An effective hydrolysis of crowded chiral esters

Article abstract of DOI:10.1055/s-2002-34873

Trifluoromethanesulfonic acid-coated silica in the absence of solvents is an effective reagent for hydrolysis of sterically crowded chiral esters giving chiral acids in good chemical and optical yield. On the other hand, the method was unsuitable for the

Full text of DOI:10.1055/s-2002-34873

1886
LETTER
An Effective Hydrolysis of Crowded Chiral Esters
Effective
H
a
ydrolysis
nof Crowded ChiralVEsters ávra, Ludvík Streinz,* Petr Vodi ka, Miloš Bud ínský, Bohumír Koutek
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
E-mail: streinz@uochb.cas.cz
Received 12 July 2002
Reduction,9 oxidation10 and many other methods also
Abstract: Trifluoromethanesulfonic acid-coated silica in the ab-
demonstrate the versatility of this technique.
sence of solvents is an effective reagent for hydrolysis of sterically
crowded chiral esters giving chiral acids in good chemical and
optical yield. On the other hand, the method was unsuitable for
the separation of optically pure alcohols from chiral esters because
dehydration usually takes place during the reaction course.
Key words: silica, hydrolysis, chiral, catalysis, trifluoromethane-
sulfonic acid
We had occasion to prepare pure (R)- and (S)-(1-naph-
thyl)phenylacetic acids (1). The most convenient way to
obtain 1 (Figure 1) seemed to be hydrolysis of ester 1a af-
ter separation of the diastereomers by crystallization.
However, all attempts to hydrolyze 1a or to use the other
currently used methods of C-O bond fission failed due to
the steric problems since the reaction was slow and, con-
sequently, it was accompanied by racemization or acid/es-
ter decomposition. For instance, 1a resisted alkaline
hydrolysis1 for three days giving racemic 1 in a negligible
yield, while in acidic media2 no hydrolysis took place
at all. Similarly, reaction with trimethylsilyl iodide3 or
t-BuOK4 did not afford any product. Alkaline hydrolysis
with phase-transfer catalysis5 or in a water-tetrahydrofu-
ran-lithium hydroxide system,6 both reported as giving ac-
ids without racemization, also failed. A synthetic route to
the desired product, reduction of 1a with lithiumalumini-
um hydride and subsequent oxidation led to the racemic
acid 1 in low yield. However, we noted that 1a did not
change its optical rotation when refluxed in diluted sulfu-
ric acid for several days, indicating high optical stability
in acidic medium. Since base could not be used, acid hy-
drolysis appeared to be the only simple way to obtain the
desired product.
Figure 1
Here we report successful hydrolysis of crowded chiral
esters using trifluoromethanesulfonic acid-modified silica
as a hydrolysis-mediating reagent. Model studies for this
novel reagent were carried out with several compounds
derived from optically pure acids.
Table 1 Composition of the Prepared Esters, Reaction Time and the
Yield of their Hydrolysis
Ester
Composition
Acid
Reaction Timea
[min]
Yieldb
[%]
Alcohol
1a
2a
3a
1b
1c
1d
1e
1
2
3
1
1
1
1
a
a
a
b
c
12
3
76
86
48
61
53
0c
Methanesulfonic acid in methylene chloride has already
been proposed as a possible medium for ester hydrolysis
because its pKa is about equivalent to that of mineral ac-
ids.7 On the other hand, its trifluoromethyl analog has a
higher pKa and its efficiency might be increased even by
further activation, e.g., on a silica surface. Similar tech-
niques are widely used and a variety of reagents non-
bonded chemically to the silica surface have been pub-
lished as potent catalysts. For instance, fission of the
C–O–C bond, dehydration of alcohols as well as acetal-
ization of aldehydes and ketones is well documented.8
30
5
3
d
e
270
30
56
a Reaction time was estimated from at least three repeated experi-
ments at 125 °C when the ester disappeared from the reaction mixture
(TLC).
b Overall yield including the hydrolysis with subsequent re-esterifica-
tion with (–)-menthol.
c No acid detected, dodecan-1-ol obtained instead (86%).
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1886,1888,ftx,en;G19602ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Effective Hydrolysis of Crowded Chiral Esters
1887
ester), the solid was transferred to the top of a silica column (10 g)
and eluted with 15 mL of light petroleum (non-polar compounds)
and then with 15 mL of diethyl ether (product). Evaporation of the
solvent afforded the acid pure enough for further processing.
Representative analyses of starting esters:
In addition to acid 1, two additional of crowded chiral
acids were chosen for the experiment. They were com-
bined with five structurally different alcohols (a–e) so that
two different groups of esters are listed in the Table 1. All
compounds were prepared using either the DCC method11
(1) or the acylchloride/ pyridine esterification [2, 3; op-
tically pure 2-(1-naphthyl)-2-phenylacetic acid (1) spon-
taneously racemized during the DCC-mediated reaction].
(1R,2S,5R)-2-Isopropyl-5-methylcyclohexyl (2R)-2-(1-naphthyl)-2-
phenylethanoate (1a)
Anal. Cald for C28H32O2: C 83.96% C, H 8.05%; Found: C 83.68%,
H 7.76%; 1H NMR (200 MHz, CDCl3/TMS): 0.64 [d, 3 H, J(8,7) =
7.0 Hz, C(8)H3]; 0.74 [d, 3 H, J(9,7) = 7.0 Hz, C(9)H3]; 0.89 [d, 3
H, J(10,5) = 6.6 Hz, C(10)H3]; 0.83 and 1.67 [2 m, 2 1 H,
C(4)H2]; 0.95 and 2.05 (2 m, 2 1 H, C(6)H2]; 1.00 and 1.62 [2
m, 2 1 H, C(3)H2]; 1.33 [m, 1 H, C(2)H]; 1.48 [m, 1 H, C(5)H];
1.65 [m, 1 H, C(7)H]; 4.74 [dt, 1 H, J(1,2) = J(1,6a) = 10.6 Hz,
J(1,6b) = 4.4 Hz, C(1)H]; 5.75 (s, 1 H, Ar2-CH-CO); 7.25–7.37 (m,
6 H, Ar-H); 7.41–7.48 (m, 3 H, Ar-H); 7.79 (m, 1 H, Ar-H); 7.86
(m, 1 H, Ar-H); 7.98 (m, 1 H, Ar-H). MS (EI, m/z, %): 400 [M+]
(17), 262 (4), 217 (100), 139 (16), 97 (18), 83 (96); IR (CCl4,
cm–1): 1725, 1625, 1599, 1585, 1590, 1511, 1496, 1455, 1307,
1080, 1038, 955, 699; [ ]D –64,7 (c 2.56, CHCl3) {lit.11 [ ]D –68.7
(CHCl3)}.
All esters were subjected to the trifluoromethanesulfonic
acid-modified silica treatment under different tempera-
tures and 125 °C was finally found to be optimal. In addi-
tion to trifluoromethanesulfonic acid, FeCl3- and H2SO4-
coated silica as well as neat silica have also been tried.
Trifluoromethanesulfonic acid-modified silica showed
the best results. Depending on the ester composition, the
whole process took minutes or several hours (see
Table 1): while the esters of tertiary or allylic alcohols (1c
or 1b) or ester 2a gave the free acid within minutes, esters
of secondary alcohols (1a, 1e, 3a) liberated the acid with-
in 30 minutes. Surprisingly, the only product of 1d de-
composition was dodecan-1-ol, probably from
decarboxylation of free acid during the long reaction time.
On the other hand, relatively unstable ester (3a)12 derived
from Mosher’s acid (3) showed surprising high stability
(2E)-3,7-Dimethyl-2,6-octadienyl 2-(1-naphthyl)-2-phenylethan-
oate (1b)
Anal. Cald for C28H30O2: C 84.38%, H 7.59%; Found: C 84.52%, H
7.46%; 1H NMR (200 MHz, CDCl3/TMS): 1.58, 1.64 and 1.66 (3
s, 3 3 H, 3 CH3); 2.01 [m, 2 H, C(4)H2]; 2.06 [m, 2 H, C(5)H2];
4.67 and 4.71 [2 m, 2 1 H, C(1)H2]; 5.06 [m, 1 H, C(6)H2]; 5.33
[m, 1 H, C(2)H]; 5.78 (s, 1 H, Ar2-CH-CO); 7.26–7.36 (m, 6 H, Ar-
giving acid 3 in a relatively good yield. A salient feature H); 7.40–7.49 (m, 3 H, Ar-H); 7.79 (m, 1 H, Ar-H); 7.86 (m, 1 H,
Ar-H); 8.00 (m, 1 H, Ar-H). MS (EI, m/z, %): 398 [M+](14),
of the procedure is the absence of acid racemization dur-
ing the hydrolysis even in the case of very optically labile
molecule (1). This result was confirmed by evaluating the
290(17), 262(11), 217(100), 202(16), 136(19), 69(68); IR (CCl4,
cm–1): 3091, 3064, 1739, 1627, 1512, 1496, 1304, 1080, 1033, 697.
1-Methylheptyl 2-(1-naphthyl)-2-phenylacetate(1e)
NMR spectra of esters prepared from liberated acids by
Anal. Cald for C26H30O2: C 83.38%, H 8.07%; Found: C 83.31%, H
8.37; 1H NMR (200 MHz, CDCl3/TMS, two diastereomers in the ra-
tio 3: 2 – some signals are doubled): 0.85 (t, 3 H, 3J = 7.2 Hz, CH3);
1.19 and 1.21 (2 d, 3 H, 3J = 6.2 Hz, CH3); 5.00 (m, 1 H, >CH-O);
5.75 and 5.74 (2 s, 1 H, Ar2-CH-CO); 7.25–7.36 (m, 6 H, Ar-H);
7.40–7.50 (m, 3 H, Ar-H); 7.78 (m, 1 H, Ar-H); 7.86 (m, 1 H, Ar-
H); 8.02 (m, 1 H, Ar-H). MS (EI, m/z, %): 374 [M+] (17), 217 (100),
202 (11), 149 (8), 71 (15), 57 (23); IR (CCl4, cm–1): 3089, 3065,
re-esterification with (–)-menthol.
Apart from the expected product, an alcohol is a logical
counterpart of every hydrolytic process. The results indi-
cate that either, i) the preferential fission of the oxygen-
alkyl group bond takes place during the reaction (see
Table 1, compare the reaction time vs. structure) or, ii) the
subsequent dehydration occurs thus affording hydrocar- 3032, 1735, 1627, 1512, 1496, 1427, 1379, 1306, 1033, 698.
bons as side-products. Therefore, the method cannot be
used for separation of optically pure alcohols.
Acknowledgement
In conclusion, we demonstrated that trifluoromethane-
sulfonic acid-modified silica can be used to efficiently
mediate hydrolysis of sterically hindered esters under sol-
vent-free conditions. The acids are produced in medium to
high yield, with retention of configuration of the optically
labile model compound. This method can be added to ex-
isting methodologies for hydrolysis of hindered esters fre-
quently synthesized to allow separation of diastereomeric
pairs.
The authors wish to acknowledge the Grant Agency of the Czech
Republic for financial support (grant No. 203/01/116).
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General procedure for hydrolysis of esters:
To 400 mg of trifluoromethanesulfonic acid-coated silica (10%),
ester (1–3, a–e, 100 mg) was added at room temperature in CH2Cl2
(500 L). The solvent was evaporated under reduced pressure and
the reaction mixture was placed in an oil bath preheated to 125 °C.
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reaction was finished (as indicated by the disappearance of starting
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