Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide)

[23319-63-3]  · C11H23MoN4O6P  · Oxodiperoxymolybdenum(pyridine)(hexamethylphosphoric triamide)  · (MW 434.29)

(hydroxylation of enolates1 and nitrile anions;2 preparation of carbonyl compounds by oxidative degradation of anions of sulfones;3 nitroalkanes;4 phosphonates;5 for N-hydroxylation of amides;6 for oxidative cleavage of C-B bonds7)

Alternate Name: MoOPH.

Physical Data: mp 103-105 °C (dec).

Solubility: insol ether; sparingly sol THF; sol dichloromethane.

Form Supplied in: finely divided yellow crystals; not available commercially.

Analysis of Reagent Purity: no convenient assay has been reported. Decomposition is indicated if the reagent smells of pyridine or becomes sticky.1b

Preparative Methods: a detailed procedure is available:1b (1) MoO3 + 30% H2O2 (<40 °C); (2) add HMPA; vacuum dry MoO5.HMPA.H2O to MoO5.HMPA; (3) pyridine in THF gives MoOPH.

Purification: attempted recrystallization causes decomposition of MoOPH. Purity depends on the quality of MoO5.HMPA.H2O, which can be recrystallized from methanol.

Handling, Storage, and Precautions: MoOPH should be stored in the freezer and protected from light.1b The reagent should be treated as an explosion hazard due to its peroxidic nature.1b,8 Properly stored MoOPH is a freely flowing, yellow crystalline powder, and can be handled in the air at room temperature using a safety shield and protective gloves.

Enolate Hydroxylation.

MoOPH1,9 is a useful reagent for the hydroxylation of lithium, sodium, and potassium enolates of ketones,1,10 aldehydes,11 esters,1,12 and lactones,1,13,14 and related anions.15 Similar hydroxylations can be performed with 1-p-toluenesulfonyl-2-phenyloxaziridine (Davis' reagent; see (±)-trans-2-(Phenylsulfonyl)-3-phenyloxaziridine), but the latter reagent works best with Na or K enolates that are sensitive to equilibration.16 MoOPH oxidation of the lithium enolate in THF is the method of choice when regiospecific hydroxylation is desired [examples (1)-(6)].

Byproducts may include a-diketones (with aryl n-alkyl ketone enolates) or aldol adducts (methyl ketone or enone enolates), and recovery of 5-20% unreacted ketone is common. Inverse addition techniques and temperature optimization (usually -78 to -20 °C) may prevent side reactions with difficult substrates.1a Cyclohexanone enolates prefer axial hydroxylation [(1) 7:1 a:b;1a (3) only isomer reported;10a (6) 2:1 b:a10d]. Several stereoselective ester12 and lactone13,14 hydroxylations have also been reported [(8) 7:1 a:b;13a (9) 8.5:1 a:b14a]. The MoOPH hydroxylation of the Evans imide enolates has a small selectivity advantage compared to the Davis oxaziridine, but yields are lower.15a MoOPH is relatively bulky, and prefers bonding to the less hindered enolate face in the absence of stereoelectronic factors. These oxidations involve enolate attack at the O-O bond (eq 1).

Hydroxylation of Other Stabilized Anions.

Nitrile anions are hydroxylated by MoOPH to afford cyanohydrins.2,17 The cyanohydrins can be isolated starting from unbranched nitriles2,17c or strained cyclic nitriles (eq 2).17a More typical a-branched nitrile anions afford the ketones directly,2,17b and condensation of this ketone with the starting nitrile anion may complicate these reactions.2

Sulfone anions can also be hydroxylated.3 The resulting a-hydroxy sulfones fragment spontaneously to the corresponding ketone3,18 or aldehyde.19 Condensation between the carbonyl product and the sulfone anion can be a major reaction pathway.19b Similar oxidative degradation occurs with nitroalkane and phosphonate anions.4,5

Miscellaneous Hydroxylations with MoOPH.

Other strongly basic carbanions have been hydroxylated with MoOPH, including an aryllithium derivative,20 a dipole-stabilized benzyllithium PhC(O)N(Me)CH(Li)Ph,21 and a lithiated vinylogous amide.22 Certain relatively nonbasic substrates can also react with MoOPH, resulting in net hydroxylation. The reagent cleaves C-B bonds with retention,7 and is useful for the oxidative workup of boron enolate aldol reactions.23 In the presence of t-Butyl Hydroperoxide, MoOPH converts a- or b-naphthols into ketols derived from ortho hydroxylation of the naphthalene ring.24 Finally, MoOPH reacts with N-trimethylsilylamides to afford the N-hydroxy amides (eq 3).6,25

1. (a) Vedejs, E. JACS 1974, 96, 5944. (b) Vedejs, E.; Engler, D. A.; Telschow, J. E. JOC 1978, 43, 188. (c) Vedejs, E.; Larsen, S. OS 1985, 64, 127.
2. Vedejs, E.; Telschow, J. E. JOC 1976, 41, 740.
3. Little, R. D.; Myong, S. O. TL 1980, 21, 3339.
4. Galobardes, M. R.; Pinnick, H. W. TL 1981, 22, 5235.
5. Kim, S.; Kim, Y. G. Bull. Korean Chem. Soc. 1991, 12, 106.
6. Matlin, S. A.; Sammes, P. G. CC 1972, 1222.
7. Midland, M. M.; Preston, S. B. JOC 1980, 45, 4514.
8. An explosion, apparently due to friction with a steel spatula, has been reported with a related complex MoO5.DMPU: Paquette, L. A.; Koh, D. C & E News 1992 (Sept. 14 issue; Letters to the Editor). For use of MoO5.DMPU.Py in hydroxylations, see Anderson, J. C.; Smith, S. C. SL 1990, 2, 107.
9. Mimoun, H.; Seree de Roch, I.; Sajus, L. BSF 1969, 1481.
10. (a) Maestro, M. A.; Sardina, F. J.; Castedo, L.; Mourino, A. JOC 1991, 56, 3582. (b) Kuwahara, S.; Mori, K. T 1990, 46, 8075. (c) Grieco, P. A.; Lis, R.; Ferrino, S.; Jaw, J. Y. JOC 1984, 49, 2342. (d) Murai, A.; Ono, M.; Abiko, A.; Masamune, T. BCJ 1982, 55, 1195. (e) Franck-Neumann, M.; Miesch, M.; Barth, F. T 1993, 49, 1409. (f) Tanis, S. P.; Johnson, G. M.; McMills, M. C. TL 1988, 29, 4521.
11. (a) Tanis, S. P.; Nakanishi, K. JACS 1979, 101, 4398. (b) Harapanhalli, R. S. JCS(P1) 1988, 3149.
12. (a) Hollinshead, D. M.; Howell, S. C.; Ley, S. V.; Mahon, M.; Ratcliffe, N. M.; Worthington, P. A. JCS(P1) 1983, 1579. (b) Gamboni, R.; Tamm, C. HCA 1986, 69, 615. (c) Morizawa, Y.; Yasuda, A.; Uchida, K. TL 1986, 27, 1833. (d) Augé, C.; Gautheron, C.; David, S.; Malleron, A.; Cavayé, B.; Bouxom, B. T 1990, 46, 201. (e) Sardina, F. J.; Paz, M. M.; Fernandez-Megia, E.; deBoer, R. F.; Alvarez, M. P. TL 1992, 33, 4637. (f) Swenton, J. S.; Anderson, D. K.; Jackson, D. K.; Narasimhan, L. JOC 1981, 46, 4825.
13. (a) Hanessian, S.; Sahoo, S. P.; Murray, P. J. TL 1985, 26, 5631. (b) Takano, S.; Morimoto, M.; Ogasawara, K. CC 1984, 82. (c) Hanessian, S.; Cooke, N. G.; Dehoff, B.; Sakito, Y. JACS 1990, 112, 5276. (d) Rao, A. V. R.; Bhanu, M. N.; Sharma, G. V. M. TL 1993, 34, 7078; (e) Yadav, J. S.; Praveen, K. T. K.; Maniyan, P. P. TL 1993, 34, 2965. (f) Hanessian, S.; Murray, P. J. CJC 1986, 64, 2231. (g) Stork, G.; Rychnovsky, S. D. JACS 1987, 109, 1564. (h) Nagano, H.; Masunaga, Y.; Matsuo, Y.; Shiota, M. BCJ 1987, 60, 707. (i) Mander, L. N.; Robinson, R. P. JOC 1991, 56, 3595. (j) Gais, H. J.; Ball, W. A.; Lied, T.; Lindner, H. J.; Lukas, K. L.; Rosenstock, B.; Sliwa, H. LA 1986, 1179.
14. (a) Thurkauf, A.; Tius, M. A. CC 1989, 1593. (b) Anderson, J. C.; Ley, S. V.; Santafianos, D.; Sheppard, R. N. T 1991, 47, 6813. (c) Takano, S.; Ohkawa, T.; Tamori, S.; Satoh, S.; Ogasawara, K. CC 1988, 189. (d) Bhatnagar, S. C.; Caruso, A. J.; Polonsky, J.; Rodriguez, B. S. T 1987, 43, 3471.
15. (a) Evans, D. A.; Morrissey, M. M.; Dorow, R. L. JACS 1985, 107, 4346. (b) Ogilvie, W. W.; Durst, T. CJC 1988, 66, 304. (c) Dolle, R. E.; McNair, D.; Hughes, M. J.; Kruse, L. I.; Eggelston, D.; Saxty, B. A.; Wells, T. N. C.; Groot, P. H. E. JMC 1992, 35, 4875. (d) Pattenden, G.; Shuker, A. J. TL 1991, 32, 6625. (e) Hua, D. H.; Saha, S.; Roche, D.; Maeng, J. C.; Iguchi, S.; Baldwin, C. JOC 1992, 57, 399.
16. Davis, F. A.; Vishwakarma, L. C.; Billmers, J. M.; Finn, J. JOC 1984, 49, 3241.
17. (a) VanCantfort, C. K.; Coates, R. M. JOC 1981, 46, 4331. (b) Burnell, R. H.; Caron, S. CJC 1992, 70, 1446. (c) Kelly, T. R.; Chandrakumar, N. S.; Cutting, J. D.; Goehring, R. R.; Weibel, F. R. TL 1985, 26, 2173.
18. (a) Nemoto, H.; Kurobe, H.; Fukumoto, K.; Kametani, T. JOC 1986, 51, 5311. (b) Harirchian, B.; Bauld, N. L. JACS 1989, 111, 1826. (c) Classen, A.; Scharf, H.-D. LA 1990, 123.
19. (a) Okamura, W. H.; Peter, R.; Reischl, W. JACS 1985, 107, 1034. (b) Capet, M.; Cuvigny, T.; duPenhoat, C. H.; Julia, M.; Loomis, G. TL 1987, 28, 6273.
20. Cambie, R. C.; Higgs, P. I.; Rutledge, P. S.; Woodgate, P. D. JOM 1990, 384, C6.
21. Williams, R. M.; Kwast, E. TL 1989, 30, 451.
22. Niwa, H.; Kuroda, A.; Yamada, K. CL 1983, 125.
23. Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. JACS 1981, 103, 3099.
24. Krohn, K.; Brüggmann, K.; Döring, D.; Jones, P. G. CB 1992, 125, 2439.
25. (a) Weidner-Wells, M. A.; DeCamp, A.; Mazzocchi, P. H. JOC 1989, 54, 5746. (b) Rigby, J. H.; Qabar, M. JOC 1989, 54, 5852.

Edwin Vedejs

University of Wisconsin, Madison, WI, USA

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