Selective thioacetalization of aldehydes catalyzed by aqueous zinc tetrafluoroborate

Article abstract of DOI:10.1081/SCC-200026628

A wide range of cyclic dithioacetals are prepared from the corresponding aldehydes in the presence of aqueous solution of zinc tetrafluoroborate.

Full text of DOI:10.1081/SCC-200026628

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 16, pp. 2911–2916, 2004
Selective Thioacetalization of Aldehydes
Catalyzed by Aqueous Zinc
Tetrafluoroborate
1
Samimul Islam,1 Adinath Majee,1, Tanmay Mandal,
*
and A. T. Khan2
1Department of Chemistry, Visva-Bharati, Santiniketan,
West Bengal, India
2Department of Chemistry, Indian Institute of Technology,
North Guwahati, Guwahati, India
ABSTRACT
A
wide range of cyclic dithioacetals are prepared from the
corresponding aldehydes in the presence of aqueous solution of zinc
tetrafluoroborate.
Key Words: Dithioacetals; Aqueous zinc tetrafluoroborate; 1,2-Ethane-
dithiol; 1,3-Propanedithiol.
*
Correspondence: Adinath Majee, Department of Chemistry, Visva-Bharati, Santini-
ketan, West Bengal 731235, India; E-mail: adinathm@yahoo.com.
2911
DOI: 10.1081/SCC-200026628
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Islam et al.
INTRODUCTION
Protection of carbonyl functionality[1] as a dithioacetal is frequently
used in multistep organic synthesis.[2] This is due to their ease of install-
ation and removal as well as the stability under both acidic and basic
conditions. Utilization of a thioacetal as a masked acyl anion[3] and
masked methylene function[4] is also very important in organic transform-
ation. In the literature, there are many methods for the preparation of thio-
acetals from carbonyl compounds using acid catalyst such as HCl,[5]
[6]
[8]
ZnCl2 Zn or Mg (OTf)2,[7] and BF3 Et2O. Other acid catalysts used
.
for the same include AlCl3,[9] TiCl4,[10] LaCl3,[11] SiCl4,[12] (CH3)3 SiCl,[13]
Cu(OTf)2–SiO2,[14] ZrCl4–SiO2,[15] WCl6,[16] 5 M LiClO4 (LPDE)/
Et2O,[17] TaCl3–SiO2,[18] BiCl3, and Bi(SO4)3
and very recently
[19]
LiBF4,[20] InCl3,[21] LiBr,[22] molecular iodine,[23] NBS,[24] Sc(OTf)3,[25]
and NiCl2.[26] A large number of these available methods require harsh reac-
tion condition and offer poor selectivity. Only some[20–26] are chemoselective.
However, all of these methods need dry reaction conditions for good yields.
A 40% solution of zinc tetrafluoroborate in water is inexpensive and com-
mercially available.[27] We have observed that Zn(BF4)2 solution acts as a
very efficient reagent for thioacetalization of carbonyl compounds (Sch. 1).
A wide variety of carbonyl compounds underwent thioacetalization using
this procedure. The results are summarized in Table 1. It has been observed
that aromatic aldehydes having an electron-donating group formed thioacetals
faster but those with electron-withdrawing group took lesser time (entries 8,
9). This procedure was found to be effective for aldehydes containing acetyl
(entry 12), benzyl (entry 11), allyl (entry 10), olefinic double bond (entry
14), and furan (entry 15). Acyclic systems were also effectively thioacetalized
using this procedure (entries 16–20).
Scheme 2 shows the selectivity for a particular keto-aldehyde. Cyclohexa-
none reacted nicely (entry 21) but ketones such as acetophenone, propeo-
phenone did not react.
Scheme 1.

Thioacetalization of Aldehydes
Table 1. Thioacetalization of carbonyl compounds.
2913
Entry
Substrates
Reagents
Time
1.5 hr
1.5 hr
5 min
20 min
30 min
1.5 hr
5 min
Yield (%)a
1
2
3
4
5
6
7
90
92
85
85
90
88
95
8
9
12 hr
15 hr
70
80
10
1.5 hr
90
11
12
13
14
30 min
1.5 hr
95
70
75
80
2.5 hr
30 min
15
30 min
95
16
17
18
19
20
21
2 hr
2 hr
80
90
85
80
80
70
5 min
30 min
2 hr
4 hr
1
aAll are pure isolated products and were characterized by IR, H NMR.

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Islam et al.
Scheme 2.
EXPERIMENTAL
The experimental conditions are very simple: a mixture of aldehyde
(2 mmol) 1,2-ethanedithiol or 1,3-propanedithiol (3 mmol), and Zn(BF4)2
(0.5 mmol) (in 40% aqueous solution) in dichloromethane was stirred at room
temperature for a period of time as required to complete the reaction (TLC).
The reaction mixture was diluted with water and the product was isolated by
extraction with dichloromethane followed by purification using silica gel.
In conclusion, we have observed a very simple and convenient procedure
for the protection of various aldehydes as thioacetals using aqueous solution
of Zn(BF4)2.
ACKNOWLEDGMENTS
We are thankful to the Department of Chemistry, Visva-Bharati and the
Department of Chemistry, IIT Guwahati for providing general facilities to
carry out the research work. We also express our sincere thanks to Prof.
B. C. Ranu for his constant encouragement.
REFERENCES
1. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 3rd
Ed.; John Wiley and Sons Inc.: New York, 1999; 329.
2. (a) Rychnovsky, S.D. Oxopolyene macrolide antibiotics. Chem. Rev.
1995, 95, 2021; (b) Smith, A.B., III; Condon, S.M.; McCauly, J.A.
Total synthesis and immunosuppressants: unified strategies exploiting
dithiane couplings and s-bond olefin construction. Acc. Chem. Res.
1998, 31, 35.
3. (a) Seebach, D. Methods and possibilities of nucleophilic acylation.
Angew. Chem. Int. Ed. Engl. 1969, 8, 639; (b) Grobel, B.T.;
Seebach, D. Umpolung of the reactivity of carbonyl compounds
through sulfur-containing reagents. Synthesis 1977, 6, 357; (c) Bulman

Thioacetalization of Aldehydes
2915
Page, P.C.; van Niel, M.B.; Prodger, J.C. Synthetic uses of the 1,3-
dithiane grouping from 1977–1988. Tetrahedron 1989, 45, 7643.
4. Pettit, G.R.; van Tamelen, E.E. Org. React. 1962, 12, 356.
5. Bulman Page, P.C.; Prodger, J.C.; Westwood, D. Diastereoselectivity in
the addition of Grignard reagents to ketones controlled by the 1,3-dithiane
1-oxide asymmetric building block. Tetrahedron 1993, 49, 10355.
6. Evans, D.V.; Truesdale, L.K.; Grimm, K.G.; Nesbitt, S.L. Thiosilanes a
promising class of reagents for selective carbonyl protection. J. Am.
Chem. Soc. 1977, 99, 5009.
7. Corey, E.J.; Shimoji, K. Magnesium and zinc—catalyzed thioketaliza-
tion. Tetrahedron Lett. 1983, 24, 169.
8. (a) Fieser, L.F. Preparation of ethylene thioketals. J. Am. Chem. Soc.
1954, 76, 1945; (b) Nakata, T.; Nagao, S.; Oishi, T. Total synthesis of
(þ) pederin. 1. Stereocontrolled synthesis of (þ)-benzolpedamide. Tetra-
hedron Lett. 1985, 26, 6461.
9. Ong, B.S. Simple and efficient method for thioacetal and ketalization.
Tetrahedron Lett. 1980, 21, 4225.
10. Kumer, V.; Dev, S. Titanium tetrachloride, an efficient and convenient
reagent for thioacetalization. Tetrahedron Lett. 1983, 24, 1289.
11. Garlaschelli, L.; Vidari, G. Anhydrous lanthanum trichloride, a mild and
convenient reagent for thioacetalization. Tetrahrdron Lett. 1990, 31,
5815.
12. Ku, B.; Oh, D.Y. Tetrachlorosilane catalyzed dithioketalization. Synth.
Commun. 1989, 19, 433.
13. Ong, B.S.; Chan, T.H. A simple method for dithioacetal and ketalization.
Synth. Commun. 1977, 7, 283.
14. Anand, R.V.; Sarvanan, P.; Singh, V.K. Tungsten hexachloride (WCl6) in
the presence of dimethylsufoxide promoted facile and efficient one-pot
ring expansion-chlorination reaction of 1,3-dithiolanes and 1,3-dithianes.
Synlett 1999, (4), 413.
15. Patney, H.K.; Margan, S. Zirconium (IV) chloride-silica catalyzed thio-
acetalization of carbonyl compounds. Tetrahedron Lett. 1996, 37, 4621.
16. Firouzabadi, H.; Iranpoor, N.; Karimi, B. Tungsten hexachloride (WCl6)
as an efficient catalyst for chemoselective dithioacetalization of carbonyl
compounds and transthioacetalization of acetals. Synlett 1998, (7), 739.
17. Saraswathy, V.G.; Geetha, V.; Sankararaman, S. Chemoselective protec-
tion of aldehydes as dithioacetals in lithium perchlorate—diethyl ether
medium. Evidence for the formation of oxocarbenium ion intermediate
from acetals. J. Org. Chem. 1994, 54, 4665.
18. Chandrasekhar, S.; Takhi, M.; Reddy, Y.R.; Mohapatra, S.; Rao, C.R.;
Reddy, K.V. TaCl5–silica gel and TaCl5 as new lewis acid systems for

2916
Islam et al.
selective tetrahydropyranylation of alcohols and thioacetalization, trimer-
isation and aldolisation of aldehydes. Tetrahedron 1997, 53, 14997.
19. Komatsu, N.; Uda, M.; Suzuki, H. Bismuth (III) halides sulfate as highly
effeicient catalyst for the sulfenylation of carbonyl and related com-
pounds. Synlett 1995, (9), 984.
20. Yadav, J.S.; Reddy, B.V.S.; Pandey, S.K. LiBF4, catalyzed chemoselec-
tive conversion of aldehydes to 1,3-oxathiolanes and 1,3-dithianes.
Synlett 2001, (2), 238.
21. (a) Mathuswamy, S.; Arulanande Babu, S.; Gunanathan, C. Indium (III)
chloride as an efficient, convenient catalyst for thioacetalization and its
chemoselectivity. Tetrahedron Lett. 2001, 42, 359; (b) Ranu, B.C.;
Das, A.; Samanta, S. Highly efficient transthioacetalization of O,O-
acetals catalyzed by indium (III) chloride. Synlett 2002, (5), 727.
22. Firouzabadi, H.; Iranpoor, N.; Karimi, B. Lithium bromide-catalysed
highly chemoselective and efficient dithioacetalization of a,b-unsatu-
rated and aromatic aldehydes under solvent free condition. Synthesis
1999, (1), 58, and references cited therein.
23. Samajdar, S.; Basu, M.K.; Becker, F.F.; Banik, B.K. A new molecular
iodine-catalysed thioketalization of carbonyl compounds: selectivity
and scope. Tetrahedron Lett. 2001, 42, 4425, and references cited therein.
24. Kamal, A.; Chouhan, G. Mild and efficient chemoselective protection
of aldehydes as dithioacetals employing N-bromosuccinimide. Synlett
2002, (3), 474.
25. Kamal, A.; Chouhan, G. Scandium triflate as a recyclable catalyst for
chemoselective thioacetalization. Tetrahedron Lett. 2002, 43, 1347.
26. Khan, A.T.; Mondal, E.; Sahu, P.R.; Islam, S. Nickel (II) chloride as an
efficient and useful catalyst for chemoselective thioacetalization of alde-
hydes. Tetrahedron Lett. 2003, 44, 919.
27. Ranu, B.C.; Jana, U.; Majee, A. A simple effeicient method for selective
deprotection of t-butyl bimethyl silyl ethers by zinc tetra fluoroborate.
Tetrahedron Lett. 1999, 40, 1985.
Received in India April 22, 2004

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