Magnesium in methanol mediated deoxygenation of the cyclic thionocarbonates of aromatic 2,3-dihydroxy esters

Article abstract of DOI:10.1081/SCC-100000211

The cyclic thionocarbonates of aromatic 2,3-dihydroxy esters, which have an electron-withdrawing group, undergo deoxygenation with magnesium in methanol to form α-keto esters or α-hydroxy esters, depending on the type of electron-withdrawing group.

Full text of DOI:10.1081/SCC-100000211

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MAGNESIUM IN METHANOL MEDIATED
DEOXYGENATION OF THE CYCLIC
THIONOCARBONATES OF AROMATIC 2,3-DIHYDROXY
ESTERS
Ho Sik Rho a & Byoung-Seob Ko b
a Department of Applied Skin Biology Institute , Pacific Corporation, 314-1, Bora-ri,
Kiheung-eup, Yongin-Si, Kyounggi-do, 449-900, South Korea
b Institute of Oriental Medicine , Chongdam-dong, Kangnam-ku, Seoul, 135-100, South
Korea
Published online: 16 Aug 2006.
To cite this article: Ho Sik Rho & Byoung-Seob Ko (2001) MAGNESIUM IN METHANOL MEDIATED DEOXYGENATION OF THE
CYCLIC THIONOCARBONATES OF AROMATIC 2,3-DIHYDROXY ESTERS, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 31:2, 283-288, DOI: 10.1081/SCC-100000211
To link to this article: http://dx.doi.org/10.1081/SCC-100000211
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SYNTHETIC COMMUNICATIONS, 31(2), 283–288 (2001)
MAGNESIUM IN METHANOL MEDIATED
DEOXYGENATION OF THE CYCLIC
THIONOCARBONATES OF AROMATIC
2,3-DIHYDROXY ESTERS
Ho Sik Rho,1,∗ and Byoung-Seob Ko2
1Department of Applied Skin Biology Institute, Pacific
Corporation, 314-1, Bora-ri, Kiheung-eup, Yongin-Si,
Kyounggi-do 449-900, South Korea
2Institute of Oriental Medicine, Chongdam-dong,
Kangnam-ku, Seoul 135-100, South Korea
ABSTRACT
The cyclic thionocarbonates of aromatic 2,3-dihydroxy es-
ters, which have an electron-withdrawing group, undergo deoxy-
genation with magnesium in methanol to form α-keto esters or
α-hydroxy esters, depending on the type of electron-withdrawing
group.
α-Hydroxy ester functionality is frequently found in natural products and
is valuable as a synthetic intermediate (1–3). They are usually prepared by the
hydrolysis of α-halo esters (4), rearrangement of α-keto acetals (5), oxidation of
ketene silyl acetals (6), reduction of α-keto esters (7,8), ring opening of epoxy
esters, and subsequent reduction of the resulting iodohydrins (9,10). Recently, we
have reported that the cyclic thionocarbonates of 2,3-dihydroxy esters are good
∗ To whom correspondence should be addressed. E-mail: thiocar@channeli.net
283
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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RHO AND KO
Scheme 1.
precursors for α-hydroxy esters via regioselective deoxygenation process induced
by magnesium in methanol (11). Here, we wish to report deoxygenation of the
cyclic thionocarbonates of aromatic 2,3-dihydroxy esters that have an electron-
withdrawing substituent (Scheme 1).
The results of deoxygenation of cyclic thionocarbonates are summarized in
Table 1. The diols were transformed to the cyclic thionocarbonates by treating
with thiophosgene. The para nitro substituted cyclic thionocarbonates 1a reacted
with magnesium (5 equiv.) in refluxing dry methanol for 30 min to afford methyl
(2Z)-2-hydroxy-3-(4-nitrophenyl) prop-2-enoate (2a) (19,20) in 75% yield (entry
1 in Table 1). This unexpected conversion is due to the presence of an electron-
withdrawing substituent on the aromatic ring. A plausible mechanism for this
conversion is outlined in Figure 1.
The deoxygenation occurs exclusively at the β-position of the carbonyl
group (8). The chelation of the magnesium cation has an effect on the selectiv-
ity of deoxygenation. Electron-withdrawing substituents destabilize the deoxy-
genated radical intermediate at the benzylic position. The radical intermediate
is subsequently converted into the enol form by abstraction of α-hydrogen. The
destabilizing effect of the nitro group is the key factor to yield the α-keto ester
product. The enol structure was established by 300 MHz 1H NMR spectroscopy.
For the methyl sulfone-substituted cyclic thionocarbonate 1b and 1c under the
same conditions, α-keto ester 2b was obtained in 81% and 78% yields as the sole
Figure 1.

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AROMATIC 2,3-DIHYDROXY ESTERS
285
Table 1. Magnesium in Methanol Induced Deoxygenation of the Cyclic Thionocarbonate
of Aromatic 2,3-dihydroxy Estersa
Entry
Substrate
Time (min)
30
Product
Yield (%)b
75
1
2
3
35
40
81
78
2b
4
5
6
7
45
25
30
30
65
72
69
70
aAll the reactions were run with magnesium (5 equiv.) in refluxing dry MeOH.
bThe yields are for isolated compounds.
product (entry 2 and 3). The ethyl ester was transformed into the methyl ester by
transesterification. In the case of ester-substituted compound 1d, α-keto ester 2c
was obtained together with a trace amount of α-hydroxy ester (entry 4). However,
we could not obtain pure product.
In contrast to the above cases, when the fluorosubstituted cyclic thiono-
carbonate 1e was reacted with magnesium in methanol, methyl 2-hydroxy-3-
(4-fluorophenyl) propanoate 3a was obtained in 72% yield (entry 5). This result
apparantly indicates that the fluoro group does not destabilize the radical interme-
diate. The protonation of the radical intermediate must be faster than elimination
in this case. The bromo-substituted cyclic thionocarbonate 1f was also used to

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prepare α-hydroxy ester 3b (entry 6). Finally, the chloro-substituted cyclic thiono-
carbonate 1g with magnesium in methanol produced α-hydroxy ester 3c in 70%
yield without formation of α-keto ester (entry 7). Deoxygenation did not occur
when magnesium in absolute ethanol was used. Anhydrous reaction conditions are
important to reduce the formation of deprotected diol as side product.
In summary, α-keto esters or α-hydroxy esters were synthesized by magne-
sium in methanol-induced deoxygenation of the cyclic thionocarbonates of aro-
matic 2,3-dihydroxy esters containing an electron-withdrawing substituent.
EXPERIMENTAL
Typical Procedure
Methyl (2Z)-2-hydroxy-3-(4-nitrophenyl) Prop-2-enoate (2a)
To a stirred solution of the cyclic thionocarbonate 1a (200 mg, 0.70 mmol)
in dry MeOH (10 mL) under nitrogen atmosphere was added magnesium turning
(85 mg, 3.53 mmol) and the reaction mixture was heated at reflux for 30 min.
To the gray solution was added diethyl ether (30 mL) and the whole mixture
was filtered through a celite pad and concentrated in vacuo. The crude product
was purified by SiO2 column chromatography (EtOAc/hexanes 1 : 1, Rf = 0.55)
to give 2a (118 mg, 75%). Mp 150◦–151◦C. IR (neat) 3451, 3010, 1732 cm−1
.
1H NMR (CDC13, 300 MHz) δ 8.21 (d, 2H, J = 9.6 Hz), 7.89 (d, 2H, J = 8.7 Hz),
6.81 (s, 1H), 6.55 (s, 1H), 3.97 (s, 3H). MS (m/e) 223 (M+), 163 (base peak), 136.
Anal. calcd for C10H9O5N: C, 53.82; H, 4.06; N, 6.27. Found: C, 53.75; H, 3.99;
N, 6.23.
Methyl (2Z)-2-hydroxy-3-[4-(methylsulfonyl)phenyl]
Prop-2-enoate (2b)
TLC, SiO2, EtOAc/hexanes 1 : 1, Rf = 0.27. Mp 157◦–158◦C. IR (neat)
3453, 3011, 1730 cm−1. 1H NMR (CDCl3, 300 MHz) δ 7.92 (s, 4H), 6.73 (s, 1H),
6.54 (s, 1H), 3.96 (s, 3H), 3.06 (s, 3H). MS (m/e) 256 (M+), 196, 169, 107 (base
peak). Anal. calcd for C11H12O5S: C, 51.55; H, 4.72; S, 12.51. Found: C, 51.47;
H, 4.78; S, 12.46.
Methyl (2Z)-2-hydroxy-3-[4-(methoxycarbonyl)phenyl]
Prop-2-enoate (2c)
TLC, SiO2, EtOAc/hexanes 1 : 1, Rf = 0.60. Mp 117–119◦C. IR (neat) 3450,
3015, 1733 cm−1. 1H NMR (CDCl3, 300 MHz) δ 8.03 (d, 2H, J = 8.4 Hz), 7.81

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AROMATIC 2,3-DIHYDROXY ESTERS
287
(d, 2H, J = 8.4 Hz), 6.64 (s, 1H), 6.54 (s, 1H), 3.93 (s, 3H), 3.91 (s, 3H). MS
(m/e) 236 (M+), 176 (base peak), 149. Anal. calcd for C12H12O5: C, 60.01; H,
5.12. Found: C, 59.94; H, 5.10.
Methyl 2-hydroxy-(4-fluorophenyl) Propanoate (3a)
TLC, SiO2, EtOAc/hexanes1:1, Rf = 0.50. IR(neat)3451, 3010, 1732cm−1
.
1H NMR (CDCl3, 300 MHz) δ 7.26 (m, 2H), 7.08 (m, 2H), 4.42 (m, 1H), 3.77
(s, 3H), 3.12 (dd, 1H, J = 13.8, 4.2 Hz), 2.92 (dd, 1H, J = 13.8, 8.1 Hz), 2.76
(bs, 1H). MS (m/e) 198 (M+), 180, 109 (base peak). Anal. calcd for C10H11O3F:
C, 66.60; H, 5.59. Found: C, 66.71; H, 5.67.
Methyl 2-hydroxy-(4-bromophenyl) Propanoate (3b)
TLC, SiO2, EtOAc/hexanes1:1, Rf = 0.52. IR(neat)3450, 3015, 1733cm−1
.
1H NMR (CDCl3, 300 MHz) δ 7.41 (d, 2H, J = 8.1 Hz), 7.08 (d, 2H, J = 8.1 Hz),
4.43 (m, 1H), 3.77 (s, 3H), 3.01 (dd, 1H, J = 13.8, 4.2 Hz), 2,89 (dd, 1H, J = 13.8,
6.9 Hz). 2.73 (bs, 1H) MS (m/e) 261 (M2+), 259 (M+), 241, 170 (base peak). Anal.
calcd for C10H11O3Br: C, 46.35; H, 4.28. Found: C, 46.20; H, 4.30.
Methyl 2-hydroxy-(4-chlorophenyl) Propanoate (3c)
TLC, SiO2, EtOAc/hexanes 1 : 1, Rf = 0.52. Mp 117–119◦C. IR (neat) 3451,
3010, 1732 cm−1. 1H NMR (DMSO, 300 MHz) δ 7.30 (d, 2H, J = 8.1 Hz), 7.22
(d, 2H, J = 8.1 Hz), 5.58 (bs, 1H), 4.22 (m, 1H), 3.61 (s, 3H), 2.95 (dd, 1H,
J = 13.8, 4.2 Hz), 2.82 (dd, 1H, J = 13.8, 6.6 Hz). MS (m/e) 216 (M2+), 214
(M+), 196, 125 (base peak). Anal. calcd for C10H11O3Cl: C, 55.96; H, 5.16. Found:
C, 55.88; H, 5.09.
ACKNOWLEDGMENTS
The authors are grateful to Dr. Y. H. Joo, Miss S. M. Ahn, and Prof. S-K.
Kang, Sung Kyun Kwan University, for valuable discussions during the preparation
of this manuscript.
REFERENCES AND NOTES
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Received in the UK September 1, 1999

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