4472
J . Org. Chem. 1996, 61, 4472-4475
dium acetylide to trimethylaluminum at 0 °C in toluene-
THF (eq 1). THF is required as a cosolvent to get a clear
solution since STEA is sparingly soluble in toluene alone.
The addition of carbonyl compounds to this solution at
room temperature produced the corresponding ethynyl
carbinols in good yield (eq 2).
Sod iu m Tr im eth yleth yn yla lu m in a te, a New
Ch em oselective Eth yn yla tin g Agen t
Meyoung J u J oung, J in Hee Ahn, and Nung Min Yoon*
Department of Chemistry, Sogang University,
Seoul 121-742, Korea
Received J anuary 19, 1996
Ethynylation is an important reaction for extending
carbon chains and introducing other functional groups
in organic synthesis. Ethynylation has been traditionally
carried out by using alkali metal (Na, Li) acetylides or
ethynyl Grignard reagents,1 but these reagents are
sometimes difficult to prepare and react efficiently with
carbonyl compounds. Thus, monolithium acetylide dis-
proportionates into dilithium acetylide and acetylene in
tetrahydrofuran at above -78 °C,2 requiring preparation
at -78 °C or a complexing agent like ethylenediamine
that stabilizes monolithium acetylide. Alkali metal
acetylides react with aldehydes and ketones at low
temperature (-78 °C) to give good yields of the corre-
sponding ethynyl carbinols,3 but also give moderate yields
in their reactions with alkyl halides,4 epoxides,5 esters,6
and amides.7 Ethynyl Grignard reagents react simi-
larly.8-10
Recently, we reported the highly chemoselective reac-
tions of sodium diethyldialkynylaluminate (SDAA)11 with
carbonyl compounds. SDAA reacts readily with carbonyl
compounds, but does not react with many other func-
tional groups such as halides, epoxides, esters, amides,
and nitriles. SDAA also showed excellent 1,2-regiose-
lectivity in the reactions with cyclic or acyclic R,â-
unsaturated carbonyl compounds. However, one disad-
vantage of this reagent was that only one alkynyl group
of SDAA was transferred in the alkynylation of carbonyl
compounds. We report here a new chemoselective ethyn-
ylating agent, sodium trimethylethynylaluminate (STEA),
which not only gives good yields of ethynyl carbinols at
room temperature, but also exhibits excellent chemose-
lectivity and regiospecificity like SDAA.11 STEA can be
readily prepared by adding commercially available so-
Reactions of STEA with representative carbonyl com-
pounds have been examined, and the results are sum-
marized in Table 1. As shown in the Table 1, all the
aldehydes and ketones examined were readily ethyn-
ylated with STEA to afford the corresponding ethynyl
carbinols in 73-93% yields under mild conditions. The
ethynylation of benzaldehyde gave 1-phenyl-2-propyn-1-
ol (1) in an isolated yield of 93% at room temperature.
However, sodium acetylide in liquid ammonia3a and
lithium acetylide in tetrahydrofuran3b are known to
produce 1 at -78 °C in 82-84% and 93% yields, respec-
tively. The ethynylation of aliphatic carbonyl compounds
such as hexanal, 2-heptanone, cyclohexanone, and nor-
camphor provided the expected ynols in slightly lower
yields (80-88%) as compared with benzaldehyde, possibly
due to deprotonation. Hexanal was ethynylated to give
a 80% yield of 1-octyn-3-ol (2). Using lithium acetylide
in tetrahydrofuran, the ethynylation of hexanal has been
reported to give 1-octyn-3-ol in 98% yield at -78 °C, but
a decreased yield of 39% at 0 °C due to the irreversible
formation of a dilithium acetylide.3b In the case of
cyclohexanone, we could conveniently obtain 1-ethynyl-
cyclohexanol (4) in 81% yield at room temperature, but
the ethynylation with sodium acetylide in liquid am-
monia12 is known to produce only 65-75% yield of 4.
STEA was found to be an excellent 1,2-ethynylating
agent of cyclic or acyclic R,â-unsaturated carbonyl com-
pounds. Thus, STEA regioselectively ethynylated 2-cy-
clohexen-1-one, cinnamaldehyde, and benzalacetone to
provide the corresponding 1,2-addition products exclu-
sively. It has been reported that sodium acetylide and
ethynylmagnesium bromide also gave mainly 1,2-addi-
tion products from conjugated enones.13,14 However, the
1,2-ethynylation with sodium acetylide had to be carried
out at -80 °C to get a good yield (72-79%),13 and the
reaction of ethynylmagnesium bromide with cinnamal-
dehyde gave 1-phenyl-1-penten-4-yn-3-ol (6) in yields
ranging from 58% to 69%.14 But STEA produced 6 in
higher yield (84%) at room temperature.
(1) Brandsma, L. Preparative Acetylenic Chemistry; Elsevier: Am-
sterdam, 1988, p 79.
(2) (a) Beumel, O. F., J r.; Harris, R. F. J . Org. Chem. 1963, 28, 2775.
(b) Beumel, O. F., J r.; Harris, R. F. J . Org. Chem. 1964, 29, 1872.
(3) (a) Fisch, A.; Coisne, J . M.; Figeys, H. P. Synthesis 1982, 211.
(b) Midland, M. M. J . Org. Chem. 1975, 40, 2250.
(4) Campbell, K. N.; Campbell, B. K. Organic Syntheses; Wiley: New
York, 1963; Coll. Vol. IV, p 117.
(5) Corey, E. J .; Trybulski, E. J .; Melvin, L. S., J r.; Nicolaou, K. C.;
Secrist, J . A.; Lett, R.; Sheldrake, P. W.; Falck, J . R.; Brunelle, D. J .;
Haslanger, M. F.; Kim, S.; Yoo, S.-E. J . Am. Chem. Soc. 1978, 100,
4618.
(6) (a) Yamaguchi, M.; Shibato, K.; Fujiwara, S.; Ichiro, H. Synth.
Commun. 1986, 16, 421. (b) Hauptmann, H.; Mader, M. Synthesis
1978, 307.
(7) (a) Cupps, T. L.; Boutin, R. H.; Rapoport, H. J . Org. Chem. 1985,
50, 3972. (b) Honda, Y.; Ori, A.; Tsuchihashi, G. I. Chem. Lett. 1986,
13.
STEA was also found to be highly chemoselective.
Thus, the reagent did not react with representative
halides (benzyl chloride and octyl bromide), an epoxide
(8) (a) Fried, J .; Lin, C. H.; Sih, J . C.; Dalven, P.; Cooper, G. F. J .
Am. Chem. Soc. 1972, 94, 4342. (b) Montijn, P. P.; Schmidt, H. M.;
van Boom, J . H.; Bos, H. J . T.; Brandsma, L.; Arens, J . F. Recl. Trav.
Chim. Pays-Bas 1965, 84, 271.
(9) J ones, E. R. H.; Lee, H. H.; Whiting, M. C. J . Chem. Soc. 1960,
3483.
(10) Schaap, A.; Arens, J . F. Recl. Trav. Chim. Pays-Bas 1968, 87,
1249.
(11) (a) Yoon, N. M.; Ahn, J . H.; J oung, M. J . J . Org. Chem. 1995,
60, 6173. (b) Alkynyl titanium compounds are also known to be highly
chemoselective: Seebach, D.; Krause, N. Chem. Ber. 1987, 120, 1845.
(12) Saunders, J . H. Organic Syntheses; Wiley: New York, 1955;
Coll. Vol. III, p 416.
(13) Shackelford, J . M.; Michalowicz, W. A.; Schwartzman, L. H. J .
Org. Chem. 1962, 27, 1631.
(14) Skattebol, L.; J ones, E. R. H.; Whiting, M. C. Organic Syntheses;
Wiley: New York, 1963; Coll. Vol. IV, p 792.
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