Potassium t-Butoxide-Hexamethylphosphoric Triamide


[865-47-4]  · C4H9KO  · Potassium t-Butoxide-Hexamethylphosphoric Triamide  · (MW 112.23) (HMPA)

[680-31-9]  · C6H18N3OP  · Potassium t-Butoxide-Hexamethylphosphoric Triamide  · (MW 179.24)

(useful base for deprotonating weakly acidic substrates2)

Preparative Method: prepared in situ from anhydrous t-BuOK and anhydrous HMPA. Anhydrous HMPA is obtained by distillation from Sodium metal or Calcium Hydride under reduced pressure at 60 °C.1

Handling, Storage, and Precautions: see Potassium t-Butoxide and Hexamethylphosphoric Triamide. HMPA is a cancer-suspect agent which should be handled with extreme care; do not breathe the vapor and avoid contact of the solid or liquid with eyes, skin, or clothing. Store over 4 Å molecular sieves. Use in a fume hood.


HMPA is capable of strongly solvating potassium cations and producing solutions of t-BuOK which contain substantial amounts of highly basic ligand-separated ion pairs and dissociated t-butoxide anions.2 Deprotonation reactions are favored by the highly polar medium. Unlike Dimethyl Sulfoxide, HMPA is not deprotonated by the t-butoxide anion.

Michael Addition-Intramolecular Alkylation Reactions.

t-BuOK is an effective additive for accelerating the rates of cycloalkylation of lithium enolates produced in the Michael addition of lithium enolates of esters to ε-iodo-a,b-unsaturated esters.3 Three-, five-, six-, and seven-membered ring carbocyclic diesters are available by these reactions. When a six-membered ring is produced in the cycloalkylation reaction (eq 1), the stereochemistry of the cyclic diester products is strongly dependent upon the nature of the solvent. If THF alone is employed, the syn-diester is the major product, but if a 4:1 mixture of THF-HMPA is used, the anti-diester is highly favored.3 The observation of such a high degree of stereochemical control in the production of extracyclic stereocenters is remarkable.

Autooxidation Reactions.

HMPA is more effective than sulfolane, Dimethyl Sulfone, or DMSO as an activator for t-BuOK in the base-promoted autooxidation of alkylbenzene derivatives to aromatic acids.4 The medium is also useful for the autooxidation of acetophenone to benzoic acid,5 and for oxidation of a variety of other benzene derivatives.6

Other Reactions.

The expansion of the 12-membered ring of the epoxy sulfone shown in eq 2 to a 15-membered ring enone occurs in a reasonable yield with t-BuOK in t-BuOH-HMPA.7 This reaction involves formation of an a-sulfonyl carbanion, intramolecular nucleophilic opening of the epoxide ring by this species, and Grob fragmentation of the g-sulfonyl alkoxide intermediate. t-BuOK/HMPA efficiently isomerizes 2-alkynyl dialkylamines to dialkylamino allenes and 2-alkynyl ethers to allenic ethers.8 A catalytic amount of t-BuOK in HMPA has been used to generate 1,1-difluoroallyl anions from difluoroallyl(dimethylphenyl)silanes by attack of the t-butoxide anion on silicon.9 These anions undergo addition to carbonyl compounds (eq 3).9

1. Perrin, D. D.; Armarego, W. L. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 193.
2. Pearson, D. E.; Buehler, C. A. CRV 1974, 74, 45.
3. Yamaguchi, M.; Tsukamoto, M.; Hirao, I. TL 1985, 26, 1723.
4. Hofmann, J. E.; Schriesheim, A.; Rosenfeld, D. D. JACS 1965, 87, 2523.
5. Wallace, T. J.; Pobiner, H.; Schriesheim, A. JOC 1965, 30, 3768.
6. (a) Wallace, T. J.; Pobiner, H.; Baron, F. A.; Schriesheim, A. JOC 1965, 30, 3147. (b) Schmitt, G.; Oezman, S.; Klein, P. CZ 1980, 104, 241 (CA 1981, 94, 30 309r).
7. Fischli, A.; Branca, Q.; Daly, J. HCA 1976, 59, 2443.
8. (a) Verkruijsse, H. D.; Bos, H. J. T.; de Noten, L. J.; Brandsma, L. RTC 1981, 100, 244. (b) Verkruijsse, H. D.; Verboom, W.; Van Rijn, P. E.; Brandsma, L. JOM 1982, 232, C1.
9. Hiyami, T.; Obayashi, M.; Sawahata, M. TL 1983, 24, 4113.

Drury Caine

The University of Alabama, Tuscaloosa, AL, USA

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