Fe(III) chloride catalyzed conversion of epoxides to acetonides

Article abstract of DOI:10.1016/j.tetlet.2008.07.147

A mild and efficient method for the preparation of acetonides from epoxides catalyzed by iron(III) chlorides has been developed.

Full text of DOI:10.1016/j.tetlet.2008.07.147

Tetrahedron Letters 49 (2008) 5928–5930
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Tetrahedron Letters
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Fe(III) chloride catalyzed conversion of epoxides to acetonides
*
Sumit Saha, Samir Kumar Mandal, Subhas Chandra Roy
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A mild and efficient method for the preparation of acetonides from epoxides catalyzed by iron(III)
chlorides has been developed.
Received 3 July 2008
Revised 22 July 2008
Accepted 28 July 2008
Available online 31 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Acetonides
Epoxides
Acetone
Fe(III) chloride
Catalysis
Acetonides constitute important synthetic intermediates during
the synthesis of complex organic molecules, more specially, in the
field of carbohydrate and steroid chemistry.1 Traditionally, ace-
tone, 2,2-dimethoxypropane or 2-methoxypropene undergo con-
densation under acidic conditions with a diol, prepared via either
hydrolysis of epoxides or osmium-catalyzed dihydroxylation of
alkenes, to produce acetonides.2
Acetone
O
O
O
R
5 mol% FeCl3
rt
69-94%
R
Scheme 1.
Epoxides are attractive intermediates in organic synthesis due
to their wide range of chemo-, regio- and stereo-selective transfor-
mations with concomitant ring opening.3 Epoxides can be con-
verted to acetonides directly catalyzed by a Lewis acid. Several
procedures are reported in the literature for the preparation of
acetonides from epoxides using Lewis acid catalysts such as
BF3ꢀEt2O,4 SnCl4,5 SnCl2,6 anhydrous CuSO4,7 2,4,4,6-tetrabromo-
2,5-cyclohexadienone (TABCO),8 tetracyanoethylene,9 Er(OTf)3,10
Cu(OTf)2,11 LiBF4,12 Zeolite,13 K5CoW12O40ꢀ3H2O,14 Sn(IV)(tpp)-
(OTf)2,15 Bi(III)-salt,16 Fe(OTf)3,17 RuCl3,18 TiCl4,19 TiO(TFA)2,20
K10-Montmorillonite,21 CH3ReO3,22 heteropolyacids23electro-gen-
erated acids,24 and by other methods.25 Table 1 shows a compari-
son between different reported procedures. However, there is still
scope for further improvement in this field since most of the
reported methods suffer from long reaction times, elevated tem-
peratures, functional group intolerance and the use of expensive
and toxic catalysts. Herein, we disclose a mild and efficient method
for the direct conversion of epoxides to acetonides using inexpen-
sive anhydrous Fe(III) chloride as the catalyst at room temperature
in acetone as substrate and solvent (Scheme 1). In a preliminary
Table 1
A comparison of different reported procedures for the conversion of epoxides to
acetonides
Ref.
Reagent used
Reaction conditionsa
Yieldb (%)
4
5
6
7
8
BF3ꢀEt2O
rt, 15–120 min
40–50 °C, 80 min
Reflux, 1–7 h
rt-reflux, 2–24 h
reflux, 2.5–24 h
rt-reflux, 0.5–48 h
rt, 0.5–48 h
0–95
SnCl4
22–35
48–87
0–100
22–95
0–87
SnCl2
Anhyd CuSO4
TABCO
Tetracyanoethylene
Er(OTf)3
Cu(OTf)2
LiBF4
Zeolite
K5CoW12O40ꢀ3H2O
Sn(IV)(tpp)(OTf)2
Bi(III)-salt
Fe(OTf)3
RuCl3
TiCl4
TiO(TFA)2
K10-Montmorillonite
CH3ReO3
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
30–99
62–87
90–96
11–56
25–95
88–98
87–99
85–92
86–91
63–94
92–98
50–80
<5–39
19–91
30–97
rt, 4 h
Reflux, 15–120 min
Reflux, 1.5 h
rt-reflux, 5–420 min
rt-reflux, 0.4–4 h
Reflux, 0.25–2.5 h
Reflux, 2–5 h
Reflux, 1.5–5 h
ꢁ78 °C, 6 h
rt, 10 min
rt, 8 h
rt, 2–5 d
rt, 5 min
Heteropolyacid
Electro-generated acid
rt, few min
a
In most cases reflux in acetone.
Range of yields refers to products derived from the different substrated.
* Corresponding author. Tel.: +91 33 2473 4971; fax: +91 33 2473 2805.
E-mail address: ocscr@iacs.res.in (S. C. Roy).
b
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.147

S. Saha et al. / Tetrahedron Letters 49 (2008) 5928–5930
5929
Table 2 (continued)
Table 2
Iron(III) chloride catalyzed synthesis of acetonides
Entry
Epoxide
Producta
Time
4 h
Yieldb (%)
89
Ref.
6,9
Entry Epoxide
Producta
Time
4.5 h
Yieldb (%) Ref.
O
O
O
O
O
O
O
16
1
82
8,10
O
O
O
16a
16b
1a
1b
O
H
O
O
H
O
O
O
H
O
O
O
2
5 h
5 h
76
78
10
25
O
17
8 h
74
28
O
2a
MeO
H
2b
O
MeO
17b
17a
O
O
O
O
O
a
3
All products were characterized by IR, NMR and HRMS.
Yield refer to pure isolated products.
Cl
b
c
Cl
3a
3b
Isomeric ratios were determined from 1H NMR spectra.
O
O
O
O
O
4
5
6
7
5 h
85
83
87
79
76
—
—
—
—
experiment, epoxide 1a was stirred in the presence of 5 mol %
anhydrous FeCl3 and acetone at room temperature for 4.5 h to pro-
duce the acetonide 1b in 82% yield.26 It was observed that a mini-
mum of 5 mol % of catalyst was required to obtain the optimum
yield of the product. Thus, a series of epoxides were subjected to
the reaction conditions, and the results are summarized in Table
4a
4b
O
O
O
2.5 h
2 h
OBn
5a
OBn
5b
2. The reaction proceeds smoothly with aliphatic, styrene and
a-
keto epoxides to yield the corresponding acetonides in excellent
yields. All the products gave satisfactory spectral data and were
compared with reported values. In all cases, the acetonide exhib-
ited two separate singlets between d 1.2 and 1.7 for the methyl
groups in the 1H NMR spectra and two signals between d 25 and
27 in the 13C NMR spectra.
Conversion of styrene epoxides 9a–14a to the corresponding
1,3-dioxolanes was much faster than the conversion of aliphatic
epoxides. This can be rationalized by the stability of the benzylic
carbonium ion formed during epoxide cleavage. Epoxides 11a
and 12a were also converted to the corresponding acetonides but
a small amount of aldehyde was observed as a side product due
to rearrangement of the oxiranes to carbonyl compounds.11 Forma-
tion of the aldehyde proceeds via coordination of Fe(III) to the oxy-
gen atom of the epoxide followed by C–O bond cleavage to form an
electron-deficient carbon centre. Then, the aryl substituent
migrates to the adjacent carbon centre with simultaneous
formation of a carbonyl compound (Scheme 2).
O
O
O
O
6a
O
CO2Et
CO2Et
6b
Cl
O
O
O
Cl
5 h
OMe
OMe
7a
7b
O
O
O
8
9
4 h
—
O
O
CO2Me
CO2Me
8a
8b
O
O
O
12 min 92
10 min 94
8,10
—
9b
9a
O
O
O
It is noteworthy that trans-epoxides 11a–14a resulted in diaste-
reomeric mixtures of acetonides in different ratios, which were
determined from the 1H NMR spectra of the crude reaction prod-
ucts. On the other hand, a 1:1 mixture of the epoxide 15a furnished
acetonide 15b as a mixture of isomers in the same ratio. In con-
trast, the enantiopure epoxide 17a (entry 17)27 furnished solely
10
Cl
Cl
10a
10b
O
O
O
O
O
Ph
11
12
8 min
6 min
70
69
25b
11
Ph
Ph
1,2:5,6-di-O-isopropylidene-a-D-glucofuranose (17b) where the
Ph
11a
11b (1:0.6)c
stereochemistry is retained in the product.28 The stereoselectivity
of the products can be rationalized by analogy with Hanzlik.7 The
loss of stereochemistry from the epoxides 11a–14a must be due
to the formation of a common symmetrical intermediate, such as
D for example, from which both products could be formed (Scheme
3). Thus, because of the greater stability of the benzylic carbonium
ion A generated from 11a to 14a, formation of complexes B and C
O
O
O
Ph
Ph
Ph
Ph
12a
12b (1:0.5)c
O
O
O
13
14
15 min 84
18 min 76
—
Ph
Ph
OBn
13a
OBn
Ph
13b (1:1)c
Fe(III)
Ph
Ph
OFe(III)
FeCl3
O
O
+
+
Ph
O
O
O
Ph
A
Ph
Ph
25c
OAc
Ph
OAc
14b (1:1)c
14a
Fe(III)
OHC
Ph
migration
O
Ph
+
Ph
OH
O
OH O
O
Ph
15
3 h
73
—
Cl
Cl
15a (1:1)
15b (1:1)c
Scheme 2.

5930
S. Saha et al. / Tetrahedron Letters 49 (2008) 5928–5930
Fe(III)
Ph
Supplementary data
O
O
Acetone
FeCl3
Ph
Ph
Ph
Ph
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.07.147.
+
A
12a
OFe(III)
Ph
OFe(III)
References and notes
+
Ph
O
O
+
1. (a) Sharma, G. V. M.; Gopinath, T. Tetrahedron Lett. 2005, 46, 1307; (b) Ichege,
T.; Okano, Y.; Kanoh, N.; Nakata, M. J. Am. Chem. Soc. 2007, 129, 9862; (c) Ohrui,
H.; Emoto, S. Tetrahedron Lett. 1975, 3657; (d) Hudlicky, T.; Rinner, U.; Finn, K.
J.; Ghiviriga, I. J. Org. Chem. 2005, 70, 3490; (e) Jong-Dae Lee, J.-D.; Ueno, M.;
Miyajima, Y.; Nakamura, H. Org. Lett. 2007, 9, 323.
Ph
B
C
2. (a) Greene, T. W.; Wuts, P. G. M. Protecting Groups in Organic Synthesis, 2nd ed.;
John Wiley
& Sons: New York, 1991; pp 188–195; (b) Larock, R. C.
(III)FeO
Ph
Comprehensive Organic Transformations, 2nd ed.; Wiley-VCH: New York, 1999.
3. Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Tetrahedron 1983, 39, 2323.
4. Torok, D. S.; Figueroa, J. J.; Scott, W. J. J. Org. Chem. 1993, 58, 7274.
5. Bogert, M. T.; Roblin Jr, R. O. J. Am. Chem. Soc. 1933, 55, 3741.
6. Vyvyan, J. R.; Meyer, J. A.; Meyer, K. D. J. Org. Chem. 2003, 68, 9144.
7. Hanzlik, R. P.; Leinwetter, M. J. Org. Chem. 1978, 43, 438.
8. Firouzabadi, H.; Iranpoor, N.; Shaterian, H. R. Bull. Chem. Soc. Jpn. 2002, 75,
2195.
O
H
+
O
O
O
O
Ph
Ph
Ph
Ph
O
Ph
12b/
D
12b//
O
9. Masaki, Y.; Miura, T.; Ochiai, M. Chem. Lett. 1993, 17.
10. Procopio, A.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.; Russo, B. Adv.
Synth. Catal. 2005, 347, 1447.
H
(III)Fe
FeCl3
O
H
+
O
O
O
O
11. Lee, S. H.; Lee, J. C.; Kim, N. S. Bull. Korean Chem. Soc. 2005, 26, 221.
12. Kazemi, F.; Kiasat, A. R.; Ebrahimi, S. Synth. Commun. 2005, 35, 1441.
13. Zatorski, L. W.; Wierzchowski, P. T. Catal. Lett. 1991, 10, 211.
14. Habibi, M. H.; Tangestaninejad, S.; Mirkhani, V.; Yadollahi, B. Catal. Lett. 2001,
75, 205.
15. Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.; Shaibani, R. Tetrahedron
2004, 60, 6105.
16. Mohammadpoor-Baltork, I.; Khosropour, A. R.; Aliyan, H. Synth. Commun. 2001,
31, 3411.
O
MeO
H
O
MeO
H
E
17a
O
H
O
O
H
O
O
MeO
17. Iranpoor, N.; Adibi, H. Bull. Chem. Soc. Jpn. 2000, 73, 675.
18. Iranpoor, N.; Kazemi, F. Synth. Commun. 1998, 28, 3189.
19. Nagata, T.; Takai, T.; Yamada, T.; Imagawa, K.; Mukaiyama, T. Bull. Chem. Soc.
Jpn. 1994, 67, 2614.
17b
Scheme 3.
20. Iranpoor, N.; Zeynizadeh, B. J. Chem. Res. (S) 1998, 466.
21. Bucsi, I.; Meleg, A.; Molnar, A.; Bartok, M. J. Mol. Catal. A: Chem. 2001, 168, 47.
22. Zhu, Z.; Espenson, J. H. Organometallics 1997, 16, 3658.
23. Li, G.; Wang, B.; Wang, J.; Ding, Y.; Yan, L.; Suo, J. J. Mol. Catal. A: Chem. 2005,
236, 72.
24. Uneyama, K.; Isimura, A.; Fujii, K.; Torii, S. Tetrahedron Lett. 1983, 24, 2857.
25. (a) Altman, R. A.; Shafir, A.; Choi, A.; Lichtor, P. A.; Buchwald, S. L. J. Org. Chem.
2008, 73, 284; (b) Memarian, H. R.; Nikpour, F. Monatsh. Chem. 2002, 133, 1045;
(c) Banwell, M. G.; Coster, M. J.; Karunaratne, O. P.; Smith, J. A. J. Chem. Soc.,
Perkin Trans. 1 2002, 1622.
requires relatively little nucleophilic assistance or solvation from
acetone and is inter-convertible through the common intermediate
D. As a result, the epoxide 12a gave acetonide 12b as a mixture of
two isomers 12b0 and 12b00. In contrast, opening of epoxide 17a
probably requires much more assistance from the acetone carbonyl
due to the reduced stability of the non-benzylic carbonium ion E,
and thus acetonide formation is completely stereospecific leading
to 17b as the sole product. There may be other factors which con-
trol the approach of the acetone molecule to furnish 17b exclu-
sively. Sensitive functional groups such as chloride, methyl and
benzyl ethers, esters and hydroxyl remained unaffected under
the reaction conditions.
26. Typical procedure: To a well-stirred solution of 1a (150 mg, 1.0 mmol) in
acetone (10 mL), anhydrous FeCl3 (8 mg, 0.05 mmol) was added at room
temperature. After completion of the reaction (monitored by TLC) it was
quenched with saturated aqueous sodium bicarbonate solution, and the
volatiles were removed under reduced pressure. The residue obtained was
extracted with ether (2 ꢂ 50 mL). The combined ether extract was washed
successively with water (20 mL), brine (20 mL) and finally dried (Na2SO4). The
solvent was removed under reduced pressure and the residue obtained was
purified by column chromatography over silica gel (5% ethyl acetate in
petroleum ether) to obtain pure acetonide 1b (170 mg, 82%) as a crystalline
In conclusion, we have developed a mild and efficient method
for the conversion of epoxides to acetonides using cheap and com-
mercially available Fe(III) chloride as the catalyst. This reaction
worked smoothly for a wide range of epoxides.
solid, mp 65–67 °C. IR (neat): 2977, 1602, 1456, 1255 cmꢁ1 1H NMR (300 MHz,
;
CDCl3): d 1.41 (s, 3H), 1.47 (s, 3H), 3.88–3.97 (m, 2H), 4.07 (dd, J = 5.4, 9.5 Hz,
1H), 4.17 (dd, J = 6.6, 8.4 Hz, 1H), 4.45–4.52 (m, 1H), 6.91–6.99 (m, 3H), 7.29
(appeared as a triplet, J = 8.2 Hz, 2H); 13C NMR (75 MHz, CDCl3): d 25.5, 26.9,
67.0, 68.8, 74.1, 109.8, 114.6 (2C), 121.2, 129.6 (2C), 158.7; HRMS: calcd for
Acknowledgements
C
12H16O3Na 231.0997 [M+Na]+, found 231.0995.
27. Jana, S.; Guin, C.; Roy, S. C. Ind. J. Chem. 2007, 46B, 1648.
We sincerely thank DST, New Delhi for financial support. S.S.
and S.K.M. thank CSIR, New Delhi for research fellowships.
28. Dang, H. S.; Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin Trans. 1 2001,
2452.