Tertiary amine-accelerated allylgallation of terminal alkynes

Article abstract of DOI:10.1246/cl.2002.172

Allylic gallium sesquibromides prepared by reduction of allylic bromides with gallium metal in the presence of a catalytic amount of indium, add to terminal alkynes with the aid of a tertiary amine to give 1,4-dienes.

Full text of DOI:10.1246/cl.2002.172

172
Chemistry Letters 2002
Tertiary Amine-Accelerated Allylgallation of Terminal Alkynes
Kazuhiko Takai,Ã Yoshito Ikawa, Keijiro Ishii, and Makoto Kumanda
Department of Applied Chemistry, Faculty of Engineering, Okayama University, Tsushima, Okayama 700-8530
(Received November 19, 2001; CL-011165)
Allylic gallium sesquibromides prepared by reduction of
more effective for the allylation, and the reaction completed in 2 h
and 3 was obtained in 97% yield (eq 2). In contrast, pyridine and
DABCO did not accelerate the reaction and 88% and 95% of 1
were recovered, respectively, after 24 h stirring. In addition to
basicity, steric hindrance is an important factor for the
acceleration, as it influences the coordination of the amine to
gallium(III).
allylic bromides with gallium metal in the presence of a catalytic
amount of indium, add to terminal alkynes with the aid of a
tertiary amine to give 1,4-dienes.
Addition of allylic metal compounds to carbon-carbon triple
bonds is an important method for constructing carbon skeletons,
and employs such metals as Al, Zn, B, and In.1{3 In 1997,
Yamaguchi reported the addition of allylic gallium compounds to
alkynes, and the reaction was conducted in cyclohexane, a non-
polar solvent.4 We have recently found that allylic gallium
compounds are prepared from allylic halides and gallium metal in
THF usingindium as amediator.5 Thus, we examined the addition
of the allylic gallium compounds to alkynes in the THF solvent,
and found that trialkylamines have an accelerating effect on the
addition.
Under the conditions in eq. 2, an internal alkyne, 5-phenyl-2-
pentyne (5), did not react with the allylgallium compound, and
99% of the alkyne 5 was recovered. This suggests that the addition
proceeded via deprotonation of the terminal alkyne. In order to
examine this postulate, the reaction was quenched with
deuterated hydrochloric acid, and deuterium was introduced at
both the olefinic positions with a content of over 90% (eq 3).
In contrast to the reaction in cyclohexane,4 the addition of the
allylgallium compound 26 to alkyne 1 in THF did not proceed at
25 ꢀC, and the starting alkyne 1 was recovered in 98% yield after
24 h stirring (eq 1). Upon heating at reflux, the reaction completed
in 12 h and the 1,4-diene 3 was obtained in 97% yield after acidic
workup. Such allylations of alkynes are sometimes accelerated
using alkynylmagnesium compounds. Thus, the alkyne 1 was
ꢀ
treated with ethylmagnesium bromide (1.0equiv) at 50 C for 2 h
before addition of 2, and the addition proceeded at 25 ꢀC in 1.5 h
to give 3 in 95% yield (eq 1).
We assume the following mechanism for the reaction
(Scheme 1). An allylalkynylgallium species 7 is produced by
deprotonation of the terminal alkyne 6 with an amine and
metalation (upper pathway). Gallium(III)-assisted allylgallation
generates the 1,1-digallium compound 8.2b;2e;3b;8;9 Hydrolysis of
8 with DCl gives the dideuterated 1,4-diene 9. When the alkyne 6
is treated with EtMgBr, the magnesium acetylide 10 is formed
(lower pathway). Transmetalation to 11 followed by rearrange-
ment and hydrolysis affords 9.
Because the formation of the alkynyl Grignard reagent 4
requires heating at 50 ꢀC, we examined several additives to
promote the reaction under milder conditions. Addition of an
equimolar amount of a tertiary amine was found to accelerate the
reaction at 25 ꢀC. For example, when the alkyne 1 (1.0equiv) was
treated with a solution of allylgallium (2, 3.0equiv) 6 in THF at
25 ꢀC for 20h in the presence of Et 3N (1.0equiv), 7 the 1,4-diene 3
was obtained in 99% yield after workup with aqueous
hydrochloric acid (1 M). Addition of i-Pr2NEt (1.0equiv) was
Scheme 1.
The results of the addition of allylic gallium compounds to
terminal alkynes are shown in Table 1. 2-Substituted 1,4-dienes
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
173
at 25 ꢀC, and a solution of 1 (0.13 g, 1.0 mmol) in THF (2 mL),
successively. After stirring at 25 ꢀC for 2 h, the mixture was
poured into aq. hydrochloric acid (6 M, 10mL), and extracted
with hexane (3 Â 10 mL). The organic extracts were washed with
brine, and concentrated by an evaporator. Purification by column
chromatography (hexane) gave 3 in 97% yield (0.17 g).
Table 1. Addition of allylic gallium compounds to terminal
alkynesa
Dedicated to Professor Teruaki Mukaiyama on the occasion
of his 75th birthday.
References and Notes
1
For reviews, see: a) J. F. Normant and A. Alexakis, Synthesis,
1981, 841. b) P. Knochel, ‘‘Carbometallation of Alkenes and
Alkynes,’’ in ‘‘Comprehensive Organic Synthesis,’’ ed. by
B. M. Trost, Pergamon, Oxford (1991), Vol. 4, Chap. 4.4,
p 865. c) I. Marek and J. F. Normant, ‘‘Carbometallation
Reactions,’’ in ‘‘Metal-catalyzed Cross-coupling Reactions,’’
ed. by F. Diederich and P. J. Stang, Wiley-VCH, Weinheim
(1998), p 271.
2
For allylmetalation of alkynes, see: a) Al: J. A. Miller and E.
Negishi, Tetrahedron Lett., 25, 5863 (1984). b) Zn: Y.
Frangin and M. Gaudemar, Bull. Soc. Chim. Fr., 1976, 1173.
c) E. Negishi and J. A. Miller, J. Am. Chem. Soc., 105, 6761
(1983). d) G. A. Molander, J. Org. Chem., 48, 5409 (1983). e)
I. Creton, I. Marek, and J. F. Normant, Tetrahedron Lett., 36,
7451 (1995). f) B: N. Bubnov, M. S. Grigorian, A. V. Tsyban,
and B. M. Mikhailov, Synthesis, 1980, 902; Y. N. Bubnov,
A. V. Tsyban, and B. M. Mikhailov, Synthesis, 1980, 904. g)
Mg: K. Okada, K. Oshima, and K. Utimoto, J. Am. Chem.
Soc., 118, 6076 (1996). h) Ti: J. J. Eisch and M. P.
Boleslawski, J. Organomet. Chem., 334, C1 (1987). i) Zr: S.
Yamanoi, T. Imai, T. Matsumoto, and K. Suzuki, Tetrahedron
Lett., 38, 3031 (1997).
3
4
In: a) S. Araki, A. Imai, K. Shimizu, M. Yamada, A. Mori, and
Y. Butsugan, J. Org. Chem., 60, 1841 (1995). b) N. Fujiwara
and Y. Yamamoto, J. Org. Chem., 62, 2318 (1997); N.
Fujiwara and Y. Yamamoto, J. Org. Chem., 64, 4095 (1999).
c) B. Ranu and A. Majee, Chem. Commun., 1997, 1225.
M. Yamaguchi, T. Sotokawa, and M. Hirama, Chem.
Commun., 1997, 743.
are obtained selectively in all cases. In the case of crotyl bromide,
the reaction proceeded slowly, and the carbon–carbon bond was
produced at the more substituted carbon of the crotylmetal
species, which is the same tendency as for the indium case.3b,c
Such functional groups as ether and ester groups were not affected
during the allylation of alkynes.
Allylaluminum sesquibromide derived from allyl bromide
and aluminum metal under indium catalysis did not react with the
alkyne 1 at 25 ꢀC.
The geminal digallium alkene 12 could be trapped with
iodine at 25 ꢀC to give the 1,1-diiodo-1,4-alkadiene 13 in 94%
yield (eq 4).
5
6
K. Takai and Y. Ikawa, submitted for publication.
A solution of allylgallium in THF (ca. 1.35 M solution) was
prepared as follows. A catalytic amount of indium powder
(1.0mmol) was added toa mixture of allyl bromide (30mmol)
and gallium metal (shot, 20mmol) in THF (20mL), and the
mixture was stirred at 10 ꢀC for 24 h. When gallium powder
was used, all the gallium dissolved at 10 ꢀC within 2 h. The
solution of allylgallium in THF could be stored at 5 ꢀC (in a
refrigerator) for 1 month without decreasing the reactivity,
but the reactivity decreased gradually at 25 ꢀC.
7
8
Y. Han and Y.-Z. Huang, Tetrahedron Lett., 36, 7277 (1995).
M. Yamaguchi, A. Hayashi, and M. Hirama, Chem. Lett.,
1995, 1093.
9
For addition of allylmetal species to alkenylmetals, see: K.
Suzuki, T. Imai, S. Yamanoi, M. Chino, and T. Matsumoto,
Angew. Chem., Int. Ed. Engl., 36, 2469 (1997); A. Hirai, M.
Nakamura, and E. Nakamura, J. Am. Chem. Soc., 121, 8665
(1999); I. Marek, P. R. Schreiner, and J. F. Normant, Org.
Lett., 1, 929 (1999).
Typical procedure for 3 (eq 2): To a solution of allylgallium
sesquibromide in THF prepared from allyl bromide (0.36 g,
3.0mmol), gallium powder (0.14 g, 2.0mmol), and indium metal
(12 mg, 0.10 mmol),6 were added i-Pr2NEt (0.17 mL, 1.0 mmol)