POTASSIUM HYDRIDE 1
Acid Base Reactions.
Potassium Hydride1
Oxygen Acids. Potassium hydride reacts rapidly and quantita-
KH
tively 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
[7693-26-7] HK (MW 40.11)
or elemental Potassium react sluggishly or not at all. For example,
InChI = 1/K.H/rHK/h1H
triethylcarbinol and 2,6-di-t-butylphenol are quantitatively depro-
InChIKey = NTTOTNSKUYCDAV-YPAVOLDLAP
ć%
tonated 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
(base and hydride donor to Lewis acids such as boranes and
sluggish in comparison.4
borates; used for deprotonation, cyclization condensation, elimi-
nation, rearrangement reactions, and as a reducing agent).
Et Et
KH
(1)
Et OH Et OK
THF
Physical Data: solid; dec on heating; d 1.47 g cm-3; nD 1.453.
Et Et
Solubility: dec in cold and hot water; insol CS2, ether, benzene.
t-Bu t-Bu
Form Supplied in: as a dispersion in mineral oil, 20 35% by
KH
weight. A standardization procedure has been published.1
(2)
OH OK
THF
Purification: commercial KH dispersion is made by reduction of
metallic potassium,2 and so KH is often contaminated with t-Bu t-Bu
traces of potassium or potassium superoxide. These can be
An interesting conformational effect is seen when p-t-butylcalix
removed by pretreatment with iodine to produce a reagent with
[4]arene is tetraethylated. When KH is used as the base, the partial
superior consistency in several reactions that are sensitive to
cone conformation predominates, whereas with NaH, the cone is
such impurities.3
produced exclusively (eq 3).5
Handling, Storage, and Precautions: dispersion is a liquid, and
tends to settle upon standing. Prolonged storage produces a
t-Bu
t-Bu
t-Bu t-Bu
EtI
compacted solid that must be broken up to achieve a homo-
KH
geneous dispersion. Brown suggests1 using a long-handled
DMF or THF
screwdriver to break up the compacted material and leaving a
Teflon-covered stir bar in the container to aid dispersion.
OH OH
OH OH
Clamping the sealed polyethylene bottle containing the
dispersion to a Parr shaker for 15 min also works well.
t-Bu
t-Bu t-Bu t-Bu
t-Bu t-Bu
t-Bu
The mineral oil may be removed by adding pentane to small
quantities of the dispersion, stirring the slurry, then allowing the
EtO
+ (3)
hydride to settle. The pentane/mineral oil supernatant may be
pipetted off, but care should be exercised to quench carefully
OEt OEt
OEt OEt OEt OEt
OEt
any hydride present in the supernatant with a small amount of
methanol or ethanol before disposal. Two or three such rinses are
t-Bu
partial cone, 64% cone, 2%
sufficient to remove all traces of mineral oil.
Irritant. Great care must be taken in handling, and all operations
An unusual cyclization of hydroxyallenes to dihydrofurans is
involving the manipulation of the dry solid material should be
mediated by KH (eq 4).6 The reaction only proceeds when the
conducted under an inert atmosphere in a fume hood.
K is complexed to 18-Crown-6, or when the base is Potassium
tert-Butoxide in refluxing t-butanol. Interestingly, no products of
[1,3]- or [3,3]-rearrangement were detected.
Original Commentary
"
Robert E. Gawley & Xiaojie Zhang
HO OMe KH, 18-crown-6
O
University of Miami, Coral Gables, FL, USA
OMe
(4)
THF
74%
Introduction. The following is divided into two major classes
of reactions: KH as a base, and KH as a reducing agent. The
Cyclization of a KH-generated alkoxide is a method for the
acid base reactions are further divided into the type of acid (OH,
100% stereoselective formation of spiroacetals by an intramolec-
NH, CH, or Sn/GeH). Secondary effects, such as rate acceleration
ular 1,4-addition to sulfoxides (eqs 5 and 6).7 Lower selectivity
in oxy-Cope reactions, are listed under the appropriate acid base
resulted when either NaH or Butyllithium was used in the first
reaction.
step.
The reactions of saline hydrides occur at the crystal surface. The
crystal lattice energies decrease from LiH to CsH; KH appears to
O
have the optimum lattice energy and hydride radius for surface
S
1. KH, THF (90%)
Ph
reactions. It is thus usually superior to LiH or NaH in the reactions (5)
OH
2. Raney Ni (79%)
O
O
discussed below.
O
Avoid Skin Contact with All Reagents
2 POTASSIUM HYDRIDE
O
solvent.4a N-Isopropylaniline and Hexamethyldisilazane are kali-
S
1. KH, THF (90%)
Ph
ated effectively and quantitatively in THF (eqs 11 and 12).1,4b
(6)
OH
2. Raney Ni (88%)
O
O K
H
O
KH
N N
(11)
THF
The elimination of trimethylsilanol from ²-hydroxysilanes is a
highly selective syn elimination when mediated by KH (eq 7).8
TMS TMS
In contrast, acid-catalyzed elimination is anti selective. The KH KH
NH N K (12)
reaction is complete in 1 h at rt, whereas NaH requires 20 h in
THF
TMS TMS
HMPA and results in a lower yield of product.
Deprotonation of indoles is also effective, and has been used
TMS
KH, THF
to  protect the N H bond prior to a lithium halogen exchange.13
(7)
96% Subsequent reaction with an electrophile occurs selectively at the
95% ds
OH
lithiated position (eq 13).
The syn elimination (eq 7) can be coupled with an intramolec-
1. KH
Br E
2. t-BuLi
ular epoxide ring-opening to effect a stereoselective synthesis of
(13)
Ä…-alkylidenetetrahydrofurans (eq 8).9
3. E+
N N
H H
C5H11 O
O TMS
C5H11 KH, THF
(8)
OH E = CHO, MeCO, CONH2, TMS, SnMe3
70%
H H
90 95% ds
Carbon Acids. Dimethyl Sulfoxide is deprotonated in
Rate enhancements on the order of 1010 to 1017 are observed
d"10 min with KH in THF at rt (eq 14).1 Under similar condi-
for a [3,3]-sigmatropic rearrangement (oxy-Cope) of an endo-
tions, NaH is essentially unreactive. Cyclopentadiene (eq 15) and
vinylbicyclo[2.2.2]octene alkoxide (generated with KH in the
fluorene are deprotonated quantitatively as well.1
presence of HMPA or crown ether) vs. the alcohol (eq 9).10 Cer-
O O
tain substrates for this reaction are quite sensitive to impurities in
KH
S S K (14)
the KH, but pretreatment with Iodine eliminates the problem.3
Me Me Me
THF
H
O
KH
KH, HMPA
 K+
(15)
OH THF
THF
MeO
MeO
H
Triphenylmethane is not deprotonated directly by KH, unless a
catalytic amount of DMSO1 (via in situ formation of dimsylpotas-
H
O
sium, which in turn deprotonates triphenylmethane) or a crown
(9)
ether is present (eq 16).14
MeO
H
Ph
Ph
KH, 18-crown-6
98%

Ph K+ (16)
Ph Ph
THF
Ph
Rate accelerations of e" 106 by alkoxides have been observed
90%
for a [4 + 2] cycloreversion (Alder Rickert reaction).11 Eq 10
illustrates an example; replacement of the methyls with either Potassium hydride deprotonates ketones such as acetone,
BOM or acetonide protecting groups is also possible.12 cyclohexanone, and isobutyrophenone with little or no self-
condensation or reduction.1 For unsymmetrical ketones such as
OMe
2-methylcyclohexanone, a mixture of regioisomers is produced.
MeO
O-Acylation15 and silylation16 are thus facilitated. Permethyla-
MeO
KH
tion of cyclopentanone can be achieved by addition of the ketone
MeO
to a THF suspension of KH, followed by Iodomethane (eq 17).17
dioxane
99%
OH
O O
1. KH
2. MeI
OMe (17)
OK
THF
MeO
+ (10)
Monoalkylation can be achieved by treating the potassium
MeO
enolate with Triethylborane prior to alkylation (eq 18).18
OMe
O 1. KH O
2. BEt3
Nitrogen Acids. Amines such as Diisopropylamine are not
(18)
3. CH2=CHCH2Br
deprotonated by KH, although 1,2-Diaminoethane, diisobuty-
90%
lamine, and Pyrrolidine may be kaliated in excess amine
A list of General Abbreviations appears on the front Endpapers
POTASSIUM HYDRIDE 3
KH, THF
Ä…,²-Unsaturated ketones give Å‚-alkylation, although polymer-
RnXXRn RnX K+ (24)
ization can be a problem.1 The enamines of ²-diketones, however,
X = Se (n = 1), Si, Sn (n = 3)
can be alkylated in good yield (eq 19).19 KH also mediates the
R = Me, Ph
Claisen condensation of esters (eq 20).20
1. KH Potassium hydride reduces hindered boranes and borates to
2. MeI
trialkyl (or trialkoxy) borohydrides.1,26 For example, tri-s-butyl-
(19)
O N O N
84% borane is reduced in 93% yield (eq 25).
KH, THF
O O (25)
BBH K+
O
KH, THF
3 3
(20)
OEt
OEt
82%
Reduction of butylpotassium with hydrogen produces a  super-
active form of KH that reduces ketones and alkyl halides in high
Potassium hydride facilitated a tandem intramolecular Michael
reaction Claisen condensation in the synthesis of aklavinones.21 yields (eq 26).27 This active hydride also deprotonates aldehy-
des and ketones at low temperature, but reduction is often a side
In the absence of any additive, the  unnatural C-10 isomer was
reaction.
the only product observed in the NMR, but in the presence of
2.2.2-cryptand, the desired isomer was produced in 53% isolated
KH*, THF
yield (eq 21).
C9H19CH2Br C9H19Me (26)
95%
TBDMSO
KH, HMPA
2,2,2-cryptand
CO2Me
THF
53%
OMe O O First Update
Qunzhao Wang
TBDMSO CO2Me
H
Albert Einstein College of Medicine, Bronx, NY, USA
10 OH
(21)
Introduction. As a general reagent in organic synthesis, potas-
H
sium hydride continues to find new applications, mostly as a
OMe O
strong base. This update follows the category arrangement of
the previous review and discusses recent applications of KH in
Ester enolate formation has been used to eliminate an
organic synthesis.
acylamino group in a synthesis of condensed heterocycles, such
Potassium hydride is not soluble in any common solvents and
as the indanone shown in eq 22.22 The azabicycloheptene starting
is usually provided and used as a dispersion in solution. To study
material is available by a Diels Alder reaction, and the N-acyl
the reaction mechanism of potassium hydride with acid, Cerofolini
group is removed in situ.
and Boara used 18-crown-6 and were able to obtain a homoge-
COMe
neous solution of KH in dioxane. Interestingly, this solution does
CO2Et
N
not react or reacts very slowly with strong acids such as HI, HBr,
KH, THF
CO2Et
H2SO4, but reacts easily with weak acids such as MeOH, H2O,
(22)
O
60 75%
HOAc, etc.28 It was reasoned that the reaction between the hydride
N
CHCO2Et
and the acid does not occur via an acid base path (H- reacts with
H
H+ dissociated from acid HA), but rather through an electron-
transfer path with a transition state depicted as [H" (H´+A´-)-].
Silicon, Tin, and Germanium Acids. Trimethylsilane, trib- The reaction of solid KH with acid is more complicated. It is pro-
utylstannane, and tributylgermane are efficiently metalated by KH
posed that besides the electron-transfer pathway, an autocatalytic
(eq 23).23 These reactions are sensitive to impurities in the KH,24
acid base reaction path also exists as the superficial layer KA (A
but pretreatment of the KH with iodine alleviates the difficulties.3
= counteranion) facilitates the absorption of HA and reduces the
activation energy of the acid base reaction path. The proposed
KH, THF
model can generate an oscillating reaction process which is
R3XH R3X K+ (23)
60 80% validated by experiment.
X = Si, Sn, Ge
R = Me, Bu, Ph Acid Base Reactions.
Oxygen Acids. One interesting application of KH as a base
Reductions. Potassium salts of selenanes,25 silanes, and stan- for O H is to direct a macrodilactonization in the synthesis of
nanes are also produced by reduction of Se Se, Si Si, and Sn Sn Cycloviracin B (eq 27)29 and Glucolipsin A.30 The result with
bonds by KH (eq 24).23 KH is much superior to that with NaH and CsH, indicating that
Avoid Skin Contact with All Reagents
4 POTASSIUM HYDRIDE
Ph
K+ ion is essential to bring the cyclization precursor together for
KH, NMP
direct macrodilactonization.
Ph
(29)
72%
N
H
OBn
NH2
BnO OBn
Cl
N
TBDPSO(CH2)14
Cl
KH,
Potassium hydride has also been used to deprotonate amide or
N
DMAP
O O
imide nitrogen protons. The amide anion reacts smoothly with
OH
CH2Cl2
acid chlorides,34 anhydrides (eq 30),35 etc. With catalysis by CuI,
O OH
75%
cyclic and acyclic amide anions, which have Ä…-carbon protons,
O
HO
HO
can react with alkenyl bromides, providing enamides in moderate
O
O yields, while cyclic imide anions give higher yields (eq 31).36
Sodium hydride is not successful for similar coupling reactions.
(CH2)14OTBDPS
Amide anions have been reacted intramolecularly with esters for
OBn
BnO
dioxosuccinimide and monothiosuccinimide synthesis (eq 32).37
OBn
OBn
BnO OBn
O
TBDPSO(CH2)14
Ph
KH, (Boc)2O
O
O O
NH2 DMF
(27)
O
O 89%
OBn
O
O O
O
O
O
Ph
(CH2)14OTBDPS
(30)
O
OBn
BnO
NHBoc
OBn
OBn
O
Potassium hydride is the most generally used base for an-
Ph
ionic oxy-Cope rearrangements (eq 9), as indicated in Paquette s O O
Ph
KH, Br
review.31 Compared to Na+ cation, the more highly dissociable (31)
NH2 CuI, HMPA
N
K+ can be better separated from the alkoxide anion; in addition,
45%
H
18-crown-6 can be used to chelate K+ to obtain more activity
of the alkoxide anion. The amount of 18-crown-6 can also
affect the stereochemistry of the product. When cis-cyclohexenyl-
KH, THF
cyclobutanol was treated with KH and 18-crown-6, a mixture of
(32)
racemic ring expansion product and nonracemic epimerization X=O: 62%
MeO2C
X OX
X=S: 88%
product trans-cyclohexenyl-cyclobutanol was obtained with a N
H2N
H
ratio of about 1:2.5. The enantiopurity of the epimerization prod-
uct is highly dependent on the 18-crown-6 usage (eq 28).32
Similar to amides, alkyl sulfonamides and aryl sulfonamides
can be deprotonated by KH effectively (eq 33).38 Deprotonation of
phenylphosphanyl amine by KH has also been reported (eq 34).39
KH (11 equiv)
18-c-6
H
O
THF,  20 °C
O
KH, THF
X S
OH
(33)
X S N
NH2 X=Me, Ph O
(+)
O
H
+
KH
H
H (34)
(Ph2P)2NH (Ph2P)2N
(28)
THF
OH
OH
( )
Ä…
( )
enantio
18-c-6 selectivity
Carbon Acids. Deprotonation of ketones to form an enolate
0.5 equiv: 33 ee%
by KH has been utilized in a one-pot alkylation cyclization reac-
2.6 equiv: 90 ee%
tion (eq 35).40 By using excess KH, 2-methylcyclohexanone is
alkylated by 1,4-dibromobutene at the C-2 position, the ketone
Nitrogen Acids. Potassium hydride deprotonates 2-alkynyl formed undergoes further enolazation, cyclization through
anilines readily in NMP at rt and promotes a smooth cyclization, intramolecular O-alkylation, and hydrolization of the enol ether
providing 2-substituted indole-type products (eq 29).33 Replace- double bond providing a bicyclic system. The bicyclic system
ment of KH by KOt-Bu gives similar results. The reaction requires formed is highly stereoselective, with the vinyl group oriented
a higher temperature and is sluggish with NaH or CsOH. anti to the methyl group.
A list of General Abbreviations appears on the front Endpapers
POTASSIUM HYDRIDE 5
8. Hudrlik, P. F.; Peterson, D., J. Am. Chem. Soc. 1975, 97, 1464.
KH (excess)
O
O
9. Luo, F.-T.; Negishi, E.-I., J. Org. Chem. 1983, 48, 5144.
HO
BrCH2CH=CHCH2Br
(35)
10. Evans, D. A.; Golob, A. M., J. Am. Chem. Soc. 1975, 97, 4765.
THF
11. Papies, O.; Grimme, W., Tetrahedron Lett. 1980, 21, 2799.
62%
12. Knapp, S.; Ornaf, R. M.; Rodriques, K. E., J. Am. Chem. Soc. 1983, 105,
5494.
Study of the deprotonation of dihydrothiophene-type com-
13. Yang, Y.-H.; Martin, A. R.; Nelson, D. L.; Regan, J., Heterocycles 1992,
pounds by different bases indicates an order of reactivity
34, 1169.
KH>NaH>LiH (eq 36).41 WhenX=SO2, the reaction with KH
14. Buncel, E.; Menon, B., J. Chem. Soc., Chem. Commun. 1976, 648.
is instantaneous, proceeding through deprotonation by CH3S(O)
15. Jung, F.; Ladjama, D.; Riehl, J. J., Synthesis 1979, 507.
CH2- formed by deprotonation of DMSO by KH. With NaH, 25
16. Baigrie, L. M.: Lenoir, D.; Seikaly, H. R.; Tidwell, T. T., J. Org. Chem.
min of ultrasound is required for the completion of the reaction;
1985, 50, 2105.
with LiH, no product is obtained after 4.5 h of ultrasound treat-
17. Millard, A. A.; Rathke, M. W., J. Org. Chem. 1978, 43, 1834.
ment. In accordance with the reactivity of metal hydride, the salt
18. Negishi, E.-I.; Idacavage, M. J., Tetrahedron Lett. 1979, 845.
formed has stability with the order: KA>NaA>>LiA (A: corre-
19. Gammill, R. B.; Bryson, T. A., Synthesis 1976, 401.
sponding dihydrothionyl anion). The results are consistent with
20. Brown, C. A., Synthesis 1975, 326.
theoretical studies and predictions.
21. Uno, H.; Naruta, Y.; Maruyama, K., Tetrahedron 1984, 40, 4725.
22. Kozikowski, A. P.; Kuniak, M. P., J. Org. Chem. 1978, 43, 2083.
KH, DMSO
K (36)
23. (a) Corriu, R. J. P.; Guerin, C., J. Chem. Soc., Chem. Commun. 1980,
X
X = S, SO, SO2
X
168. (b) Corriu, R. J. P.; Guerin, C., J. Organomet. Chem. 1980, 197,
C19.
24. Newcomb, M.; Smith, M. G., J. Organomet. Chem. 1982, 228, 61.
Reductions. Potassium hydride can cleave silyl enol ethers
25. Krief, A.; Trabelsi, M.; Dumont, W., Synthesis 1992, 933.
and induce a conjugate addition of the resulted enolates to eno-
26. Brown, C. A., J. Am. Chem. Soc. 1973, 95, 4100.
nes (eq 37).42 The reaction is also achievable with 50% aqueous
27. Pi, R.; Friedl, T.; Schleyer, P. v. R.; Klusener, P.; Brandsma, L., J. Org.
NaOH in conjunction with TBAF in CH2Cl2. Potassium hydride
Chem. 1987, 52, 4299.
can also cleave the silyl group of arylsilanes complexed with
28. (a) Cerofolini, G. F.; Boara, G., Gazz. Chim. Ital. 1992, 122, 195.
Cr(CO)3 (eq 38).43 The desilylation is selective and does not
(b) Cerofolini, G. F.; Boara, G.; Agosteo, S.; Para, A. F., Langmuir 1997,
13, 913.
occur with uncomplexed aryl silyl ethers. Aryl anions resulting
from the desilylation can be trapped in situ by electrophiles. 29. (a) Furstner, A.; Albert, M.; Mlynarski, J.; Matheu, M., J. Am. Chem.
Soc. 2002, 124, 1168. (b) Furstner, A.; Mlynarski, J.; Albert, M., J. Am.
O
Chem. Soc. 2002, 124, 10274. (c) Furstner, A.; Albert, M.; Mlynarski,
O Ph O
OSiMe3 KH, J.; Matheu, M.; Declercq, E., J. Am. Chem. Soc. 2003, 125, 13134.
Ph Ph
(37)
30. Furstner, A.; Ruiz-Caro, J.; Prinz, H.; Waldmann, H., J. Org. Chem.
DMF Ph Ph
Ph
2004, 69, 459.
64%
31. Paquette, L. A., Tetrahedron 1997, 53, 13971.
OH
32. Kim, S.-H.; Cho, S. Y.; Cha, J. K., Tetrahedron Lett. 2001, 42,
SiMe3 KH, ether Ph
8769.
Ph
18-crown-6
(38) 33. Rodriguez, A. L.; Koradin, C.; Dohle, W.; Knochel, P., Angew. Chem.,
Ph2CO
Int. Ed. 2000, 39, 2488.
85%
Cr(CO)3
Cr(CO)3
34. Aicher, T. D.; Bebernitz, G. R.; Bell, P. A.; Brand, L. J.; Dain, J. G.;
Deems, R.; Fillers, W. S.; Foley, J. E.; Knorr, D. C.; Nadelson, J.; Otero,
Related Reagents. Calcium Hydride; Potassium Hydride s- D. A.; Simpson, R.; Strohschein, R. J.; Young, D. A., J. Med. Chem.
1999, 42, 153.
Butyllithium N,N,N ,N -Tetramethylethylenediamine; Potassium
35. Hayashi, Y.; Shoji, M.; Yamaguchi, S.; Mukaiyama, T.; Yamaguchi, J.;
Hydride Hexamethylphosphoric Triamide; Sodium Hydride.
Kakeya, H.; Osada, H., Org. Lett. 2003, 5, 2287.
36. Ogawa, T.; Kiji, T.; Hayami, K.; Suzuki, H., Chem. Lett. 1991,
1443.
1. Brown, C. A., J. Org. Chem. 1974, 39, 3913.
37. Bishop, J. E.; Dagam, S. A.; Rapoport, H., J. Org. Chem. 1989, 54,
2. Wiberg, E.; Amberger, E. Hydrides of the Elements of Main Groups I IV; 1876.
Elsevier: New York, 1971; p 34.
38. (a) Talanova, G. G.; Hwang, H.-S.; Talanov, V. S.; Bartsch, R. A., Chem.
3. Macdonald, T. L.; Natalie, K. J., Jr.; Prasad, G.; Sawyer, J. S., J. Org. Commun. 1998, 419. (b) Talanova, G. G.; Elkarim, N. S. A.; Talanov, V.
Chem. 1986, 51, 1124. S.; Bartsch, R. A., Anal. Chem. 1999, 71, 419. (c) Metivier, R.; Leray,
I.; Lebeau, B.; Valeur, B., J. Mat. Chem. 2005, 15, 2965.
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Synthesis 1974, 427. 39. Roesky, P. W.; Gamer, M. T.; Puchner, M.; Greiner, A., Chem. Eur. J.
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5. Groenen, L. C.; Ruël, B. H. M.; Casnati, A.; Timmerman, P.; Verboom,
W.; Harkema, S.; Pochini, A.; Ungaro, R.; Reinhoudt, D. N., Tetrahedron 40. Wang, T.; Chen, J.; Zhao, K., J. Org. Chem. 1995, 60, 2668.
Lett. 1991, 32, 2675.
41. Gamero-Melo, P.; Villanueva-Garcia, M.; Robles, J.; Contreras, R.; Paz-
6. Gange, D.; Magnus, P., J. Am. Chem. Soc. 1978, 100, 7746. Sandoval, M. A., J. Organomet. Chem. 2005, 690, 1379.
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Avoid Skin Contact with All Reagents