Efficient and chemoselective acetalization and thioacetalization of carbonyls and subsequent deprotection using InF3 as a reusable catalyst

Article abstract of DOI:10.1016/j.tetlet.2011.11.135

An efficient and chemoselective method for preparation of acetals and dithioacetals of aldehydes and their deprotection under catalysis of InF ₃ is described.

Full text of DOI:10.1016/j.tetlet.2011.11.135

Tetrahedron Letters 53 (2012) 697–701
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Efficient and chemoselective acetalization and thioacetalization
of carbonyls and subsequent deprotection using InF3 as a reusable catalyst
⇑
Sridhar Madabhushi , Kishore Kumar Reddy Mallu, Narsaiah Chinthala, China Ramanaiah Beeram,
Venkata Sairam Vangipuram
Fluoroorganics Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and chemoselective method for preparation of acetals and dithioacetals of aldehydes and
their deprotection under catalysis of InF3 is described.
Received 24 October 2011
Revised 24 November 2011
Accepted 26 November 2011
Available online 3 December 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Acetalization
Thioacetalization
InF3
Catalysis
Deprotection
Acetalization and thioacetalization are important transforma-
tions for the protection of a carbonyl group in multistep organic
synthesis. Acetals and dithioacetals tolerate a wide range of nucle-
ophilic, basic and organometallic reagents, reducing agents, and
nonacidic oxidants. Dithioacetals or dithianes are also useful for
the generation of masked carbonyl anions which are employed in
a C–C bond formation reaction known as Corey-Seebach reaction.1
Hence, studies on acetalization and thioacetalization of carbonyls
continue to receive high attention and several methods were
developed for acetalization and thioacetalization of carbonyls in
the literature.2 However, there is a dearth of methods for chemose-
lective acetalization and thioacetalization of carbonyls and the
existing methods3 suffer from one or more of the practical limita-
tions such as long reaction times, high catalyst loading, limited
substrate scope, use of toxic reagents and lack of commercial avail-
ability of the catalyst. In our recent study, we found an efficient
method for selective acetalization and thioacetalization of a variety
of aliphatic, aromatic, and heteroaromatic aldehydes using InF3 as
the catalyst as shown in Scheme 1 and under similar conditions,
ketones remained unreactive.
applications in organic synthesis have remained scarce in the
literature.
MeOH
R-CH(OMe)2
reflux
2a-h (>82%)
PhCH2OH
toluene, reflux
R-CH(OCH2Ph)2
3a-h (>83%)
O
Me2C(CH2OH)2
toluene, reflux
(CH2OH)2
R
O
4a-h (>92%)
No Reaction
toluene, reflux
InF3 (5 mol%)
R-CHO
H2C(CH2OH)2
1a-h
No Reaction
toluene, reflux
R= alkyl, aryl or heteroaryl
PhSH
R-CH(SPh)2
toluene, reflux
5a-h (>80%)
S
(CH2SH)2
toluene, reflux
R
In recent years, Indium (III) reagents, particularly InCl3, InBr3,
InI3, and In(OTf)3, have emerged as promising catalysts for various
organic transformations.4 When compared to these indium
reagents, InF3 has, however, less significance as a catalyst and its
S
6a-h (>82%)
S
R
CH2(CH2SH)2
toluene, reflux
S
7a-h (>80%)
⇑
Corresponding author. Tel.: +91 040 27191772; fax: +91 040 27160387.
E-mail address: smiict@gmail.com (S. Madabhushi).
Scheme 1. Acetalization and thioacetalization of an aldehyde using InF3 as
catalyst.
a
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.135

698
S. Madabhushi et al. / Tetrahedron Letters 53 (2012) 697–701
O
O
Cl
O
CHO
InF3
CH2Cl2, r.t., 3 h
InCl3
CH2Cl2, r.t., 3 h
OH
Ph
Scheme 2. Reactions of benzaldehyde and homoallyl alcohol in the presence of InF3 and InCl3.
Table 1
InF3 catalyzed synthesis of acetals and dioxanes
Entry
Acetal 2 % yielda (reaction time)
Acetal 3 % yielda (reaction time)
Dioxane 4 % yielda (reaction time)
OMe
OCH2Ph
Ph
O
Ph
Ph
a
OCH2Ph
O
OMe
87 (5h)
94 (4.5h)
86 (4h)
O
OMe
OCH2Ph
S
S
S
b
c
O
OMe
OCH2Ph
95 (4h)
87 (4.5h)
87 (4h)
O
OMe
OCH2Ph
O
O
O
O
OMe
OCH2Ph
96 (4h)
85 (4.5h)
85 (4h)
OMe
OCH2Ph
O
OMe
OCH2Ph
O
d
85 (5h)
82 (4h)
85 (4.5h)
98 (4.5h)
OMe
OMe
OCH2Ph
O
O
O2N
O2N
O2N
e
f
OCH2Ph
92 (5h)
83 (5h)
OMe
OCH2Ph
O
5
OCH2Ph
5
87 (4h)
OMe
5
O
86 (4h)
95 (3.5h)
OMe
OMe
OCH2Ph
O
g
OCH2Ph
O
86 (4h)
97 (3.5h)
90 (4h)
O
OMe
OMe
O
OCH2Ph
O
O
OCH2Ph
O
h
O
O
O
84 (4h)
86 (5h)
(95 (5h)
Isolated yields and all products gave satisfactory 1H, 13C NMR, IR, and Mass spectral data.
a
Recently, we were interested in the preparation of 4-fluoropy-
of InF3. In our preliminary study, we found a variety of aldehydes
such as benzaldehyde 1a, thiophene-2-carboxaldehyde 1b, furfural
1c, 2-napthaldehyde 1d, 4-nitrobenzaldehyde 1e, heptanal 1f,
cyclohexanecarboxaldehyde 1g, and chromone-3-carboxaldehyde
1h to undergo efficient acetalization with methanol and InF3 as a
catalyst under reflux condition producing corresponding acetals
2a–h in 82–87% yields. In a similar study, we observed efficient
acetalization of aldehydes 1a-h with benzylalcohol, which gave
corresponding dibenzylacetals 3a–h in 83–90% yields and also
with 2,2-dimethyl-1,3-propanediol giving corresponding dioxanes
rans by Prins reaction of a homoallylic alcohol and benzaldehyde
and we envisioned that InF3 could possibly promote this reaction
as Lee et al.,5 reported earlier formation of 4-chloropyrons using
InCl3. In our study, the expected Prins reaction, however, did not
proceed with InF3 but it was found to catalyze formation of acetal
of benzaldehyde with homoallyl alcohol in good yield (86%) as
shown in Scheme 2, which is hitherto not known in the literature.
The above observation prompted us to study the scope of ace-
talization of carbonyl groups with other alcohols under catalysis

S. Madabhushi et al. / Tetrahedron Letters 53 (2012) 697–701
699
Table 2
InF3 catalyzed synthesis of dithioacetals, dithiolanes, and dithianes
Entry
Thioacetal 5 % yielda (reaction time)
Dithiolanes 6 % yielda (reaction time)
Dithiane 7 % yielda (reaction time)
SPh
Ph
S
S
Ph
S
Ph
a
SPh
S
85 (5h)
85 (3h)
87 (4h)
S
S
SPh
S
S
S
85 (4h)
b
c
S
S
SPh
85 (4h)
87 (2,5h)
S
S
SPh
O
O
S
85 (4h)
O
S
SPh
87 (4h)
86 (2.5h)
SPh
S
S
S
SPh
S
d
86 (5h)
85 (3h)
85 (3.5h)
SPh
S
S
O2N
O2N
O2N
e
f
S
SPh
S
82 (5h)
80 (4h)
80 (4.5h)
SPh
S
S
S
5
SPh
5
S
5
85 (3.5h)
85 6h)
85 (3.5h)
SPh
S
S
S
g
S
SPh
84 (6h)
90 (3h)
83 (4.5h)
O
SPh
SPh
O
S
O
S
S
S
h
O
O
O
84 (4h)
86 (5h)
95(3.5h)
Isolated yields and all products gave satisfactory 1H, 13C NMR, IR, and Mass spectral data.
a
Table 3
4a–h in 92–98% yields as shown in Table 1.6 In our study,
acetalization reactions did not proceed with 1,2-ethanediol and
1,3-propanediol under similar conditions.
Next, we studied the scope of thioacetalization of carbonyls 1a–
h under InF3 catalysis using benzenethiol, 1,2-ethanedithiol, and
Reusability of InF3 as a catalyst in acetalization and thioacetalization of furfural
Acetal/thioacetal
% Yielda
3rd run
1st run
87
2nd run
87
4th run
83
5th run
80
OMe
85
80
89
O
OMe
S
O
OCH2Ph
84
96
84
93
79
89
79
87
S
O
OCH2Ph
O
O
O
InF3
89%
O
MeCN-H2O (4:1)
reflux, 4h
SPh
86
85
85
86
85
82
82
80
80
81
78
79
80
78
77
S
O
SPh
S
S
O
O
S
S
93%
S
a
Isolated yields.
Scheme 3. Deprotection of dithioacetals under InF3 catalysis.

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S. Madabhushi et al. / Tetrahedron Letters 53 (2012) 697–701
Table 4
Deprotection of acetals and dithioacetals of furfural using InF3 as the catalyst
InF3(5mol%)
MeCN-H2O (4:1)
reflux
OR
InF3(5mol%)
THF-H2O (4:1)
reflux
SR
SR
CHO
O
O
1c
O
OR
2c, 3c and 4c
5c, 6c and 7c
Entry
1
Acetal
Reaction time (h)
2
% Yeilda of 1c
Entry
Dithioacetal
Reaction time (h)
% Yeild of 1c
OMe
OMe
SPh
87
85
89
4
5
6
3
90
O
O
SPh
S
OCH2Ph
2
3
2
3.5
3.5
89
93
O
O
O
O
S
S
OCH2Ph
O
2.5
S
O
a
Isolated yields.
1,3-propanedithiol and obtained corresponding dithioacetals 5a–h
in 80–90% yields, dithiolanes 6a–h in 82–86% yields and dithianes
7a–h in 80–87% yields, respectively, under reflux in toluene as
shown in Table 2.7
Acknowledgments
K.K.R.M. and C.R.B. are thankful to CSIR, New Delhi and C.N. is
thankful to UGC, New Delhi for the award of research fellowships.
V.S.V. is thankful to the Director, IICT for the financial support in
the form of project fellowship.
In our study, only aldehydes were found to undergo acetaliza-
tion and thioacetalization under InF3 catalysis and ketones such
as cyclohexanone and acetophenone were found to be unreactive
under similar conditions. For example, acetalization and thioace-
talization of chromone-3-carboxaldehyde 1h proceeded selectively
on its aldehyde functionality as shown in Table 1 (entries 2h, 3h,
and 4h) and Table 2 (entries 5h, 6h, and 7h), respectively. Simi-
larly, when a 1:1 mixture of benzaldehyde and acetophenone
was subjected to acetalization with methanol in the presence of
InF3, dimethyl acetal of benzaldehyde was obtained in an 85%
yield, while acetophenone was recovered unreacted.
Unlike other indium (III) salts, InF3 is insoluble in organic sol-
vents and water. In the present study of acetalization and thioace-
talization reactions, it was easily separated quantitatively by
simple filtration and reused it to observe consistent activity in five
consecutive cycles as shown in Table 3.
References and notes
1. (a) Smith, A. B.; Xian, M. J. Am. Chem. Soc. 2006, 128, 66–67; (b) Chen, Y. L.;
Leguijt, R.; Redlich, H.; Fröhlich, R. Synthesis 2006, 4212–4218; (c) Yus, M.;
Najera, C.; Foubelo, F. Tetrahedron 2003, 59, 6147; (d) Seebach, D.; Corey, E. J. J.
Org. Chem. 1975, 40, 231–237; (e) Corey, E. J.; Seebach, D. Angew. Chem., Int. Ed.
Engl. 1965, 4, 1075–1077.
2. (a) Cox, D. J.; Smith, M. D.; Fairbanks, A. J. Org. Lett. 2010, 12, 1452–1455; (b)
Wu, Y.-C.; Zhu, J. J. Org. Chem. 2008, 73, 9522–9524; (c) Procuranti, B.; Connon,
S. J. Org. Lett. 2008, 10, 4935–4938; (d) Gregg, B. T.; Golden, K. C.; Quinn, J. F.
Tetrahedron 2008, 64, 3287–3295; (e) Fujioka, H.; Okitsu, T.; Ohnaka, T.; Li, R.;
Kubo, O.; Okamoto, K.; Sawama, Y.; Kita, Y. J. Org. Chem. 2007, 72, 7898–7902;
(f) Polshettiwar, V.; Varma, R. S. J. Org. Chem. 2007, 72, 7420–7422; (g)
Barbasiewicz, M.; Makosza, M. Org. Lett. 2006, 8, 3745–3748; (h) Kotke, M.;
Schreiner, P. R. Tetrahedron 2006, 62, 434–439; (i) Smith, B. M.; Graham, A. E.
Tetrahedron Lett. 2006, 47, 9317–9319; (j) Ranu, B. C.; Jana, R.; Samanta, S. Adv.
Synth. Cat. 2004, 346, 446–450; (k) Gopinath, R.; Haque, Sk. J.; Patel, B. K. J. Org.
Chem. 2002, 67, 5842–5845; (l) Leonard, N. M.; Oswald, M. C.; Freiberg, D. A.;
Nattier, B. A.; Smith, R. C.; Mohan, R. S. J. Org. Chem. 2002, 67, 5202–5207; (m)
Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. J. Org. Chem. 2001, 66, 7527–7529;
(n) Muthusamy, S.; Babu, S. A.; Gunanathan, C. Tetrahedron Lett. 2001, 42, 359–
362.
Unlike acetals,8 dithioacetals do not easily undergo deprotec-
tion by acid catalyzed hydrolysis and oxidative conditions are
essentially employed in most of the existing methods for depro-
tection of dithioacetals.9 In the literature, only a few methods
are available for hydrolytic deprotection of dithioacetals10 and
in the present study, we observed a highly efficient hydrolytic
deprotection of dithioacetals of both aldehydes and ketones using
InF3 as a catalyst and aqueous organic solvents as shown in
Scheme 3.
3. (a) Yan-Chao, W.; Jieping, Z. J. Org. Chem. 2008, 73, 9522–9524; (b) Dong, D.;
Ouyang, Y.; Yu, H.; Liu, Q.; Liu, J.; Wang, M.; Zhu, J. J. Org. Chem. 2005, 70, 4535–
4537; (c) De, S. K. Tetrahedron Lett. 2004, 45, 2339–2341; (d) Velusamy, S.;
Punniyamurthy, T. Tetrahedron Lett. 2004, 45, 4917–4920; (e) Karimi, B.;
Golshani, B. Synthesis 2002, 784–788.
4. (a) Sridhar, M.; Raveendra, J.; Ramanaiah, C. B.; Narsaiah, C. Tetrahedron Lett.
2011, 52, 5980–5982; (b) Yadav, J. S.; Antony, A.; George, J.; Basi, V. S. R. Eur. J.
Org. Chem. 2010, 591–605; (c) Nakamura, M.; Endo, K.; Nakamura, E. Org. Lett.
2005, 7, 3279–3281; (d) Araki, S.; Hirashita, T. In Main Group Metals in Organic
Synthesis; Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim, Germany,
2004; pp 323–386. Vol. 1; (e) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347–2356; (f)
Li, C. J. Green Chemistry Frontiers in Benign Chemical Syntheses and Processes;
Oxford University Press: New York, 1998. pp. 234–23.
In our study, dithioacetals were found to undergo deprotection
essentially in aqueous acetonitrile as a solvent,11 while acetals
were found to undergo deprotection also in aqueous mixtures
of other organic solvents such as tetrahydrofuran, dichlorometh-
ane, and toluene. For example, results observed in deprotection
of dithioacetals of furfural (5c, 6c, and 7c) in 4:1 mixture of
acetonitrile-water and deprotection of acetals of furfural 2c, 3c,
and 4c in 4:1 mixture of tetrahydrofuran and water is shown in
Table 4.
5. Lee, C.-H. A; Loh, T. –P. Tetrahedron Lett. 2006, 47, 5980–5982.
6. (a) Typical procedure for preparation of a dimethoxy acetal 2 using InF3 as a
catalyst: Furfural 1c (0.50 g, 5.2 mmol), methanol (5 ml), and InF3 (0.04 g,
0.26 mmol), were taken into
a 25 ml round-bottomed flask fitted with a
condenser and calcium chloride guard tube. The mixture was refluxed for 4.5 h
and after completion of the reaction (TLC), the reaction mixture was cooled to
room temperature and catalyst was removed by filtration. Catalyst was washed
with methanol and the washings were combined with filtrate. The combined
organic layer was concentrated under reduced pressure and the resulting crude
product was purified by column chromatography using deactivated silica gel
(100–200 mesh) with Et3N and ethyl acetate–hexane (1:20) as eluent to obtain
2-(dimethoxymethyl) furan 2c (0.63 g, 85%) in the form of a colorless oil and it
was characterized by the following spectral data : 1H NMR (300 MHz, CDCl3):
In summary, this work shows a simple and practical method for
the chemoselective acetalization and thioacetalization of a variety
of aldehydes in high yields using InF3 as a mild Lewis acid catalyst.
In this study, we demonstrated InF3 as a reusable catalyst for a
number of cycles with consistent activity and showed efficient
hydrolytic deprotection of acetals and dithioacetals using InF3 as
a catalyst in aqueous organic solvents.

S. Madabhushi et al. / Tetrahedron Letters 53 (2012) 697–701
701
d = 7.31–7.30 (d, 1H, J = 2.3 Hz), 6.25–6.24 (dd, 1H, J = 3.0 Hz, 2.3 Hz), 6.18-6.19
(d, 1H, J = 3.0 Hz), 5.71 (s, 1H), 3.24 (s, 6H); 13C NMR (75 MHz, CDCl3):
spectral data : 1H NMR (300 MHz, CDCl3): d = 7.35–7.32 (m, 5H), 7.24–7.22 (m,
6H), 6.21–6.20 (d, 1H, J = 3.0 Hz), 6.12–6.10 (d, 1H, J = 3.0 Hz), 5.4 (s, 1H); 13C
NMR (75 MHz, CDCl3): d = 151.66, 143.74, 134.30, 132.73, 128.73, 127.89,
d = 154.80, 141.72, 110.71, 107.96, 102.31, 51.63; IR (neat):
t 3029, 2928, 1496,
1453, 1366, 1189, 1121, 1069, 977, 832, 748, 699 cmÀ1; EIMS (m/z, %) : 142
(M+), 137, 111, 81; Exact mass observed for C7H10O3 : 142.0622 (calculated:
142.0630).
126.33, 125.58, 55.63; IR (neat): t 3058, 2923, 1477, 1438, 1303, 1228, 1069,
1012, 936, 885, 739, 690 cmÀ1 ; EIMS (m/z, %) : 298 (M+), 189, 122, 100; Exact
mass observed for C17H14OS2: 298.0479 (calculated: 298.0486).
(b) Typical procedure for preparation of a dibenzyl acetal 3 using InF3 as a catalyst:
Furfural 1c (0.50 g, 5.2 mmol), benzyl alcohol (1.24 g, 11.4 mmol), toluene(5 ml),
andInF3 (0.04 g, 0.26 mmol), were takenintoa 25 ml round-bottomedflask fitted
withacondenserandcalciumchlorideguardtube.Themixturewasrefluxedfor4 h
andaftercompletionofthereaction(TLC),thereactionmixturewasfilteredandthe
catalystwas washed withtoluene. Thewashingswere combinedwithfiltrateand
thecombinedorganiclayerwasconcentratedunderreducedpressure.Theresulting
crudeproductwaspurifiedbycolumnchromatographyusingdeactivatedsilicagel
(100–200mesh)withEt3Nandethylacetate–hexane(1:20)aseluenttoobtain2-bis
(benzyloxy) methyl) furan 3c (1.3 g, 85 %) in the form of a colorless oil and it was
characterizedbythefollowingspectraldata:1HNMR(300 MHz, CDCl3):d = 7.37-
7.38 (d, 1H, J = 1.55 Hz), 7.28–7.30 (m, 8H), 7.22–7.25 (m, 2H), 6.48–6.49 (d, 1H,
J = 3.0 Hz), 6.32–6.34 (dd, 1H, J = 3.0 Hz, 1.55 Hz), 5.73 (s,1H), 4.57–4.58 (d, 4H,
J = 2.26 Hz);13CNMR(75 MHz,CDCl3):d = 142.41,137.65,128.38,127.78,127.62,
(b) Typical procedure for preparation of a dithiolane 6 using InF3 as a catalyst:
Furfural 1c (0.50 g, 5.2 mmol), 1,2-ethanedithiol (0.58 g, 6.2 mmol), toluene
(5 ml), and InF3 (0.04 g, 0.26 mmol), were taken into a 25 ml round-bottomed
flask fitted with a condenser and calcium chloride guard tube and the mixture
was refluxed for 4 h. After completion of the reaction (TLC), the reaction
mixture was filtered, catalyst was washed with toluene and the washings were
combined with filtrate. The combined organic layer was concentrated and
purified by normal column chromatography (silica gel 100–200 mesh, ethyl
acetate–hexane = 1:20) to obtain 2-(1,3-dithiolan-2-yl)furan 6c (0.76 g, 85 %)
in the form of a colorless oil and it was characterized by the following spectral
data : 1H NMR (300 MHz, CDCl3): d = 7.31–7.32 (m, 1H), 6.22–6.25 (m, 2H), 5.55
(s, 1H), 3.34–3.42 (m, 2H), 3.24–3.32 (m, 2H); 13C NMR (75 MHz, CDCl3):
d = 154.10, 142.17, 110.08, 106.76, 47.22, 38.84; IR (neat):
t 3117, 2925, 1585,
1499, 1421, 1276, 1171, 1147, 1010, 936, 851, 739 cm-1 ; EIMS (m/z, %) :
172(M+), 143, 111, 105; Exact mass observed for C7H8OS2: 172.0009
(calculated: 172.0017).
126.81,110.09,108.75,95.30,67.21;IR(neat):t3030,2925,1494,1452,1205,1079,
1014, 911, 737, 697, 594 cmÀ1 ; EIMS (m/z, %) : 294 (M+), 187, 107, 91; Exact mass
observedforC19H18O3:294.1261(calculated:294.1256).
(c) Typical procedure for preparation of dithiane 7 using InF3 as a catalyst: Furfural
1c (0.50 g, 5.2 mmol), 1,3-propanedithiol (0.58 g, 6.2 mmol), toluene (5 ml),
and InF3 (0.04 g, 0.26 mmol), were taken into a 25 ml round-bottomed flask
fitted with a condenser and calcium chloride guard tube and the mixture was
refluxed for 4 h. After completion of the reaction (TLC), the reaction mixture
was filtered, catalyst was washed with toluene and the washings were
combined with filtrate. The combined organic layer was concentrated and
purified by normal column chromatography (silica gel 100–200 mesh, ethyl
acetate–hexane = 1 : 20) to obtain 2-(1,3-dithian-2-yl)furan 7c (0.84 g, 87%) in
the form of a colorless oil and it was characterized by the following spectral
data : 1H NMR (300 MHz, CDCl3): d = 7.33–7.34 (d, 1H, J = 2.27 Hz), 6.35–6.36
(d, 1H, J = 3.0 Hz), 6.30–6.31 (dd, 1H, J = 3.0 Hz, 2.27 Hz), 5.13 (s,1H), 2.86–2.98
(m, 4H), 1.95–2.17 (m, 2H); 13C NMR (75 MHz, CDCl3): 152.00, 141.88, 110.58,
(c)Typicalprocedureforpreparationofadioxane4usingInF3asacatalyst:Furfural1c
(0.50 g, 5.2 mmol), 2,2-dimethylpropane-1,3-diol (0.64 g, 6.2 mmol), toluene
(5 ml), and InF3 (0.04 g, 0.26 mmol), were taken into a 25 ml round-bottomed
flask fitted with a condenser and calcium chloride guard tube. The mixture was
refluxedfor4 handaftercompletionofthereaction(TLC),thereactionmixturewas
filtered and the catalyst was washed with toluene. The washings were combined
with the filtrate and the combined organic layerwas concentrated under reduced
pressure. Purification of the crude product by column chromatography using
deactivatedsilicagel(100–200mesh)withEt3Nandethylacetate–hexane(1:20)as
eluentgave2-(furan-2-yl)-5,5-dimethyl-1,3-dioxane4c(0.90 g,96%)intheformof
a white solid and it was characterized by the following spectral data : 1H NMR
(300 MHz,CDCl3):d = 7.33–7.35(m,1H),6.38–6.39(d,1H,J = 3.0 Hz),6.31–6.33(m,
1H),5.40(s,1H),3.69–3.72(d,2H,J = 11.33 Hz),3.54–3.57(d,2H,J = 11.33 Hz),1.26
(s, 3H), 0.78 (s, 3H); 13C NMR (75 MHz, CDCl3):d = 150.81, 141.94, 109.85, 106.96,
107.75, 41.95, 30.22, 25.25; IR (neat):
t 2925, 1496, 1420, 1274, 1161, 1069,
1010, 939, 878, 740, 642 cmÀ1; EIMS (m/z, %) : 186 (M+), 141, 127, 111; Exact
mass observed for C8H10OS2: 186.0178 (calculated: 186.0173).
95.78, 71.30, 30.03, 22.69, 21.54; IR (neat): t3056, 2952, 1508, 1466, 1393, 1343,
1232,1173,1099,1015,830.35,746 cmÀ1;EIMS(m/z,%):182(M+),117,91,69;Exact
massobservedforC10H14O3:182.0937(calculated:182.0943).
(d) Characterization data for new compounds:
Compound 5b: 1H NMR (300 MHz, CDCl3): d = 7.33–7.37 (m, 4H), 7.20–7.25 (m,
6H), 7.15–7.18 (d, 1H, J = 5.09 Hz), 6.86–6.88 (d, 1H, J = 3.58 Hz), 6.78–6.81 (dd,
1H, J = 5.09 Hz, 3.58 Hz), 5.6 (s, 1H); 13C NMR (75 MHz, CDCl3): d = 143.73,
(d)Characterizationdatafornewcompounds:
Compound3b:1HNMR(300 MHz,CDCl3):d = 7.29–7.31(m,8H),7.26–7.27(d,1H,
J = 0.94 Hz), 7.21–7.25 (m, 2H), 7.04–7.05 (d, 1H, J = 3.77 Hz), 6.89–6.92 (dd, 1H,
J = 3.77 Hz,0.94 Hz),5.93(s,1H),4.61(s,4H);13CNMR(75 MHz,CDCl3):d = 147.35,
134.20, 132.73, 128.73, 127.89, 126.33, 125.57, 96.13, 55.62; IR (neat):
t 3062,
2924, 1464, 1340, 1231, 1120, 1015, 934, 740 cmÀ1; EIMS (m/z, %): 314 (M+),
205, 84, 77, 56; Exact mass observed for C17H14S3: 314.0245 (calculated:
314.0258).
135.63, 127.39, 126.91, 126.43, 125.96, 125.13, 124.45, 96.86, 67.93; IR (neat):
t
3059, 2965, 1510, 1359, 1235, 1185, 1075, 963, 834, 748 cm-1; EIMS (m/z, %): 310
(M+),219,203,112,91;ExactmassobservedforC19H18O2S:310.1034(calculated:
310.1028).
Compound 5h: 1H NMR (300 MHz, CDCl3): d = 8.24–8.27 (dd, 1H, J = 9.82 Hz,
8.31 Hz), 8.02 (s, 1H), 7.61–7.67 (m, 1H), 7.38–7.43 (m, 6H), 7.18–7.27 (m, 6H),
5.94 (s,1H); 13C NMR (75 MHz, CDCl3): d = 179.51, 157.23, 135.83, 131.28,
130.74, 129.88, 127.87, 127.07, 126.13, 125.78, 122.93, 116.45, 115.21, 46.67;
Compound3h:1HNMR(300 MHz,CDCl3):d = 7.98–8.02(d,1H,J = 9.65 Hz),7.71–
7.76 (m, 5H), 7.63 (s, 1H), 7.28–7.36 (m, 8H), 5.63 (s, 1H), 4.56 (s, 4H); 13C NMR
(75 MHz,CDCl3):d = 180.10,157.12,149.56,137.45,130.64,128.79,127.69,127.36,
IR (neat):
t ;
3062, 2928, 1728, 1496, 1366, 1187, 1069, 976, 832, 748 cmÀ1
123.94,122.68,121.22,120.61,115.67,97.32,68.89;IR(neat):t3054,2940,1743,
EIMS (m/z, %): 376 (M+), 267, 189, 102, 88, 60; Exact mass observed for
1485,1366,1204,1065,954,790 cmÀ1;EIMS(m/z,%):372(M+),265,158,91;Exact
massobservedforC24H20O4:372.1355(calculated:372.1362).
C22H16O2S2: 376.0583 (calculated: 376.0592).
Compound 7h: 1H NMR (300 MHz, CDCl3): d = 8.23–8.26 (d, 1H, J = 7.93 Hz),
8.15 (s, 1H), 7.61–7.67 (m, 1H), 7.36–7.43 (m, 2H), 5.55 (s, 1H), 3.07–3.16 (m,
2H), 2.84–2.91 (m, 2H), 2.14–2.23 (m, 1H), 1.20–1.89 (m, 1H); 13C NMR
(75 MHz, CDCl3): d = 178.06, 157.23, 151.64, 135.34, 130.61, 123.92, 117.71,
Compound 4b: 1H NMR (300 MHz, CDCl3): d = 7.24–7.26 (dd, 1H, J = 5.28 Hz,
3.77 Hz),7.06–7.07(d,1H,J = 3.77 Hz),6.93–6.96(dd,1H,J = 5.28 Hz,3.77 Hz),5.57
(s,1H), 3.70–3.74 (d, 2H, J = 11.33 Hz), 3.57–3.60 (d, 2H, J = 11.33 Hz), 1.27 (s, 3H),
0.79 (s, 3H); 13C NMR (75 MHz, CDCl3): d = 141.20, 126.22, 125.41, 124.84, 98.05,
115.32, 39.04, 32.46, 25.25; IR (neat):
t 3101, 2954, 1732, 1484, 1289, 1184,
77.20, 22.79, 21.69; IR (neat):
t
3106, 2960, 1540, 1449, 1377, 1309, 1218, 1186,
1074, 954, 793 cmÀ1; EIMS (m/z, %) : 264 (M+), 232, 145, 117, 106; Exact mass
observed for C13H12O2S2: 264.0291 (calculated: 264.0279).
1021,844,778 cmÀ1;EIMS(m/z,%):198(M+),127,113,85,56;Exactmassobserved
forC10H14O2S:198.0708(calculated:198.0715).
8. (a) Gregg, B. T.; Golden, K. C.; Quinn, J. F. J. Org. Chem. 2007, 72, 5890–5893; (b)
Chang, C. –C.; Liao, B.-S.; Liu, S.-T. Synlett 2007, 283–287; (c) Kumar, R.; Kumar,
D.; Chakraborti, A. K. Synthesis 2007, 299–303; (d) Dalpozzo, R.; De Nino, A.;
Maiuolo, L.; Procopio, A.; Tagarelli, A.; Sindona, G.; Bartoli, G. J. Org. Chem. 2002,
67, 9093–9095; (e) Carrigan, M. D.; Sarapa, D.; Smith, R. C.; Wieland, L. C.;
Mohan, R. S. J. Org. Chem. 2002, 67, 1027.
9. (a) Burghardt, T. E. J. Sulfur Chem. 2005, 26, 411–427; (b) Dalpozzo, R.; De Nino,
A.; Maiuolo, L.; Nardi, M.; Procopio, A.; Tagarelli, A. Synthesis 2004, 496–498;
(c) Kamal, A.; Reddy, P. S. M. M.; Reddy, D. R. Tetrahedron Lett. 2003, 44, 2857–
2860; (d) Langille, N. F.; Dakin, L. A.; Panek, J. S. Org. Lett. 2003, 5, 575–578; (e)
Nicolaou, K. C.; Mathison, C. J. N.; Montagnon, T. Angew. Chem., Int. Ed. 2003, 42,
4077–4082; (f) Carrigan, M. D.; Sarapa, D.; Smith, R. C.; Wieland, L. C.; Mohan,
R. S. J. Org. Chem. 2002, 67, 1027–1030.
Compound4d:1HNMR(300 MHz,CDCl3):d = 7.90(s,1H),7.76–7.82(m,3H),7.55–
7.58 (d, 1H, J = 8.49 Hz), 7.39–7.44 (m, 2H), 5.48 (s, 1H), 3.75–3.80 (d, 2H,
J = 10.95 Hz), 3.62–3.67 (d, 2H, J = 10.95 Hz), 1.31 (s, 3H), 0.81 (s, 3H); 13C NMR
(75 MHz,CDCl3):d = 135.80,132.95,128.26,128.06,127.56,126.11,125.91,125.38,
123.72,101.70,77.62,23.01,21.79;IR(neat):t3048,2922,1577,1471,1362,1270,
1178, 1063, 860, 752 cmÀ1; EIMS (m/z, %): 242 (M+), 155, 127, 91, 55; Exact mass
observedforC16H18O2:242.1298(calculated:242.1307).
Compound4g:1HNMR(300 MHz,CDCl3):d = 4.08–4.10(d,1H,J = 4.72 Hz),3.53–
3.57 (d, 2H, J = 10.76 Hz), 3.31–3.35 (d, 2H, J = 10.76 Hz), 1.46–1.79 (m, 6H), 1.04–
1.25(m,8H),0.70(s,3H);13CNMR(75 MHz,CDCl3):d = 104.89,76.99,42.21,30.15,
27.19, 26.53, 25.88, 22.94, 21.87; IR (neat):
t 2950, 1453, 1350, 1231, 1194,
841 cmÀ1;EIMS(m/z,%):198(M+),168,102,83;ExactmassobservedforC12H22O2:
198.1632(calculated:198.1620).
10. (a) Ganguly, N. C.; Barik, S. K. Synthesis 2009, 1393–1399; (b) McHale, W. A.;
Kutateladze, A. G. J. Org. Chem. 1998, 63, 9924–9931.
7. (a) Typical procedure for preparation of a dithioacetal 5 using InF3 as a catalyst:
Furfural 1c (0.50 g, 5.2 mmol), thiophenol (1.26 g, 11.4 mmol), toluene (5 ml),
and InF3 (0.04 g, 0.26 mmol), were taken into a 25 ml round-bottomed flask
fitted with a condenser and calcium chloride guard tube and the mixture was
refluxed for 2.5 h. After completion of the reaction (TLC), the reaction mixture
was filtered, catalyst was washed with toluene and the washings were
combined with filtrate. The combined organic layer was concentrated and
purified by normal column chromatography (silica gel 100–200 mesh, ethyl
acetate–hexane = 1:20) to obtain 2-(bis (phenylthio) methyl) furan 5c (1.34, 86
%) in the form of a colorless oil and it was characterized by the following
11. Typical procedure for deprotection of a dithioacetal: 2-(1,3-dithiolan-2-yl)furan
6c (0.5 g, 2.9 mmol), InF3 (24 mg, 0.14 mmol), acetonitrile (8 ml), water (2 ml)
were taken into a 50 ml round bottomed flask fitted with a condenser and the
mixture was refluxed for 3.5 h. After completion of the reaction (TLC),
acetonitrile was removed under reduced pressure and extracted with
diethylether (2 Â 5 ml). The combined organic layer was washed with brine
(1 Â 5 ml), concentrated and the crude product was purified by normal column
chromatography to obtain furfural 1c (0.25 g, 89 %), which gave spectral data
(1H NMR, IR, and Mass) identical to that of the authentic sample.