Highly efficient transthioacetalization of O,O-acetals catalyzed by indium(III) chloride

Article abstract of DOI:10.1055/s-2002-25347

A simple, efficient and general procedure has been developed for the transthioacetalization of O,O-acetals catalyzed by indium(III) chloride in 1,2-dichloroethane.

Full text of DOI:10.1055/s-2002-25347

LETTER
727
Highly Efficient Transthioacetalization of O,O-Acetals Catalyzed by
Indium(III) Chloride
T
B
ransthioacetaliz
r
ationof
i
,
O
-A
n
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta – 700 032, India
Fax +91(33)4732805; E-mail: ocbcr@mahendra.iacs.res.in
Received 7 January 2002
Abstract: A simple, efficient and general procedure has been de-
veloped for the transthioacetalization of O,O-acetals catalyzed by
indium(III) chloride in 1,2-dichloroethane.
Key words: transthioacetalization, indium(III) chloride, O,O-ace-
tals, S,S-thioacetals
Scheme
The protection and subsequent deprotection of a function- (5 mol%) of indium(III) chloride for a certain period of
al group is a usual practice in a multistep synthetic strate- time as required to complete the reaction (TLC). The re-
gy and a switchover of one protective group to another is action mixture was then quenched with an aqueous solu-
also often required as demanded by their stability under tion of NaOH (10%, 5 mL) and extracted with ether
the reaction conditions in subsequent steps. Thus, a direct (3 10 mL). The ether extract was washed with brine,
method for this transformation bypassing the intermediate dried (Na SO ) and evaporated to leave the crude product,
2
4
1
step of going back to the parent functionality is becoming which was reasonably pure (> 95% by H NMR). Howev-
much more important in order to improve the overall syn- er, further purification by column chromatography over
1
thetic efficiency. O,O-Acetals and S,S-acetals are two silica gel provides analytically pure sample.
useful protecting groups for carbonyl functionalities and
are widely used in organic synthesis. However, S,S-ace-
tals are quite stable toward a variety of reagents including
A wide range of structurally varied O,O-acetals derived
from open-chain, cyclic, heterocyclic and aromatic alde-
hydes and ketones underwent clean transthioacetaliza-
acidic ones, while O,O-acetals are not suitable for being
tions with a variety of thiols and dithiols by this procedure
2
handled in acidic environment. Moreover, S,S-acetals are
to furnish the corresponding S,S-acetals in nearly quanti-
used in organic synthesis as acyl carbanion equivalents3
tative yields. The results are presented in the Table. The
and intermediates for the conversion of carbonyl function
present method is equally effective for the transformation
4
to the parent hydrocarbons. Thus, transthioacetalization
of open-chain and cyclic acetals to the corresponding
of O,O-acetals to S,S-acetals is a synthetically useful
open-chain or cyclic dithioacetals depending on the use of
transformation and is usually carried out under the cataly-
thiol or dithiol. The presence of electron-donating and
5
a
5b
sis of a variety of Lewis acids such as MgBr , TeCl ,
2
4
electron-withdrawing group on the aromatic ring of ace-
tals (entries 5–11) does not make any difference in tran-
sthioacetalization. Acetals of conjugated carbonyl
compounds (entries 15, 16, 20 and 21) are also converted
to the corresponding thioacetals without any isomeriza-
5
c
5d
5e
5f
LPDE, WCl , ZrCl4, SiO /SOCl , trichloroisocya-
nuric acid, and elements like I . However, many of
6
2
2
5
g
6
2
these reported methods require long reaction times, stoi-
chiometric use of expensive and hazardous reagents and
lack general applicability. Thus, an improved alternative
procedure for this useful transformation is appreciated.
tion. A variety of functional groups such as NO , Cl,
2
CO Et, OMe, O-allyl, OTBDMS, OTHP, methylenedioxy
2
Recently, indium(III) chloride has emerged as a Lewis are found to be quite stable during the reaction. In general,
catalyst of high potential imparting remarkable regio- and the reactions are very fast and clean. A catalytic amount
chemoselectivity in various chemical transformations, as (5 mol%) of indium trichloride is sufficient to push the re-
7
8
demonstrated by several groups and us. As a part of this action efficiently.
continuing program we wish to disclose here an efficient
transthioacetalization of O,O-acetals under catalysis of in-
dium(III) chloride (Scheme).
In conclusion, the present indium(III) chloride catalyzed
procedure provides a highly efficient methodology for the
transthioacetalization of O,O-acetals. The significant ad-
In a typical general procedure, a solution of O,O-acetal (1 vantages of this procedure are : (a) high yields (85–93%);
mmol) and thiol (1.2 mmol) in 1,2-dichloroethane (2 mL) (b) fast reaction (7–20 min); (c) general applicability to a
was heated under reflux in presence of a catalytic amount varied acetals and thiols and (d) operational simplicity.
Thus, it offers a better and more practical alternative to the
existing methodologies.5
,6
Synlett 2002, No. 5, 03 05 2002. Article Identifier:
1
©
437-2096,E;2002,0,05,0727,0730,ftx,en;G00402ST.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

7
28
B. C. Ranu et al.
LETTER
Table Transthioacetalization of O,O-Acetals Catalyzed by InCl3
a
Entry
Acetal
Thiol
Time (min)
Product
Yield (%)
1
2
3
PhCH(OMe)2
PhCH(OEt)2
EtSH
12
8
PhCH(SEt)2
PhCH(SPh)2
91
92
92
PhSH
HS(CH ) SH
10
2
2
4
5
HS(CH ) H
8
7
93
92
2
3
HS(CH ) SH
2
2
6
7
PhSH
PhSH
10
12
10
93
90
91
8
9
HS(CH ) SH
2 2
HS(CH ) H
14
12
90
92
2
3
1
1
0
1
HS(CH ) SH
2 2
HS(CH ) SH
9
90
91
2
2
1
2
t-BuSH
12
1
1
3
4
HS(CH ) SH
10
20
88
85
2
2
HS(CH ) SH
2
2
1
1
5
6
HS(CH ) SH
10
12
88
85
2
2
t-BuSH
1
1
7
8
t-BuSH
HS(CH ) SH
15
13
86
85
2
2
1
9
HS(CH ) SH
15
85
2
2
Synlett 2002, No. 5, 727–730 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Transthioacetalization of O,O-Acetals
729
Table Transthioacetalization of O,O-Acetals Catalyzed by InCl (continued)
3
a
Entry
Acetal
Thiol
Time (min)
15
Product
Yield (%)
2
0
HS(CH ) SH
85
2
2
2
1
HS(CH ) SH
15
18
86
86
2
2
2
2
HS(CH ) SH
2 2
2
2
3
4
PhSH
18
15
90
85
HS(CH ) SH
2
2
2
2
5
6
HS(CH ) H
15
13
90
90
2
3
HS(CH ) SH
2
2
2
2
7
8
HS(CH )SH
12
15
89
90
2
HS(CH )SH
2
2
3
3
9
0
1
2
3
HS(CH )SH
20
15
18
86
87
85
86
90
2
HS(CH )SH
2
HS(CH )SH
2
3
3
a
HS(CH )SH
15
10
1
2
HS(CH )SH
2
Yields refer to those of pure isolated products characterized by spectral data ( H and 13C NMR).
Acknowledgement
References
We are pleased to acknowledge the financial support from CSIR,
New Delhi for this investigation. A. D. and S. S. are also thankful
to CSIR for their fellowships.
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