Potassium Hydride1

KH

[7693-26-7]  · HK  · Potassium Hydride  · (MW 40.11)

(base and hydride donor to Lewis acids such as boranes and borates; used for deprotonation, cyclization-condensation, elimination, rearrangement reactions, and as a reducing agent).

Physical Data: solid; dec on heating; d 1.47 g cm-3; nD 1.453.

Solubility: dec in cold and hot water; insol CS2, ether, benzene.

Form Supplied in: as a dispersion in mineral oil, 20-35% by weight. A standardization procedure has been published.1

Purification: commercial KH dispersion is made by reduction of metallic potassium,2 and so KH is often contaminated with traces of potassium or potassium superoxide. These can be removed by pretreatment with iodine to produce a reagent with superior consistency in several reactions that are sensitive to such impurities.3

Handling, Storage, and Precautions: dispersion is a liquid, and tends to settle upon standing. Prolonged storage produces a compacted solid that must be broken up to achieve a homogeneous dispersion. Brown suggests1 using a long-handled screwdriver to break up the compacted material and leaving a Teflon-covered stir bar in the container to aid dispersion. Clamping the sealed polyethylene bottle containing the dispersion to a Parr shaker for 15 min also works well.

The mineral oil may be removed by adding pentane to small quantities of the dispersion, stirring the slurry, then allowing the hydride to settle. The pentane/mineral oil supernatant may be pipetted off, but care should be exercised to quench carefully any hydride present in the supernatant with a small amount of methanol or ethanol before disposal. Two or three such rinses are sufficient to remove all traces of mineral oil.

Irritant. Great care must be taken in handling, and all operations involving the manipulation of the dry solid material should be conducted under an inert atmosphere in a fume hood.

Introduction.

The following is divided into two major classes of reactions: KH as a base, and KH as a reducing agent. The acid-base reactions are further divided into the type of acid (OH, NH, CH, or Sn/GeH). Secondary effects, such as rate acceleration in oxy-Cope reactions, are listed under the appropriate acid-base reaction.

The reactions of saline hydrides occur at the crystal surface. The crystal lattice energies decrease from LiH to CsH; KH appears to have the optimum lattice energy and hydride radius for surface reactions. It is thus usually superior to LiH or NaH in the reactions discussed below.

Acid-Base Reactions.

Oxygen Acids.

Potassium hydride reacts rapidly and quantitatively with acids such as carboxylic acids, phenols, and alcohols.1 Of particular note is its ability to rapidly deprotonate tertiary alcohols and hindered phenols, instances where Sodium Hydride or elemental Potassium react sluggishly or not at all. For example, triethylcarbinol and 2,6-di-t-butylphenol are quantitatively deprotonated in less than 5 min by KH in either ether or diglyme at 20 °C (eqs 1 and 2). For triethylcarbinol, NaH is ineffective, and K is sluggish in comparison.4

An interesting conformational effect is seen when p-t-butylcalix[4]arene is tetraethylated. When KH is used as the base, the partial cone conformation predominates, whereas with NaH, the cone is produced exclusively (eq 3).5

An unusual cyclization of hydroxyallenes to dihydrofurans is mediated by KH (eq 4).6 The reaction only proceeds when the K is complexed to 18-Crown-6, or when the base is Potassium t-Butoxide in refluxing t-butanol. Interestingly, no products of [1,3]- or [3,3]-rearrangement were detected.

Cyclization of a KH-generated alkoxide is a method for the 100% stereoselective formation of spiroacetals by an intramolecular 1,4-addition to sulfoxides (eqs 5 and 6).7 Lower selectivity resulted when either NaH or n-Butyllithium was used in the first step.

The elimination of trimethylsilanol from b-hydroxysilanes is a highly selective syn elimination when mediated by KH (eq 7).8 In contrast, acid-catalyzed elimination is anti selective. The KH reaction is complete in 1 h at rt, whereas NaH requires 20 h in HMPA and results in a lower yield of product.

The syn elimination (eq 7) can be coupled with an intramolecular epoxide ring-opening to effect a stereoselective synthesis of a-alkylidenetetrahydrofurans (eq 8).9

Rate enhancements on the order of 1010 to 1017 are observed for a [3,3]-sigmatropic rearrangement (oxy-Cope) of an endo-vinylbicyclo[2.2.2]octene alkoxide (generated with KH in the presence of HMPA or crown ether) vs. the alcohol (eq 9).10 Certain substrates for this reaction are quite sensitive to impurities in the KH, but pretreatment with Iodine eliminates the problem.3

Rate accelerations of &egt;106 by alkoxides have been observed for a [4 + 2] cycloreversion (Alder-Rickert reaction).11 Eq 10 illustrates an example; replacement of the methyls with either BOM or acetonide protecting groups is also possible.12

Nitrogen Acids.

Amines such as Diisopropylamine are not deprotonated by KH, although 1,2-Diaminoethane, diisobutylamine, and Pyrrolidine may be kaliated in excess amine solvent.4a N-Isopropylaniline and Hexamethyldisilazane are kaliated effectively and quantitatively in THF (eqs 11 and 12).1,4b

Deprotonation of indoles is also effective, and has been used to protect the N-H bond prior to a lithium-halogen exchange.13 Subsequent reaction with an electrophile occurs selectively at the lithiated position (eq 13).

Carbon Acids.

Dimethyl Sulfoxide is deprotonated in <=10 min with KH in THF at rt (eq 14).1 Under similar conditions, NaH is essentially unreactive. Cyclopentadiene (eq 15) and fluorene are deprotonated quantitatively as well.1

Triphenylmethane is not deprotonated directly by KH, unless a catalytic amount of DMSO1 (via in situ formation of dimsylpotassium, which in turn deprotonates triphenylmethane) or a crown ether is present (eq 16).14

Potassium hydride deprotonates ketones such as acetone, cyclohexanone, and isobutyrophenone with little or no self-condensation or reduction.1 For unsymmetrical ketones such as 2-methylcyclohexanone, a mixture of regioisomers is produced. O-Acylation15 and silylation16 are thus facilitated. Permethylation of cyclopentanone can be achieved by addition of the ketone to a THF suspension of KH, followed by Iodomethane (eq 17).17

Monoalkylation can be achieved by treating the potassium enolate with Triethylborane prior to alkylation (eq 18).18

a,b-Unsaturated ketones give g-alkylation, although polymerization can be a problem.1 The enamines of b-diketones, however, can be alkylated in good yield (eq 19).19 KH also mediates the Claisen condensation of esters (eq 20).20

Potassium hydride facilitated a tandem intramolecular Michael reaction-Claisen condensation in the synthesis of aklavinones.21 In the absence of any additive, the unnatural C-10 isomer was the only product observed in the NMR, but in the presence of 2.2.2-cryptand, the desired isomer was produced in 53% isolated yield (eq 21).

Ester enolate formation has been used to eliminate an acylamino group in a synthesis of condensed heterocycles, such as the indanone shown in eq 22.22 The azabicycloheptene starting material is available by a Diels-Alder reaction, and the N-acyl group is removed in situ.

Silicon, Tin, and Germanium Acids.

Trimethylsilane, tributylstannane, and tributylgermane are efficiently metalated by KH (eq 23).23 These reactions are sensitive to impurities in the KH,24 but pretreatment of the KH with iodine alleviates the difficulties.3

Reductions.

Potassium salts of selenanes,25 silanes, and stannanes are also produced by reduction of Se-Se, Si-Si, and Sn-Sn bonds by KH (eq 24).23

Potassium hydride reduces hindered boranes and borates to trialkyl (or trialkoxy) borohydrides.1,26 For example, tri-s-butylborane is reduced in 93% yield (eq 25).

Reduction of butylpotassium with hydrogen produces a superactive form of KH that reduces ketones and alkyl halides in high yields (eq 26).27 This active hydride also deprotonates aldehydes and ketones at low temperature, but reduction is often a side reaction.

Related Reagents.

Calcium Hydride; Potassium Hydride-s-Butyllithium-N,N,N,N-Tetramethylethylenediamine; Potassium Hydride-Hexamethylphosphoric Triamide; Sodium Hydride.


1. Brown, C. A. JOC 1974, 39, 3913.
2. Wiberg, E.; Amberger, E. Hydrides of the Elements of Main Groups I-IV; Elsevier: New York, 1971; pp 34-35.
3. Macdonald, T. L.; Natalie, K. J., Jr.; Prasad, G.; Sawyer, J. S. JOC 1986, 51, 1124.
4. (a) Brown, C. A. JACS 1973, 95, 982. (b) Brown, C. A. S 1974, 427.
5. Groenen, L. C.; Ruël, B. H. M.; Casnati, A.; Timmerman, P.; Verboom, W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N. TL 1991, 32, 2675.
6. Gange, D.; Magnus, P. JACS 1978, 100, 7746.
7. Iwata, C.; Hattori, K.; Uchida, S.; Imanishi, T. TL 1984, 25, 2995.
8. Hudrlik, P. F.; Peterson, D. JACS 1975, 97, 1464.
9. Luo, F.-T.; Negishi, E.-I. JOC 1983, 48, 5144.
10. Evans, D. A.; Golob, A. M. JACS 1975, 97, 4765.
11. Papies, O.; Grimme, W. TL 1980, 21, 2799.
12. Knapp, S.; Ornaf, R. M.; Rodriques, K. E. JACS 1983, 105, 5494.
13. Yang, Y.-H.; Martin, A. R.; Nelson, D. L.; Regan, J. H 1992, 34, 1169.
14. Buncel, E.; Menon, B. CC 1976, 648.
15. Jung, F.; Ladjama, D.; Riehl, J. J. S 1979, 507.
16. Baigrie, L. M.: Lenoir, D.; Seikaly, H. R.; Tidwell, T. T. JOC 1985, 50, 2105.
17. Millard, A. A.; Rathke, M. W. JOC 1978, 43, 1834.
18. Negishi, E.-I.; Idacavage, M. J. TL 1979, 845.
19. Gammill, R. B.; Bryson, T. A. S 1976, 401.
20. Brown, C. A. S 1975, 326.
21. Uno, H.; Naruta, Y.; Maruyama, K. T 1984, 40, 4725.
22. Kozikowski, A. P.; Kuniak, M. P. JOC 1978, 43, 2083.
23. (a) Corriu, R. J. P.; Guerin, C. CC 1980, 168. (b) Corriu, R. J. P.; Guerin, C. JOM 1980, 197, C19.
24. Newcomb, M.; Smith, M. G. JOM 1982, 228, 61.
25. Krief, A.; Trabelsi, M.; Dumont, W. S 1992, 933.
26. Brown, C. A. JACS 1973, 95, 4100.
27. Pi, R.; Friedl, T.; Schleyer, P. v. R.; Klusener, P.; Brandsma, L. JOC 1987, 52, 4299.

Robert E. Gawley & Xiaojie Zhang

University of Miami, Coral Gables, FL, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.