; less sol H2O (0.03 g/100 mL).

Form Supplied in: the adduct is not commercially available. Ph3P: odorless monoclinic platelets or prisms; purity ~99%; typical impurity: Ph3PO ~1%. I2: bluish-black scales or plates with metallic luster; characteristic odor; sharp, acrid taste and violet corrosive vapor; purity &egt;99.8%

Analysis of Reagent Purity: adduct.2 Ph3P and Ph3PO: 31P NMR (PhMe/MeCN, MeCN, pyridine; CCl4) -5 to -8 and +29 to +25.

Preparative Method: for synthetic purposes the reagent is generally prepared in situ just before use, by addition of Iodine to Triphenylphosphine (or vice versa) in different solvents.

Handling, Storage, and Precautions: Ph3P: irritant; harmful; do not get in eyes, on skin, or on clothing; avoid contact and inhalation; use with adequate ventilation; keep containers tightly closed and store in a cool dry place; incompatible with strong oxidizing agents. I2: harmful; corrosive; severe lachrymator; do no get in eyes, on skin, or on clothing; avoid prolonged or repeated exposure; keep containers tightly closed in a cool dry place; incompatible with Mg, Zn, Al, Sb, and NH3; reacts violently with acetaldehyde. These reagents should be handled in a fume hood.

Alkyl Iodides from Alcohols and Thiols.

The Ph3P.I2 adduct contains two replaceable iodo groups which can be substituted by nucleophiles. Its reaction with alcohols involves the rapid and irreversible formation of an alkoxyphosphonium iodide that decomposes by a slow SN2 reaction, leading to an alkyl iodide (eq 1).

Primary and secondary alcohols are converted into alkyl iodides5-8 by use of the Ph3P.I2 reagent. The iodination of b-cholestanol in boiling PhH gives a-iodocholestane with inversion of configuration, albeit in low yield (25%); use of the more polar solvent DMF, at 75 °C, leads to complete epimerization to the thermodynamically more stable b-iodide.6 Retention of configuration, observed in the nucleoside field, occurs via double inversion; initial formation of the cyclic O2,3-anhydro derivative (2) is followed by ring opening by iodide ion (eq 2).5a,b

Ph3P.I2 provides better yield5c than the related reagent Methyltriphenoxyphosphonium Iodide (MTPI) in the iodination of the primary alcohol (4) (eq 3), whereas MTPI is more efficient in the preceding conversion of the secondary alcohol (1) into the iodide (3) (70%).5a

Although MeCN, (PhO)3PO,5d and DMF are often recommended as solvents for these reactions, the latter can react with the Ph3PX2 reagent to produce halomethylene-N,N-dimethyliminium halide (6).8 In the case of Ph3P.I2, this iminium iodide then reacts in turn with the alcohol to form an alkoxymethylene-N,N-dimethyliminium iodide (7), which gives mixtures of both iodide and formate after heating and hydrolytic workup; the same result could be obtained by assuming reaction of DMF with the alkoxyphosphonium iodide (8) (eq 4). Consequently, reactions of secondary alcohols with Ph3P.I2 in DMF can lead to formylation to the ester together with iodination.8

Addition of Imidazole to the Ph3P.I2 reagent leads to better yields. Alternatively, the 2,4,5-triodo derivative of imidazole and Ph3P alone can be used. In the carbohydrate field especially,7 higher yields are obtained in the conversion of primary (70-97%) and secondary (60-87%) alcohols, with inversion of configuration for the latter. At lower temperatures, primary hydroxyl groups may be selectively replaced by iodo groups.7b,d Besides the initially preferred refluxing PhMe,7a,b mixed solvents such as PhMe-MeCN (2:1) have been used,7c,d allowing certain transformations which are difficult to achieve with PhMe alone as solvent.

Alkanesulfonic acids, sulfinic acids, disulfides, thiosulfonic S-esters, and sulfonates are readily reduced to the corresponding thiols by treatment with a mixture of Ph3P and a catalytic amount of I2 (see below). Upon treatment with a mixture of Ph3P and an excess of I2, however, all these aliphatic sulfur compounds are eventually transformed to the corresponding alkyl iodides (67-100%) (eq 5).11b,c

Vinyl Iodides from Enols.

Treatment of cyclic b-diketones with Ph3P.I2, in MeCN at reflux in the presence of NEt3, affords b-iodo-a,b-unsaturated ketones in good yields (eq 6).9 Unsymmetrical 1,3-cyclohexanediones give isomeric mixtures of 3-iodo-a,b-unsaturated ketones accompanied by deconjugated iodo enones. In MeCN-HMPA this reagent stereoselectively and regioselectively transforms a-hydroxymethylenecyclohexanone and -pentanone into (E)-2-iodomethylenecyclohexanone (94%) and -pentanone (73%).9b Other reagents useful for similar syntheses of alkyl iodides include Methyltriphenoxyphosphonium Iodide,1,5a,c Ph3P/CI4,1,5b and Ph3P/N-iodosuccinimide.5b

Reduction of Sulfur Derivatives to Sulfides or Thiols.

Aryl and alkyl sulfoxides are readily deoxygenated to sulfides with the Ph3P/I2/NaI reagent system in refluxing MeCN (eq 7).10a Use of the more reactive (Me2N)3P instead of Ph3P10b provides a good alternative to the previous reagent; it requires no heating and leads to an easily removed (unlike Ph3PO) water-soluble HMPA byproduct.

Arylsulfonic acids, their sodium salts, halides, esters and thioesters, and arylsulfinic acids and their salts are also readily reduced to the corresponding aromatic thiols in good yields with Ph3P (3-5 mol equiv) in the presence of I2 (0.5-1 mol equiv) (eq 8).11a,c

Reduction of Allylic Alcohols.

The reduction of allylic alcohols to the corresponding hydrocarbons by Ph3P.I2 is another valuable reduction achieved by this reagent.12 This transformation takes place through the corresponding iodide, which is further reduced to the hydrocarbon by the HI resulting from the preceding step. Several allylic alcohols have been reduced in this fashion in moderate yields to the corresponding unsaturated hydrocarbons (24-95%).

Reduction of Epoxides and Iodohydrins to Alkenes.

Attempts to prepare vicinal diiodides from reaction of vicinal iodohydrins with the Ph3P.I2 reagent lead not to the expected products, but instead directly to the corresponding alkenes.13 The reaction proceeds in high yields and is a stereospecific trans elimination (>98%). As iodohydrins may be obtained by anti opening of epoxides with HI, this reaction serves as the basis for a convenient method for the deoxygenation of epoxides to alkenes with retention of configuration. The transformation is typically achieved employing 1.1 equiv each of Ph3P.I2 and Ph3P.HI (eq 9). Despite the fact that only 1 equiv of Ph3P is consumed and that HI and I2 act only as catalysts, the first attempts to reduce the stoichiometry in reagents were unsuccessful; this problem was later solved16 by using other reaction conditions (see below).

Iodohydrins from Epoxides.

Contrasting results14,15 have been reported in the steroid field in the transformation of identically trisubstituted epoxides with Ph3P.I2. Although the experimental conditions were apparently the same in both cases (Ph3P.I2, 1.1 equiv, CH2Cl2, rt), the reaction products are halohydrins in the first case,14a,b and alkenes in the second one.15 As mentioned elsewhere,13,16 iodohydrins are readily transformed into alkenes by several routes (e.g. with HI or I2 and H2O as catalyst, in the presence of Ph3P); the presence of traces of water in the solvent or further transformation during workup or the purification steps (in the second case15) would account for such discrepancies. The former preparation14a,b of iodohydrins under anhydrous conditions was later confirmed14c by the use of a polymer-supported phosphine-I2 adduct. The method requires only a filtration and evaporation for product isolation, avoiding the often tedious Ph3PO removal. Oxirane-ring opening remains regio- and stereoselective, the yields being somewhat higher than with Ph3P, most probably due to the simplified workup procedure (eq 10).

Further work16 with Ph3P.I2 in moist MeCN clearly demonstrates the importance of both reagent stoichiometry and the presence of water in determining the reaction pathway. The active species is in fact HI, generated in situ from Ph3P.I2 in moist MeCN. Use of 0.5 equiv of Ph3P.I2 in moist MeCN provides iodohydrins (75-85%) from epoxides; alkenes are obtained from both iodohydrins (70-90%) and epoxides (70-95%) using respectively 0.6:0.1-0.6:1 and 1.1:0.6:1 molar ratios of Ph3P, I2, and substrate, at 80 °C (eq 11).

Alkenes from Vicinal Diols.

The combination of Ph3P, I2, and imidazole17a in refluxing toluene (or better, in the mixed solvent PhMe-MeCN17c) at 50 °C effects the conversion of vicinal diols into alkenes. Hexopyranosidic diols are transformed to alkenes in fair to good yields (eq 12). A further significant improvement over the original system can be achieved by using the combination of Ph3P alone with 2,4,5-triiodoimidazole and imidazole (ImH).17b

Esterification of Carboxylic Acids.

The adduct of polystyryl(diphenyl)phosphine with iodine,14c previously used to convert epoxides into iodohydrins, is a convenient condensing agent for the esterification of carboxylic acids18 under very mild conditions. The reaction is assumed to proceed via the acyl iodide. The iodine adduct proves to be the most convenient among the three halogen adducts since the chloride complex provides somewhat sluggish ester formation and the use of the bromine analog is inadvisable with unsaturated material due to the occurrence of some bromination of the double bond. The reaction has been applied to a number of acids using MeOH and also cumbersome, difficult to esterify alcohols such as 5a-cholestan-3-ol (eq 13). The high yield and easy isolation of the ester (by a simple filtration and evaporation process) are among the attractive features of this preparation.

Acetalization of Carbonyl Compounds.

Carbonyl compounds are smoothly and rapidly acetalized by treatment with alcohols or thiols in anhydrous MeCN in the presence of the polystyryl(diphenyl)phosphine-iodine adduct as a dehydrating agent.19 Open-chain and cyclic acetals, including 1,3-dioxolanes, 1,3-oxathiolanes, and 1,3-dithiolanes, of miscellaneous aldehydes and ketones have been successfully prepared in this way with high yields (eq 14). The isolation of the product is easily performed by simple filtration of the polymer-linked Ph3PO which is formed during the reaction.

Other Applications.

In combination with imidazole as described previously, Ph3P.I2 allows the one-pot synthesis of alkyl nitrates from alcohols.20 Treatment of alcohols with the Ph3P-I2-ImH reagent system, followed by in situ reaction of the generated iodides with the AgNO3 in ether/MeCN mixture, leads to the formation of alkyl nitrates. The Ph3P.I2 reagent has also been used to promote the Beckmann rearrangement;21 the reaction of cycloalkanone oxime with iodine in the presence of Ph3P provides lactams in one step. In the presence of Et3N, the Ph3P.I2 adduct, acting as a dehydrating agent, effects the 3-aza-Claisen rearrangement of a-heteroatom substituted N-allyl amides into the corresponding nitriles under very mild conditions.22 Other phosphine-halogen adducts are studied for this purpose in the same work.

1. Castro, B. R. OR 1983, 29, 1.
2. There are only three recent references (including 3b,c) in the chemical literature. The adduct must be prepared under an inert atmosphere, in strictly anaerobic and anhydrous conditions using standard Schlenk techniques.3 Physical studies3 show that the balance between four-coordinate covalent and ionic forms, and the five-coordinate covalent form, in solution is solvent dependent; solid material prepared in ether exhibits a four-coordinate covalent form of charge-transfer complex type, while solid samples from PhNO2 display a four-coordinate ionic form. Raman (nujol) 160 (I-I) (solid form from ether: Ph3P-I-I); 31P NMR (1,2-ClCH2CH2Cl, MeCN, or CHCl3): +45 to +49 (ionic form); 31P NMR (solid form NMR, PhMe/MeCN or pyridine) -18 to -21 (covalent form). Other physical studies on the related Ph3P-dihalide adducts also conclude that the extent of ionic behavior is a function of the solvent polarity.
3. (a) Garregg, P. J.; Regberg, T.; Stawinski, J.; Strömberg, R. JCS(P2) 1987, 271. (b) Godfrey, S. M.; Kelly, D. G.; McAuliffe, C. A.; Mackie, A. G.; Pritchard, R. G.; Watson, S. M. CC 1991, 1163. (c) Bricklebank, N.; Godfrey, S. M.; Mackie, A. G.; McAuliffe, C. A.; Pritchard, R. G.; Kobryn, P. J. JCS(D) 1993, 101, and references cited therein.
4. Three different melting points are given depending either on the purity level or on the nature of the solvent used in preparing them. See Ref. 2.
5. (a) Verheyden, J. P. H.; Moffatt, J. G. JACS 1964, 86, 2093. (b) Verheyden, J. P. H.; Moffatt, J. G. JOC 1972, 37, 2289. (c) Prisbe, E. J.; Smejkal, J.; Verheyden, J. P. H.; Moffatt, J. G. JOC 1976, 41, 1836. (d) Haga, K.; Yoshikawa, M.; Kato, T. BCJ 1970, 43, 3922.
6. Bayless, A. V.; Zimmer, H. TL 1968, 3811.
7. (a) Garegg, P. J.; Samuelsson, B. CC 1979, 978. (b) Garegg, P. J.; Samuelsson, B. JCS(P1) 1980, 2866. (c) Garegg, P. J.; Johansson, R.; Ortega, C.; Samuelsson, B. JCS(P1) 1982, 681. (d) Garegg, P. J. PAC 1984, 56, 845.
8. Herr, M. E.; Johnson, R. A. JOC 1972, 37, 310.
9. (a) Piers, E.; Nagakura, I. SC 1975, 5, 193. (b) Piers, E.; Grierson, J. R.; Lau, C. K.; Nakagura, I. CJC 1982, 60, 210.
10. (a) Olah, G. A.; Gupta, B. G. B.; Narang, S. C. S 1978, 137. (b) Olah, G. A.; Gupta, B. G. B.; Narang, S. C. JOC 1978, 43, 4503.
11. (a) Fujimori, K.; Togo, H.; Oae, S. TL 1980, 21, 4921. (b) Oae, S.; Togo, H. S 1981, 371. (c) Oae, S.; Togo, H. BCJ 1983, 56, 3802.
12. Bohlmann, F.; Staffeldt, J.; Skuballa, W. CB 1976, 109, 1586.
13. Sonnet, P. E. S 1980, 828.
14. (a) Palumbo, G.; Ferreri, C.; Caputo, R. TL 1983, 24, 1307. (b) Caputo, R.; Chianese, M.; Ferreri, C.; Palumbo, G. TL 1985, 26, 2011. (c) Caputo, R.; Ferreri, C.; Noviello, S.; Palumbo, G. S 1986, 499.
15. Paryzek, Z.; Wydra, R. TL 1984, 25, 2601.
16. Garlaschelli, L.; Vidari, G. G 1987, 117, 251.
17. (a) Garegg, P. J.; Samuelsson, B. S 1979, 469. (b) Garegg, P. J.; Samuelsson, B. S 1979, 813. (c) Garegg, P. J.; Johansson, R.; Samuelsson, B. J. Carbohydr. Chem. 1984, 3, 189.
18. Caputo, R.; Corrado, E.; Ferreri, C.; Palumbo, G. SC 1986, 16, 1081.
19. Caputo, R.; Ferreri, C.; Palumbo, G. S 1987, 386.
20. Castedo, L.; Marcos, C. F.; Monteagudo, M.; Tojo, G. SC 1992, 22, 677.
21. Sakai, I.; Kawabe, N.; Ohno, M. BCJ 1979, 52, 3381.
22. Walters, M. A.; Hoem, A. B.; Arcand, H. R.; Hegeman, A. D.; McDonough, C. S. TL 1993, 34, 1453.

Jean-Robert Dormoy & Bertrand Castro

SANOFI Chimie, Gentilly, France

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