Mild and efficient protection of diol and carbonyls as cyclic acetals catalysed by iron (III) chloride

Article abstract of DOI:10.1016/j.crci.2010.12.001

A friendly method for the protection of diols and carbonyls catalysed by hexahydrated iron (III) chloride has been developed. This method, which consists of the transformation of diols and carbonyls to cyclic acetals, functions in mild conditions and it is efficient for a wide range of diols.

Full text of DOI:10.1016/j.crci.2010.12.001

C. R. Chimie 14 (2011) 525–529
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Preliminary communication/Communication
Mild and efficient protection of diol and carbonyls as cyclic acetals
catalysed by iron (III) chloride
a,
a
a
a
*
´
´
Iyad Karame , Mohamad Alame , Ali Kanj , Ghinwa Nemra Baydoun ,
Hassan Hazimeh a, Mirvat el Masri a, Lorraine Christ b
a Department of chemistry and biochemistry, laboratory of organometallic catalysis and coordination chemistry, Lebanese University,
faculty of sciences I, Haddath, Lebanon
b Institut de recherche sur la catalyse et l’environnement de Lyon, UMR 5256, 2, avenue Einstein, 69626 Villeurbanne cedex, France
A R T I C L E I N F O
A B S T R A C T
Article history:
A friendly method for the protection of diols and carbonyls catalysed by hexahydrated iron
(III) chloride has been developed. This method, which consists of the transformation of
diols and carbonyls to cyclic acetals, functions in mild conditions and it is efficient for a
wide range of diols.
Received 27 August 2010
Accepted after revision 6 December 2010
Available online 3 February 2011
ß 2011 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
Keywords:
Cyclic acetal
Diol
´
´
R E S U M E
Carbonyl
Iron
´
´
Une methode simple pour la protection des diols et des carbonyls catalysee par le chlorure
´ ´
´
´
´
`
de fer (III) a ete developpee. Cette methode qui consiste a la transformation des diols et des
carbonyls en ace´tales cycliques, fonctionne dans des conditions douces et elle est efficace
Protection
´ ´
pour une variete large des diols.
´
´
´
´
ß 2011 Academie des sciences. Publie par Elsevier Masson SAS. Tous droits reserves.
Reactions which generate cyclic acetals are important
for the protection of carbonyl groups in organic synthesis
[1] as well as for the protection of alcohol groups in
carbohydrates [2]. Cyclic acetals are equally important for
the generation of chiral auxiliaries for asymmetric induc-
tion [3] and for the production of polymers, pharmaceu-
ticals, cosmetics and fragrances [4–6]. The development of
new methods and the modification of existing ones for
making acetals are therefore considered as an important
challenge. Recently, it has been described that cyclic
acetals with five to eight membered rings can be obtained
by reactions between alkynes and diols catalysed by
cationic gold (I) catalyst [7]. Epoxides can be converted
directly to cyclic acetals, with only five membered rings,
called acetonides, in the presence of acetone and catalysed
by a Lewis acid [8]. Classical methods to obtain cyclic
acetals involve the reaction of an aldehyde or a ketone with
an alcohol, catalysed by toluenesulfonic acid, with
azeotropic removal of water or transacetalization reac-
tions. When the ketone is not stable, this procedure
involves a large excess of reactant and tedious work-up
procedures [1,9]. More convenient and useful methods,
under mild conditions, for the production of cyclic acetals
of various carbonyls compounds in excellent yields were
recently reported, some were using catalytic amounts of
tetrabutylammonium tribromide [10] or ZrCl4 [11] in the
presence of trialkyl orthoformate, and others were using
silylated alcohols with catalytic amounts of trimethylsilyl
trifluoromethanesulfonate (TMSOTf) as Lewis acid [12].
Recently, it has been shown that ZrCl4 is an efficient
catalyst for one-pot protection/deprotection of diols,
where 2,2-dimethoxypropane (DMP) is the protecting
agent, forming cyclic acetals [13]. However, there is still a
scope for further improvement in this field since there is no
* Corresponding author.
E-mail address: iyad.karameh@ul.edu.lb (I. Karame´).
1631-0748/$ – see front matter ß 2011 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.crci.2010.12.001

[
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I. Karame et al. / C. R. Chimie 14 (2011) 525–529
´
hexahydrated Fe (III) trichloride as a catalyst (Scheme 1).
FeCl3.6H2O (10 mol%)
Acetone, r.T.
OH OH
R'
O
O
n
This method is proved to be useful for a wide range of
substrates. A few examples using anhydrous FeCl3 as a
catalyst have been reported in carbohydrate chemistry
[14].
R
n
R
R'
Scheme 1. Iron (III) chloride catalyses the transformation of diols into
In a preliminary experiment, 1,2-butanediol d5 (Table
1, entry five) was stirred with 10 mol% of hexahydrated
FeCl3 and acetone at room temperature for two hours and
were subjected to the conditions of the reactions. The
results are summarized in Table 1.
acetonides.
efficient method yet for the preparation of cyclic acetals
directly from carbonyls and diols without the assistance of
additives or co-catalysts.
The conversion of 1,2-diol type d1-d5,
a-aromatic
We report here an efficient and easy method for the
preparation of cyclic acetals from diols and carbonyls using
substituted and aliphatic diols (Table 1, entries one to five)
to the corresponding 1,3-dioxalanes was much faster than
Table 1
FeCl3.6H2O catalyses conversion of diol to acetonides in acetone.
Entry
1
Substrate
OH
Conversion (%)
100a
Product
Isolated yield (%)
98
O
OH
[TD$INLINE]
[
O
d1
OH OH
1
2
100
98
O
[DT$INLE]
O
[TD$INLINE]
d2
HO
2
3
100
98
OH
O
O
[TD$INLINE]
[DT$INLE]
d3
HO
3
4
74 (100)b
98
OH
[TD$INLINE]
O
O
[DT$INLE]
d4
4
5
6
100
100
98
98
OH
[TD$INLINE]
O
[DT$INLE]
OH
O
d5
OH OH
[TD$INLINE]
5
[DT$INLE]
O
O
d6
6
65 (78)b
74
50
OH
[TD$INLINE]
O
O
OH
[TD$INLE]
7
8
d7
7
50
OH
O
O
[
[TD$INLE]
OH
d8
8
a
After 30 minutes.
b
After 24 hours.

I. Karame´ et al. / C. R. Chimie 14 (2011) 525–529
527
the conversion of 1,4-diols type d7-d8 (Table 1, entries
seven and eight). This is due to the chelation effect, where
diols with closer hydroxyl functions can be coordinated
more easily than diols with farther hydroxyl functions.
However, the transformation of 1,3-diols such as 2,4-
pentanediol was as easy as 1,2-diols type. A diastereomeric
mixture of diols d3, d4, d6 and d8 yielded a diastereomeric
mixture of acetonides in different ratios as observed by GC-
MS and 1H NMR of the reaction products.
In order to further explore the scope of the catalytic
process presented here, we have studied a series of
reactions involving different combinations of two selected
diols with four different carbonyls (Table 2). The diol d1 or
d6 was dissolved in THF with one equivalent of carbonyl
Table 2
FeCl3.6H2O catalyses direct formation of cyclic acetals from diols and carbonyls.
Entry
1
Diol
d1
Carbonyl
Conv.a
30
Product
Isolated yield (%)
30
O
[DT$INLE]
O
[
9
O
2
3
d1
d1
97
95
60
O
[DT$INLE]
O
]
10
O
16(60)b
[DT$INLE]
O
O
O
]
11
O
4
d1
73
70
O
O
[DT$INLE]
H
]
12
O
5
d6
8
6
[DT$INLE]
[
13
O
O
O
6
7
d6
d6
100
98
60
O
[DT$INLE]
]
14
O
64
[DT$INLE]
O
[
15
O
O
O
O
8
d6
100
99
O
[DT$INLE]
H
E
16
a
Conversion of carbonyl.
After 24 hours.
b

[
´
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I. Karame et al. / C. R. Chimie 14 (2011) 525–529
R1 R2
OH OH
R'
O
O
O
n
FeCl3.6H2O (10 mol %)
+
R
R1
R2
R
R'
n
THF, r.T.
d1: R= Ph, R'= H
d6: R=R'= Me
Scheme 2. Iron (III) catalyses the transformation of diols and carbonyls into cyclic acetals.
compound and 10 mol% of hexahydrated FeCl3 and stirred
at room temperature for two hours producing the
corresponding cyclic acetal1 (Scheme 2).
Reactions between cyclohexanone and d1 as well as
d6 were almost completely done with a quantitative yield
(> 95 %) (Table 2, entries two and six). However, when 2-
phenylpropanone is used, yields were less important than
those obtained with cyclohexanone (Table 2, entries three
and seven) but much higher than the yields obtained with
acetophenone (Table 2, entries one and five).
It seems that this reaction is easier with aliphatic
ketones than benzylic and aromatic ones where the
conversions were not completed. The reaction of ortho-
methylbenzaldehyde with the diol d1 (Table 2, entry four)
leads to a good conversion, whereas, complete conversion
was obtained with diol d6 (Table 2, entry eight). The cyclic
acetals (entries one, three, four, five, seven and eight)
obtained in the examples shown in Table 2, exhibit new
stereogenic centre except those with cyclohexanone. The
use of optically pure diols may induce the stereochemistry
of the formed stereogenic centre, this will constitute the
object of a future study.
In conclusion, a new method for the preparation of
acetonides and cyclic acetals was developed using FeCl3, a
very cheap and friendly catalyst. This method uses diols as
substrates for the preparation of cyclic acetals of not only
five membered rings (as with the use of epoxides) but also
for cyclic acetals of six, seven and eight membered rings.
Furthermore, this friendly procedure uses ketones, which
are commercially available worldwide, and it can be also
used for the protection of diols as well as of ketones and
aldehydes.
1
General procedure of the protection of diols with acetone: a 10 mL
vial containing a Teflon1-coated stirring bar was charged with FeCl3
(27 mg, 0.1 mmol), acetone (1 mL) and the diol (1 mmol). The resulting
solution was stirred at room temperature for two hours. Acetone was
removed with a rotary evaporator, and the product was purified on silica
gel column chromatography (cyclohexane-AcOEt = 80:20). Its purity
(> 98%) was determined by 1H NMR. Conversions were determined by
GC coupled with MS. All the final products were isolated and
characterized by comparison of their 1H NMR spectra with already
reported data (1, [15] 2, [16] 3, [17] 4, [18] 5, [19] 6, [20]). We report here
the 1H and 13C NMR for the new compounds: 7, 1H NMR (CDCl3, 300 MHz),
d (ppm): 3.85 (m, 1H, O-CH), 3.35 (t, 2H, J = 6.8 Hz), 1.2–1.5 (m, 4H, CH2),
1.25 (s, 6H, O2C(CH3)2, 1.2 (d, 3H, J = 6 Hz). 13C NMR (CDCl3, 75.5 MHz), d
(ppm): 108, 73, 67, 34, 27, 25, 21.7. 8 1H NMR (CDCl3, 300 MHz), d (ppm):
3.85 (m, 2H, O-CH), 1.2–1.5 (m, 4H, CH2), 1.25 (s, 6H, O2C(CH3)2), 1.2 (d,
6H, J = 6 Hz). 13C NMR (CDCl3, 75.5 MHz), d (ppm): 105, 74, 32, 28,
22.procedure for the protection of diols/ketones: a 10 mL vial containing a
Teflon1-coated stirring bar was charged with FeCl3 (27 mg, 0.1 mmol),
THF (1 mL), ketone (1mmol) and diol (1 mmol). The resulting solution was
stirred at room temperature for two hours. Then THF was removed and
the product was purified on silica gel column chromatography
(cyclohexane-AcOEt = 80:20). Its purity (> 98%) was determined by 1H
NMR. Conversions were determined by GC-MS. All the final products were
isolated and characterized by comparison of their 13C and 1H NMR spectra
with already reported data (9, [21] 10, [22] 13, [7] 14, [23]). We report
here the 1H and 13C NMR for the new compounds: 11 (tow
diastereomers): 1H NMR (CDCl3, 300 MHz), d (ppm): 7.1–7.3 (m, 20H,
Ar), 4.95 (dd, 1H, JHH = 6.7 and 8.9 Hz) 4.7 (dd, 1H, JHH = 3.5 and 8.2 Hz),
4.61 (dd, 1H, JHH = 6.7 and 8.4 Hz), 4.13 (dd, 1H, JHH = 0.8 and 6.15 Hz), 4.1
(dd, 1H, JHH = 0.87 and 6.2 Hz), 3.32 (dd, 1H, JHH = 7.9 and 8.8 Hz), 3.02 (s,
2H, CH2-Ar), 2.95 (s, 2H, CH2-Ar), 1.4 (s, 3H, CH3), 1.35 (s, 3H, CH3). 13C
NMR (CDCl3, 75.5 MHz), d (ppm): 138, 137, 131, 130.6, 128.5, 128, 127,
126.7, 110, 77, 72, 46, 25. 12 (two diastereomers): 1H NMR (CDCl3,
300 MHz), d (ppm): 7.65 (m, 1H, Ar), 7.59 (m, 1H, Ar), 7.15–7.45 (m, 14H,
Ar), 6.3 (s, 1H, -(O)2-CH-Ar), 6.13 (s, 1H, -(O)2-CH-Ar), 5.18 (dd, 2H,
JHH = 7.4 and 6.8 Hz), 4.5 (dd, 1H, JHH = 8.3 and 6.33 Hz), 4.0 (dt, 1H,
JHH = 7.6 Hz), 3.9 (dt, 1H, JHH = 7 and 0.6 Hz), 3.75 (dt, 1H, JHH = 7.5 Hz),
2.45 (s, 3H, CH3-Ar), 2.44 (s, 3H, CH3-Ar). 13C NMR (CDCl3, 75.5 MHz), d
(ppm): 137, 136.6, 135, 130, 128.5, 128, 127, 126.7, 126, 125.7, 103, 79,
72, 17. 15 (tow diastereomers): 1H NMR (CDCl3, 300 MHz), d (ppm): 7–7.4
(m, 10H, Ar), 3.85 (m, 4H, -CH-), 3.07 (s, 2H, -CH2-Ar), 2.82 (s, 2H, -CH2-
Ar), 1.05–1.26 (m, 4H, -CH2-), 1.2 (s,3H, CH3), 1.13 (d, 3H, CH3,
JHH = 5.8 Hz), 1.1 (s, 3H, CH3), 1 (d, 3H, CH3, JHH = 5.6 Hz). 13C NMR
(CDCl3, 75.5 MHz), d (ppm): 139, 128, 127, 126, 101, 73, 45, 40, 25, 22. 16
(two diastereomers): for one diastereomer 1H NMR (CDCl3, 300 MHz), d
(ppm): 7.6 (m, 1H, Ar), 7.22 (m, 2H, Ar), 7.12 (m, 1H, Ar), 5.97 (s, 1H, CH-
Ar), 4.5 (m, 1H, OCH-), 4.2 (m, 1H, OCH-), 2.4 (CH3-Ar), 1.65 (m, 1H, -HCH-
), 1.51 (d, 3H, -CH3, JHH = 6.5 Hz), 1.46 (m, 1H, -HCH-), 1.29 (d, 3H, -CH3,
JHH = 6.5 Hz). For other diastereomer 1H NMR (CDCl3, 300 MHz), d (ppm):
7.6 (m, 1H, Ar), 7.22 (m, 2H, Ar), 7.12 (m, 1H, Ar), 5.62 (s, 1H, CH-Ar), 9.96
(m, 2H, OCH2-), 2.4 (CH3-Ar), 1.6 (m, 1H, -HCH-), 1.4–1.42 (m, 1H, -HCH-),
1.30 (d, 3H, -CH3, JHH = 6.5 Hz). 3C NMR (CDCl3, 75.5 MHz), d (ppm): 137,
135, 130, 128, 126, 125.7, 99, 73, 40.5, 21.6, 17.
Acknowledgments
We acknowledge Dr. Iman Saad, director of the
department of chemistry and biochemistry, and Prof.
Bassam Badran for their logistical support.
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