Indium-mediated highly regioselective reaction of prop-2-ynyl bromides with acyl cyanides in aqueous media: A convenient synthesis of allenic and propargylic ketones

Article abstract of DOI:10.1016/S0040-4039(01)01494-0

Indium-mediated reaction of acyl cyanides 1 with prop-2-ynyl bromides 2 in aqueous media occurs regioselectively to afford either allenic 3 or propargylic ketones 4 depending on the γ-substituent of the prop-2-ynyl bromide under the mild conditions.

Full text of DOI:10.1016/S0040-4039(01)01494-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7287–7289
Indium-mediated highly regioselective reaction of prop-2-ynyl
bromides with acyl cyanides in aqueous media: a convenient
synthesis of allenic and propargylic ketones
Byung-Woo Yoo,a,* Sung-Jae Lee,a Kwang-Hyun Choi,a Sam-Rok Keum,a Jae-Jung Ko,a
Kyung-Il Choib and Joong-Hyup Kimb
aDepartment of Chemistry, Korea University, Chochiwon, Chungnam 339-700, South Korea
bBiochemicals Research Center, Korea Institute of Science and Technology, Cheongryang, Seoul 130-650, South Korea
Received 2 July 2001; revised 6 August 2001; accepted 10 August 2001
Abstract—Indium-mediated reaction of acyl cyanides 1 with prop-2-ynyl bromides 2 in aqueous media occurs regioselectively to
afford either allenic 3 or propargylic ketones 4 depending on the g-substituent of the prop-2-ynyl bromide under the mild
conditions. © 2001 Elsevier Science Ltd. All rights reserved.
The development of organometallic-type reactions in
aqueous media is of current interest because they offer
the possibility of environmentally benign reaction con-
ditions.1 Particularly, indium-mediated reactions in
aqueous media have recently attracted considerable
attention in organic synthesis over the last decade.2
Relative to allylation, much less attention has been paid
to the reaction of carbonyl compounds with propargyl
bromide and indium. It has recently been reported that
indium-mediated propargylation and allenylation of a
variety of carbonyl compounds give either homo-
propargylic alcohols or allenic alcohols.3 However, the
indium-mediated propargylation of carboxylic acid
derivatives has not been well studied. Allenyl and
propargyl metal derivatives are of particular interest
since they equilibrate in solution in many cases.4 This
metallotropic rearrangement often results in poor
regioselection in the final organic product, because both
organometallic species can react differently with the
carbonyl compounds. Allenic and propargylic ketones
are valuable substrates for a variety of synthetic targets
in organic chemistry, but relatively few methods have
been employed for their preparation.5 Those methods
frequently result in a mixture of isomers (3 and 4) and
was thus synthetically not too useful. We have found
that acyl cyanide can act as an electrophile in the
indium-mediated propargylation or allenylation to give
the corresponding propargylic or allenic ketones in
good yields (Scheme 1). Recently, we have found that
the reaction of acyl cyanides with allyl bromides in
aqueous media was successfully carried out to afford
b,g-unsaturated ketones.6 To the best of our knowledge
the indium-mediated propargylation or allenylation has
never been applied to acyl cyanides. We now wish to
report our study on the regioselective synthesis of
allenic ketones and propargylic ketones mediated by
indium using acyl cyanide as substrate in aqueous
media. For the reaction is carried out in aqueous
O
O
Y
O
.
Br
In
+
+
Y
R
R
R
CN
H2O/THF
Y
2
3
4
1
2a Y = H
2b Y = Me
2c Y = Ph
Scheme 1.
Keywords: propargylation; allenylation; acyl cyanides; indium and compounds.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01494-0

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B.-W. Yoo et al. / Tetrahedron Letters 42 (2001) 7287–7289
We believe this will make a useful and important
addition to the existing methods and will find practical
applications in organic synthesis. Further studies to
develop other new reactions using indium in aqueous
media are currently in progress.
tetrahydrofuran solution and in the air, the procedure
is simple and convenient.7 In the reactions, substituents
such as methoxy, chloro, or bromo groups on aromatic
rings remained unaffected (entries 2, 3, 8 and 9). As one
can see from the results in Table 1, the reaction was
found to be general being applicable to aromatic,
aliphatic acyl cyanides. All the compounds obtained
showed IR, NMR and mass spectral data compatible
with the structure.8 With the parent prop-2-ynyl bro-
mide, indium-mediated coupling with aliphatic or aro-
matic acyl cyanides in aqueous media gave mainly the
allenic ketones 3 in good yields. In contrast, when the
prop-2-ynyl bromide is g-substituted, the coupling
products were exclusively the propargylic ketones 4.
For related indium-mediated reactions, regioselectivity
has been proposed to be controlled by both steric and
electronic effects.9 The organoindiums act as ambident
nucleophiles and the acetylene/allene distribution
appears to be influenced by the steric property of the
propargyl bromide. Presumably the regiochemistry
obtained in the present case is highly dependent on
Acknowledgements
This work was financially supported by Korea Institute
of Science and Technology(2E16800) and partially by
Korea University.
References
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steric hindrance and thus
a substituent in the
organoindium compounds enhances the formation of
acetylenic ketones 4.
In conclusion, we have discovered that the present
procedure provides a simple and convenient method for
the regioselective synthesis of propargylic and allenic
ketones in aqueous media under the mild conditions.
Table 1. Indium-mediated coupling of propargyl bromides
with acyl cyanides
Entry
Acyl cyanide 1
Propargyl bromides 2
Yield (%)a
R
Y
3
4
1
2
3
4
Ph
H
69
–
–
75
–
–
73
–
–
81
–
–
73
75
73
63
67
73
–
Me
Ph
H
Me
Ph
H
Me
Ph
H
Me
Ph
H
73
83
–
67
81
–
76
67
–
87
57
–
4-CH3OC6H4
2-ClC6H4
CH3(CH2)8
5
6
7
8
9
10
4-CH3C6H4
2-CH3C6H4
4-t-BuC6H4
2-BrC6H4
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H
H
H
H
–
–
–
–
4-BrC6H4
H
–
6. Yoo, B.; Choi, K.; Lee. S.; Nam, G.; Chang, K.; Kim. S.;
Kim. J. Synth. Commun. 2001, in press.
7. Representative experimental procedure: Indium metal pow-
der (137 mg, 1.20 mmol) was added to a stirred solution of
prop-2-ynyl bromides (152 mg, mmol) in water (5 mL) and
the stirring was continued for 30 min at room temperature.
Acyl cyanide (1 mmol) in THF (1 mL) was then added
dropwise. The resulting mixture was stirred at room tem-
perature for 1 h and the progress of the reaction was
monitored by TLC. The reaction was quenched with dilute
11
H
69
–
a Isolated yields.

B.-W. Yoo et al. / Tetrahedron Letters 42 (2001) 7287–7289
7289
sodium hydroxide (1N) and extracted with ethyl acetate.
Evaporation of the solvent followed by purification via
silica gel chromatography gave allenic ketone 3 (92.1 mg,
69%).
191.5, 137.9, 133.2, 129.1, 128.8, 93.7, 79.7; GC–MS m/z:
144 (M+). Compound 2b (1-phenylpent-3-yn-1-one): 1H
NMR (300 MHz, CDCl3): l 7.74 (d, 2H, J=8.4 Hz), 7.47
(m, 1H), 7.38 (m, 2H), 5.02 (s, 2H), 2.01 (s, 3H); 13C NMR
(75 MHz, CDCl3): l 217.4, 138.1, 131.9, 129.0, 127.7,
101.9, 78.3, 29.7, 14.7; GC–MS m/z: 158 (M+).
8. Typical physical data of representative compounds. Entry
1 in Table 1: Compound 2a (1-phenylbuta-2,3-dien-1-one):
1H NMR (300 MHz, CDCl3): l 7.90 (d, 2H, J=7.4 Hz),
7.54 (br t, 2H), 7.43 (m, 1H), 6.44 (t, 1H, J=6.5 Hz), 5.26
(d, 1H, J=6.5 Hz); 13C NMR (75 MHz, CDCl3): l 217.5,
9. (a) Isaac, M. B.; Chan, T. H. J. Chem. Soc., Chem.
Commun. 1995, 1003; (b) Yi, X.-H.; Meng, Y.; Hua,
X.-G.; Li, C.-J. J. Org. Chem. 1998, 63, 7472.