Indium-mediated formation of propargyl ketones from aldehydes or acyl chlorides

Article abstract of DOI:10.1016/S0040-4039(02)02635-7

Propargyl ketones were prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They were also obtained via an indium-mediated alkynylation of the relevant acyl chlorides.

Full text of DOI:10.1016/S0040-4039(02)02635-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 819–821
Indium-mediated formation of propargyl ketones from aldehydes
or acyl chlorides
Jacques Aug e´ ,* Nad e` ge Lubin-Germain and Latifa Seghrouchni
UMR 8123 CNRS-UCP-ESCOM, 5 mail Gay-Lussac, Neuville sur Oise, 95031 Cergy-Pontoise, France
Received 19 November 2002; accepted 20 November 2002
Abstract—Propargyl ketones were prepared from aldehydes via an indium-mediated alkynylation reaction followed by an
indium-mediated Oppenauer oxidation. They were also obtained via an indium-mediated alkynylation of the relevant acyl
chlorides. © 2003 Elsevier Science Ltd. All rights reserved.
Barbier-type indium-mediated reactions have become
popular in the alkylation of carbonyl compounds with1
allylic bromides or iodides, especially in water media.
The reaction was applied to propargylic and a-carbonyl
benzaldehyde with respect to this stoichiometric ratio
gave the best results (Table 1).
In a typical experiment, indium powder (172 mg, 1.5
mmol) was placed in a Schlenk tube under argon,
followed by the addition of dichloroethane (6 mL) and
phenylalkynyl iodide (228 mg, 1 mmol) and then benz-
aldehyde (244 mg, 2.3 mmol). The heterogeneous mix-
ture was stirred at reflux during 6 h. The reaction was
quenched by addition of a sodium bicarbonate aqueous
solution. The product was extracted with ether, washed
1
halides. Recently we reported that alkynyl iodides
could be reduced by indium to react with aldehydes and
ketones to produce propargylic alcohols in good
2
yields. Propargyl ketones were observed as by-prod-
ucts in the alkynylation of aldehydes; we suggested that
an Oppenauer-type oxidation of the indium(III) alkox2-
ide intermediate was responsible for this behaviour.
This oxidation step might be formally explained by a
b-elimination reaction and therefore might be facili-
tated by heating. Thus we chose to perform the reaction
at 80°C at the reflux of dichloroethane rather than at
with brine, dried with anhydrous MgSO , concentrated
4
under reduced pressure, and separated with silica gel
chromatography using a mixture of cyclohexane and
ethyl acetate as the eluent, affording 1,3-diphenylpropy-
none in 86% yield.
4
0°C at the reflux of dichloromethane as previously
2
described for the formation of propargyl alcohols.
The reaction was tested with various aldehydes (Scheme
2
) under the same conditions and with another alkynyl
iodide (Table 2). The yields were good for aromatic or
hindered aldehydes (Table 2, runs 1–4, 6, 8–9); for
straight aldehydes and for aldehydes with an a-acidic
proton (Table 2, runs 5 and 7) the alkynylation step
occurred but the following Oppenauer oxidation failed.
This was probably due to an aldol condensation since
dichloroethane at 80°C (Scheme 1). In these conditions
the benzylic alcohol 3 was observed along with the
alkynyl ketone 2. The small excess of 3 compared to 2
could arise from a direct reduction of benzaldehyde.
The stoichiometric ratio between benzaldehyde and
phenylalkynyl iodide is equal to 2; a small excess of
Scheme 1.
Keywords: indium; propargyl ketone; alkynylation; Barbier reaction; Oppenauer oxidation.
*
Corresponding author. Tel.: 33 134257051; fax: 33 134257067; e-mail: jacques.auge@chim.u-cergy.fr
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02635-7

8
20
J. Aug e´ et al. / Tetrahedron Letters 44 (2003) 819–821
Table 1. Indium-mediated alkynylation of phenylalkynyl iodide with benzaldehyde
PhCHO (equiv.)
In (equiv.)
Time (h)
Yield of 2 (%)
Ratio 2/1
Ratio 2/3
1
2
3
2
.2
.2
1.2
1.2
1.2
1.5
7
9
9
6
41
73
77
86
67/33
83/17
90/10
99/1
45/55
37/63
47/53
47/53
.3
Since linear aliphatic aldehydes failed to lead to the
corresponding propargyl ketones, we investigated the
straightforward alkynylation of acyl chlorides mediated
by indium (Scheme 4). Acyl chlorides were formerly
used as electrophiles in indium-mediated allylation
5
Scheme 2.
leading to homoallylic ketones in good yields.
Table 2. Indium-mediated preparation of propargyl
Thus, in a typical experiment indium powder (138 mg,
1.2 mmol) was placed in a Schlenk tube under argon,
followed by the addition of dichloromethane (6 mL),
phenylalkynyl iodide (228 mg, 1 mmol) and then
decanoyl chloride (210 mg, 1.1 mmol). The uncoloured
mixture became dark red within 2 min and was stirred
at room temperature during 1 h. The reaction was
quenched by addition of a sodium bicarbonate aqueous
solution. The product was extracted with ether, washed
ketones from aldehydes
Run Aldehyde R
Alkynyl
Time (h)
Yield (%)
iodide R%
1
2
3
4
5
6
7
8
9
Ph
CF C H
CH C H
4
Anthracenyl
CH (CH )
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
n-Bu
6
3
4.5
6
8
8
9
5
6
86
83
62
61
–
84
–
93
70
3
6
4
3
6
with brine, dried with anhydrous MgSO , concentrated
4
3
2 6
under reduced pressure, and separated with silica gel
chromatography using a mixture of cyclohexane and
ethyl acetate as the eluent, affording 205 mg of 1-
phenyldodec-1-yn-3-one (80% yield).
C H
6
11
PhCH(CH3)
(CH3)3
Ph
The reaction was applied to various acyl chlorides
giving rise to the corresponding propargyl ketones in
good yields (Table 3).
such a side-reaction has been frequently observed dur-
ing Oppenauer oxidation.
3
The mechanism of the reaction of propargyl ketone
formation lies on the indium secondary alkoxide tran-
sient formation during the alkynylation step (Scheme
In summary, aromatic and hindered aldehydes were
easily transformed into propargyl ketones by an
indium-mediated alkynylation followed by an indium-
mediated Oppenauer oxidation. Propargylic ketones
could also be obtained by a straightforward alkynyla-
tion of acyl chlorides mediated by indium. All the
reactions were performed in chlorinated solvents which
are rather unusual in Barbier-type reactions. These
3
). This secondary alkoxide is easily oxidable giving rise
to a propargylic ketone which cannot react with a
second propargylic indium species as an unsaturated
ketone. Side-reactions might be the aldolisation of the
2
enolisable propargylic ketones or aldehydes (Scheme 3).
A similar mechanism was recently described to explain
the formation of allyl ketones via Hiyama–Nozaki reac-
tions followed by a chromium-mediated Oppenauer
oxidation but the tandem reaction was limited to aro-
4
matic aldehydes, which are not enolisable.
Scheme 4.
Table 3. Indium-mediated preparation of propargyl
ketones from acyl chlorides
R
R%
Time (h)
Yield (%)
C H
Ph
Ph
Ph
Ph
Ph
Ph
n-Bu
1
1
1
0.5
3.5
1
80
78
82
54
50
73
55
9
18
15
C H
7
(
CH ) C
3
3
CH3
Ph
ClC H
6
4
(
CH ) C
2.5
3
3
Scheme 3.

J. Aug e´ et al. / Tetrahedron Letters 44 (2003) 819–821
821
non-coordinating solvents allowed us to increase the
reactivity of the organoindium species involved in the
process.
2. Aug e´ , J.; Lubin-Germain, N.; Seghrouchni, L. Tetrahedron
Lett. 2002, 43, 5255–5256.
3. De Graauw, C. F.; Peters, J. A.; van Bekkum, H.;
Huskens, J. Synthesis 1994, 1007–1017.
4
. Schrekker, H. S.; de Bolster, M. W. G.; Orru, R. V. A.;
Wessjohann, L. A. J. Org. Chem. 2002, 67, 1975–1981.
. Yadav, J. S.; Srinivas, D.; Reddy, G. S.; Bindu, K. H.
Tetrahedron Lett. 1997, 38, 8745–8748.
References
5
1
. Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149–11176.