Indium-mediated carbonyl alkynylation

Article abstract of DOI:10.1016/S0040-4039(02)01052-3

Indium mediates a Barbier-type reaction between alkynyl halides and aldehydes or ketones to give secondary or tertiary propargyl alcohols. Secondary alcohols can be oxidised in situ according an Oppenauer process.

Full text of DOI:10.1016/S0040-4039(02)01052-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5255–5256
Indium-mediated carbonyl alkynylation
Jacques Auge´,* Nade`ge Lubin-Germain and Latifa Seghrouchni
Unite´ Mixte de Recherche CNRS-UCP-ESCOM ꢀSynthe`se Organique Se´lective et Chimie Organome´talliqueꢁ,
5 mail Gay-Lussac, Neuville-sur-Oise, 95031 Cergy-Pontoise, France
Received 3 May 2002; accepted 2 June 2002
Abstract—Indium mediates a Barbier-type reaction between alkynyl halides and aldehydes or ketones to give secondary or tertiary
propargyl alcohols. Secondary alcohols can be oxidised in situ according an Oppenauer process. © 2002 Elsevier Science Ltd. All
rights reserved.
Barbier-type carbonyl alkylation mediated by indium is
We have then formulated the hypothesis that the
ketone 2 came from the Oppenauer oxidation of the
transient indium alkoxide (corresponding to the alcohol
1) with the subsequent reduction of benzaldehyde into
benzylic alcohol. Such an oxidation during an alkynyla-
tion process was formally mentioned with vanadium
acetylides.4 The results presented in Table 1 confirmed
this hypothesis. The increase of the molar amount of
benzaldehyde allowed us to force the Oppenauer oxida-
tion, whereas an excess of phenylalkynyl iodide pre-
vented the oxidation (Table 1).
a
well-known reaction involving generally allylic,
propargylic or a-carbonyl halides.1 We report herein
Barbier-type reactions of alkynyl iodides with alde-
hydes or ketones mediated by indium powder (Scheme
1).
Relevant Barbier reactions were already described with
chromium chloride in DMF2 or samarium iodide in the
presence of hexamethylphosphoric triamide.3 Since
indium is tolerant of water, we investigated first the
reaction with aqueous solvents. In each case a reduc-
tion of the phenylalkynyl iodide used as the model was
obtained, which prompted us to study the reaction in
conventional organic solvents. The best yields were
obtained with dichloromethane at reflux but a mixture
of the propargyl alcohol 1 and the ketone 2 was
observed (Scheme 2).
In a typical experiment to produce exclusively propar-
gylic alcohol, indium powder (138 mg, 1.2 mmol) was
placed in a Schlenk tube under argon, followed by the
addition of dichloromethane (6 mL) and phenylalkenyl
iodide (228 mg, 1 mmol) and then benzaldehyde (53
mg, 0.5 mmol). The heterogeneous mixture was stirred
at reflux for 24 h. The reaction was quenched with a
sodium bicarbonate aqueous solution. The product was
extracted with ether, washed with brine, dried with
anhydrous Mg2SO4, concentrated under reduced pres-
sure, and separated with silica gel chromatography
using a mixture of cyclohexane and ethyl acetate as the
eluent, affording 1,3-diphenylprop-2-ynol in 83% yield.
OH
R1
R2
H2O
In
R1
R2
+
O
R
I
R
CH2Cl2
Scheme 1.
OH
O
Ph
H2O
In
CH2Cl2
+
+
Ph
Ph
I
O
Ph
H
Ph
Ph
1
2
Scheme 2.
Keywords: indium; alkynylation; propargyl alcohol; Barbier reaction; Oppenauer oxidation.
* Corresponding author. Tel.: 33 134257051; fax: 33 134257067; e-mail: jacques.auge@chim.u-cergy.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01052-3

5256
J. Auge´ et al. / Tetrahedron Letters 43 (2002) 5255–5256
Table 1. Indium-mediated alkynylation of phenylalkynyl iodide with benzaldehyde
Iodide (equiv.)
PhCHO (equiv.)
In (equiv.)
Time (h)
Yield of 1 (%)
Yield of 2 (%)
1
1
1
2
2
1.2
2
3
1
1
1.2
1.2
1.2
1.2
2.4
24
24
48
24
24
42
35
38
65
44
Trace
Trace
70
83
Table 2. Indium-mediated alkynylation of alkynyl iodide with carbonyl compoundsa
Run
Alkynyl iodide R
Carbonyl compound R1, R2
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph, H
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
7
83
87
90
70
78
25
0
CH3(CH2)6, H
CH3(CH2)2, H
C6H4-pCH3, H
C6H4-pCF3, H
C6H4-pNMe2, H
Naphtyl, H
Anthryl, H
PhCH(CH3), H
Tbu
0
9
89b
96
99
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
C6H11, H
PhCHꢀCH, H
CH3CHꢀCH, H
-(CH2)5-
0
94
85
89
72
0
33
83
90
26
97
-(CH2)4-
CH3CH2, CH3CH2
(CH3)2CH, (CH3)2CH
Ph, Ph
Ph, CH3
Ph, H
C6H11, H
Ph, CH3
-(CH2)5-
Ph
Ph
Ph
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
CH3(CH2)3
7
24
11
a Alkynyl iodide (2 equiv.), In (2.4 equiv. with aldehyde, 1.8 equiv. with ketone), reflux of dichloromethane.
b diastereomeric excess: 30%.
The reaction was tested with various aldehydes under the
H2O
In
same conditions (Table 2, runs 1–13) and with another
alkynyl iodide (Table 2, runs 20–23). The yield in
propargylic alcohol was generally high except for unsat-
urated aldehydes. In the case of anthraldehyde (run 8),
we detected the formation of the oxidation product (20%)
of the expected propargylic alcohol. For such an aldehyde
the Oppenauer oxidation was certainly more rapid than
the preceding alkynylation; this is probably due to the
p-stacking ofthe reactants facilitating thehydride transfer
between them.
Ph
Ph
I
CH2Cl2
Ph
3
Scheme 3.
bonꢁcarbon bonds which is reminiscent of a relevant
reaction with allyl- and benzylindium reagents.5
References
The alkynylation reaction of ketones was generally slower
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alkynyl iodide was necessary to get a good yield; 2 equiv.
of alkynyl iodide was therefore engaged in the reaction
which proceeded nicely except with aromatic ketones for
the previously invoked reason (Table 2). The formation
of the enyne 3, which was independently achieved with
indium and phenylalkenyl iodide in dichloromethane at
reflux (Scheme 3), is due to a carboindation of car-
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