-
access of ester group to the reductant BH4 ions. Keeping
this view in mind, we have introduced polar substitutions
(Table 1, entries 2-6) in the benzene ring and, as expected,
a notable (47-84%) yield increase was observed in the case
of -OH- and -NO2-substituted esters (Table 1, entries 2-4).
In contrast, a significant decrease in yield was observed for
-NHCOCH3- and -Cl-substituted esters (Table 1, entries
5 and 6), where hydrophobicity plays the dominant role. To
confirm further that the observed reduction is micelle-
mediated, n-hexyl-p-nitrobenzoate, being the highest reduc-
ible substrate, was reduced in varying concentrations of
CTAB solutions in a manner similar to that discussed for
n-hexylbenzoate. Here also, reduction was not observed in
pure aqueous or submicellar solution and maximum conver-
sion was obtained at g50 mM (see Supporting Information).
To ascertain the role of HLB on the reaction yield, further
investigations were carried out using esters containing
extended aromatic rings such as naphthalene and anthracene
(Table 1, entries 7-9). The yield (80%) was very promising
in the case of n-hexyl ester of R-naphthylacetic acid (Table
1, entry 7). In accord with the previous observation,4d,e the
high conversion might be due to the interaction between the
naphthalene π-system and the cationic headgroup. Further-
more, the presence of the n-hexyl chain probably provides
flexibility to the molecule, allowing better accessibility of
Table 2. NaBH4 Reduction of Esters (RCOOR′) in Aqueous
Micelle
a See footnote a in Table 1. b Concentration of V ) 5 mM; aqueous
solution of V was not isotropic in higher concentration. Proportionately,
concentrations of ester and NaBH4 were 0.5 and 2 mM, respectively.
-
to the easier access of BH4 ions to esters.4c-f The yields
for n-hexyl benzoate and n-hexyl o-chlorobenzoate reduction
were increased by at least 2- and 3-fold in the micelles of
the surfactants II and III, respectively, compared to that in
the CTAB system. The highest yield (92%) was obtained
using surfactant IV (Table 2, entry 5), where that hydroxyl
group at the polar head may further increase the interaction
-
the ester group to the BH4 ions. The yields were modest
for p-nitrophenyl ester of R-naphthylacetic acid and an-
thracene-9-carboxylic acid (Table 1, entries 8 and 9) possibly
due to constrained orientation of the molecules diverting the
ester group away from the interface.
-
between BH4 ions and esters presumably via hydrogen
bonding interactions.
Much attention is being given to the search for routes for
synthesizing enantiopure products because of the growing
demand for optically pure materials in chemical and phar-
maceutical industries.8 To this end, the present methodology
was adopted to reduce DL-pairs of esters (Table 2, entries 6
and 7) in aqueous chiral micelle of surfactant V (Scheme 2)
containing L-tryptophan as a polar head. The chiral interface
was found to induce a notable enantioselectivity (43% (S)
and 11% (R) ee, respectively) during the formation of
corresponding alcohols.9 This initial finding supports the
notion that the present method holds promise for future
exploitation in the area of enantioselective alcohol synthesis.
To summarize, we have developed an efficient and simple
method of reducing esters under ambient conditions using
NaBH4 at a cationic micellar surface. In addition to being
applicable for reducing simple aromatic or aliphatic ester
molecules, the present method holds promise for future use
in selective functional group reduction and stereocontrolled
alcohol synthesis.
Toward studying the scope of the present method, aliphatic
esters containing two different surfactants (Table 1, entry
10, 11) were comicellized with CTAB as a cosurfactant and
reduced by NaBH4. Significant yields (69 and 83%, respec-
tively) were obtained. The present method was also found
to be useful for reducing ester groups with excellent
functional group selectivity. For instance, selective reduction
of ester group for -NO2 and -NHCOCH3 substrates (Table
1, entries 2, 3, and 5) is not possible using lithium aluminum
hydride and also no ester reduction with NaBH4 was
observed in a simple methanol-water solvent mixture. In
accordance with the above perception, we have tried to
reduce a particular ester moiety selectively in a diester
substrate, namely, benzyl-p-nitrophenylsuccinate with vary-
ing HLB of the two ester functionalities. The reduction of
benzyl p-nitrophenyl succinate produced 71% p-nitrophenol,
while only 27% of the benzyl ester was found to be reduced,
showing 44% selectivity toward p-nitrophenyl ester.
The efficiency of the ester reduction was significantly
improved (Table 2, entries 1-5) in the aqueous cationic
micelles of three different surfactants (Scheme 2, II-IV)
containing bulkier headgroups. The increase in the size of
polar head enhances the second-order rate constants possibly
due to the greater electrostatic interaction between the
substrates and headgroups. Disruption of the hydration shell
of halide counterions by a bulkier headgroup might have led
Acknowledgment. D.P.D. and S.R. acknowledge Council
of Scientific and Industrial Research, India, for Junior
Research Fellowships, and P.K.D. is thankful to Department
of Science and Technology, Government of India, for
(8) Asymmetric Catalysis on Industrial Scale; Blaser, H. U., Schmidt,
E., Eds.; Wiley-VCH: Weinheim, 2003.
(9) Racemic 2-acetamido-3-phenylpropanol and 2-hydroxy-1-phenyle-
thanol were isolated using the CTAB micellar-assisted NaBH4 reduction
of the corresponding esters. Lithium aluminium hydride reduction of these
esters was not successful for preparing the alcohols.
(7) Menger, F. M.; Jerkunica, J. M.; Johnston, J. C. J. Am. Chem. Soc.
1978, 100, 4676.
Org. Lett., Vol. 6, No. 22, 2004
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Das, Debapratim
