Effective and mild method for converting 3β-hydroxysteroids to 3-keto steroids via DDQ/TEMPO

Article abstract of DOI:10.1016/j.steroids.2015.01.010

A mild and efficient oxidation of 3β-hydroxysteroids to the corresponding 3-keto steroids can be carried out at room temperature, using DDQ in the presence of catalytic TEMPO. Oxidation of saturated 3β-hydroxysteroids gave the corresponding ketones in excellent yield. The 5-unsaturated 3β-hydroxysteroids are oxidized selectively to 4-en-3-one or 4,6-diene-3-one derivatives according to the amount of DDQ in reaction. This is a good method for the synthesis of 4,6-diene-3-one from the corresponding 3β-hydroxy-5-ene steroids. Meanwhile, configurations of the oxidation compounds 2a, 2b, 3b, 2c, 2f and 2g were identified by X-ray diffraction. A possible mechanism is presented and discussed.

Full text of DOI:10.1016/j.steroids.2015.01.010

STE 7715
No. of Pages 5, Model 5G
23 January 2015
Steroids xxx (2015) xxx–xxx
1
Contents lists available at ScienceDirect
Steroids
journal homepage: www.elsevier.com/locate/steroids
5
6
Effective and mild method for converting 3b-hydroxysteroids to 3-keto
3
steroids via DDQ/TEMPO
4 Q1
⇑
Wu Zhang, Dan Pan, Aiqun Wu, Liqun Shen
7 Q2
8
9
College of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Key Laboratory of Development and Application of Forest Chemicals of Guangxi,
Nanning 530006, China
10
11
a r t i c l e i n f o
a b s t r a c t
1 3
2 6
14
15
16
17
18
Article history:
Received 16 July 2014
Received in revised form 26 December 2014
Accepted 8 January 2015
Available online xxxx
27
28
29
30
31
32
33
34
35
A mild and efficient oxidation of 3b-hydroxysteroids to the corresponding 3-keto steroids can be carried
out at room temperature, using DDQ in the presence of catalytic TEMPO. Oxidation of saturated 3b-
hydroxysteroids gave the corresponding ketones in excellent yield. The 5-unsaturated 3b-hydroxyster-
oids are oxidized selectively to 4-en-3-one or 4,6-diene-3-one derivatives according to the amount of
DDQ in reaction. This is a good method for the synthesis of 4,6-diene-3-one from the corresponding
3b-hydroxy-5-ene steroids. Meanwhile, configurations of the oxidation compounds 2a, 2b, 3b, 2c, 2f
and 2g were identified by X-ray diffraction. A possible mechanism is presented and discussed.
Ó 2015 Published by Elsevier Inc.
19
20
21
22
23
Keywords:
3b-Hydroxysteroids
DDQ
TEMPO
Oxidation
24
25
3-Keto steroids
36
37
38
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
1. Introduction
In recent years, 2,2,6,6-tetramethyl piperidinyl 1-oxyl (TEMPO)
catalyzed alcohol oxidation has gained increasing priority not only
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
Steroidal ketones are important intermediates to synthesize a
wide variety of vital biologically active steroid hormones, including
control of carbohydrate metabolism (glucocorticoids), reproduc-
tion (male and female sexual hormones), as well as antibacterial
and antitumor activities [1–3]. It is necessary to study of the syn-
thesis of steroidal ketones due to the large-scale industrial produc-
tion of steroid drugs. Previous studies have shown that the
introduction of 3-one based on Cr(VI) reagents proved to be capri-
cious in this particular case and hardly applicable to industry on a
large scale [4]. Steroidal 4-ene-3-ones are synthesized by oxidation
of 3b-hydroxy-5-en steroids with the classical Oppenauer oxida-
tion using (i-PrO)3Al and a large excess of cyclohexanone. With this
method, however, the product is always contaminated with the
substances of aldol condensation of cyclohexanone, for whose sep-
aration steam distillation has to be used, further increasing the
cost. Steroidal 4,6-diene-3-ones are synthesized by oxidation of
3b-hydroxy-5-en steroids with MnO2 or aluminum isopropoxide
[5–6]. However, these methods give pretty low yield. Steroidal
4,6-diene-3-ones can also be are synthesized by dehydrogenation
of steroidal ketones with 2,3-dichloro-5,6-dicyano-benzoquinone
(DDQ) or chloranil [7].
in academic laboratories, but also in the chemical industries, par-
ticularly in the pharmaceutical industry, as an efficient, mild, and
environmentally acceptable method [8–10]. DDQ are powerful oxi-
dants capable of performing a wide variety of organic transforma-
tions [11,12]. Initially introduced for the dehydrogenation agent in
the 1950’s [13], its use was extended to the steroids field. Previous
review articles on DDQ have been published, which may provide
readers with a more in depth perspective [14–17]. The oxidation
of alcohols to the corresponding carbonyl compounds by using
DDQ and co-oxidant has been developed, for example, Shen et al.
[18] have recently demonstrated the selective oxidation of non-
sterically hindered benzylic alcohols using catalytic amounts of
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tert-butyl
nitrite with molecular oxygen. Wang et al. [19] have developed
for the oxidation of allylic and propargylic alcohols over benzylic
alcohols to the corresponding carbonyl compounds by using
DDQ, NaNO2 as a cocatalyst, and molecular oxygen as terminal oxi-
dant. Cosner et al. [20] have described chemoselective oxidation of
electron-rich benzylic alcohols and allylic alcohols employing DDQ
as the oxidant and Mn(OAc)3 as the co-oxidant. DDQ was used for
selectively oxidations steroidal allylic alcohol to the corresponding
ab-unsaturated ketone in excellent [21]. Steroidal 5-en-3-ol(s) can
be oxidized directly to 1,4,6-trien-3-one by DDQ at reflux [22].
DDQ oxidation of alcohols appears to be even more strongly
⇑
Corresponding author. Tel.: +86 771 3260558.
E-mail address: liqunshen@126.com (L. Shen).
http://dx.doi.org/10.1016/j.steroids.2015.01.010
0039-128X/Ó 2015 Published by Elsevier Inc.
Q1
Please cite this article in press as: Zhang W et al. Effective and mild method for converting 3b-hydroxysteroids to 3-keto steroids via DDQ/TEMPO. Steroids
(2015), http://dx.doi.org/10.1016/j.steroids.2015.01.010

STE 7715
No. of Pages 5, Model 5G
23 January 2015
2
W. Zhang et al. / Steroids xxx (2015) xxx–xxx
86
87
88
89
90
91
123
124
dependent upon steric factors than chromic acid oxidation [23].
Hence, there is clearly a need for a more efficient method of the
oxidation of sterol with DDQ. Herein we report the oxidation of
3b-hydroxysteroids to 3-keto steroids with DDQ/TEMPO coupled
at room temperature, where catalytic amounts of TEMPO are used
in combination with DDQ as stoichiometric oxidation.
17.2, 16.5, 14.7, 11.7 ppm. HRMS: [M+] calcd for C27H42O3:
414.3134; found: 414.3138.
125
2.3. Methyl 3-oxo-androst-4-ene-17b-carboxylate (2b)
126
127
128
129
130
131
132
Methyl 3-oxo-androst-4-ene-17b-carboxylate (2b) from 3b-
hydroxy-5-androstene-17b-carboxylate (1b). 1H NMR (600 MHz,
CDCl3): d: 5.73 (s, 1H), 3.66 (s, 3H), 1.18 (s, 3H), 0.69 (s, 3H). 13C
NMR (150 MHz, CDCl3): d: 199.6, 174.5, 124.1, 118.1, 56.2, 55.2,
54.9, 53.5, 44.0, 42.7, 38.1, 37.8, 35.7, 34.0, 32.3, 31.7, 24.4, 23.6,
20.9, 19.1, 13.5 ppm. HRMS: [M+] calcd for C21H30O3: 330.2195;
found: 330.2199.
92
2. Experiment
93
94
Melting points were determined using a WRS-1B apparatus and
were uncorrected. The 1H and 13C NMR spectra were recorded on
600/150 MHz NMR spectrometers (a Bruker AV600 spectrometer),
using tetramethylsilane (TMS) as the internal standard and CDCl3
as the solvent. High resolution mass (HRMS) spectra were obtained
in ESI mode on a Finnigan MAT95XP HRMS system (Thermo Elec-
tron Corporation). Diffraction experiments for oxidation product
were carried out on with Mo Ka radiation (k = 0.71073 Å) using a
bruker SMART APEX CCD diffractometer at 296 K. All chemicals
were of reagent grade and used as commercially purchased with-
out further purification. All solvents were dried and distilled before
95
96
97
133
2.4. Methyl 3-oxo-androst-4,6-diene-17b-carboxylate (3b)
98
99
134
135
136
137
138
139
140
Methyl 3-oxo-androst-4,6-diene-17b-carboxylate (3b) from 3b-
hydroxy-5-androstene-17b-carboxylate (1b). 1H NMR (600 MHz,
CDCl3): d: 6.10 (s, 2H), 5.70 (s, 1H), 3.67 (s, 3H), 1.10 (s, 3H), 0.74
(s, 3H). 13C NMR (150 MHz, CDCl3): d: 197.6, 175.5, 155.9, 132.6,
126.1, 121.1, 55.7, 48.0, 46.5, 42.5, 39.0, 38.9, 38.1, 31.0, 28.5,
20.9, 20.3, 20.1, 19.1, 18.9, 13.7 ppm. HRMS: [M+] calcd for
C21H28O3: 328.2038; found: 328.2042.
100
101
102
103
104
105
use. The reactions were monitored by TLC on silica gel 60 F254
.
Chromatography was conducted by using 200–300 mesh silica gel.
106
2.1. General procedure
141
2.5. 25(R)-4,6-Spirostadien-3-one (2c)
107
108
109
110
111
112
113
114
115
To a stirred solution of steroids (1 mmol) in dry CH2Cl2 at 0 °C
was added DDQ (1.2 mmol or 2.2 mmol) and TEMPO (0.1 mmol).
After the addition, the mixture was warmed to room temperature
and stirred for the required time until completion by TLC. The mix-
ture was filtered on Celite, the filtrate was respectively washed
with 2% sodium hydroxide, saturated sodium chloride solution
and distilled water. The solution was dried, concentrated in a rot-
ovap. The residue was then purified by flash chromatography
(petroleum ether/ethyl acetate) to obtain the desired product.
142
143
144
145
146
147
148
149
25(R)-4,6-Spirostadien-3-one (2c) from (3b, 25R)-spirost-5-en-
3-ol (1c). 1H NMR (600 MHz, CDCl3): d: 6.11 (d, J = 2.4 Hz, 2H),
5.67 (s, 1H), 1.26 (s, 3H), 0.98 (d, J = 6.4 Hz, 3H), 0.88 (s, 3H), 0.79
(d, J = 6.4 Hz, 3H). 13C NMR (150 MHz, CDCl3): d: 199.7, 163.8,
141.0, 128.1, 123.9, 109.5, 80.6, 67.1, 62.2, 53.3, 50.9, 41.8, 41.6,
39.7, 37.4, 36.3, 34.1, 34.0, 31.5, 31.4, 30.4, 28.9, 20.6, 17.3, 16.5,
16.4, 14.6 ppm. HRMS: [M+H+] calcd for C27H39O3: 411.2821;
found: 411.2825.
150
2.6. Pregna-4,6-diene-3,20-dione (2d)
116
2.2. 5
a-Spirostan-3-one (2a)
151
152
153
154
155
156
157
Pregna-4,6-diene-3,20-dione (2d) from 3b-hydroxy-5-preg-
nene-20-one (1d). 1H NMR (600 MHz, CDCl3): d: 6.12 (d,
J = 2.4 Hz, 2H), 5.69 (s, 1H), 2.15 (s, 3H), 1.12 (s, 3H), 0.72 (s, 3H).
13C NMR (150 MHz, CDCl3): d: 208.8, 199.5, 163.3, 140.6, 128.3,
123.9, 63.4, 53.8, 50.7, 44.8, 38.7, 37.7, 36.2, 34.0, 34.0, 31.6,
24.0, 23.0, 20.8, 16.4, 13.4 ppm. HRMS: [M+] calcd for C21H28O2:
312.2089; found: 312.2091.
-Spirostan-3-one (2a) from tigogenin (1a). 1H NMR
117
118
119
120
121
122
5
a
(600 MHz, CDCl3): d: 4.40 (q, J = 11.2 Hz, 1H), 3.39 (m, 1H), 3.37
(t, J = 10.8 Hz, 1H), 1.02 (s, 3H), 0.96 (d, J = 3.6 Hz, 3H), 0.79 (s,
3H), 0.78 (d, J = 2.0 Hz, 3H) ppm. 13C NMR (150 MHz, CDCl3): d:
212.0, 109.3, 80.8, 67.0, 62.3, 56.3, 54.0, 46.7, 44.8, 41.7, 40.7,
40.0, 38.6, 38.3, 35.8, 35.2, 32.0, 31.8, 31.4, 30.4, 29.0, 28.9, 21.3,
Table 1
The oxidation of tigogenin with DDQ in the presence of TEMPO.
O
O
O
DDQ/TEMPO
solvent
O
O
HO
2a
1a
Entry
Solvent
Reaction time (h)
Yield (%)
1
2
3
4
5
6
CH2Cl2
Toluene
Dioxane
CHCl3
Ethyl acetate
ClCH2CH2Cl
24
24
24
24
24
24
80.2
30.4
50.8
73.6
36.4
71.4
Q1
Please cite this article in press as: Zhang W et al. Effective and mild method for converting 3b-hydroxysteroids to 3-keto steroids via DDQ/TEMPO. Steroids
(2015), http://dx.doi.org/10.1016/j.steroids.2015.01.010

STE 7715
No. of Pages 5, Model 5G
23 January 2015
W. Zhang et al. / Steroids xxx (2015) xxx–xxx
3
Fig. 1. X-ray diffraction crystal structures of 2b and 3b.
COOCH3
COOCH3
COOCH3
DDQ/TEMPO
solvent
+
O
HO
O
1b
3b
2b
Scheme 1.
2a
2 c
2f
2g
Fig. 2. X-ray diffraction crystal structures of 2a, 2c, 2f and 3b.
158
165
2.7. Androsta-4,6-diene-3,17-dione (2e)
2.8. Androstane-3,17-dione (2f)
159
160
161
162
163
164
166
167
168
169
170
171
Androsta-4,6-diene-3,17-dione (2e) from 17b-hydroxy-5-and-
rost-17-one (1e). 1H NMR (600 MHz, CDCl3): d: 6.18 (s, 2H), 5.70
(s, 1H), 1.14 (s, 3H), 0.97 (s, 3H); 13C NMR (CDCl3, 150 MHz), d:
219.7, 199.6, 163.1, 138.6, 129.0, 124.4, 51.0, 49.0, 48.5, 37.2,
36.4, 35.9, 34.1, 34.1, 31.5, 21.7, 20.2, 16.6, 13.9 ppm. HRMS:
[M+] calcd for C19H24O2: 284.1776; found: 284.1779.
Androstane-3,17-dione (2f) from 3b-hydroxy-17-androstanone
(1f). 1H NMR (600 MHz, CDCl3): d: 1.04 (s, 3H), 0.89 (s, 3H); 13C
NMR (CDCl3, 150 MHz), d: 220.9, 211.5, 53.9, 51.2, 47.7, 46.6,
44.5, 38.4, 38.0, 35.8, 35.8, 34.9, 31.5, 30.5, 28.6, 21.7, 20.7, 13.8,
11.4 ppm. HRMS (M+) for C19H28O2, calcd 288.2089, found
288.2084.
Q1
Please cite this article in press as: Zhang W et al. Effective and mild method for converting 3b-hydroxysteroids to 3-keto steroids via DDQ/TEMPO. Steroids
(2015), http://dx.doi.org/10.1016/j.steroids.2015.01.010

STE 7715
No. of Pages 5, Model 5G
23 January 2015
4
W. Zhang et al. / Steroids xxx (2015) xxx–xxx
Table 2
Oxidations of 3b-hydroxy steroids with DDQ/TEMPO system.
Entry
1
Reactant
Product
Steroid/DDQ
1/2.2
Time (h)
36
Yield (%)
68.3
O
O
O
O
HO
O
1c
2c
2
1/2.2
36
70.2
O
O
HO
O
1d
2d
3
4
5
1/2.2
1/1.2
1/1.2
36
24
24
71.5
O
O
HO
O
1e
2e
82
O
O
HO
O
2f
O
1f
78
O
HO
O
1g
2g
OH
Cl
Cl
CN
CN
N
O
HO
HO
OH
O
O
O
Cl
Cl
CN
CN
Cl
Cl
CN
CN
N
OH
O
O
H
O
O
OH
Cl
Cl
CN
CN
OH
Scheme 2.
172
185
186
2.9. Pregn-16-ene-3,20-dione (2g)
at room temperature, the data in Table 1 shows that the solvents
do have a major effect on the yield. The highest yield was obtained
by utilizing CH2Cl2 as solvent (see Fig. 1).
173
174
175
176
177
178
179
Q3 187
188
Pregn-16-ene-3,20-dione (2g) from 3b-hydroxy-5
en-20-one (1g).
a-pregn-16-
When methyl 3b-hydroxy-5-androstene-17b-carboxylate (1b)
and DDQ (1.2 eq) were reacted in the presence of 10% TEMPO in
CH2Cl2 at room temperature, unexpectedly, two compounds,
methyl 3-oxo-androst-4-ene-17b-carboxlate (2b) and methyl 3-
oxo-androst-4,6-diene-17b-carboxylate (3b) were produced at a
80:20 ratio with a total yield of 75% (Scheme 1). Further optimiza-
tion showed that increasing the amount of DDQ (2.2 eq) could
yield a 80% conversion as well as 98: 2 3b/2b ratio. The configura-
tions of the compounds 2b and 3b were confirmed by X-ray crystal
diffraction analysis (Fig. 2).
1H NMR (600 MHz, CDCl3): d: 6.69 (m, 1H), 2.26 (s, 3H), 1.04 (s,
3H), 0.91 (s, 3H); 13C NMR (CDCl3, 150 MHz) : d: 208.6, 196.7,
146.0, 136.5, 43.5, 42.3, 39.0, 37.6, 37.1, 36.8, 36.3, 32.2, 32.0,
30.9, 28.8, 25.7, 24.8, 23.0, 20.8, 16.8, 13.6 ppm. HRMS (M+H+)
for C21H31O2, calcd 315.2246, found 315.2250.
189
190
191
192
193
194
195
180
3. Results and discussion
196
197
181
182
183
184
Initially, in order to explore this reaction condition, we selected
tigogenin (1a) as the substrate for the investigation of the effect of
different solvents for the same reaction (Table 1). When tigogenin
(1a) and DDQ (1.2 eq) were reacted in the presence of 10% TEMPO
198
Under the above optimized conditions, the protocol was applied
to another five 3b-hydroxysteroids, and corresponding products
were isolated in gram quantities with moderate to good yields
199
200
Q1
Please cite this article in press as: Zhang W et al. Effective and mild method for converting 3b-hydroxysteroids to 3-keto steroids via DDQ/TEMPO. Steroids
(2015), http://dx.doi.org/10.1016/j.steroids.2015.01.010

STE 7715
No. of Pages 5, Model 5G
23 January 2015
W. Zhang et al. / Steroids xxx (2015) xxx–xxx
5
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
[3] Arlt W, Biehl M, Taylor AE, Hahner S, Libe R, Hughes BA, et al. Urine steroid
metabolomics as a biomarker tool for detecting malignancy in adrenal tumors.
J Clin Endocrinol Metab 2011;96:3775.
201
202
203
204
205
206
207
208
209
210
211
212
213
214
ranging from 68.3% to 82% (Table 2, entries 1–5). Incidentally, this
is a good method for the synthesis of 4,6-diene-3-one derivatives
from the corresponding 3b-hydroxy-5-ene steroids. It is important
to mention that under our reaction conditions, no 1,4-diene-3-one
was observed. The configurations of the compounds 2c, 2f and 2g
were confirmed by X-ray crystal diffraction analysis (Fig. 2).
A possible mechanism for the oxidation of steroidal alcohols is
proposed in Scheme 2. The alcohol is oxidized by TEMPO+ to obtain
the desired oxidation product and TEMPOH. TEMPOH could be
converted into TEMPO+ by reaction with DDQ, which resulted in
DDHQ. The mechanism by which DDQ affects 4,6-diene-3-one is
believed to involve an initial rate-determining transfer of hydride
ion from the steroids followed by a rapid proton transfer leading
to hydroquinone formation [14,24].
[4] Rasmusson GH, Arth GE. Organic reactions in steroid chemistry, volumes I and
II. New York: Van Nostrand Reinhold Co.; 1972.
[5] Sondheimer F, Amendolla C, Rosenkranz GJ. Steroids L1 44,6-diene-3-one. J Am
Chem Soc 1953;75:5932.
[6] Mandell L. The mechanism of the Wettstein–Oppenauer oxidation. J Am Chem
Soc 1956;78:3199.
[7] Turner AB, Ringold AB. Applications of high-potential quinones. Part I. The
mechanism of dehydrogenation of steroidal ketones by 2,3-dichloro-5,6-dicy
dicyanobenzoquinone. J Chem Soc 1967:1720.
[8] Bailey WF, Bobbitt JM. Mechanism of the oxidation of alcohols by
oxoammonium cations. J Org Chem 2007;72:4504.
[9] Luca LD, Giacomelli G, Masala S, Porcheddu A. Trichloroisocyanuric/TEMPO
oxidation of alcohols under mild conditions: a close investigation. J Org Chem
2003;68:4999.
[10] Wang XL, Liu RH. TEMPO/HCl/NaNO2 Catalyst:
a transition-metal-free
approach to efficient aerobic oxidation of alcohols to aldehydes and ketones
under mild conditions. Chem Eur J 2008;14:2679.
[11] Batista VS, Crabtree RH, Konezny SJ, Luca OR, Praetorius JM. Oxidative
functionalization of benzylic C–H bonds by DDQ. New J Chem 2012;36:1141.
[12] Memarian HR, Saffar-Teluri A. Microwave-assisted and light-induced catalytic
215
4. Conclusion
216
217
218
219
220
221
222
Insummary, a mild and efficient procedure was developed for the
oxidation of 3b-hydroxysteroids in the DDQ/TEMPO system at room
temperature. This methods allows to synthesize 4,6-diene-3-one
derivatives from the corresponding 3b-hydroxy-5-ene steroids in a
single step. Moreover, under these mild conditions, no 1,4-diene-
3-one were detected. Thus, the procedure described offers signifi-
cant advantages over previous oxidation methods.
ring opening of
a-epoxyketones using DDQ. J Mol Cat A: Chem 2007;274:224.
[13] Braud EA, Brook AG, Linstead RP. Hydrogen transfer Part IV The use of
quinones of high potential as dehydrogenation reagents.
1954:3569.
J Chem Soc
[14] Walker D, Hiebert JD. 2,3-Dichloro-5,6-dicyanobenzoquinone and its
reactions. Chem Rev 1967;67:153.
[15] Turner AB. 2,3-Dichloro-5,6-dicyanobenzoquinone (DDQ). Synthetic reagents
1977;3:193.
[16] Bharate SB. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Synlett
2006;3:496–7.
[17] Tanemura K, Nishida Y, Suzuki T. 2,3-Dichloro-5,6-dicyano-p-benzoquinone
(DDQ) as the useful synthetic reagent. Bullet Nippon Dental Univ Gen Educ
2011;40:31.
223
Acknowledgements
224
225
226
227
This work was supported by colleges and universities in Guan-
gxi Science and Technology Research projects (ZD2014046,
2013YB079) and Natural Science Foundation of Guangxi Zhuang
Autonomous Region (No. 2014GXNSFAA118032).
[18] Shen ZL, Dai JL, Xiong J, He XJ, Mo WM, Hu BX, Sun N, Hua XQ. 2,3-Dichloro-
5,6-dicyano-1,4-benzoquinone (DDQ)/tert-butyl nitrite/oxygen:
catalytic oxidation system. Adv Synth Catal 2011;353:3031.
A versatile
[19] Wang LY, Li J, Yang H, Lv Y, Gao S. Selective oxidation of unsaturated alcohols
catalyzed by sodium nitrite and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
with molecular oxygen under mild conditions. J Org Chem 2012;77:790.
[20] Cosner CC, Cabrera PJ, Byrd KM, Adams Thomas AM, Helquist P. Selective
oxidation of benzylic and allylic alcohols using Mn(OAc)3/catalytic 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone. Org Lett 2011;13:2071.
228
Appendix A. Supplementary data
[21] Burn D, Petron V, Weston GO. A new reagent for the selective oxidation of
229
230
231
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.steroids.2015.01.
010.
steroidal allylic alcohols to
ab-unsaturated ketones. Tetra Lett 1960;9:14–5.
[22] Morisaki M, Rubio-Lightbourn J, Ikekawa N, Takeshita T. Synthesis of active
forms of vitamin D.V. practical route to 1a,25-dihydroxycholesterol. Chem
Pharm Bull 1973;21:2568.
[23] Turner AB. 2, 3-Dichloro-5, 6-dicyanobenzoquinone (DDQ). Synth. Reagents
232
References
1977;3:193.
[24] Vogler T, Studer A. Applications of TEMPO in synthesis. Synthesis
2008;13:1979.
233
234
235
[1] Lednicer D. Steroid chemistry at a glance. Chichester, UK: John Wiley & Sons;
2010.
[2] Zeelen FJ. Pharmaceutical chemistry of steroids. Amsterdam: Elsevier; 1990.
290
Q1
Please cite this article in press as: Zhang W et al. Effective and mild method for converting 3b-hydroxysteroids to 3-keto steroids via DDQ/TEMPO. Steroids
(2015), http://dx.doi.org/10.1016/j.steroids.2015.01.010