Silica phosphoric acid: An efficient and recyclable catalyst for the solvent-free synthesis of acylals and their deprotection in MeOH

Article abstract of DOI:10.1080/00397910903398650

Silica phosphoric acid was used as an efficient, mild, and recyclable solid catalyst for the synthesis of acylals from various structurally diverse aldehydes and acetic anhydride under solvent-free conditions. The acylation of aldehydes was highly chemoselective, and no ketone was acylated, which provided a method for the synthesis of acylals from aldehydes in the presence of ketones. Silica phosphoric acid-catalyzed deprotection of acylals to the corresponding aldehydes in MeOH has also been developed with excellent yield. The deprotection of the acylals of aromatic aldehydes took priority over those of aliphatic aldehydes. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903398650

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Silica Phosphoric Acid: An Efficient and
Recyclable Catalyst for the Solvent-
Free Synthesis of Acylals and Their
Deprotection in MeOH
Fuyi Zhang a , Hong Liu a , Qing-Ju Zhang a , Yu-Fen Zhao a & Feng-
Ling Yang a
a Chemistry Department , Key Laboratory of Chemical Biology and
Organic Chemistry of Henan Province, New Drug Research and
Development Center, Zhengzhou University , Zhengzhou, China
Published online: 04 Oct 2010.
To cite this article: Fuyi Zhang , Hong Liu , Qing-Ju Zhang , Yu-Fen Zhao & Feng-Ling Yang (2010)
Silica Phosphoric Acid: An Efficient and Recyclable Catalyst for the Solvent-Free Synthesis of Acylals
and Their Deprotection in MeOH, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:21, 3240-3250, DOI: 10.1080/00397910903398650
To link to this article: http://dx.doi.org/10.1080/00397910903398650
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Synthetic Communications1, 40: 3240–3250, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903398650
SILICA PHOSPHORIC ACID: AN EFFICIENT AND
RECYCLABLE CATALYST FOR THE SOLVENT-FREE
SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
IN MeOH
Fuyi Zhang, Hong Liu, Qing-Ju Zhang, Yu-Fen Zhao, and
Feng-Ling Yang
Chemistry Department, Key Laboratory of Chemical Biology and Organic
Chemistry of Henan Province, New Drug Research and Development Center,
Zhengzhou University, Zhengzhou, China
Silica phosphoric acid was used as an efficient, mild, and recyclable solid catalyst for the
synthesis of acylals from various structurally diverse aldehydes and acetic anhydride under
solvent-free conditions. The acylation of aldehydes was highly chemoselective, and no
ketone was acylated, which provided a method for the synthesis of acylals from aldehydes
in the presence of ketones. Silica phosphoric acid–catalyzed deprotection of acylals to the
corresponding aldehydes in MeOH has also been developed with excellent yield. The depro-
tection of the acylals of aromatic aldehydes took priority over those of aliphatic aldehydes.
Keywords: Acylal; acylation; silica phosphoric acid; solvent-free
INTRODUCTION
Acylals (1,1-diacetates) are one of the essential carbonyl protecting groups
because of their stability in basic media as well as under acidic conditions.[1,2] In
addition, acylals are useful precursors and important synthons that have many syn-
thetic applications. For example, acylals are synthetically important precursors for
the preparation of 1-diacetoxydienes for Diel–Alder reactions.[3] The acylal function-
ality can be converted into other functional groups by reaction with appropriate
nucleophiles.[4–6] The preparation of homoallyl acetates by allylation of 1,1-diace-
tates has also been reported.[7] A novel synthesis of chiral allylic esters have been
developed using palladium-catalyzed asymmetric allylic alkylation of gem-diesters.[8,9]
Moreover, acylals are also used in the total syntheses of sphingofungins E and F.[10]
Generally, acylals can be prepared by the reaction of the aldehydes with acetic
anhydride in the presence of an acid catalyst, and some of the reported catalysts
include strong protic acid,[11,12] PCl3,[13] I2,[14] Sc(OTf)3,[15] Cu(OTf)2,[16] NBS,[17]
Bi(OTf)3,[18] FeCl3,[2,19] ceric ammonium nitrate (CAN),[20] LiBF4,[21] H2NSO3H,[22]
Received July 26, 2009.
Address correspondence to Fuyi Zhang, Chemistry Department, Key Laboratory of Chemical
Biology and Organic Chemistry of Henan Province, New Drug Research and Development Center,
Zhengzhou University, Zhengzhou, China. E-mail: zhangfy@zzu.edu.cn
3240

SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
3241
(NH4)3PW12O40,[23]
H6P2W18O62 ꢀ 24H2O,[24]
AlPW12O40,[25]
In(OTf)3,[26]
Bi(NO3)3 ꢀ 5H2O,[27] b-zeolite,[28] Zn–montmorillonite,[29] and P2O5=Al2O3.[30] Some
of the reported methods have convenient protocols, but many of them suffer from
the disadvantages such as oxidizing conditions, corrosion or moisture sensitivity
of the catalyst, high temperature, long reaction times, high cost, high toxicity, and
cumbersome procedures. Moreover, some of these are not chemoselective in terms
of aldehydes and ketones, and very few reports are applicable to both the synthesis
and deprotection of acylals.[15,23] Consequently, it is necessary to develop alternative
methodology using a mild, highly efficient, inexpensive, and reusable catalyst for the
synthesis and deprotection of acylals.
Solid-acid catalysts and solvent-free reactions have many advantages such as
safety, economy, ease in handling, low toxicity, fast reaction times, easy separation, reu-
sability of the catalyst, and easy workup procedures. In continuation of our studies on
the application of solid acids, we report the synthesis of acylals from aldehydes under
solvent-free conditions and their cleavage into parent aldehydes in MeOH catalyzed by
silica phosphoric acid (SPA), a highly efficient and reusable catalyst.
RESULTS AND DISCUSSION
SPA was easily and cleanly prepared by stirring a mixture of silica chloride[31]
and phosphoric acid in CH2Cl2 at rt followed by filtration (Scheme 1). The reaction
of benzaldehyde 1a (Table 1) with 2.8 equivalents of acetic anhydride was performed
in the presence of SPA (2.5 mol%) to produce the corresponding acylal 2a in 88% yield
in a short time under solvent-free conditions. When the reaction was carried out in
various solvents such as cyclohexane, CH2Cl2, MeCN, and EtOAc, the acylal 2a
was afforded in less yield than under solvent-free conditions. The effect of the catalyst
loading on the reaction indicated that less than 2.5 mol% of SPA led to incomplete
acylation. We therefore employed the optimal conditions for conversion of various
aromatic and aliphatic aldehyde 1a–x to the corresponding acylals 2a–x (Table 1).
Acylation of aldehydes using Ac2O catalyzed by SPA under solvent-free con-
ditions at rt exhibited high efficiency. Various structurally diverse aldehydes were
converted to their corresponding acylals in excellent yield in a short reaction time.
A
wide variety of aromatic aldehydes with both electron-donating and
electron-withdrawing groups underwent acylation in good to excellent yields
(Table 1, entries 2–13). 4-Hydroxybenzaldehyde 1l and vanillin 1m (Table 1, entries
12 and 13) gave a mixture of products under identical reaction conditions, but using
4.0 equivalents of acetic anhydride led to the corresponding triacetates in 82% and
80% yield, respectively, within 50 min. However, when their free 4-hydroxy groups
were acetylated and then reacted with 2.8 equivalents of acetic anhydride in the
presence of 2.5 mol% SPA, the aldehydes were converted into the corresponding
triacetates cleanly within 40 min. Under the same conditions, acylation of
Scheme 1. The preparation of silica phosphoric acid.

3242
F. ZHANG ET AL.
Table 1. Silica phosphoric acid–catalyzed synthesis of acylals under solvent-free conditions and their
deprotection in MeOH at rt
Acylal
Yield (%)a,b
Deprotection
Entry
Aldehyde=ketone
C6H5CHO (1a)
Time (min)
Time (min)
Yield (%)a
1
2
35
40
40
40
30
30
35
25
25
25
30
50
45
10d
35
45
50
30
35
35
35
30
10d
10d
88[26]
90[13]
86[26]
78[26]
91[26]
91[32]
83[23]
91[30]
94[26]
93[26]
88[30]
82[30],c
80[26],c
NR
50
65
60
65
45
45
55
45
50
40
40
55
50
91
90
89
86
90
92
87
90
92
90
92
85
82
4-MeC6H4CHO (1b)
3- MeOC6H4CHO (1c)
4-MeOC6H4CHO (1d)
Piperonal (1e)
3
4
5
6
4-BrC6H4CHO (1f)
4-ClC6H4CHO (1g)
2,6-Cl2C6H3CHO (1h)
2- NO2C6H4CHO (1i)
4-NO2C6H4CHO (1j)
4-CNC6H4CHO (1k)
4-OHC6H4CHO (1l)
Vanillin (1m)
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4-Me2NC6H4CHO (1n)
4-MeCOC6H4CHO (1o)
4-AllylOC6H4CHO (1p)
4-TBDMSOC6H4CHO (1q)
Cinnamaldehyde (1r)
2-Furfuraldehyde (1s)
Me(CH2)4CHO (1t)
3-Ph(CH2)2CHO (1u)
Me2CHCHO (1v)
83[32]
87[32]
84[32]
88[30]
70[30]
84[23]
83[30]
80[30]
NRe
65
70
65
70
50
89
85
81
80
90
92
90
87
3d
4d
3.5d
C6H5COMe (1w)
Cyclohexanone (1x)
NRe
aThe isolated yield.
bAll the products were characterized by 1H NMR, IR, and mass spectroscopy.
c4.0 equivalents of Ac2O.
dTime in hours.
eNR, no reaction.
4-(dimethylamino)benzaldehyde 1n failed even after stirring for more than 10 h at rt,
and the starting material 1n was recovered (Table 1, entry 14). This may be because
the strong electron-donating dimethylamino group reduced the reactivity.[22] 4-Acet-
ylaldehyde 1o can be chemoselectively converted into the corresponding 4-acetylben-
zaldiacetate 2o in good yield, and no side product from the acylation of the keto
group was observed (Table 1, entry 15). This procotol was then extended to aromatic
aldehydes with allyl and TBDMS group (Table 1, entries 16 and 17). The acylation
reactions proceeded smoothly with the protecting group kept intact, indicating the
tolerance of acid-sensitive groups under the present conditions. Likewise,
acid-sensitive aldehydes like cinnamaldehyde 1r and 2-furfuraldehyde 1s (Table 1,
entries 18 and 19) can also be converted into the desired acylals in moderate or good
yield within short times.

SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
3243
The present protocol was also very effective for the aliphatic aldehydes, and the
acylation reaction proceeded successfully in excellent high yield (Table 1, entries
20–22). Steric hindrance seems to have no effect on the efficiency of this conversion.
We also investigated acylation of ketones such as 4-acetophenone 1w and cyclohex-
anone 1x (Table 1, entries 23 and 24). Unfortunately, no corresponding products
were obtained.
To check the reusability of the catalyst, the reaction of 4-methylbenzaldehyde
1b with 2.8 equivalents of acetic anhydride was performed using 2.5 mol% SPA at rt.
After completion of the reaction, the catalyst was filtered off, washed with CH2Cl2,
and dried under vaccum. It was used for the next run, and the recovered SPA was
reused for two more subsequent runs. The third run even gave the desired acylal
2b in 80% yield.
To investigate the chemoselectivity for acylation of aldehydes using SPA as a
catalyst, we compared the acylation of 4-nitrobenzaldehyde versus benzaldehyde,
4-methoxybenzaldehyde, and hexanal (Table 2, entries 1–3) and found the presence
of electron-withdrawing group ꢁNO2 on the aromatic aldehyde facilitated the acyla-
tion and led to high chemoselectivity. The acylation of benzaldehyde versus aceto-
phenone and cyclohexanone was also compared (Table 2, entries 4 and 5). The
benzaldehyde was fully acylated, keeping keto substrates intact.
Deprotection of acylals to their parent aldehydes is another important manipu-
lation. The (H2SO4, HCl[11]) reported methods included the use of solid acids such as
protonic acids and Lewis acids [Sc(OTf)3,[15] BiCl3,[33] ceric ammonium nitrate
Table 2. Chemoselective acylation of aldehydes using Ac2O catalyzed by silica phosphoric acid at rt
Entry
1
Aldehyde=Ketone
Producta
2
3
4
5
aThe yields refer to the isolated pure products.

3244
F. ZHANG ET AL.
(CAN),[20] (NH4)3PW12O40,[23] CBr4,[34] and InBr3-PEG-400[35]]. However, most of
the catalysts were expensive and not reusable. We developed a method for solid acid
SPA-catalyzed deprotection of acylals to the corresponding aldehydes using pre-
viously prepared acylals. As shown in Table 1, benzaldiacetate 2a (10 mmol) in
MeOH (5 ml) was stirred at rt in the presence of SPA (3.0 mol%). The corresponding
benzaldehyde was obtained in 95% yield within 50 min. The generality of this pro-
cedure was then proved by the deprotection of various acylals, and the results are
summarized in Table 1. It is noteworthy that the deprotection of acylals catalyzed
by SPA in MeOH media is tolerant of acid-sensitive groups such as allyl, TBDMS,
styrenyl, and furyl (Table 1, entries 16–19). The deprotection of the acylals of ali-
phatic aldehydes needed much longer times than those of aromatic aldehydes
(Table 1, entries 20–22). Thus, SPA-catalyzed chemoselective deprotection of the
acylals of aromatic aldehydes took priority over the acylals of aliphatic aldehydes.
CONCLUSION
In conclusion, a mild, efficient, inexpensive, and reusable catalyst, SPA, has
been reported for the synthesis and deprotection of acylals at rt in excellent yield.
The synthesis of acylals from aldehydes was performed under solvent-free conditions
with high chemoselectivity, and no ketone was acylated under this conditions, which
provided a method for the synthesis of acylals from aldehydes in the presence of
ketones. Deprotection was carried out in MeOH, and the acylals of aromatic alde-
hydes took priority over those of aliphatic aldehydes. The generality for both syn-
thesis and deprotection was proved through the acylation of various structurally
diverse aldehydes under solvent-free conditions and the deprotection of acylals in
MeOH media. This method was tolerant of acid-sensitive groups. Further investi-
gation on the new application of SPA is currently under way in our laboratory.
EXPERIMENTAL
General
All of the products are known compounds and were characterized by compari-
sion of their spectroscopic data with those reported in the literature. Melting points
were determined on a WC-1 melting-point apparatus and are uncorrected. Infrared
(IR) spectra were recorded on a Perkin-Elmer Fourier transform (FT)–IR 1750
1
spectrometer. H and 13C NMR spectra were recorded at ambient temperaturon
in CDCl3 on a Bruker DPX 400 instrument (400 MHz and 100 MHz, respectively).
High-resolution mass spectra (HRMS) were obtained on a Waters Micromass
Q-TOF MicroTM mass spectrometer.
Preparation of Silica Phosphoric Acid
A mixture of silica gel (3.0 g) and thionyl chloride (15 ml) in a flask equipped
with a condenser and a drying tube was refluxed for 40 h. The mixture was evapo-
rated to dryness and then dried completely in a high vacuum to give silica chloride
as a whitish-gray powder. A mixture of silica chloride (2.0 g) and phosphoric acid

SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
3245
(0.21 g, 2.1 mmol) in CH2Cl2 (5.0 ml) was stirred at rt for 2.5 h and then filtered,
washed with CH2Cl2, and dried in vacuo to give SPA as a white powder.
General Procedure for the Synthesis of Acylals
SPA (60 mg, 2.5 mol%) was added to a stirred solution of aldehyde 1a–1x
(15 mmol) in Ac2O (5.3 ml, 56 mmol). The mixture was stirred at rt until thin-layer
chromatography (TLC) (petroleum ether–EtOAc, 6:1 to 3:1) indicated the com-
pletion conversion of aldehyde. The mixture was then diluted with EtOAc, filtered,
and washed with EtOAc. The combined organic layer was washed with saturated
NaHCO3 solution and saturated brine, dried over anhydrous Na2SO4, and evapo-
rated in vacuo to afford the corresponding acylal (Table 1). The crude product
was recrystallized from CH3OH or chromatographed on silica gel (petroleum
ether–EtOAc, 8:1 to 4:1) for 2c, 2d, 2t, and 2u.
Selected Data
1,1-Diacetoxy-1-phenylmethane (2a). Mp 44–45 ꢂC; IR (KBr) n, cmꢁ1
,
3072, 3043, 2925, 1762, 1371, 1243, 1205, 1059, 1009, 763, 698; 1H NMR
(400 MHz, CDCl3) d, ppm, 7.61 (s, 1H), 7.42–7.21 (m, 5H), 1.92 (s, 6H); HRMS
(ESI): calcd. for C11H12NaO4([M þ Na]þ): 231.0633; found: 231.0610.
1,1-Diacetoxy-1-(4-methylphenyl)methane (2b). Mp 80–82 ꢂC; IR (KBr)
n, cmꢁ1, 2952, 1770, 1743, 1511, 1397, 1252, 1011, 960; 1H NMR (400 MHz, CDCl3)
d, ppm, 7.66 (s, 1H), 7.37 (d, J ¼ 8.2 Hz, 2H), 7.23 (d, J ¼ 8.2 Hz, 2H), 2.41 (s, 3H),
2.13 (s, 6H); HRMS (ESI): calcd. for C12H14NaO4([M þ Na]þ): 245.0790; found:
245.0753.
1,1-Diacetoxy-1-(3-methoxyphenyl)methane (2c). Oil; IR (film) n, cmꢁ1
,
1
3030, 2941, 2802, 1752, 1610, 1500, 1383, 1222, 1204, 1012, 790, 723; H NMR
(400 MHz, CDCl3) d, ppm, 7.56 (s, 1H), 7.31 (t, J ¼ 7.5 Hz, 1H), 7.14–7.03 (m,
2H), 6.81 (d, J ¼ 7.5 Hz, 1H), 3.71 (s, 3H), 2.02 (s, 6H); HRMS (ESI): calcd. for
C12H14NaO5([M þ Na]þ): 261.0739; found: 261.0731.
1,1-Diacetoxy-1-(4-methoxyphenyl)methane (2d). Oil; IR (film) n, cmꢁ1
3030, 2961, 2842, 1752, 1614, 1591, 1522, 1443, 1361, 1240, 1163, 1112, 1053,
,
1
1005, 970, 931, 832; H NMR (400 MHz, CDCl3) d, ppm, 7.62 (s, 1H), 7.45 (d,
J ¼ 8.7 Hz, 2H), 6.92 (d, J ¼ 8.7 Hz, 2H), 3.83 (s, 3H), 2.11 (s, 6H); HRMS (ESI):
calcd. for C12H14NaO5([M þ Na]þ): 261.0739; found: 261.0741.
1,1-Diacetoxy-1-(3,4-methylenedioxyphenyl)methane (2e). Mp 79–80 ꢂC;
IR (KBr) n, cmꢁ1, 3074, 3048, 2913, 1760, 1495, 1445, 1368, 1235, 1198, 1038,
1
1012, 926, 819; H NMR (400 MHz, CDCl3) d, ppm, 7.56 (s, 1H), 7.01–6.99 (m,
2H), 6.80 (d, J ¼ 8.4 Hz, 1H), 5.98 (s, 2H), 2.11 (s, 6 H); 13C NMR (100 MHz,
CDCl3) d, ppm, 168.7, 148.7, 147.8, 129.2, 120.9, 108.1, 106.9, 101.4, 89.6, 20.8;
HRMS (ESI): calcd. for C12H12NaO6([M þ Na]þ): 275.0532; found: 275.0523; calcd.
for C12H12KO6([M þ K]þ): 291.0271; found: 291.0325.

3246
F. ZHANG ET AL.
1,1-Diacetoxy-1-(4-bromophenyl)methane (2f). Mp 83–85 ꢂC; IR (KBr) n,
1
cmꢁ1, 3060, 2996, 1754, 1594, 1488, 1373, 1235, 1208, 1063, 1012, 973, 942, 826; H
NMR (400 MHz, CDCl3) d, ppm, 7.62 (s, 1H), 7.53 (d, J ¼ 8.4 Hz, 2H), 7.39 (d,
J ¼ 8.4 Hz, 2H), 2.12 (s, 6H); 13C NMR (100 MHz, CDCl3) d, ppm, 168.7, 134.4,
131.8, 128.4, 123.9, 89.1, 20.8; HRMS (ESI): calcd. for C11H11BrNaO4([M þ Na]þ):
308.9738; found: 308.9740; calcd. for C11H11BrKO4([M þ K]þ): 324.9478; found:
324.9544.
1,1-Diacetoxy-1-(4-chlorophenyl)methane (2g). Mp 82–83 ꢂC; IR (KBr)
n, cmꢁ1, 3060, 3002, 2938, 1756, 1597, 1486, 1373, 1085, 1061, 1013, 973, 942,
1
831, 552; H NMR (400 MHz, CDCl3) d, ppm, 7.63 (s, 1H), 7.45 (d, J ¼ 8.5 Hz,
2H), 7.37 (d, J ¼ 8.5 Hz, 2H), 2.12 (s, 6H); 13C NMR (100 MHz, CDCl3) d, ppm,
168.6, 135.7, 133.9, 128.8, 128.1, 89.0, 20.8; HRMS (ESI): calcd. for
C11H11ClNaO4([M þ Na]þ): 265.0244; found: 265.0232.
1,1-Diacetoxy-1-(2,6-dichlorophenyl)methane (2h). Mp 88–90 ꢂC; IR
(KBr) n, cmꢁ1, 3075, 1765, 1600, 1490, 1385, 1250, 1200, 1020, 930, 815; 1H
NMR (400 MHz, CDCl3) d, ppm, 8.31 (s, 1H), 7.34–7.12 (m, 3H), 2.11 (s, 6H);
HRMS (ESI): calcd. for C11H11Cl2NaO4([M þ Na]þ): 298.9854; found: 298.9843.
1,1-Diacetoxy-1-(2-nitrophenyl)methane (2i). Mp 85–86 ꢂC; IR (KBr) n,
cmꢁ1, 3105, 3053, 1760, 1742, 1524, 1360, 1232, 1200, 1090, 1013, 752, 710, 690;
1H NMR (400 MHz, CDCl3) d, ppm, 8.20 (s, 1H), 8.06 (d, J ¼ 8.0 Hz, 1H),
7.75–7.67 (m, 2H), 7.63–7.55 (m, 1H), 2.14 (s, 6H); HRMS (ESI): calcd. for
C11H11NNaO6([M þ Na]þ): 276.0484; found: 276.0479.
1,1-Diacetoxy-1-(4-nitrophenyl)methane (2j). Mp 125–127 ꢂC; IR (KBr) n,
1
cmꢁ1, 3092, 1763, 1612, 1535, 1342, 1212, 1203, 1093, 1005, 960, 850; H NMR
(400 MHz, CDCl3) d, ppm, 8.11 (d, J ¼ 9.0 Hz, 2H), 7.54 (d, J ¼ 9.0 Hz, 2H), 7.44
(s, 1H), 2.12 (s, 6H); HRMS (ESI): calcd. for C11H11NNaO6([M þ Na]þ):
276.0484; found: 276.0482; calcd. for C11H11NKO6([M þ K]þ): 292.0223; found:
292.0221.
1,1-Diacetoxy-1-(4-cyanophenyl)methane (2k). Mp 100–102 ꢂC; IR (KBr)
n, cmꢁ1, 3075, 2212, 1764, 1382, 1232, 1203, 1011, 830; 1H NMR (400 MHz, CDCl3)
d, ppm, 7.67 (s, 4H), 7.31 (s, 1H), 2.14 (s, 6H); HRMS (ESI): calcd. for
C12H11NNaO4([M þ Na]þ): 256.0586; found: 256.0581; calcd. for C12H11NKO4
([M þ K]þ): 272.0325; found: 272.0322.
1,1-Diacetoxy-1-(4-acetoxyphenyl)methane (2l). Mp 90–92 ꢂC; IR (KBr)
n, cmꢁ1, 3078, 3019, 2938, 1765, 1741, 1511, 1371, 1240, 1209, 1164, 1061, 1009,
956, 909, 673; 1H NMR (400 MHz, CDCl3) d, ppm, 7.66 (s, 1H), 7.54 (d, J ¼ 8.8 Hz,
Hz, 2H), 7.12 (d, J ¼ 8.6 Hz, 2H), 2.30 (s, 3H), 2.11 (s, 6H); 13C NMR (100 MHz,
CDCl3) d, ppm, 169.2, 168.7, 151.5, 133.0, 128.0, 121.8, 89.1, 21.1, 20.8; HRMS
(ESI): calcd. for C13H14NaO6([M þ Na]þ): 289.0688; found: 289.0671.
1,1-Diacetoxy-1-(4-acetoxy-3-methoxyphenyl)methane (2m). Mp 90–91 ꢂC;
IR (KBr) n, cmꢁ1, 3031, 3002, 2958, 2933, 1769, 1515, 1427, 1378, 1248, 1206, 1159,
1117, 995, 950, 895, 780; 1H NMR (400 MHz, CDCl3) d, ppm, 7.64 (s, 1H), 7.13–7.04
(m, 3H), 3.86 (s, 3H), 2.31 (s, 3H), 2.12 (s, 6H); 13C NMR (100 MHz, CDCl3) d, ppm,

SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
3247
168.8, 168.6, 151.1, 140.7, 134.2, 122.9, 119.2, 110.8, 89.2, 55.9, 20.8, 20.6; HRMS
(ESI): calcd. for C14H16NaO7([M þ Na]þ): 319.0794; found: 319.0800; calcd. for
C14H16KO7([M þ K]þ): 335.0533; found: 335.0580.
1,1-Diacetoxy-1-(4-acetylphenyl)methane (2o). Mp 58–60 ꢂC; 1H NMR
(400 MHz, CDCl3) d, ppm, 7.97 (d, J ¼ 8.4 Hz, 2H), 7.70 (s, 1H), 7.60 (d, J ¼ 8.4 Hz,
Hz, 2H), 2.61 (s, 3H), 2.11 (s, 6H); 13C NMR (100 MHz, CDCl3) d, ppm, 197.3,
168.6, 139.9, 137.8, 128.5, 126.8, 88.9, 26.6, 20.7; HRMS (ESI): calcd. for
C13H14NaO5 ([M þ Na]þ): 273.0739; found: 273.0730.
1,1-Diacetoxy-1-(4-allyloxyphenyl)methane (2p). Mp 40–42 ꢂC; IR (KBr)
n, cmꢁ1, 3105, 2988, 2952, 1758, 1613, 1529, 1427, 1372, 1243, 1208, 1068, 1005, 920;
1H NMR (400 MHz, CDCl3) d, ppm, 7.61 (s, 1H), 7.44 (d, J ¼ 8.6 Hz, 2H), 6.91 (d,
J ¼ 8.6 Hz, 2H), 5.97–6.11 (m, 1H), 5.40 (br d, J ¼ 17.4 Hz, 1H), 5.30 (br d,
J ¼ 10.4 Hz, 1H), 4.55 (d, J ¼ 4.8 Hz, 2H), 2.12 (s, 6H); 13C NMR (100 MHz, CDCl3)
d, ppm, 168.7, 158.6, 133.0, 128.1, 127.8, 118.0, 114.7, 89.9, 68.8, 20.8; HRMS (ESI):
calcd. for C14H16NaO5([M þ Na]þ): 287.0895; found: 287.0891.
1,1-Diacetoxy-1-(4-tertbutyldimethylsilyloxyphenyl)methane (2q). Mp
91–94 ꢂC; IR (CHCl3) n, cmꢁ1, 2935, 1768, 1612, 1512, 1374, 1238, 1214, 1160,
1006, 959, 862; 1H NMR (400 MHz, CDCl3) d, ppm, 7.58 (s, 1H), 7.02 (d, J ¼ 8.2 Hz,
Hz, 2H), 6.71 (d, J ¼ 8.2 Hz, 2H), 2.09 (s, 6H), 0.96 (s, 9H), 0.27 (s, 6H); HRMS
(ESI): calcd. for C17H26NaO5Si ([M þ Na]þ): 361.1447; found: 361.1442.
1,1-Diacetoxy-3-phenylprop-2-ene (2r). Mp 84–86 ꢂC; IR (KBr) n, cmꢁ1
,
1
3083, 3037, 2990, 2932, 1760, 1374, 1242, 1200, 1136, 1062, 995, 943, 749, 691; H
NMR (400 MHz, CDCl3) d, ppm, 7.43–7.29 (m, 6H), 6.85 (d, J ¼ 16.0 Hz, 1H),
6.20 (dd, J1 ¼ 16.0 Hz, J2 ¼ 6.4 Hz, 1H), 2.12 (s, 6H); 13C NMR (100 MHz, CDCl3)
d, ppm, 168.7, 135.6, 135.1, 128.8, 128.6, 127.0, 121.6, 89.7, 20.9; HRMS (ESI):
calcd. for C13H14NaO4([M þ Na]þ): 257.0790; found: 257.0790; calcd. for
C13H14NaO4([M þ K]þ): 273.0529; found: 273.0592.
1,1-Diacetoxy-1-(2-furyl)methane (2s). Mp 52–53 ꢂC; IR (KBr) n, cmꢁ1
,
1
3113, 2996, 1765, 1374, 1241, 1202, 1012, 751, 600; H NMR (400 MHz, CDCl3)
d, ppm, 7.71 (s, 1H), 7.40 (s, 1H), 6.45–6.31 (m, 2H), 2.10 (s, 6H); HRMS (ESI):
calcd. for C9H10NaO5([M þ Na]þ): 221.0426; found: 221.0423.
1,1-Diacetoxyhexane (2t). Oil; IR (film) n, cmꢁ1, 2970, 1751, 1460, 1372,
1
1235, 1202, 1090, 1024, 990, 650; H NMR (400 MHz, CDCl3) d, ppm, 6.61 (t,
J ¼ 5.52 Hz, 1H), 2.12 (s, 6H), 1.82–1.20 (m, 8H), 0.91 (t, J ¼ 5.5 Hz, 3H); HRMS
(ESI): calcd. for C10H18NaO4([M þ Na]þ): 225.1103; found: 225.1101.
1,1-Diacetoxy-3-phenylpropane (2u). Oil; IR (film) n, cmꢁ1, 3072, 3051,
1
2933, 1752, 1604, 1493, 1252, 1020, 752, 703, 610; H NMR (400 MHz, CDCl3) d,
ppm, 7.11 (s, 5H), 6.82 (t, J ¼ 6.0 Hz, 1H), 2.81–2.56 (m, 4H), 1.86 (s, 6H); HRMS
(ESI): calcd. for C13H16NaO4([M þ Na]þ): 259.0946; found: 259.0941.
1,1-Diacetoxy-2-methylpropane (2v). IR (film) n, cmꢁ1, 2982, 1773, 1480,
1384, 1232, 1210, 1011, 610; 1H NMR (400 MHz, CDCl3) d, ppm, 6.23 (d, J ¼ 5.6 Hz,
Hz, 1H), 1.71 (s, 6H), 0.82 (m, 1H), 0.64 (d, J ¼ 8.5 Hz, 6H); HRMS (ESI): calcd. for
C6H11O2([M ꢁ AcO]þ): 115.0759; found: 115.0751.

3248
F. ZHANG ET AL.
General Procedure for Deprotection of Acylals
SPA (47 mg, 3.0 mol%) was added to a stirred solution of acylal (10 mmol) in
MeOH (5 ml). The mixture was stirred at rt until TLC (petroleum ether–EtOAc, 6:1
to 3:1) indicated the completion conversion of acylal. The catalyst was filtered off
and washed with CH2Cl2. The combined organic layer was evaporated under
reduced pressure, and the residue was purified by flash chromatography on silica
gel (petroleum ether–EtOAc, 10:1 to 6:1) to give the pure corresponding aldehyde.
The products were characterized, and the spectroscopic data were identical with
those of the corresponding known aldehydes. The yields of the products are shown
in Table 1.
ACKNOWLEDGMENTS
The authors thank NNSF of China (No. 20972142), the State Key Laboratory
of Bio-organic and Natural Products Chemistry, Chinese Academy of Sciences (CAS),
the Natural Science Project of Henan Province (2009A150030, 082300420110), and
the Innovation Fund of Zhengzhou University (2008CXSY147) for financial support.
REFERENCES
1. Green, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; 3rd ed.; John Wiley
& Sons, Inc.: New York, 1999.
2. Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyaksha, S. N.; Pinnick, H. W.
Protecting groups in organic synthesis, part 8: Conversion of aldehydes into geminal
diacetates. J. Org. Chem. 1983, 48, 1765–1767.
3. Snider, B. B.; Amin, S. B. An improved synthesis of 1a,3b-dihydroxycholesta-5,7-diene.
Synth. Commun. 1978, 8, 117–125.
4. Sydnes, L. K.; Sandberg, M. The chemistry of acylals, part I: The reactivity of acylals
towards Grignard and organolithium reagents. Tetrahedron 1997, 53, 12679–12690.
5. Heerden, F. R.; Huyser, J. J.; Williams, B. D. G.; Holzapfel, C. W. Palladium-catalysed
substitution reactions of geminal allylic diacetates. Tetrahedron Lett. 1998, 39, 5281–5284.
6. Sandberg, M.; Sydnes, L. K. The chemistry of acylals, part II: Formation of nitriles by
treatment of acylals with trimethylsilyl azide in the presence of a Lewis acid. Tetrahedron
Lett. 1998, 39, 6361–6364.
7. Yadav, J. S.; Subba Reddy, B. V.; Madhuri, C.; Sabitha, G. Indium(III) chloride–
catalyzed allylation of gem-diacetates: A facile synthesis of homoallyl acetates. Chem.
Lett. 2001, 30, 18–19.
8. Trost, B. M.; Lee, C. B. Geminal dicarboxylates as carbonyl surrogates for asymmetric
synthesis, part I: Asymmetric addition of malonate nucleophiles. J. Am. Chem. Soc.
2001, 123, 3671–3686.
9. Trost, B. M.; Lee, C. B. Geminal dicarboxylates as carbonyl surrogates for asymmetric
synthesis, part II: Scope and applications. J. Am. Chem. Soc. 2001, 123, 3687–3696.
10. Trost, B. M.; Lee, C. gem-Diacetates as carbonyl surrogates for asymmetric synthesis:
Total syntheses of sphingofungins E and F. J. Am. Chem. Soc. 2001, 123, 12191–12201.
11. Tomita, M.; Kikuchi, T.; Bessho, K.; Hori, T.; Inubushi, Y. Studies on pilocereine and
related compounds, III: Synthesis of 2,20,3-trimethoxydiphenyl ether-40,5- and 40,6-dicar-
dicarboxaldehyde. Chem. Pharm. Bull. 1963, 11, 1484–1490.

SYNTHESIS OF ACYLALS AND THEIR DEPROTECTION
3249
12. Marshall, J. A.; Wuts, P. G. M. Stereoselective synthesis of racemic occidentalol and
related cis-fused hexahydronaphthalenes from m-toluic acid. J. Org. Chem. 1977, 42,
1794–1798.
13. Michie, J. K.; Miller, J. A. Phosphorus trichloride as catalyst in the preparation of 1,1-dia-
cetates from aldehydes. Synthesis 1981, 824.
14. Deka, N.; Kalita, D. J.; Borah, R.; Sarma, J. C. Iodine as acetylation catalyst in the
preparation of 1,1-diacetates from aldehydes. J. Org. Chem. 1997, 62, 1563–1564.
15. Agarwal, V. K.; Fonquerna, S.; Vennall, G. P. Sc(OTf)3, an efficient catalyst for forma-
tion and deprotection of geminal diacetates (acylals): Chemoselective protection of
aldehydes in presence of ketones. Synlett 1998, 849–850.
16. Chandra, K. L.; Saravanan, P.; Singh, V. K. An efficient method for diacetylation of
aldehydes. Synlett 2000, 359–360.
17. Karimi, B.; Seradj, H.; Ebrahimian, R. G. Mild and efficient conversion of aldehydes to
1,1-diacetates catalyzed with N-bromosuccinimide (NBS). Synlett 2000, 623–624.
18. Carrigan, M. D.; Eash, K. J.; Oswald, M. C.; Mohan, R. S. An efficient method for
the chemoselective synthesis of acylals from aromatic aldehydes using bismuth triflate.
Tetrahedron Lett. 2001, 42, 8133–8135.
19. Wang, C.; Li, M. A novel and efficient conversion of aldehydes to 1,1-diacetates catalyzed
with FeCl3=SiO2 under microwave irradiation. Synth. Commun. 2002, 32, 3469–3473.
20. Roy, S. C.; Banerjee, B. A mild and efficient method for the chemoselective synthesis of
acylals from aldehydes and their deprotections catalysed by ceric ammonium nitrate.
Synlett 2002, 1677–1678.
21. Yadav, J. S.; Reddy, B. V. S.; Venugopal, C.; Ramalingam, T. LiBF4-mediated conver-
sion of aldehydes to gem-diacetates. Synlett 2002, 604–606.
22. Jin, T. S.; Sun, G.; Li, Y. W.; Li, T. S. An efficient and convenient procedure for the prep-
aration of 1,1-diacetates from aldehydes catalyzed by H2NSO3H. Green Chem. 2002, 4,
255–256.
23. Satam, J. R.; Jayaram, R. V. (NH4)3PW12O40 as an efficient and reusable catalyst for the
synthesis and deprotection of 1,1-diacetates. Synth. Commun. 2008, 38, 595–602.
24. Romanelli, G. P.; Thomas, H. J.; Baronetti, G. T.; Autino, J. C. Solvent-free catalytic
preparation of 1,1-diacetates from aldehydes using a Wells–Dawson acid (H6P2W18O62
24H2O). Tetrahedron Lett. 2003, 44, 1301–1303.
ꢀ
25. Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F.; Amani, K. Aluminum dodecatungstopho-
sphate (AlPW12O40) as an efficient heterogeneous inorganic catalyst for the chemoselec-
tive synthesis of geminal diacetates (acylals) under solvent-free conditions. Tetrahedron
Lett. 2003, 44, 3951–3954.
26. Ghosh, R.; Maiti, S.; Chakraborty, A.; Halder, R. Indium triflate: A reusable catalyst for
expeditious chemoselective conversion of aldehydes to acylals. J. Mol. Catal. A 2004, 215,
49–53.
27. Aggen, D. H.; Arnold, J. N.; Hayes, P. D.; Smoter, N. J.; Mohan, R. S. Bismuth com-
pounds in organic synthesis: Bismuth nitrate–catalyzed chemoselective synthesis of acylals
from aromatic aldehydes. Tetrahedron 2004, 60, 3675–3679.
28. Kumar, P.; Hegde, V. R.; Kumar, T. P. An efficient synthesis of diacetates from aldehydes
using b-zeolite. Tetrahedron Lett. 1995, 36, 601–602.
29. Nagy, N. M.; Jakab, M. A.; Konya, J.; Antus, S. Convenient preparation of 1,1-diacetates
from aromatic aldehydes catalysed by zinc–montmorillonite. Appl. Clay. Sci. 2002, 21,
213–216.
30. Hajipour, A. R.; Zarei, A.; Ruoho, A. E. P2O5=Al2O3 as an efficient heterogeneous
catalyst for chemoselective synthesis of 1,1-diacetates under solvent-free conditions.
Tetrahedron Lett. 2007, 48, 2881–2884.

3250
F. ZHANG ET AL.
31. Zolfigol, M. A.; Shirini, F.; Zamani, K.; Ghofrani, E.; Ebrahimi, S. Silica phosphoric
acid=NaNO2 as a novel heterogeneous system for the coupling of thiols to their corre-
sponding disulfides. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 2177–2182.
32. Khan, A. T.; Choudhury, L. H.; Ghosh, S. Silica-supported perchloric acid (HClO4-SiO2):
A highly efficient and reusable catalyst for geminal diacylation of aldehydes under
solvent-free conditions. J. Mol. Catal. A 2006, 255, 230–235.
33. Mohammadpoor-Baltork, I.; Aliyan, H. Bismuth(III) chloride: An efficient and selective
catalyst for deprotection of 1,1-diacetates. Synth. Commun. 1999, 29, 2741–2746.
34. Ramalingam, T.; Srinivas, R.; Reddy, B. V. S.; Yadav, J. S. A mild and efficient cleavage
of gem-diacetates to aldehydes by CBr4. Synth. Commun. 2001, 31, 1091–1095.
35. Zhang, Z. H.; Yin, L.; Wang, Y. M.; Liu, J. Y.; Li, Y. Indium tribromide in poly(ethylene
glycol)(PEG): A novel and efficient recycle system for chemoselective deprotection of
1,1-diacetates. Green Chem. 2004, 6, 563–565.