A simple, convenient and chemoselective formylation of sterols by Vilsmeier reagent

Article abstract of DOI:10.1016/j.steroids.2006.03.005

Vilsmeier reagent (DMF-POCl₃) was used as an efficient formylating agent. Several sterols having sec-hydroxyl group at 3/17-position have been modified into respective formate esters. The method is simple, mild, chemoselective and provides sec-alcoholic protection in good yields.

Full text of DOI:10.1016/j.steroids.2006.03.005

steroids 7 1 ( 2 0 0 6 ) 632–638
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Short communication
A simple, convenient and chemoselective formylation
of sterols by Vilsmeier reagent
∗
Vandana Srivastava, Arvind Singh Negi , J.K. Kumar, M.M. Gupta
1
Central Institute of Medicinal and Aromatic Plants (CIMAP) , P.O. CIMAP, Kukrail Road, Lucknow 226 015, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Vilsmeier reagent (DMF-POCl3) was used as an efficient formylating agent. Several sterols
having sec-hydroxyl group at 3/17-position have been modified into respective formate
esters. The method is simple, mild, chemoselective and provides sec-alcoholic protection
in good yields.
Received 2 February 2006
Received in revised form 16 March
2006
Accepted 26 March 2006
© 2006 Elsevier Inc. All rights reserved.
Published on line 15 May 2006
Keywords:
Formylation
Vilsmeier reagent
Chemoselective
Protection
1
.
Introduction
formylation of alcohols has been less preferred in synthetic
strategies. It might be due to drastic reaction conditions, unde-
Generally, during a multistep synthesis of a natural prod-
uct, several groups are first protected and then deprotected
after the completion of desired reactions. Formylation of alco-
hols is one of the most useful and versatile reactions in
protective organic chemistry [1]. In the recent years, sev-
eral methodologies have been developed by using HCOOH [2],
HCOOH-HClO4 [3], HCOOH-BF3·2MeOH [1], HCOOH-Al(HSO4)3
sirable side products, poor yields and use of uncommon and
unstable reagents [1,17].
Vilsmeier reagent has been used for the formylation of elec-
tron rich aromatic systems to introduce an aldehyde group
in the ring system [18–21]. Use of this reagent as a formy-
lating agent for alcohols was found to be ineffective [22].
However, conversion of O-silyl protected sugars into their
corresponding formates by using dimethyl formamide (DMF)-
phosphorus oxychloride (POCl3) complex has been reported
recently [23,24]. Morimura et al. [25] used this reagent for the
formylation of phenols to obtain the corresponding aryl for-
mates in good yields. We herein report the use of this reagent
for the formylation of sec-sterols. We found that dimethyl for-
mamide and phosphorus oxychloride is an effective reagent
[
4], Ph3P-CBr4 in ethyl formate [5], potassium dodecatungsto-
cobaltate trihydrate (K5CoW12O40·3H2O) in ethyl formate [6],
chloral-K2CO3 [7], 2,2,2-trifluoroethyl formate [8], DMF-2,4,6-
trichloro-1,3,5-triazine in acetone [9]. Formate esters have also
been found quite useful in developing other transformations
[
10–15]. Formylation has been thought of as a better protec-
tive group for sterols in several transformations [16]. However,
∗
Corresponding author. Tel.: +91 522 2717529x327; fax: +91 522 2342666.
E-mail address: arvindcimap@rediffmail.com (A.S. Negi).
CIMAP Communication No. 2005-58J.
1
0039-128X/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.steroids.2006.03.005

steroids 7 1 ( 2 0 0 6 ) 632–638
633
Scheme 1 – Chemoselective formylation of sec-sterols by Vilsmeier reagent.
for synthesizing formate esters of sterols even in the presence
of phenolic hydroxyls. The reaction is simple, efficient and
undergoes in mild reaction conditions (10 C to room temper-
ature) to give formate esters in good yields (40–91%).
We have synthesized formate esters of different sterols
having sec-alcoholic hydroxyls at 3- or 17-positions as shown
on Scheme 1 and Table 1 (entries 1–10).
Substrate 10 was obtained on Baeyer–Villiger oxidation of 2-
formyl, 3-methoxyestra-1,3,5(10)-trien,17␤-acetate by stirring
it with dry dichloromethane-m-chloro perbenzoic acid for 18 h
at room temperature and subsequent hydrolysis with aqueous
methanolic-KOH. Dry solvents were prepared as per standard
methods [28]. Acetone was first treated with KMnO4 and then
dried over fused CaCl2. Dichloromethane was also dried over
fused CaCl2, while DMF was dried over CaH2. All the reac-
tions were performed as per standard procedures. Reactions
were monitored on Merck aluminium thin layer chromatog-
raphy (TLC, UV254 nm) plates. Visualization was accomplished
by spraying TLC plates with 2% ceric sulphate-10% aqueous
sulphuric acid solution and charring them at higher temper-
◦
2
.
Experimental
2
.1.
General procedures
◦
Starting material substrates 1–4 were purchased from Sigma
Biochemicals, USA. For substrates 5–10, estrone was used as
a starting material, which was also purchased from Sigma
Biochemicals. Substrate 5 was synthesized by methylating
estrone with dimethyl sulphate/anhydrous K2CO3 in dry ace-
tone under refluxing conditions and subsequent sodium
atures (100–120 C). Column chromatography was carried out
on silica gel (60–120 mesh, LOBA chemicals). H NMR, 13C NMR
and DEPT experiments were obtained on a Bruker Avance-
300 MHz instrument with tetramethyl silane as an internal
standard. Chemical shifts are given in ı ppm values. All the
1H and necessary 13C spectral data are reported. Electrospray
mass spectra were recorded on API-3000, LC-MS/MS (Applied
Biosystem) after dissolving the compounds in acetonitrile. Ele-
mental analysis was carried out in Heraus CHN analyser.
1
◦
borohydride reduction in methanol at 50 C. Substrate 6
was obtained from estradiol, 3-methyl ether, 17␤-acetate by
performing formylation using phosphorus oxychloride and
◦
dimethyl formamide at 80 C [26] and then saponifying with
1
N aqueous methanolic KOH. Substrate 7 was synthesized
by reducing estrone with sodium borohydride in methanol
at room temperature. Substrate 8 was synthesized from 2-
formyl-estradiol, 3-methyl ether-17␤-acetate on stirring with
dry dichloromethane-anhydrous AlCl3 at room temperature
2.2.
Typical experimental procedure: synthesis of
formylated products of entries 1–10
2.2.1. Synthesis of 3-methoxyestra-1,3,5(10)-trien-17ˇ-yl
formate [entry 5 (product), Table 1]
[
27] and subsequent hydrolysis with 1N aqueous-methanolic
KOH. Substrate 9 was obtained on reduction of substrate 8
with sodium borohydride in methanol at room temperature.
In a 25 ml round bottom flask, estra 1,3,5 (10)-trien-3,17␤-diol-
3-methyl ether [entry 5 (substrate), 100 mg, 0.35 mmol] was

Table 1 – Formylation of sterols by Vilsmeier reagent (DMF-POCl3)
Entrya
Substrate
Product
Temperatureb
Time (h)
3.0
Isolated yield (%)
Molar ratios
substrate:DMF:POCl3)
(
1
RT
64
1:5.2:4.5
1:5.6:4.9
2
3
RT
RT
4.0
3.5
91
48
1:5.1:4.5
1:5.4:4.7
4
RT
3.5
67
5
6
RT
RT
4.5
4.0
79
73
1:5.2:4.5
1:4:3.5
7
RT
3.0
52
1:3.5:3.1

Table 1 – (Continued )
Entrya
Substrate
Product
Temperatureb
Time (h)
Isolated yield (%)
Molar ratios
(
substrate:DMF:POCl3)
8
9
RT
4.0
59
1:3.8:3.3
1:3.8:3.4
1:3.8:3.4
RT
RT
4.0
3.5
42
40
1
0
a
b
(
1
2
1) 5-cholesten-3␤-ol (cholesterol), (2) 8,24,(5␣)-cholestadien-4,4,14-trimethyl-3␤-ol (lanosterol), (3) (22E) ergosta-5,7,22-trien-3␤-ol (ergosterol), (4) 5-cholesten-24␤-ethyl-3␤-ol (␤-sitosterol), (5) estra-
,3,5(10)-trien-3,17␤-diol,3-methyl ether, (6) 2-formyl-estra-1,3,5(10)-trien-3,17␤-diol,3 methyl ether (2-formyl,17␤-estradiol 3-methyl ether), (7) estra-1,3,5(10)-trien-3,17␤-diol (17␤-estradiol), (8)
-formyl,estra-1,3,5(10)-trien-3,17␤-diol, (9) 2-hydroxymethyl,estra-1,3,5(10)-trien-3,17␤-diol and (10) estra-1,3,5(10)-trien-2,3,17␤-triol,3-methyl ether.
◦
◦
Initial temperature of the reaction mixture was 5–10 C at the time of addition of POCl3 and later on it went up to 30–35 C.

6
36
steroids 7 1 ( 2 0 0 6 ) 632–638
stirred in dry DMF (0.2 ml, 2.59 mmol). The reaction mixture
was cooled to 5–10 C by using ice bath. After 10 min, phos-
23.36, 28.53, 28.53, 30.01, 33.49, 37.01, 37.51, 38.24, 39.48, 40.63,
43.23, 43.27, 46.52, 54.96, 56.28, 73.22, 116.69, 120.88, 132.49,
135.91, 138.45, 141.97, 160.83. Electrospray mass (CH3CN): 425.3
[M + H] , 447.4 [M + Na] , 463.4 [M + K] . Elemental analysis
calcd for C29H44O2: C, 82.02; H, 10.44; Found: C, 81.77; H, 10.82.
◦
phorus oxychloride (0.2 ml, 2.26 mmol) was added drop wise
to the reaction mixture. The reaction mixture was kept at
this temperature for next 30 min and then further stirred at
room temperature for 4 h. After completion of the reaction, it
was poured into crushed ice and extracted with chloroform
+
+
+
2.2.5. (24R)-24-Ethyl-5-cholesten-3ˇ-yl formate
(3ˇ-sitosteryl formate; 4)
(
25 ml × 3). The organic layer was washed with water, dried
Yield 67. m.p. 113–116 C. 1H NMR (CDCl3, 300 MHz): ı 0.61 (s,
3H, 18-CH3), 0.76 (d, 6H, C-28 and C-29 CH3, J = 6.36 Hz), 0.86
(distorted t, 3H, C-26 CH3), 0.95 (d, 3H, C-21 CH3), 1.18 (bs, 3H, C-
19 CH3), 2.30 (bd, 2H, 7-CH2, J = 7.62 Hz), 5.32 (bs, 1H, 6-CH), 7.96
(s, 1H, not exchangeable, O–CHO, formate). Electrospray mass
◦
over anhydrous sodium sulphate and concentrated in vacuo.
The residue thus obtained was column chromatographed over
silica gel (60–120 mesh) and eluted with hexane-ethyl acetate.
The formate was obtained in 2% ethyl acetate-hexane frac-
tion. It was recrystallised with hexane-chloroform (4:1) to get
a white crystalline solid (87 mg, 79%).
+
+
+
(CH3CN): 445.4 [M + H] , 465.4 [M + Na] , 481.3 [M + K] . Elemen-
tal analysis calcd for C30H50O2: C, 81.39; H, 11.38. Found: C,
80.97; H, 11.74.
Yield 79%. m.p. 102–104 C. 1H NMR (CDCl3, 300 MHz): ı
◦
0
.85 (s, 3H, 18-CH3), 1.32–2.28 (m, 13H), 2.84–2.86 (bs, 2H, 6-
CH2), 3.78 (s, 3H, OCH3), 4.79 (t, 1H, 17-CH, J = 8.39 Hz), 6.63
d, 1H, 4-CH, J = 8.5 Hz), 7.18 (d, 1H, 1-CH, J = 8.5 Hz), 8.10 (s,
(
2.2.6. 2-Formyl-3-methoxyestra-1,3,5(10)-trien-17ˇ-yl
formate (6)
1
7
4
1
H, not exchangeable, O–CHO, formate). 13C NMR (CDCl3,
5.47 MHz): ı 12.38, 23.64, 26.41, 27.41, 28.05, 37.37, 39.15, 43.50,
4.25, 50.55, 68.61, 83.03, 110.98, 114.46, 126.52, 132.92, 138.17,
Yield 73%. m.p. oil. 1H NMR (CDCl3, 300 MHz): ı 0.78 (s, 3H,
18-CH3), 1.185–2.31 (m, 13H), 2.85 (bs, 2H, 6-CH2), 3.82 (s, 3H,
OCH3), 4.71 (t, 1H, 17-CH, J = 8.46 Hz), 6.61 (s, 1H, 4-CH), 7.68
(s, 1H, 1-CH), 8.03 (s, 1H, not exchangeable, O–CHO, formate),
10.32 (s, 1H, CHO, aldehyde). Electrospray mass (CH3CN):
+
58.19, 161.40. Electrospray mass (CH3CN): 315.3 [M + H] , 353.3
+
[M + K] . Elemental analysis calcd for C20H26O3: C, 76.40; H,
8
.33. Found: C, 75.98; H, 8.52.
+
+
+
3
29.3 [M + H] , 351.2 [M + Na] , 367.4 [M + K] . Elemental anal-
2
.2.2. 5-Cholesten-3ˇ-yl formate (3ˇ-cholesteryl
formate, 1)
Yield 64%. m.p. 112–113 C. 1H NMR (CDCl3, 300 MHz): ı 0.61
ysis calcd for C21H26O4: C, 73.66; H, 7.65. Found: C, 74.14;
H, 6.76.
◦
(
(
s, 1H, 18-CH3), 0.78–1.92 (m, 36H), 0.96 (s, 3H, 19-CH3), 2.30
d, 2H, 7-CH2, J = 7.12 Hz), 4.65 (bs, 1H, 3-CH), 5.32 (s, 1H, 6-
CH), 7.97 (s, 1H, not exchangeable, O–CHO, formate). 13C NMR
2.2.7. 3,17ˇ-Dihydroxyestra-1,3,5(10)-trien-17ˇ-yl
formate (7)
Yield 52%. m.p. 108–110 C. 1H NMR (CDCl3, 300 MHz): ı 0.63
(s, 3H, 18-CH3), 1.04–2.06 (m, 13H), 2.59 (bs, 2H, 6-CH2), 4.57
(t, 1H, 17-CH, J = 8.3 Hz), 6.36 (s, 1H, 4-CH), 6.42 (d, 1H, 2-CH,
J = 8.3 Hz), 6.92 (d, 1H, 1-CH, J = 8.3 Hz), 7.89 (s, 1H, not exchange-
able, O–CHO, formate). 13C NMR (CDCl3, 75.47 MHz): ı 12.41,
23.64, 26.59, 27.56, 28.01, 29.87, 37.30, 39.06, 43.47, 44.20, 50.35,
83.13, 113.20, 115.70, 126.77, 138.48, 153.93, 161.47. Electrospray
◦
(
CDCl3, 75.46 MHz): ı 12.19 (18-Me), 19.09 (C-21), 19.53 (C-19),
2
1
3
1.48 (C-11), 22.75 (C-26), 22.94 (C-27), 24.27 (C-23), 24.62 (C-
5), 28.26 (C-12), 28.30 (C-25), 28.45, 29.57, 32.29, 32.42 (C-8),
6.08 (C-20), 36.66 (C-22), 37.06 (C-1), 37.42, 38.56 (C-24), 39.94
(
(
(
C-16), 40.27 (C-4), 42.85, 50.70, 56.83, 57.24, 74.39 (C-3), 123.20
C-5), 139.91 (C-4), 160.56 (O–CHO, formate). Electrospray mass
CH3CN): 415.3 [M + H] , 437.4 [M + Na] . Elemental analysis
+
+
+
+
mass (CH3CN): 301.1 [M + H] , 323.2 [M + Na] . Elemental anal-
ysis calcd for C19H24O3: C, 75.97; H, 8.05. Found: C, 76.27; H,
8.42.
calcd for C28H46O2: C, 81.10; H, 11.18. Found: C, 81.62; H,
1.36.
1
2
.2.3. Lanosta-8,24-dien-3ˇ-yl formate (3ˇ-lanosteryl
2.2.8. 2-Formyl-3,17ˇ-dihydroxyestra-1,3,5(10)-
trien-17ˇ-yl formate (8)
formate; 2)
Yield 91%. m.p. oil. 1H NMR (CDCl3, 300 MHz): ı 0.62 (s, 3H,
Yield 59%. m.p. 93–94 C. 1H NMR (CDCl3, 300 MHz): ı 0.79 (s,
3H, 18-CH3), 1.18–2.23 (m, 13H), 2.73 (bs, 2H, 6-CH2), 4.77 (bs,
1H, 17-CH), 6.62 (s, 1H, 4-CH), 7.36 (s, 1H, 1-CH), 7.94 (s, 1H,
not exchangeable, O–CHO, formate), 10.71 (s, 1H, CHO, alde-
◦
18-CH3), 0.79 (d, 3H, 27-CH3), 0.83 (d, 3H, 26-CH3), 1.08 (d, 3H,
21-CH3), 1.18 (s, 3H, 19-CH3), 1.96 (bs, 6H, 28-CH3 and 29-CH3),
4.56 (bs, 1H, 3-CH), 5.05 (bt, 1H, 24-CH, J = 6 Hz), 8.05 (s, 1H, not
+
exchangeable, O–CHO, formate). Electrospray mass (CH3CN):
hyde). Electrospray mass (CH3CN): 329.1 [M + H] . Elemental
+
4
55.3 [M + H] . Elemental analysis calcd for C31H50O2: C, 81.88;
analysis calcd for C20H24O4: C, 73.15; H, 7.37. Found: C, 73.48;
H, 7.94.
H, 11.08. Found: C, 82.34; H, 10.66.
2
.2.4. (22E) Ergosta 5,7,22-trien-3ˇ-yl formate
2.2.9. 2-Hydroxymethyl-3,17-dihydroxyestra-1,3,5(10)-
trien-17ˇ-yl formate (9)
(
3ˇ-ergosteryl formate; 3)
◦
1
Yield 42%. m.p. oil. 1H NMR (CDCl3, 300 MHz): ı 0.78 (s, 3H,
18-CH3), 1.18–2.28 (m, 13H), 2.53 (bs, 2H, 6-CH2), 3.36 (s, 2H,
CH2OH), 4.74 (t, 1H, 17-CH, J = 8.63 Hz), 6.55 (s, 1H, 1-CH), 6.84
(s, 1H, 4-CH), 8.04 (s, 1H, not exchangeable, O–CHO, formate).
Yield 48%. m.p. 141–144 C. H NMR (CDCl3, 300 MHz): ı 0.56 (s,
H, 18-CH3), 0.78 (d, 6H, 21 and 25-CH3), 0.89 (d, 6H, 27 and 28-
CH3), 1.18 (s, 3H, 19-CH3), 0.74–1.96 (m, 16H), 2.34–2.44 (m, 2H,
3
2
-CH2), 4.72–4.80 (distorted quintet, 1H, 3-CH), 5.13–5.15 (t, 2H,
+
2
2 and 23-CH, J = 5.67 Hz), 5.32 (bs, 1H, 6-CH), 5.51 (bs, 1H, 7-
Electrospray mass (CH3CN): 331.1 [M + H] . Elemental anal-
CH), 7.98 (s, 1H, not exchangeable, O–CHO, formate). 13C NMR
ysis calcd for C20H26O4: C, 72.70; H, 7.93. Found: C, 73.06;
H, 8.24.
(
CDCl3, 75.46 MHz): ı 12.42, 16.55, 17.92, 19.97, 20.24, 21.47,

steroids 7 1 ( 2 0 0 6 ) 632–638
637
Scheme 2 – An alternate strategy for the demonstration of chemoselective formylation. Reagents and conditions: (i) Me2SO4,
◦
◦
K2CO3, dry acetone, reflux, 5 h, 89%; (ii) NaBH4, MeOH, 50 C, 2 h, 92%; (iii) DMF-POCl3, 0–10 C for 30 min, then RT, 4.5 h, 79%;
(
◦
iv) DMF-POCl3, 0–10 C for 30 min, then RT, 3 h, 52% and (v) Me2SO4, K2CO3, dry acetone, reflux, 6 h, 78%.
trospray mass spectrometry. In 1H NMR, the chemical shift
of formate protons was found between ı 7.9 and 8.1 ppm
where as, in 13C NMR the corresponding formate carbonyls
were resonated between ı 160 and 161 ppm. Alternatively, the
chemoselectivity of the reaction was confirmed by another
synthetic strategy (Scheme 2), which proved the formylation
possibility at alcoholic hydroxyl only. However, benzylic alco-
hols could not be converted to corresponding formates and
in few cases, multiple products were obtained with very poor
yields (<10%). This might be due to the reduced nucleophilicity
of alcoholic oxygen as it is attached to the benzylic methylene.
This reaction did not respond to ter-alcohols, e.g. menthol and
nor-ethindrone.
2
.2.10. 2,17-Dihydroxy-3-methoxyestra-1,3,5(10)-
trien-17ˇ-yl formate (10)
Yield 40%. m.p. oil. 1H NMR (CDCl3, 300 MHz): ı 0.78 (s, 3H,
1
8-CH3), 1.18–2.28 (m, 13H), 2.72 (bs, 2H, 6-CH2), 3.78 (s, 3H,
OCH3), 4.71 (t, 1H, 17-CH, J = 8.38 Hz), 6.49 (s, 1H, 1-CH), 6.79
(
s, 1H, 4-CH), 8.03 (s, 1H, not exchangeable, O–CHO, formate).
+
Electrospray mass (CH3CN): 331.1 [M + H] . Elemental analysis
calcd for C20H26O4: C, 72 .70; H, 7.93. Found: C, 72.97; H, 7.36.
3
.
Results and discussion
Vilsmeier reagent has been found ineffective for the formy-
lation of alcohols when dimethyl formamide-phosphorus
oxychloride (DMF-POCl3) was used. However, cholesterol
could be formylated with dimethyl formamide-benzoyl chlo-
ride (DMF-BzCl) [22]. But, now we were able to formy-
late cholesterol by dimethyl formamide-phosphorus oxychlo-
ride at room temperature and the method was successfully
extended to some other sec-sterols like lanosterol, ergosterol,
In conclusion, it is demonstrated that Vilsmeier reagent
(DMF-POCl ) is a very effective formylating agent for sec-
3
steroidal alcohols. This is a simple, mild and straightforward
reaction, which completes in a short span of time. Other
functional groups such as phenol, aldehyde, acetate and aryl
methyl ether were found rigid under the reaction conditions.
Thus, this reaction may be of much helpful in the synthetic
steroidal chemistry where the protection of secondary alco-
holic group is required.
␤
-sitosterol and estradiol 3-methyl ether. It is reported that
this reagent has also been used for the formylation of phe-
nolic hydroxyls to get corresponding aryl formates [23]. But
in case of substrates 7–10, exclusively alcoholic formates
were formed and phenolic hydroxyls were intact by this
methodology.
Acknowledgements
The formylation of sec-alcohols was found to be very effec-
tive in steroidal systems by this reagent. The formylation
was chemoselective, as in the presence of phenolic hydroxyl
only sec. alcoholic group got formylated (substrates 7–10). The
products have been identified by 1H NMR, 13C NMR and Elec-
Authors are thankful to the Director, CIMAP for the constant
encouragement and providing necessary facilities. The award
of Research Internship to one of the authors (V.S.) from
Council of Scientific and Industrial Research (CSIR) is duly
acknowledged.

6
38
steroids 7 1 ( 2 0 0 6 ) 632–638
r e f e r e n c e s
arylmethaneselonates with formates. Tetrahedron Lett
005;46:2015–9.
2
[
16] Ringold HJ, Loken B, Rosenkranz G, Sondheimer F. The
direct oppenaur oxidation of steroidal formate esters. A
new synthesis of 17␣-hydroxyprogesterone. J Am Chem
Soc 1956;78:816–9.
[1] Greene TW, Wuts PGM. Protective groups in organic
synthesis. 3rd ed. New York: John Wiley and Sons; 1999. p.
1
49 [and other references sited therein].
[
17] Gramin JC, Renuson R. A new formylation reagent:
N,N-diformylacetamide. Synthesis 1982:264–5.
18] Vilsmeier A, Haack A. Uber die Einwirkung von
halogenphosphor auf alkyl-formanilide. Eine neue
methode zur Dalstellung SekundOler und tertiaue
p-alkylamino-benzaldehyde. Chem Ber 1927;60:
[
[
[
2] Gan LX, Whistler RL. Formylation of primary hydroxyl
groups in sugars. Carbohydr Res 1990;206:65–9.
3] Hughes IW, Smith F, Webb M. Formylation of bile acid. J
Chem Soc 1949:3437–8.
4] Shirini F, Zolfigol MA, Abedini M, Salehi P. Al(HSO4)3
catalyzed acetylation and formylation of alcohols. Bull
Korean Chem Soc 2003;24:1683–5.
5] Hagiwara H, Morohashi K, Sakai H, Suzuki T, Ando M.
Acetylation and formylation of alcohols with triphenyl
phosphine and carbon tetrabromide in ethyl acetate and
ethyl formate. Tetrahedron 1998;54:5845–52.
6] Habibi MH, Tangestaninejad S, Mirkhani V, Yadollahi B.
Novel catalytic acylation and formylation of alcohols with
potassium decacatengestocobaltate (K5CoW12O40·3H2O).
Tetrahedron 2001;57:8333–7.
[
119–22.
[
19] Jackson WG, Sargeson AM, Tucker PA, Watson AD.
Synthesis and X-ray crystal of a novel Vilsmeier-Haack
adduct: [Tris(2-aminoethyl)amine][3-(dimethylamino)-2-
aminoacrylyl chloride]cobalt(1 1 1)chloride-zinc
tetrachloride-water. J Am Chem Soc 1981;103:533–40.
20] Meth-Cohn O, Stanforth SP. The Vilsmeier-Haack reaction.
Compend Org Synth 1991;2:777–94.
21] Pedras MSC, Jha M. Concise syntheses of cruciferous
phytoalexins brassilexin, silalexin, wasalexins and
analogues: expanding the scope of Vilsmeier formylation. J
Org Chem 2005;70:1828–34.
[
[
[
[
[
[
7] Ram NR, Meher NK. Selective formylation of alcohols in
presence of phenols with chloral. Tetrahedron
2
002;58:2997–3001.
8] Hill DR, Hsiao CN, Kurukulasuriya R, Wittenberger S.
,2,2-Trifluoroethyl formate: a versatile and selective
[
22] Barluenga J, Campos PJ, Gonzalez-Nunez E, Asensio G.
General method for the formylation of alcohols with
dimethylformamide: an extension of the Vilsmeier-Haack
reaction. Synthesis 1985:426–8.
2
reagent for the formylation of alcohols, amines, and
N-hydroxylamines. Org Lett 2002;4:111–3.
[
23] Andrade MM, Barros MT. Facile conversion of O-silyl
protected sugars into their corresponding formates using
POCl3-DMF complex. Tertahedron 2004;60:9235–43.
24] Lellouche JP, Koeller S. A particular sensitivity of silyl
ethers of d-glucal toward two Vilsmeier-Haack reagents
POCl3·DMF and (CF3SO2)2O·DMF. Their unique and
selective conversion to corresponding C(6)-O-formates. J
Org Chem 2001;66:693–6.
[
9] Luca LD, Giacomelli G, Porcheddu A. Beckmann
rearrangement of oximes under very mild conditions. J
Org Chem 2002;67:5152–5.
10] Subramanyam V, Silver EH, Soloway AH. Reactions of
phosphoranes with formate esters. New method for
synthesis of vinyl ethers. J Org Chem 1976;41:1272–3.
11] Suda M. Short step synthesis of (± ) Bazzanene and (± )
trichodiene. Tetrahedron Lett 1982;23:427–8.
12] Mandai T, Matsumoto T, Kawada M, Tsuji J.
Stereocontrolled formation of cis and trans ring junctions
in hydrindane and decalin systems by palladium catalysed
regioselective and stereospecific hydrogenolysis of allylic
formates. J Org Chem 1992;57:1326–7.
[
[
[
[
[
[
[
25] Morimura S, Horiuchi H, Maruyama K. Vilsmeier reaction
of phenols. I. Synthesis of aryl formates. Bull Chem Soc
Jpn 1977;50:2189–90.
26] Chatterjea JN, Prasad N. Syntheses Von
Tri-O-methyl-wedelolactone und dihydroerosnin. Chem
Ber 1964:1252–5.
[
[
[
13] Garner CM, Prince ME. An improved synthesis of
tetramethylcyclopentadiene. Tetrahedron Lett
27] Negi AS, Chattopadhyay SK, Srivastava S, Bhattacharya AK.
A simple regioselective demethylation of p-aryl methyl
ethers using aluminium chloride-dichloromethane system.
Synth Commun 2005;35:15–21.
1
994;35:2463–4.
14] Ali BE, Alper H. Regioselective palladium (II) catalysed
hydroesterification of alkynes and alkynol using formate
esters. J Mol Catal A 1995;96:197–201.
15] Maeda H, Tanabe T, Hotta K, Mizuno K. Synthesis of
Se-arylmethyl Selenoformates by reaction of aluminium
[
28] Furniss BS, Hannaford AJ, Smith PWG, Tatchell AR. Vogel’s
text book of practical organic chemistry. 5th ed. England:
Addition Wesley Longman; 1998, 395–412.