sulfate in water followed by extraction with methylene
dichloride.9 In contrast to metal or ammonium peroxydis-
ulfate, (Bu4N)2S2O8 is readily soluble in organic solvents such
as acetonitrile, DMF, acetone, CH2Cl2, CHCl3, and ethyl
ether. Radicophilic cleavage of thiocarbonyl derivatives has
been examined using (Bu4N)2S2O8 and HCO2Na as a new
alkyl radical generator.
Compound 4 is regarded to be a candidate as a therapeutic
Alzheimer’s disease drug that protects neurons from Ab
toxicity and is in the preclinical stage as a hepatoprotective
drug.10 In our new alternative process for improving the
purification step, a key step in the synthesis of 4 involved
the conversion of 3 to 4 (Scheme 1).
In connection with these results, various alcohols were
subjected to this optimized deoxygenation protocol. The
results obtained are shown in Table 1. As shown, several
Table 1. Deoxygenation of Primary, Secondary, and Tertiary
Alcohols with (Bu4N)2S2O8 (3 equiv)/HCO2Na (6 equiv) in
DMF
entry substrate temp (°C) time (min) product yield (%)a
1
2
3
4
5
6
7
8
5a
6a
7a
8a
50
65
40
75
65
65
65
65
65
65
65
65
65
65
60
65
80
80
65
65
30
15
60
30
15
15
15
20
15
15
15
15
15
15
60
120
20
10
15
60
5b
6b
7b
8b
100
86
96
100
95
75
98b
90b
97b
65
75b
65b
73c
75c
95
95d
95e
95
9b
9c
10b
10b
10c
10d
11b
11b
12b
12b
12c
13
15a
15a
15a
15b
17
10e
10e
10e
10e
11c
11c
12d
12d
12d
14
16a
16a
16a
16b
18
Scheme 1. Deoxygenation of Asiatic Acid
9
10
11
12
13
14
15
16
17
18
19
20
90
86b
a Isolated yields obtained by silica gel column chromatography. b 8 equiv
Na2CO3 was added. c 8 equiv Et3N was added. d DMSO. e 3 equiv (HCO2)
2Cu.
different primary, secondary, and tertiary alcohols were
successively deoxygenated in high to excellent yields.
The S-methyl xanthate 9b was prepared from 9a,12 which
was obtained from the reduction of 7R-acetyl-6,14-endo-
ethanotetrahydrothebaine13 using DIBAL-H. As an opioid
derivative, 9c14 was obtained in excellent yield. Substrates
10b,15 10c,16 and 10d17 were prepared from glucofuranose
derivative 10a. Compounds 11b and 12b were prepared from
11a18 and 12a,19 respectively. Their 3-deoxy sugar derivatives
10e15 and 11c18 and 5-deoxy sugar derivative 12d20 obtained
are useful intermediates in pharmaceutical synthesis.
Of special note, 12d was obtained by the indirect deoxy-
genation of 12b. Because cyclic 3,5-O-thionocarbonate 12c
Barton-McCombie deoxygenation of 3 with Bu3SnH in
toluene at 110 °C gives 4 in 76% yields. Purification steps
have been needed to remove residual toxic organotin
byproducts in order to meet regulatory stipulations. This
procedure affects product isolation.
Furthermore the reaction of 1 using another method,11
using less toxic diphenylsilane and AIBN in toluene at 110
°C, gave 4 in 70% yields after a deprotection reaction with
catalytic HCl in methanol.
Substrate 3 was reacted with (Bu4N)2S2O8/HCO2Na (3
equiv/6 equiv) in DMF at 50 °C for 4 h to afford 4 in
excellent yield of 95%. In the absence of HCO2Na or
(Bu4N)2S2O8, no product 4 was obtained: starting material
3 was recovered. This result indicates that both (Bu4N)2S2O8
and HCO2Na are necessary for this deoxygenation.
(12) (a) Bentley, K. W.; Hardy, D. G.; Meek, B. J. Am. Chem. Soc. 1967,
89, 3273. (b) The 1H NMR spectral data of 9a is reported: Fulmor, W.;
Lancaster, J. E.; Morton, G. O.; Brown, J. J.; Howell, C. F.; Nora, C. T.;
Hardy, R. A., Jr. J. Am. Chem. Soc. 1967, 89, 3322.
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Park, H. K.; Jew, S.-S.; Jung, M. W. J. Neurosci. Res. 1999, 58, 417. (b)
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D. P.; Chakraborty, T. K. J. Am. Chem. Soc. 1988, 110, 4672.
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Fujishima, T.; Konno, K.; Miyata, N.; Takayama, H. J. Org. Chem. 2001,
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