An extremely simple, convenient and mild one-pot reduction of carboxylic acids to alcohols using 3,4,5-trifluorophenylboronic acid and sodium borohydride

Article abstract of DOI:10.1016/S0040-4039(03)00035-2

Acyloxyboron intermediates formed in situ from carboxylic acids and 3,4,5-trifluorophenylboronic acids react with sodium borohydride in THF to give alcohols in good to high yields.

Full text of DOI:10.1016/S0040-4039(03)00035-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3427–3428
An extremely simple, convenient and mild one-pot reduction of
carboxylic acids to alcohols using 3,4,5-trifluorophenylboronic
acid and sodium borohydride
R. H. Tale,* K. M. Patil and S. E. Dapurkar
School of Chemical Sciences, S. R. T. M. University, Nanded-431 606 Maharastra, India
Received 12 November 2002; revised 16 December 2002; accepted 20 December 2002
Abstract—Acyloxyboron intermediates formed in situ from carboxylic acids and 3,4,5-trifluorophenylboronic acids react with
sodium borohydride in THF to give alcohols in good to high yields. © 2003 Elsevier Science Ltd. All rights reserved.
7
–10
The reduction of carboxylic acids to alcohols is a key
into an activated derivative such as mixed anhydrides
(carboxylic carbonic anhydrides), carboxyl methyl eni-
1
synthetic transformation in organic chemistry. There
2
11
are several ways to bring about this transformation.
minium chlorides,
hydroxybenzotriazolyl (HOBt)
12
13
These include lithium aluminium hydride, borane and
modified sodium borohydride. These methods, however
suffer from the limitations such as the need for anhy-
drous solvents, hazards in handling the reagents, and
incompatibility with other functionalities in the sub-
strate. There have also been some reports on the use of
sodium borohydride in combination with chloro-
esters and cyanurates, which can then be reduced
with a mild reducing agent like sodium borohydride.
Although these procedures often result in good yields
of product, they can involve the use of hazardous and
expensive reagents.
In view of the great utility of the transformation of
carboxylic acids into alcohols, an alternative route to
1
3
4
5
trimethylsilane, nickel chloride-diglyme, iodine, and
6
bring about this transformation is desirable. In continu-
ation of our interest in the catalytic applications of
arylboronic acids, in particular 3,4,5-trifluorophenyl-
catechol, for the direct conversion of carboxylic acids
to the corresponding alcohols.
1
4
boronic acid 1 for organic transformations,
we
In order to achieve functional group compatibility, an
alternative approach is to transform the carboxylic acid
describe here another remarkable catalytic activity of
boronic acid 1, in this case, for the one-pot reduction of
carboxylic acids to alcohols using sodium borohydride
(
Scheme 1).
The reaction is thought to proceed via a six-membered
cyclic acyloxyboron intermediate (Scheme 2).
Scheme 1.
Scheme 2. Ar=3,4,5-trifluorophenyl.
Keywords: carboxylic acid; 3,4,5-trifluorophenylboronic acid; acyloxyboron intermediates; reduction.
*
Corresponding author. Fax: +91-2462-29245; e-mail: rkht2002@yahoo.com
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00035-2

3
428
R. H. Tale et al. / Tetrahedron Letters 44 (2003) 3427–3428
Table 1. Reduction of carboxylic acids with NaBH and
General procedure:
4
boronic acid 1
To a solution of carboxylic acid (2 mmol) and
sodium borohydride (95 mg, 2.5 mmol) in THF (10
ml) was added Na SO (1 g) and boronic acid 1 (1
Entry
Carboxylic acids
Yield of alcohola,b (%)
2
4
1
2
3
4
5
6
7
8
9
R=CH (CH ) -
90
80
90
89
85
87
89
85
78
94
99
82
3
2 7
mol%) and the mixture was stirred at room tempera-
ture for 10 h (evolution of gas was observed). After
completion of the reaction (TLC), the mixture was
filtered, the solvent was evaporated and the residue
was taken up in diethyl ether (50 ml), washed with
saturated NaHCO3 (3×10 ml) and brine (10 ml).
After drying over anhydrous Na SO , the ether was
R=Br(CH ) -
2
3
R=PhCH2-
R=Ph-
R=N (CH )
3
2 4-
R=p-ClC H -
6
4
R=p-NCC H -
6
4
R=p-HOC H -
6
4
2
4
R=p-O NC H -
2
6
4
evaporated to give the product. The product was
purified by column chromatography (silica gel, ethyl
acetate: petroleum ether, 1:9).
10
11
12
R=3,4,5-(MeO) C H -
3 6 2
R=2,4-(MeO) C H -
2
6
3
R=Cbz-Pro-OH
a
Yields refer to the pure isolated product.
b
Acknowledgements
Products were characterized by their physical constants, spectro-
scopic data (IR, 1H NMR) and elemental microanalyses.
S. E. Dapurkar thanks the Ministry of HRD (India)
for a research fellowship.
The treatment of various structurally diverse car-
boxylic acids with sodium borohydride in the pres-
ence of a catalytic amount of boronic acid 1 in THF
at room temperature resulted in the formation of the
corresponding alcohols in good to high yields. The
results are summarized in Table 1. As shown in Table
References
1
2
3
4
5
6
7
8
. Katsuki, T.; Martin, V. S. Org. React. John Wiley and
Sons, New York, 1996, 48, 1.
. Larock, R. C. Comprehensive Organic Transformations;
VCH: New York, 1989; p. 548.
. Ginnis, A.; Sandhoff, K. Angew. Chem., Int. Ed. Engl.
989, 28, 218.
. Khan, R. H.; Rastogi, R. C. Ind. J. Chem., Sect. B 1993,
2, 898.
. Bhaskar Kant, J. V.; Periasamy, M. J. Org. Chem. 1991,
6, 5964.
. Suseela, Y.; Periasamy, M. Tetrahedron Lett. 1992, 48,
71.
. Bandgar, B. P.; Modhave, R. K.; Wadgaonkar, P. P.;
Sande, A. R. J. Chem. Soc., Perkin Trans. 1 1996, 1993.
. Rodriguez, M.; Llinareo, M.; Doulet, S.; Heitz, A.; Mar-
tinez, J. Tetrahedron Lett. 1991, 32, 923.
9. Soai, K.; Yokoyama, S.; Mochinda, K. Synthesis 1987,
647.
10. Kokotas, G. Synthesis 1990, 299.
11. Fujisawa, T.; Mon, T.; Sato, T. Chem. Lett. 1983, 835.
12. McGory, R. P. Tetrahedron Lett. 1998, 39, 3319.
13. Falorni, M.; Porcheddu, A.; Teddei, M. Tetrahedron
Lett. 1999, 40, 4395.
1
, carboxylic acids bearing functionalities such as
halogeno, cyano, hydroxy, nitro, and even azido, else-
where in the molecule, underwent smooth reduction
by this method. Interestingly, an N-protected amino
acid (entry 12) was successfully transformed into the
corresponding N-protected amino alcohol under the
reaction conditions, in 82% isolated yield. Therefore
this procedure is expected to be suitable for other
protected amino acids.
1
3
5
3
It is important to note that boronic acids RB(OH)2,
are usually crystalline solids, stable to air and mois-
ture. Such evidence as exists indicates that they are of
15
relatively low toxicity and environmental impact.
Furthermore, a very small amount of boronic acid 1
was found to be an effective catalyst for the reduc-
tion of carboxylic acids to alcohols. Thus it is evident
that this method is quite safe and inexpensive, in con-
trast to other reported methods such as those involv-
1
2
ing the expensive BOP reagent and the hazardous
1
3
cyanuric chloride.
14. Tale, R. H.; Patil, K. M. Tetrahedron Lett. 2002, 43,
9
715.
In conclusion, we have developed a mild, simple, gen-
eral and relatively benign protocol for the one-pot
reduction of carboxylic acids to the corresponding
alcohols.
15. Boron, Metallo-Boron Compounds and Boranes; Adams,
R. M., Ed.; Wiley: New York, 1964; p. 693: data quoted
in Registry of Toxic Effect of Chemical Substances,
NIOSH, 2002.