Cerium(IV) triflate-catalyzed selective gem-diacetylation of aldehydes with acetic anhydride

Article abstract of DOI:10.1080/00397910701649106

It has been observed that a catalytic amount (0.1 mol%) of cerium(IV) triflate afforded geminal diacetates from aldehydes with acetic anhydride in toluene at ambient temperature. Ketones are not affected under these reaction conditions. The reaction is rapid and mild with good to high yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701649106

Synthetic Communicationsw, 38: 77–84, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701649106
Cerium(IV) Triflate-Catalyzed Selective
Gem-diacetylation of Aldehydes with Acetic
Anhydride
J. W. John Bosco and Anil K. Saikia
Department of Chemistry, Indian Institute of Technology Guwahati,
Guwahati, Assam, India
Abstract: It has been observed that a catalytic amount (0.1 mol%) of cerium(IV)
triflate afforded geminal diacetates from aldehydes with acetic anhydride in toluene
at ambient temperature. Ketones are not affected under these reaction conditions.
The reaction is rapid and mild with good to high yields.
Keywords: acetic anhydride, aldehyde, catalyst, cerium(IV) triflate, gem-diacetate,
selective
INTRODUCTION
Acylals are important intermediates in organic synthesis. They are used as an
alternative to acetals for the protection of aldehydes.[1] The acylals of a,b-
unsaturated aldehydes are important starting materials for the synthesis of syn-
thetically useful fine chemicals such as acetoxy dienes and vinyl acetate.[2]
They are also key intermediates for the synthesis of cumene,[3] bicyclo[3.3.1]-
nonan-9-one derivatives,[4] and multifunctionalized furanoid and cyclopenta-
noid compounds.[5] They act as cross-linking reagents for cellulose in cotton[6]
and serve as activators in the composition of the bleaching mixture used for
the treatment of wine-stained fabrics.[7] In addition, gem-diacetates are
useful key intermediates for the synthesis of benzonitrile[8] and homoallylic
Received May 15, 2007
Address correspondence to Anil K. Saikia, Department of Chemistry, Indian
Institute of Technology Guwahati, Guwahati 781039, Assam, India. E-mail: asaikia@
iitg.ernet.in
77

78
J. W. J. Bosco and A. K. Saikia
acetate[9] and are used as carbonyl surrogates for asymmetric synthesis.[10]
These are the key intermediates in the total synthesis of antifungal natural
product Sphingofungins E and F.[11]
Generally, acylals are prepared from aldehydes and acetic anhydride using
strong Brønsted acids (sulphuric acid[12] or Nafion-H[13]) or Lewis acids
(FeCl3[1] or ZnCl2[14]) as catalyst, but these methods are not attractive as these
reactions end up with low yields or long reaction times. Furthermore, acid-
sensitive groups are not tolerated. Some other reagents and catalysts have been
developed for this purpose, including PCl3,[15] iodine,[16] zeolite,[17]Sc(OTf)3,[18]
Cu(OTf)2,[19] N-Bromosuccinimide,[20] Bi(OTf)3,[21] WCl6,[22] zirconium sulfo-
phenyl phosphonate,[23] LiBF4,[24] ceric ammonium nitrate,[25] H2NSO3H,[26]
and Amberlyst-15.[27] Recently, AlPW12O40,[28] Zn(BF4)2,[29] Li(OTf),[30]
[32]
ZrCl4,[31] Bi(NO3)3 5H2O,
sulfated zirconia,[33] LiCl,[34] and InCl3/
.
[35]
Al2O3
have also been employed for the acylal synthesis. Many of these
methods have some drawbacks such as lack of substrate tolarence and generality,
long reaction times, high catalyst loading, low yield, noncatalytic reactions, and
use ofexpensive solvents. Therefore, the development of a more efficient alterna-
tive method that is faster, noncorrosive, clean, and environmentally benign and
has a better yield is of interest.
In continuation of our interest in acylal synthesis,[34] we were in search of
a catalytic, rapid, and high-yielding protocol for the acylal synthesis. As
[36]
is a commercially available, highly reactive, cheap,
.
Ce(OTf)4 xH2O
nontoxic, stable, and water-tolerant Lewis acid, we envisaged that this
might be a suitable catalyst for the acylal synthesis. In this article, the
.
efficacy of Ce(OTf)4 xH2O toward the selective gem-diacetylation of
aldehydes in very good yields under mild conditions is reported. When a
.
mixture of benzaldehyde, acetic anhydride and Ce(OTf)4 xH2O (0.1 mol%)
in toluene was stirred at room temperature, benzal diacetate was obtained in
95% yield within 5 min (Scheme 1).
To probe the generality of the reaction, a wide range of aromatic, unsatu-
rated, and aliphatic aldehydes were studied (Table 1). It was observed from
Table 1 that both activated and deactivated aromatic aldehydes gave the
corresponding acylals in very good yield. Interestingly, aliphatic aldehydes,
which are somehow sluggish for this transformation,[1,24,36] can be converted
to their corresponding diacetates in good yields within a few minutes.
Ketones remain unreacted under these reaction conditions. Therefore,
aldehydes can be chemoselectively protected in the presence of ketones.
Scheme 1.

Gem-diacetylation of Aldehydes with Acetic Anhydride
Table 1. Conversion of aldehydes to geminal diacetates
79
Entry
1
Substrate (a)
Time (min)
5
Product (b)
Yielda (%)
95
2
3
5
96
98
10
4
5
15
25
92
95
6
7
40
5
96
89
8
9
10
10
10
90
89
92
10
11
12
10
5
93
97
13
14
10
30
95
0
15
16
5
97
90
15
17
18
30
30
92b
95b
aYields refer to isolated yield. Compounds were characterized by GC, 1H, 13C NMR,
and IR spectra.
bTwo equivalents of acetic anhydride and 1 mol% of catalyst were used.

80
J. W. J. Bosco and A. K. Saikia
Acid-sensitive compounds such as 2-furylaldehyde, 2-thiophenecarboxalde-
hyde, and cinnamaldehyde are also protected as gem-diacetates in high
yields without any side products, which are normally observed under
strongly acidic conditions. Under these reaction conditions, many functional
groups such as methyl ether, thioether, ester, bromo, nitro, and olefins are unaf-
fected. Another advantage of this protocol is that it does not require dry or inert
reaction conditions. As far as the catalyst is concerned, it is commercially
available, stable to air and moisture, and very low catalyst loading
(0.1 mol%), which is required for this transformation.
In conclusion, an efficient catalytic method for gem-diacetylation of
aldehydes has been developed using cerium(IV) triflate as a catalyst.
TYPICAL EXPERIMENTAL PROCEDURE
In a typical experiment, a mixture of 4-methoxybenzaldehyde (4.2 m mol),
.
acetic anhydride (5.0 m mol), and Ce(OTf)4 xH2O (0.0042 m mol) in
toluene (4 ml) was stirred at room temperature for 5 min. After completion
of the reaction, the reaction mixture was diluted with ethyl acetate (10 ml)
and washed with water (10 ml). The organic layer was dried (Na2SO4) and
evaporated to leave the crude product, which was purified by column chrom-
atography over silica gel to give 96% of the product. Finally, the product was
characterized by spectroscopic methods. 1H NMR (300 MHz, CDCl3): d 2.10
(s, 6H, 2-OCOCH3), 3.80 (s, 3H, -OCH3), 6.74 (d, J ¼ 9 Hz, 2H, ArH), 7.35
(d, J ¼ 9 Hz, 2H, ArH), 7.40 [s, 1H, -CH(OAc)2]; 13C NMR (100 MHz,
CDCl3): d ¼ 21.4, 55.7, 90.0, 114.2, 127.92, 128.3, 160.7, 168.9; IR (neat):
2976, 1763, 1519, 1612, 1373, 1250 cm21
.
1,1-Diacetoxymethyl-3-nitrobenzene (6b)
1H NMR (400 MHz, CDCl3): d ¼ 2.17 (s, 6H, 2-OCOCH3), 7.60 (t, J ¼ 8.0 Hz,
1H, ArH), 7.72 (s, 1H, ArH), 7.84 (d, J ¼ 7.6 Hz, 1H, ArH), 8.25 (d, J ¼ 7.6 Hz,
1H, ArH), 8.37 [s, 1H, -CH(OAc)2]; 13C NMR (100 MHz, CDCl3): d ¼ 21.0,
88.48, 121.9, 124.6, 129.8, 132.9, 137.6, 148.3, 168.5; IR (neat): 2940, 1764,
1619, 1238, 1202, 1091, 1010 cm21
.
1,1-Diacetoxy-3-phenyl-2-propene (7b)
1H NMR (300 MHz, CDCl3): d ¼ 2.12 (s, 6H, 2-OCOCH3), 6.21 (dd,
J ¼ 15.9 and 6.3 Hz, 1H, 55CH-), 6.86 (d, J ¼ 15.9 Hz, 1H, Ph-CH55), 7.33
[m, 6 H, ArH, -CH(OAc)2]; 13C NMR (100 MHz, CDCl3): d ¼ 21.3, 90.0,
121.9, 127.2, 128.9, 129.0, 135.3, 135.8, 168.8; IR (neat): 2958, 1762,
1383, 1250, 1209, 1066 cm21
.

Gem-diacetylation of Aldehydes with Acetic Anhydride
81
1,1-Diacetoxy-2-heptene (8b)
1H NMR (400 MHz, CDCl3): d ¼ 0.90 (t, J ¼ 7.2 Hz, 3H, -CH3), 1.26–1.42
(brm, 4H, 2-CH2-), 2.06 (m, 2H, -CH2-), 2.10 (s, 6H, 2-OCOCH3), 5.50
(m, 1H, -CH-), 6.00 (m, 1H, -CH-), 7.07 [d, J ¼ 6.4 Hz, 1H, -CH(OAc)2];
13C NMR (100 MHz, CDCl3): d ¼ 14.2, 21.2, 22.5, 30.8, 31.9, 90.0, 123.2,
138.3, 168.7. IR (neat): 2961, 2932, 2874, 1763, 1372, 1242, 1206,
1008 cm21
.
1,1-Diacetoxynonane (9b)
1H NMR (400 MHz, CDCl3): d ¼ 0.87 (t, J ¼ 6.8 Hz, 3H, -CH3), 1.26–1.40
(brm, 12H, 6-CH2-), 1.74 (m, 2H, -CH2-), 2.07 (s, 6H, 2-OCOCH3), 6.75
[t, J ¼ 5.6 Hz, 1H, -CH(OAc)2]; 13C NMR (100 MHz, CDCl3): d ¼ 14.5,
21.2, 22.5, 23.7, 29.5, 29.7, 32.1, 33.5, 90.8, 169.1; IR (neat): 2927, 2859,
1760, 1245, 1114, 1009 cm21
.
1-Diacetoxymethylfuran (12b)
1H NMR (400 MHz, CDCl3): d ¼ 2.14 (s, 6H, 2-OCOCH3), 6.39 (dd, J ¼ 3.6
and 1.6 Hz, 1H), 6.52 (d, J ¼ 3.6 Hz, 1H), 7.45 (d, J ¼ 1.6 Hz, 1H), 7.71
(s, 1H); 13C NMR (100 MHz, CDCl3): d ¼ 21.1, 83.8, 110.0, 110.6, 143.8,
148.0, 168.5; IR (neat): 2940, 1767, 1240, 1066, 1009 cm21
.
4-Diacetoxymethyltoluene (15b)
1H NMR (400 MHz, CDCl3): d ¼ 2.11 (s, 6H, 2-OCOCH3), 2.36 (s, 3H,
-CH3), 7.21 (d, J ¼ 9Hz, 2H, ArH), 7.35 (d, J ¼ 9 Hz, 2H, ArH), 7.64 [s,
1H, -CH(OAc)2]; 13C NMR (100 MHz, CDCl3): d ¼ 21.4, 21.8, 90.1, 126.8,
130.0, 132.8, 140.0, 168.9; IR (neat): 2976, 1763, 1519, 1612, 1373,
1250 cm21
.
1-Diacetoxymethyl-4-methylbenzoate (16b)
1H NMR (400 MHz, CDCl3): d ¼ 2.13 (s, 6H, 2-OCOCH3), 3.91 (s, 3H,
-CO2CH3), 7.57 (d, J ¼ 9 Hz, 2H, ArH), 7.69 (s, 1H, -CH(OAc)2), 8.06
(d, J ¼ 9 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3): d ¼ 21.3, 52.7, 89.3,
126.9, 130.1, 131.5, 140.1, 166.5, 168.8; IR (neat): 2976, 1763, 1519, 1612,
1373, 1250 cm21
.

82
J. W. J. Bosco and A. K. Saikia
1-Diacetoxymethyl-4-methylthiobenzene (17b)
1H NMR (400 MHz, CDCl3): d ¼ 2.10 (s, 6H, 2-OCOCH3), 2.47 (s, 3H,
-SCH3), 7.23 (d, J ¼ 8.4 Hz, 2H, ArH), 7.40 (d, J ¼ 8.4 Hz, 2H, ArH), 7.60
(s, 1H, -CH(OAc)2]; 13C NMR (100 MHz, CDCl3): d ¼ 15.7, 21.2, 89.7,
126.2, 127.2, 132.1, 140.9, 168.7; IR (neat): 2997, 2931, 1759, 1597, 1224,
1068 cm21
.
10-Diacetoxymethylanthracene (18b)
1H NMR (400 MHz, CDCl3): d ¼ 2.07 (s, 6H, 2-OCOCH3), 7.46 (m, 2H,
ArH), 7.56 (m, 2H, ArH), 7.98 (d, J ¼ 8.4 Hz, 2H, ArH), 8.50 (s, 1H, ArH),
8.67 (d, J ¼ 9.2 Hz, 2H, ArH), 9.20 [s, 1H, -CH(OAc)2]; 13C NMR
(100 MHz, CDCl3): d ¼ 21.2, 87.61, 1248, 125.2, 126.8, 129.1, 130.0,
130.6, 131.4, 169.0; IR (neat): 2924, 2858, 1756, 1623, 1234, 1085 cm21
.
ACKNOWLEDGMENT
Authors are grateful to the Council of Scientific and Industrial Research
(CSIR), New Delhi, for financial assistance.
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