Potassium hydride in paraffin: A useful base for organic synthesis

Article abstract of DOI:10.1021/jo061420v

The preparation of potassium hydride as a 1:1 homogenate with paraffin, termed KH(P), is reported. KH(P), a solid at room temperature, is stable without special handling. On suspension in THF with a phosphonium salt, KH(P) rapidly generates the ylide. Wit

Full text of DOI:10.1021/jo061420v

TABLE 1. Wittig Homologation Using KH(P)
Potassium Hydride in Paraffin: A Useful Base
for Organic Synthesis
Douglass F. Taber* and Christopher G. Nelson
Department of Chemistry and Biochemistry, UniVersity of
Delaware, Newark, Delaware 19716
taberdf@udel.edu
ReceiVed July 7, 2006
The preparation of potassium hydride as a 1:1 homogenate
with paraffin, termed KH(P), is reported. KH(P), a solid at
room temperature, is stable without special handling. On
suspension in THF with a phosphonium salt, KH(P) rapidly
generates the ylide. Wittig condensation with aromatic,
aliphatic, and R,â-unsaturated aldehydes proceeds with high
Z selectivity. KH(P) should be a generally useful base for
organic synthesis.
Sodium hydride (NaH), potassium tert-butoxide, and n-BuLi
have long been the workhorse bases for organic synthesis.
Potassium hydride (KH), although it is a powerful base and
much faster kinetically than NaH, has not been so widely
There was the real concern that the heat from the reaction of
surface KH with ambient moisture would be sufficient to initiate
melting, leading to rapid decomposition. In fact, we have found
that the KH(P) is stable with normal handling. It is easily cut
and weighed in the air. Indeed, we have stored a sample in air
for 4 months and have observed no loss of titer. The titer was
determined by addition of n-butanol and by volumetric mea-
surement of the evolved hydrogen.
1
-3
used.
Largely, this is because it comes commercially as a
slurry in mineral oil and it is operationally difficult to dispense
precisely. We report the preparation of KH in a more convenient
4
form, as a 50% by weight homogenate in paraffin. We have
termed this new reagent “KH(P)”.
We were pleased to observe (Table 1) that the KH(P) prepared
in this fashion readily generated ylides from phosphonium salts.5
The alkenes formed from the non-stabilized phosphoranes were
predominantly Z, while the alkene (entry 5) from the stabilized
phosphorane was E. The yields in Table 1 refer to reactions
employing 1.8 equiv of KH(P) and 2.0 equiv of phosphonium
salt.
(
1) For early reports of the utility of KH as a reagent for organic synthesis,
see (a) Brown, C. A. J. Org. Chem. 1974, 39, 1324. (b) Brown, C. A.;
Yamashita, A. J. Am. Chem. Soc. 1975, 97, 891.
(
2) For an early review of organic synthesis applications of KH, see
Pinnick, H. W. Org. Prep. Proced. Int. 1983, 15, 199.
3) As of this writing, more than 4000 pages of this journal have been
(
published in 2006. The use of KH has been reported just 12 times: (a)
Kumaraswamy, G.; Padmaja, M.; Markondaiah, B.; Jena, N.; Sridhar, B.;
Kiran, M. U. J. Org. Chem. 2006, 71, 337. (b) Naya, S.; Ohtoshi, H.; Nitta,
M. J. Org. Chem. 2006, 71, 176-184. (c) Chai, C. L. L.; Elix, J. A.; Moore,
F. K. E. J. Org. Chem. 2006, 71, 992. (d) Kim, H. S.; Lee, S. Y.; Lee, H.;
Bae, J. Y.; Park, S. J.; Cheong, M.; Lee, J. S.; Lee, C.-H. J. Org. Chem.
006, 71, 911. (e) Ghosh, A. K.; Gong, G. J. Org. Chem. 2006, 71, 1085-
093. (f) Arns, S.; Barriault, L. J. Org. Chem. 2006, 71, 1809. (g) Lysen,
M.; Hansen, H. M.; Begtrup, M.; Kristensen, J. L. J. Org. Chem. 2006, 71,
518. (h) Johnsson, R.; Mani, K.; Cheng, F.; Ellervik, U. J. Org. Chem.
006, 71, 3444. (i) O’Neal, W. G.; Roberts, W. P.; Ghosh, I.; Wang, H.;
Jacobi, P. A. J. Org. Chem. 2006, 71, 3472. (j) Kadota, I.; Nishii, H.; Ishioka,
H.; Takamura, H.; Yamamoto, Y. J. Org. Chem. 2006, 71, 4183. (k)
Casarini, D.; Coluccini, C.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2006,
1, 4490. (l) Hagiwara, H.; Takeuchi, F.; Kudou, M.; Hoshi, T.; Suzuki,
T.; Hashimoto, T.; Asakawa, Y. J. Org. Chem. 2006, 71, 4619.
(4) The coating of air-sensitive catalysts with paraffin is a common
industrial practice with many references in the patent literature. For
examples, see (a) Fang, Y.; Liu, Y.; Ke, Y.; Guo, C.; Zhu, N.; Mi, X.; Ma,
Z.; Hu, Y. Appl. Catal. A 2002, 235, 33. (b) Kosak, K. M.; Kosak, M. K.
U.S. Patent 5 413 924, 1995. We have used this approach to stabilize
sensitive catalysts: (c) Taber, D. F.; Frankowski, K. J. J. Org. Chem. 2003,
68, 6047. (d) Taber, D. F.; Li, H.-Y. U.S. Pat. Appl. Publ. US 2005288257,
2005.
2
1
2
2
(5) For the use of dry combinations of phosphonium salts and KH to
generate ylides, see El-Khoury, M.; Wang, Q.; Schlosser, M. Tetrahedron
Lett. 1996, 37, 9047.
7
1
0.1021/jo061420v CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/10/2006
J. Org. Chem. 2006, 71, 8973-8974
8973

We expect that KH(P), easily handled and measured and
stable in storage, will have wide utility in organic synthesis.
CO
SO
as a colorless oil (214 mg, 0.80 mmol, 80% yield): TLC R
3
, and brine. The combined organic extracts were dried (Na
) and concentrated. The residue was chromatographed to give
2
-
6
4
7
f
1
(
6
MTBE/petroleum ether ) 1:10) ) 0.52; H NMR δ 2.65 (dq, J )
Experimental Section
.8, 1.5 Hz, 2H), 3.56 (t, J ) 6.8 Hz, 2H), 3.76 (s, 3H), 4.50 (s,
Potassium Hydride in Paraffin. In a nitrogen atmosphere (grade
2H), 5.72 (dt, J ) 11.5, 7.2 Hz, 1H), 6.48 (d, J ) 11.5 Hz, 1H),
6.87 (dd, J ) 8.3, 2.7 Hz, 1H), 6.77 (s, 1H), 6.87 (d, J ) 7.7 Hz,
1 H), 7.20-7.34 (m, 6H); 13C NMR δ d 55.2, 112.4, 114.4, 121.34,
127.3, 127.6, 127.7, 128.4, 129.1, 129.4, 130.5; u 29.5, 69.9, 73.0,
4
.8) drybox, KH (35% w/w dispersion in mineral oil) was washed
with cyclohexane and filtered. Paraffin wax (for canning, mp )
8-50 °C, 2.00 g) was warmed to melting in a small cylindrical
7
4
-
1
clear glass vial via a heating mantle. To the melted wax was added
KH (2.00 g, 50 mmol), and the slurry was rapidly stirred to
homogeneity with a Teflon coated magnetic stir bar while still
warm. Magnetic stirring was continued until the mixture began to
solidify, at which time the vial was rolled on its side on a flat surface
until the mixture was completely solid. The homogeneous 50% (w/
w) dispersion of KH in paraffin was then capped and removed from
the drybox for storage in the laboratory without further protection.
138.5, 138.8, 159.5; IR 2852, 1598, 1101 cm ; MS m/z 268 (12),
162 (27), 147 (100), 134 (60), 115 (27). HRMS calcd for C18
20 2
H O ,
268.1463; found, 268.1457.
Alkene 11. Yield 185 mg, 0.90 mmol, 90%; TLC R
f
(MTBE/
1
petroleum ether/CH Cl ) 4:20:1) ) 0.56; H NMR δ 1.13 (t, J )
2 2
7.1 Hz, 3H), 3.81 (s, 3H), 4.26 (q, J ) 7.2 Hz, 2H), 6.42 (d, J )
16.0 Hz, 1H), 6.91 (dd, J ) 8.3, 2.7 Hz, 1H), 7.03 (s, 1H), 7.10 (d,
J ) 7.9 Hz, 1H), 7.28 (t, J ) 7.9 Hz, 1H), 7.64 (d, J ) 16.0 Hz,
1H); 13C NMR δ d 14.3, 55.2, 112.9, 116.1, 118.6, 120.7, 129.9,
(
Caution: While we have never had any difficulty following this
procedure, others have observed sparking when washing KH under
house” nitrogen.)
-
1
144.5; u 60.5, 135.9, 160.0, 166.9; IR 2980, 1713, 1640 cm ; MS
“
m/z 206 (64), 178 (11), 161 (100), 134 (18), 118 (24); HRMS calcd
for C12H O , 206.0943; found, 206.0944.
14 3
The KH(P) was titrated with an apparatus for measuring H
2
evolution. To a slurry of KH(P) (78.2 mg, 39.1 mg of KH) in 5
mL of heptane was slowly added a solution of excess 1-butanol in
Acknowledgment. This work was supported by the National
Institutes of Health (GM 60287). We thank Frank Wagner of
Strem Chemicals for helpful discussions. Wilmington Phar-
maTech provided the commercial KH used in these studies.
5
mL of heptane. The gas evolved in the titration was then read
from a volumetric buret as 23.5 mL (24.4 mL was expected).
Representative ProceduresPreparation of Alkene 7. To a 25
mL flask were added phosphonium salt 4 (982 mg, 2.0 mmol),
KH(P) (144 mg of 50% w/w mixture of KH/paraffin, 1.8 mmol of
KH), and 4 mL of dry THF. The suspension was stirred for 20
min, changing to a yellow-orange color, and then cooled to 0 °C.
Aldehyde 1 (0.122 mL, 1.0 mmol) was then added, and the mixture
was stirred for 2 h at 0 °C. The mixture was then partitioned
Supporting Information Available: General experimental
procedures, 1H and C spectra, and other data for all new
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
13
JO061420V
2 2 2
between CH Cl and, sequentially, H O, saturated aqueous NaH-
(
7) 13C multiplicities were determined with the aid of a JVERT pulse
(
6) KH(P) prepared by the method outlined here is commercially available
sequence, differentiating the signals for methyl and methine carbons as “d”
and for methylene and quaternary carbons as “u”.
from Wilmington PharmaTech.
8
974 J. Org. Chem., Vol. 71, No. 23, 2006