[27126-76-7]  · C13H13IO4S  · [Hydroxy(tosyloxy)iodo]benzene  · (MW 392.22)

(reagent for the phenyliodination and oxytosylation of various functional groups;4 excellent Hofmann reagent;16 useful for bis-lactonizations,7 oxidations and oxidative transformations20)

Alternate Names: HTIB; Koser's reagent; phenyliodine(III) (hydroxyl)tosylate.

Physical Data: nearly colorless crystalline solid (pale `yellow' cast); mp 140-142 °C,2 136-138.5 °C.3

Solubility: insol Et2O; largely insol CH2Cl2, CHCl3, MeCN (rt); moderately sol H2O; sol MeCN (reflux), MeOH, DMSO.

Form Supplied in: white solid; commercially available in 96% purity.

Preparative Methods: conveniently prepared by the treatment of (Diacetoxyiodo)benzene/MeCN mixtures with warm solutions of p-Toluenesulfonic Acid in MeCN. When the acid is introduced, PhI(OAc)2 dissolves to give deep yellow solutions from which HTIB readily separates. If the reaction mixtures are kept near the reflux temperature, the crystallization of HTIB from the solvent can be controlled. At lower temperatures, HTIB separates more rapidly but can, if necessary, be recrystallized by heating the final mixtures of dissolution or from fresh MeCN. Preparations of HTIB can be readily conducted on a 50-100 g scale.

Handling, Storage, and Precautions: a fairly stable compound which may be stored at rt; for extended storage, keep refrigerated in a dark bottle.

General Considerations.

Although hydroxy(tosyloxy)iodobenzene is largely insoluble in CH2Cl2, CHCl3, and MeCN at rt, all are excellent solvents for the mediation of HTIB reactions. When HTIB is employed in CH2Cl2, the completion of a reaction is signaled by the disappearance of the crystalline phase as the iodane is consumed. Since HTIB/MeCN mixtures afford deep yellow solutions at the reflux temperature, reactions conducted under these conditions can sometimes be followed by the fading of the color. HTIB is soluble in MeOH and in this solvent may lead to products containing one or more methoxy groups. DMSO should probably be avoided since HTIB may be reduced by this solvent under some conditions. Acetone reacts with HTIB.

HTIB is mildly electrophilic at iodine and may conveniently be regarded as the chemical equivalent of hydroxy(phenyl)iodonium tosylate[Ph+IOH -OTs]. Thus HTIB reacts with a variety of organic substrates to give either phenyliodonium tosylates or tosylate esters. Phenyliodination occurs first and whether such reactions proceed to the oxytosylation stage depends on the stability of the iodonium compounds toward nucleophilic collapse. HTIB is also a mild oxidizing agent.

Selected Transformations of Organic Functional Groups.

Alkenes, Dienes.

The treatment of alkenes with HTIB (CH2Cl2) affords vic-ditosyloxyalkanes.4 Dioxytosylation is thought to be initiated by the trans addition of HTIB to the carbon-carbon double bond, and, with alkyl-substituted alkenes, ultimately proceeds with cis stereospecificity (eq 1). In some cases (i.e. norbornene, neat styrene), dioxytosylation is accompanied by skeletal rearrangements. Several dienes have been observed to undergo conjugate dioxytosylation with HTIB but the 1,4-ditosyloxyalkenes are not very stable, and the yields are low.4,5

Alkenoic and Alkenedioic Acids.

Participation of the carboxyl group occurs when unconjugated alkenoic acids are mixed with HTIB.6 Of seven alkenoic acids studied, five gave tosyloxylactones (eq 2). In two cases, TsOH was eliminated, and unsaturated lactones6 were obtained, elimination apparently being favored by alkyl substitution at the carbon-carbon double bond. The oxytosyllactonization of 5-norbornene-endo-2-carboxylic acid proceeds with skeletal rearrangement. Alkenic dicarboxylic acids react with HTIB (CH2Cl2, rt) to give bis-lactones (eq 3).7 More significantly, bis-lactonization proceeds with cis stereospecificity. The mildness and operational convenience of the HTIB procedure recommend this approach as an excellent alternative to methods requiring the treatment of alkenedioic acids or their tetrabutylammonium salts with an excess of Lead(IV) Acetate8 or the treatment of silver alkenedioates with Iodine/Silver(I) Acetate .9


Terminal alkynes react with HTIB in CHCl3 under reflux to give either alkynyl(phenyl)iodonium tosylates, b-tosyloxyvinyl(phenyl)iodonium tosylates, or mixtures of both.10 The production of alkynyliodonium salts is favored by the presence of either aryl or bulky alkyl (e.g. t-Bu, s-Bu) groups in the alkyne (eq 4), while terminal alkynes with linear alkyl groups lead exclusively to the vinyliodonium compounds (eq 5). A desiccant (silica bead) has been employed with HTIB in CH2Cl2 (rt) to facilitate the alkynyliodonium pathway with propyne and 1-hexyne, but the product yields were low.11 Internal alkynes afford b-tosyloxyvinyliodonium tosylates with HTIB.10 When HTIB is employed in methanol, both terminal and internal alkynes undergo oxidative rearrangement to give carboxylate esters, R1R2CHCO2Me.12

Ketones, b-Dicarbonyl Compounds, Silyl Enol Ethers, Silyl Ketene Acetals.

The treatment of ketones with HTIB (MeCN or CH2Cl2) affords a-toxyloxy ketones (eq 6),13 presumably via a-phenyliodonio ketone tosylates [RCOC+IPh,-OTs]. Silyl enol ethers (CH2Cl2, rt) also afford a-tosyloxy ketones with HTIB and can be employed to direct the regiochemistry of oxytosylation, while esters can be functionalized at a-carbon via their silyl ketene acetals (eq 7).14 The conversion of b-dicarbonyl compounds to their a-toxyloxy derivatives with HTIB has also been demonstrated.13 The reactions of 5-oxo- and 4,6-dioxocarboxylic acids with HTIB (CH2Cl2) eventuate in the production of keto and diketo lactones (eq 8).15


One of the most useful applications of HTIB is for the conversion of aliphatic primary carboxamides to amines (MeCN, reflux); the amines separate from the solvent (on cooling) as their hydrogen tosylate salts (eq 9).16 This is a particularly advantageous method for the production of amines from long-chain amides,17 which afford low yields (or none) of amines under the standard conditions (e.g. NaOH/Br2, D) for the Hofmann reaction. The synthesis of bridgehead amines from carboxamides in the adamantane, cubane, and homocubane series of compounds has also been described.18 Such reactions proceed via intermediate N-phenyliodoniocarboxamide tosylates [RCONH+IPh-OTs] and their rearrangement with loss of TsOH and iodobenzene to alkyl isocyanates.19 This is not a good method for the preparation of aromatic amines since they can be oxidized by HTIB as they are produced.

Further Applications of HTIB.

The synthetic utility of HTIB is further underlined by its use for the oxidation of allenes and allenyl ethers (CH2Cl2) to aldehydes or ketones,20 the ligand-transfer oxidation of iodoarenes to give [hydroxy(tosyloxy)iodo]arenes (CH2Cl2),21 the oxidative deiodination of alkyl iodides to alkyl tosylates (CHCl3 or CH2Cl2),22 including cubyl and homocubyl examples,23 and as an iodination `catalyst' for the conversion of alkynols to a- and/or b-iodoenones.24 Various [hydroxy(toxyloxy)iodo]arenes, ArI(OH)OTs, have been employed for the synthesis of diaryliodonium, aryl(2-furyl)iodonium, and aryl(2-thienyl)iodonium tosylates.25 HTIB has also been used for the conversions of flavanones to flavones (MeOH)26 and isoflavones (MeCN),27 aromatic ketones to methyl arylalkanoates (MeOH or (MeO)3CH),28 chalcones to deoxybenzoins containing the (MeO)2CH group at the a-carbon (MeOH),29 and flavonols to their vic-dimethoxy adducts (MeOH).30

Analogs of HTIB.

Various derivatives of HTIB with substituents in the iodoarene nucleus, ArI(OH)OTs,21,25,31,32 and three arenesulfonyloxy analogs33 have been reported. [Hydroxy(mesyloxy)iodo]benzene, PhI(OH)O3SMe,11,14,23,34,35 and [hydroxy((+)-10-camphorsulfonyloxy)iodo]benzene36 are also known. [Hydroxy((bis(phenyloxy)phosphoryl)oxy)iodobenzene], PhI(OH)OP(O)(OPh)2, shows considerable potential for phosphate ester synthesis. Thus far, the a-oxyphosphorylation of ketones and b-dicarbonyl compounds,37 the oxyphosphoryllactonization of alkenoic acids,37 and the conversion of terminal alkynes38 to monoketol phosphates with HPIB have been reported.

1. Moriarty, R. M.; Vaid, R. K.; Koser, G. F. SL 1990, 365.
2. Neiland, O.; Karele, B. JOU 1970, 6, 889 (first report of HTIB).
3. Koser, G. F.; Wettach, R. H.; Troup, J. M.; Frenz, B. A. JOC 1976, 41, 3609.
4. Rebrovic, L.; Koser, G. F. JOC 1984, 49, 2462.
5. Shah, M.; Ph.D. dissertation, The University of Akron, 1988, pp 96-100.
6. Shah, M.; Taschner, M. J.; Koser, G. F.; Rach, N. L. TL 1986, 27, 4557.
7. Shah, M.; Taschner, M. J.; Koser, G. F.; Rach, N. L. Jenkins, T. E.; Cyr, P.; Powers, D. TL 1986, 27, 5437.
8. Corey, E. J.; Gross, A. W. TL 1980, 21 1819.
9. Kato, M.; Kageyama, M.; Tanaka, R.; Kuwahara, K.; Yoshikoshi, A. JOC 1975, 40, 1932.
10. Rebrovic, L.; Koser, G. F. JOC 1984, 49, 4700.
11. Stang, P. J.; Surber, B. W.; Chen, Z-C.; Roberts, K. A.; Anderson, A. G. JACS 1987, 109, 228.
12. Moriarty, R. M.; Vaid, R. K.; Duncan, M. P.; Vaid, B. K. TL 1987, 28, 2845.
13. Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach, R. H. JOC 1982, 47, 2487.
14. Moriarty, R. M.; Penmasta, R.; Awasthi, A. K.; Epa, W. R.; Prakash, I. JOC 1989, 54, 1101.
15. Moriarty, R. M.; Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.; Prakash, O. TL 1990, 31, 201.
16. Lazbin, I. M.; Koser, G. F. JOC 1986, 51, 2669.
17. Vasudevan, A.; Koser, G. F. JOC 1988, 53, 5158.
18. Moriarty, R. M.; Khosrowshahi, J. S.; Awasthi, A. K.; Penmasta, R. SC 1988, 18, 1179.
19. Lazbin, I. M.; Koser, G. F. JOC 1987, 52, 476.
20. Moriarty, R. M.; Hopkins, T. E.; Vaid, R. K.; Vaid, B. K.; Levy, S. G. S 1992, 847.
21. Koser, G. F.; Wettach, R. H. JOC 1980, 45, 1542.
22. (a) Zefirov, N. S.; Zhdankin, V. V.; Kozmin, A. S. BAU 1983, 32, 1530. (b) Macdonald, T. L.; Narasimhan, N. JOC 1985, 50, 5000.
23. Moriarty, R. M.; Khosrowshahi, J. S. SC 1989, 19, 1395.
24. (a) Angara, G. J.; McNelis, E. TL 1991, 32, 2099. (b) Angara, G. J.; Bovonsombat, P.; McNelis, E. TL 1992, 33, 2285. (c) Bovonsombat, P.; McNelis, E. TL 1992, 33, 7705. (d) Bovonsombat, P.; McNelis, E. T 1993, 49, 1525.
25. (a) Koser, G. F.; Wettach, R. H.; Smith, C. S. JOC 1980, 45, 1543. (b) Carman, C. S.; Koser, G. F. JOC 1983, 48, 2534. (c) Margida, A. J.; Koser, G. F. JOC 1984, 49, 3643.
26. Prakash, O.; Pahuja, S.; Moriarty, R. M. SC 1990, 20, 1417.
27. Prakash, O.; Pahuja, S.; Goyal, S.; Sawhney, S. N.; Moriarty, R. M. SL 1990, 337.
28. Prakash, O.; Goyal, S.; Moriarty, R. M.; Khosrowshahi, J. S. IJC(B) 1990, 29B, 304.
29. Moriarty, R. M.; Khosrowshahi, J. S.; Prakash, O. TL 1985, 26, 2961.
30. Moriarty, R. M.; Prakash, O.; Musallam, H. A.; Mahesh, V. K. H 1986, 24, 1641.
31. Moriarty, R. M.; Penmasta, R.; Prakash, I. TL 1987, 28, 877.
32. Ochiai, M.; Oshima, K.; Ito, T.; Masaki, Y.; Shiro, M. TL 1991, 32, 1327.
33. Koser, G. F.; Wettach, R. H. JOC 1977, 42, 1476.
34. Zefirov, N. S.; Zhdankin, V. V.; Dan'kov, Yu, V.; Koz'min, A. S.; Chizhov, O. S. JOU 1985, 21, 2252; first report of [hydroxy(mesyloxy)iodo]benzene.
35. Lodaya, J. S.; Koser, G. F. JOC 1988, 53, 210.
36. Hatzigrigoriou, E.; Varvoglis, A.; Bakola-Christianopoulou, M. JOC 1990, 55, 315.
37. Koser, G. F.; Lodaya, J. S.; Ray, D. G., III; Kokil, P. B. JACS 1988, 110, 2987.
38. Koser, G. F.; Chen, X.; Chen, K.; Sun, G. TL 1993, 34, 779.

Gerald F. Koser

University of Akron, OH, USA

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