Selective reduction of acid chloride with a catalytic amount of an indium compound

Article abstract of DOI:10.1016/S0040-4039(99)02016-X

Indium hydride generated from tributyltin hydride and indium trichloride was coordinated by a phosphine to reduce acid chlorides to the corresponding aldehydes selectively. This reaction was achieved by a catalytic amount of indium trichloride.

Full text of DOI:10.1016/S0040-4039(99)02016-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 113–116
Selective reduction of acid chloride with a catalytic amount of an
indium compound
Katsuyuki Inoue, Makoto Yasuda, Ikuya Shibata and Akio Baba ∗
Department of Applied Chemistry, Faculty of Engineering, Osaka University, 2-1 Yamada-Oka, Suita, Osaka 565-0871, Japan
Received 24 September 1999; revised 18 October 1999; accepted 22 October 1999
Abstract
Indium hydride generated from tributyltin hydride and indium trichloride was coordinated by a phosphine to
reduce acid chlorides to the corresponding aldehydes selectively. This reaction was achieved by a catalytic amount
of indium trichloride. © 1999 Elsevier Science Ltd. All rights reserved.
Keywords: indium; indium compounds; transmetalation; catalysis; reduction.
The low level of the ionization potential of indium metal has been successfully applied to
Barbier–Grignard-type reactions and pinacol coupling.1 Few synthetic applications of organoindium
compounds, however, have been reported compared to those of aluminum or borane compounds,
perhaps because of their instability. Transmetalation with stable organometallics, such as organotin
compounds, is a promising route to organoindium derivatives.2 We recently demonstrated the generation
of dichloroindium hydride via transmetalation between tributyltin hydride (Bu3SnH) and indium
trichloride (InCl3) which facilely promoted the reduction of carbonyl compounds and the dehalogenation
of alkyl bromides.3 No reduction of acid chlorides, however, could be promoted by the indium hydride
at all, perhaps because of its lack of nucleophilicity. For the selective reduction of acyl halides to
aldehydes, molecular hydrogen was generally used, for example, the Rosenmund reaction.4 In contrast,
few metal hydrides have achieved the selective reduction, except in cases assisted by exotic or expensive
transition metals; however, some problematical decarbonylation from the intermediate acyl–transition
metal complexes is incurred.5
If reduction by dichloroindium hydride is achieved and over-reduction of the produced aldehydes is
suppressed, then a catalytic cycle for InCl3 could be drawn as shown in Scheme 1. This is the case that
we present in this paper, where the addition of a phosphine is essential for the selective transformation
from acid chlorides to aldehydes.
Table 1 summarizes the effect of additives and solvents on the InCl3-catalyzed reduction of benzoyl
chloride (1) by Bu3SnH. Without additives, no reduction proceeded at all (entry 1), even in the presence
∗
Corresponding author. Tel: +81 6 6879 7386; fax: +81 6 6879 7387; e-mail: baba@ap.chem.eng.osaka-u.ac.jp (A. Baba)
0040-4039/00/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02016-X
tetl 15944

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Scheme 1.
Table 1
Effect of additives and solventsa
of stoichiometric InCl3 (entry 2). Additives such as acetonitrile, triphenylphosphine oxide and HMPA
showed no effect, although these additives were reported as characteristic ligands to tin hydrides for
promoting interesting chemoselective reductions.6 In all these runs, benzoyl chloride was recovered
mostly (entries 1–6). In contrast, triphenylphosphine was found to effect the reduction, furnishing
benzaldehyde (2) in 87% yield along with a small degree of over-reduction to benzyl alcohol (3) (entry
7). This over-reduction could be suppressed by using 0.2 equimolar amounts of triphenylphosphine to
increase the yield of 2 up to 97% (entry 8). A bulky phosphine such as tricyclohexylphosphine also
promoted the selective reduction (entry 13).
The choice of solvent seemed unimportant, giving a high range of yield over 85% in all solvents
(entries 8 and 10–12). Although among them THF gave the best yield (entry 12), we selected toluene as
the most acceptable solvent for a wide range of acid chlorides, because increasing the polarity of solvents
increases the reducing ability of Bu3SnH toward aldehydes. For example, in methanol, aldehydes were
facilely reduced as reported by Pereyre.7 This may be the reason why a small amount of 3 was produced
in CH2Cl2 or MeCN (entries 10 and 11). Of course, THF is a complementary solvent, particularly in the
case of only slow reduction in toluene.
A general procedure is as follows: A mixture of InCl3 (0.1 mmol) and triphenylphosphine (0.2 mmol)
in 1 mL of dry toluene was stirred for 30 min at room temperature under nitrogen. After the mixture
was cooled to −30°C, Bu3SnH (1 mmol) and acid chloride (1 mmol) were subsequently added, and the
resulting mixture was treated at −30°C for 2 h. After the amount of the unreacted acid chloride was
monitored by GLC, to the mixture were added 20 mL of ether and 20 mL of water, and extracted by ether
(20 mL×2). The organic layer was dried on anhydrous MgSO4, concentrated under reduced pressure.
The crude product was purified by column chromatography on silica gel, and eluted by hexane:ethyl
acetate (19:1).
Table 2 demonstrates the effective reduction of various acid chlorides to the corresponding aldehydes.
Neither electron-withdrawing nor -releasing substituents on aromatic acid chlorides disturbed the facile

115
Table 2
Selective reduction of acid halides to aldehydesa
formation of aldehydes (entries 4–8). It is particularly notable that reducible substituents such as cyano
and nitro ones tolerated the reduction conditions (entries 7 and 8). Primary aliphatic acid chlorides also
gave good yields even in the cases of including terminal olefine and chloride (entries 9–11). Bulky
aliphatic acid chlorides, however, gave a low range of yields (39–62%) accompanied with over-reduction
to alcohols, because considerably harsh conditions were required (entries 12–14). The minimal effect of
p-dinitrobenzene or galvinoxyl indicates that the dehalogenation proceeds via an ionic process (entries 2
and 3), although either indium hydride or tributyltin hydride has some radical characters.3,8
For investigation of the role of triphenylphosphine, after the generation of dichloroindium hydride
1
was confirmed by H NMR,9 an equimolar amount of benzoyl chloride was added. When 2 equiv.
of triphenylphosphine were added, benzaldehyde was obtained in 51% yield for 15 min at –78°C. In
contrast, no reaction took place without the phosphine. The coordination of the phosphine apparently
improves the reducing ability of the indium hydride. On the other hand, the reduction of benzaldehyde
was considerably suppressed by the addition of triphenylphosphine from 74% (without PPh3) to 53%
yield (with PPh3). Next, the competitive reduction between benzoyl chloride and benzaldehyde was
carried out with the similarly generated indium hydride, where the coordination to indium hydride was
proved to clearly promote the reduction of acid chloride over aldehyde (Scheme 2).
Scheme 2.
A plausible catalytic cycle is illustrated in Scheme 3. At first, the transmetalation between InCl3 and
Bu3SnH generates a phosphine-coordinated indium hydride. Then the nucleophilic attack of the resulting
hydride to an acyl carbon is allowed to produce an aldehyde accompanied with the regeneration of InCl3.
The coordination of the phosphine to dichloroindium hydride would play key roles in the step of the
attack to the acid chloride and in inhibition of the reduction of the produced aldehyde, because the
coordination plausibly increases the nucleophilicity of the hydride anion, and at the same time, decreases
the acidity of the indium center. Consequently, in this catalytic cycle, the coordinated indium hydride
selectively interacts with an acid chloride rather than an aldehyde. In addition, Bu3SnH could not reduce
the aldehyde under the reaction conditions.
In conclusion, we have developed a simple and efficient protocol for the transformation from acid

116
Scheme 3. Plausible catalytic cycle
chlorides to the corresponding aldehydes by Bu3SnH without the assistance of a transition metal catalyst
such as Pd(0).
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1
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