Novel and facile selective reduction of carboxylic acid with a samarium diiodide-lanthanide triflate-methanol-base system

Article abstract of DOI:10.1016/S0040-4039(99)02051-1

The facile selective reduction of carboxylic acids in the presence of an aldehyde or that bearing a formyl group proceeded smoothly with a samarium diiodide-lanthanide triflate-methanol-base system at room temperature to give the corresponding alcohols in good to almost quantitative yield.

Full text of DOI:10.1016/S0040-4039(99)02051-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 341–344
Novel and facile selective reduction of carboxylic acid with a
samarium diiodide–lanthanide triflate–methanol–base system
∗
Yasuko Kamochi and Tadahiro Kudo
Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815, Japan
Received 24 August 1999; revised 27 October 1999; accepted 29 October 1999
Abstract
The facile selective reduction of carboxylic acids in the presence of an aldehyde or that bearing a formyl group
proceeded smoothly with a samarium diiodide–lanthanide triflate–methanol–base system at room temperature to
give the corresponding alcohols in good to almost quantitative yield. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: selective reduction; samarium diiodide; lanthanide triflates; carboxylic acids; aldehydes; additives.
The selective reduction of carboxylic acid bearing other functional groups sensitive to ordinary
reducing agents is a topic of much interest in synthetic chemistry. There is no efficient method for the
direct selective reduction of carboxylic acid in the presence of an aldehyde or that bearing a formyl group.
Generally, this transformation necessitates a three-step process of protection of the aldehyde moiety,
reduction of carboxylic acid and, finally, liberation of the aldehyde moiety. Taking into account the
utility of direct selective reduction of carboxylic acid in the presence of an aldehyde or that bearing a
formyl group to alcohol, the development of a facile selective reduction method has been desirable from
a synthetic viewpoint.
We reported previously that the electron transfer from samarium diiodide (SmI ) was highly promoted
2
1
in the presence of an additive, and carboxylic acids were reduced smoothly with this system. In general,
the direct selective reduction of carboxylic acid incurs certain difficulties in the co-existence of an
aldehyde. However, it can be assumed that it is possible to perform the selective reduction of carboxylic
acid in the co-existence of aldehyde with SmI if acetalization of the aldehyde takes place immediately
2
under the reduction conditions of carboxylic acid. Consequently, the present paper deals with a new
selective reduction of carboxylic acid with a SmI –samarium triflate (Sm(OTf) )–MeOH–base system as
2
3
the following method.
Our first trial was conducted with the acetalization of aldehydes in MeOH solution with lanthanide
2
triflate (Ln(OTf) ) having the strong ability as a Lewis acid in the presence of water. The acetalization
3
of aldehydes proceeded rapidly with Ln(OTf) within five minutes at room temperature in almost
3
∗
Corresponding author. Tel: +81 92 541 0161; e-mail: kamochi@daiichi-cps.ac.jp (Y. Kamochi)
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02051-1
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quantitative yield, and the esterification of carboxylic acid could have occurred only to an extent of
1
% under similar conditions. The results of acetalization are tabulated in the References.3
Our next trial was conducted with the reaction of aldehyde and carboxylic acid with a
SmI –Sm(OTf) –MeOH–base system. As shown in Table 1, cyclohexanecarboxaldehyde was reduced
2
3
with SmI in THF–MeOH at room temperature in quantitative yield (entry 2). However, the reduction did
2
not entirely proceed under similar conditions adding Sm(OTf) or with a SmI –Sm(OTf) –MeOH–base
3
2
3
system, and all of the aldehyde was recovered (entries 1 and 3). On the contrary, adding a MeOH
solution of aldehyde into a THF solution of SmI and Sm(OTf) , the aldehyde was reduced rapidly in
2
3
almost quantitative yield (entry 4). These results showed that the acetalization occurred immediately
with the Sm(OTf) under the tested conditions. Contrary to these results, cyclohexanecarboxylic acid
3
was reduced rapidly with the SmI –Sm(OTf) –MeOH–base system (entry 6). Moreover, in the reduction
2
3
of carboxylic acid with SmI –Sm(OTf) –MeOH–base system, it can therefore be presumed that the
2
3
reduction preferentially proceeded over acetalization of the aldehyde which is anticipated as a reduction
intermediate.
Table 1
Reduction
of
cyclohexanecarboxaldehyde
and
cyclohexanecarboxylic
acid
with
SmI –Sm(OTf)
2
3
–MeOH–base systema
These results demonstrate that this system provides the possibility to selectively reduce carboxylic
acids in the co-existence of an aldehyde or that bearing a formyl group. Therefore, we investigated the
selective reduction of carboxylic acid in the following manner.
The reactions were carried out as follows: The aldehydes (0.5 mmol) and the carboxylic acids (0.5
mmol) were dissolved in methanol solution (5 ml) of Sm(OTf) (0.2 mmol) and the solution was kept
3
at room temperature for five minutes. The solution was added with a syringe pump to SmI (0.1 M in
2
THF, 2 mmol) and 20% KOH (2 ml) or H O (1 ml) was immediately added with a syringe pump with
2
stirring under an atmosphere of argon at room temperature. After the typical deep purple color of SmI2
disappeared and then removal of the solvent under reduced pressure, the residue was quenched with 10%
HCl (10 ml) during five minutes following usual work-up.
Irrespective of the presence of an aldehyde, only aliphatic carboxylic acids were reduced selectively to
alcohols within a few minutes at room temperature in good to almost quantitative yield as shown in Table
2
(entries 1–7). α,β-Unsaturated carboxylic acid was reduced with this system using 6 equiv. mol of
2
SmI to give saturated alcohol in excellent yield (entry 9). Similarly, the selective reduction of aromatic
carboxylic acids in the presence of an aldehyde or that bearing a formyl group, except for toluic acids

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Table 2
Selective reduction of carboxylic acids in the presence of an aldehyde or that bearing a formyl group
2 3 2
with the SmI –Sm(OTf) –MeOH–base or H
O system in THFa

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(entries 11 and 13), proceeded easily even by a similar system using water instead of KOH under mild
conditions (entries 10 and 15–19). In addition, aldehydes were mostly unaffected by this system under
the tested conditions.
In this method, though the actual reductant and the detailed mechanism of these selective reductions
have not been clarified at the present stage, it has been surmised that the rapid acetalization of aldehyde
proceeded with Sm(OTf) –MeOH at first. Subsequently, the reducing ability of SmI can greatly be
3
2
2+
enhanced by the addition of an additive (KOH, MeOH and H O) to Sm and the reduction of carboxylic
2
acids has been facilitated by this system leading to alcohol.
Little work has been reported so far on the selective one-pot reduction of carboxylic acid in the
presence of an aldehyde or that bearing a formyl group. As mentioned above, it can be presumed that the
new SmI –Sm(OTf) –MeOH–base/H O system provides a useful and convenient method in synthetic
2
3
2
chemistry for the selective one-pot reduction of carboxylic acid bearing a formyl group under mild
conditions.
References
1
2
3
. See for review and references cited therein: Kamochi, Y.; Kudo, T. J. Syn. Org. Chem. Jpn. 1994, 52, 45. Idem Rev.
Heteroatom Chem. 1994, 11, 165. Idem Chem. Lett. 1991, 893. Idem Tetrahedron Lett. 1991, 32, 3511. Idem Tetrahedron
1
992, 48, 4301.
. It has been reported that lanthanide triflates are found to be stable in aqueous solution and can act as strong Lewis acid
catalysts. Kobayashi, S. Chem. Lett. 1991, 2187. Kobayashi, S.; Hachiya, I. Tetrahedron Lett. 1992, 33, 1625. Idem J. Org.
Chem. 1994, 59, 3590.
. Luche et al. reported that lanthanide chlorides are efficient catalysts for the acetalization of aldehydes in the presence of
4
trimethyl orthoformate as a water scavenger and also the lanthanide chloride–methanol–sodium borohydride system is used
5
for selective reduction of ketones in the presence of aldehyde. Furthermore, Fukuzawa et al. achieved the chiral acetalization
3
of carbonyl compounds catalyzed by Ln(OTf) . However, these acetalizations necessitated long reaction time for 13 hours–2
6
days until completion of the reactions. We tested the rapid acetalization of aldehydes in MeOH solution with lanthanide
triflates having the strong ability as a Lewis acid in the absence of a water scavenger as shown in Table 3.
Table 3
Acetalization and esterification with lanthanide triflate
4
5
. Luche, J. L.; Gemal, A. L. J. Chem. Soc., Chem. Commun. 1978, 976.
. Gemal, A. L.; Luche, J. L. Tetrahedron Lett. 1981, 22, 4077. Idem J. Am. Chem. Soc. 1979, 101, 5848. Idem J. Org. Chem.
1
979, 23, 4187.
6. Fukuzawa, S.; Tsuchimoto, T.; Hotaka, T.; Hiyama, T. Synlett 1995, 1077.