Lithium bromide, a novel and highly effective catalyst for monothioacetalization of acetals under mild reaction conditions

Article abstract of DOI:10.1055/s-2001-17477

Lithium bromide is efficient as a catalyst for the monothioacetalization of acetals under mild reaction conditions to provide products in excellent yields with high chemoselectivity.

Full text of DOI:10.1055/s-2001-17477

LETTER
1581
Lithium Bromide, a Novel and Highly Effective Catalyst for
Monothioacetalization of Acetals under Mild Reaction Conditions
L
ithiumBrom
u
ide
a
s
Effect
m
ive Catalystfor
M
o
i
nothioa
a
c
etalizationki Ono, Ryojyu Negoro, Tsuneo Sato*
Department of Chemistry and Bioscience, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax +81(86)4401062; E-mail: sato@chem.kusa.ac.jp
Received 4 July 2001; revised 15 July 2001
dropyranyl (THP) ethers of butanol afforded selectively
2-phenylthiotetrahydrofuran or 2-phenylthiotetrahydro-
pyran in 82% or 91% yields, respectively (entries 15 and
16).6 Methoxymethyl (MOM) and (2-methoxyethoxy)me-
thyl (MEM) ethers were smoothly converted into the cor-
responding phenylthiomethyl ethers in good yields
(entries 17-19). It is worthy of note that toluene without
any purification could also be successfully employed (en-
try 2).7
Abstract: Lithium bromide is efficient as a catalyst for the mono-
thioacetalization of acetals under mild reaction conditions to pro-
vide products in excellent yields with high chemoselectivity.
Key words: acetals, chemoselectivity, Lewis acids, lithium bro-
mide, monothioacetals
In view of the tremendous versatility of monothioacetals
as useful carbonyl protective groups1 and intermediates2
in organic synthesis, a wide variety of methods have been
developed for their preparations. Monothioacetals are
usually prepared by the transacetalization of acetals using
such combination of reagents as RSH/BF3·OEt2,3a-d
Me2BBr/RSH/i-Pr2NEt,3e,f (i-PrS)2BBr,3g RSH/MgBr2,3h
Et2AlSPh,3i,j Me2S/TMSOTf/RSLi,3k Bu4-nSn(SR)n/
BF3·OEt2,3l,m PhSH or PhSTMS/dicyanoketene acetal,3n,o
and PhSH or PhSTMS/polymer-supported dicyanoketene
acetal.3p However, many of these methods require harsh
reaction conditions, expensive reagents, and give unsatis-
factory yields; consequently there is a need to develop
new reagents for this reaction. Lithium bromide has been
applied in organic synthesis as a mild, effective Lewis
acid catalyst for a variety of reactions such as Friedel-
Crafts acylation,4a,b preparation of acylals,4c dithioacetal-
ization of aldehydes,4d transesterification,4e rearrange-
ment of epoxides,4f and Knoevenagel condensation.4g
Here, we wish to report that in the presence of a catalytic
amount of lithium bromide and a thiol 2 (1.3 equiv) sev-
eral types of acetals 1 could be efficiently converted to the
corresponding monothioacetals 3 (Scheme).5
The high chemoselectivity of the present method is dem-
onstrated by competition experiments using structurally
differing acetals.8 The results are shown in Table 2. Ace-
tals of benzaldehyde and 2-octanone both were preferen-
tially monothioacetalized in the presence of octanal
dimethyl acetal (entries 1 and 2). THP ether and MOM
ether remain intact under the reaction conditions. The
complete selectivity for aldehyde acetals was attained in
competition with THP ether and MOM ether (entries 3
and 4).
In summary, lithium bromide can be used as a very mild,
efficient, and highly chemoselective catalyst for mono-
thioacetalization of acetals. The product yields are good to
high and the procedure is easy. Works on other reactions
catalyzed by lithium bromide and related compounds are
currently underway in our laboratory.
R1 OR3
R1 OR3
LiBr (20 mol%)
toluene, 25 h
Some of results that we have obtained for the preparation
of monothioacetals are summarized in Table 1. When
dimethyl acetals of aromatic aldehydes (entries 1, 7-9), al-
iphatic aldehydes (entries 10-12), acyclic and cyclic ke-
tones (entries 13 and 14) were allowed to react with
benzenethiol (2a) in dry toluene, the corresponding O-me-
thyl-S-phenyl acetals were obtained in excellent yields.
Under the similar reaction conditions, diethyl and diiso-
propyl acetals worked equally well (entries 5 and 6). Em-
ploying 4-methylbenzenethiol (2b) and ethanethiol (2c) in
the same manner as benzenethiol furnished the corre-
sponding O-methyl-S-tolyl and O-methyl-S-ethyl acetals
(entries 3 and 4). Tetrahydrofuranyl (THF) and tetrahy-
+
R4SH
R2 OR3
R2 SR4
2a: PhSH
2b: p-MeC6H4SH
2c: EtSH
3
1
Scheme
References and Notes
(1) (a) Loewenthal, H. J. E. Protective Groups in Organic
Chemistry; McOmie, J. F. W., Ed.; Plenum: London, 1973,
Chap. 9. (b) Kocienski, P. J. Protecting Groups; Thieme:
New York, 1994, Chap. 5. (c) Greene, T. W.; Wuts, P. G.
M. Protective Groups in Organic Synthesis, 3rd ed.; Wiley:
New York, 1999, Chap. 4.
Synlett 2001, No. 10, 28 09 2001. Article Identifier:
1437-2096,E;2001,0,10,1581,1583,ftx,en;Y13701st-pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1582
F. Ono et al.
LETTER
Table 1 Monothioacetalization of Acetals with LiBr
Table 2 Selective Monothioacetalization of Acetals Catalyzed by
LiBra
Entry Acetal 1
Thiol 2 Temp
3, Yielda
(°C)
(%)
Entry Substrates
Products
Yield (%)b
1
2c
3
4
5
6
7
8
9
PhCH(OMe)2
2a
2a
2b
2c
2a
2a
2a
25
25
25
-10
25
0
99 (90)b
93b
OMe
OMe
1
98
2
PhCH(OMe)2
PhCH(OMe)2
PhCH(OMe)2
PhCH(OEt)2
Ph
OMe
OMe
OMe
Ph
SPh
OMe
SPh
91b
n-C7H15
n-C6H13
n-C7H15
68d
2
3
100
0
100
OMe
OMe
OMe
SPh
n-C6H13
PhCH(O-i-Pr)2
p-ClC6H4CH(OMe)2
93 (87)
85
OMe
OMe
OMe
SPh
25
0
n-C7H15
n-C7H15
p-MeOC6H4CH(OMe)2 2a
97 (88)d
89d
81
0
OMe
OMe
2a
0
Ph
OMe
Ph
SPh
CH(OMe)2
O
10
n-C7H15CH(OMe)2
c-C6H11CH(OMe)2
t-C4H9CH(OMe)2
2a
2a
2a
25
25
80
25
25
81 (78)
100
O
OBu
OMe
OMe
O
SPh
OMe
SPh
11
12
13
14
4
86
0
81 (73)d
98 (86)e
98e
n-C7H15
n-C8H17
n-C7H15
n-C8H17
n-C6H13(CH3)C(OMe)2 2a
O
O
2a
CH2(CH2)4C(OMe)2
OMe
SPh
15
16
2a
60
60
82
a Substrate 1 (1 mmol), substrate 2 (1 mmol), PhSH (1 mmol), LiBr
(0.2 mmol), toluene (0.5 cm3), 25 °C, 25 h.
OBu
O
b Yields based on GC and 1H NMR.
2a
91 (80)
O
OBu
17
18
n-C8H17OMOM
2a
2a
40
60
70
(3) (a) Nakatsubo, F.; Cocuzza, A. J.; Keeley, D. E.; Kishi, Y. J.
Am. Chem. Soc. 1977, 99, 4835. (b) Kieczykowski, G. R.;
Schlessinger, R. H. J. Am. Chem. Soc. 1978, 100, 1938.
(c) Naruto, M.; Ohno, K.; Naruse, N. Chem. Lett. 1978,
1419. (d) Cohen, T.; Matz, J. R. J. Am. Chem. Soc. 1980,
102, 6900. (e) Morton, H. E.; Guindon, Y. J. Org. Chem.
1985, 50, 5379. (f) Guindon, Y.; Bernstein, M. A.;
73 (70)
OMOM
19
2a
70
78
Anderson, P. C. Tetrahedron Lett. 1987, 28, 2225.
(g) Corey, E. J.; Hua, D. H.; Seitz, S. P. Tetrahedron Lett.
1984, 25, 3. (h) Kim, S.; Park, J. H.; Lee, S. Tetrahedron
Lett. 1989, 30, 6697. (i) Masaki, Y.; Serizawa, Y.; Kaji, K.
Chem. Lett. 1985, 1933. (j) Masaki, Y.; Serizawa, Y.;
Nagata, K.; Oda, H.; Nagashima, H.; Kaji, K. Tetrahedron
Lett. 1986, 27, 231. (k) Kim, S.; Park, J. H.; Lee, J. M.
Tetrahedron Lett. 1993, 34, 5769. (l) Sato, T.; Kobayashi,
T.; Gojo, T.; Yoshida, E.; Otera, J.; Nozaki, H. Chem. Lett.
1987, 1661. (m) Sato, T.; Otera, J.; Nozaki, H. Tetrahedron
1989, 45, 1209. (n) Miura, T.; Masaki, Y. Tetrahedron Lett.
1994, 35, 7961. (o) Miura, T.; Masaki, Y. Tetrahedron
1995, 51, 10477. (p) Tanaka, N.; Miura, Y.; Masaki, Y.
Chem. Pharm. Bull. 2000, 48, 1010.
OMEM
a Based on GC. Isolated yields are given in the parentheses.
b 1% of the dithioacetal was detected.
c Wet toluene was used.
d 3% of the dithioacetal was contaminated.
e Based on 1H NMR.
(2) (a) Otera, J. J. Synth. Org. Chem. Jpn. 1986, 44, 459.
(b) Otera, J. Synthesis 1988, 95. (c) Cohen, T.; Bhupath, M.
Acc. Chem. Res. 1989, 22, 152. (d) Sato, T. J. Synth. Org.
Chem. Jpn. 1997, 55, 217. (e) Nakata, D.; Kusaka, C.; Tani,
S.; Kunishima, M. Tetrahedron Lett. 2001, 42, 415; and
references cited therein.
Synlett 2001, No. 10, 1581–1583 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Lithium Bromide as Effective Catalyst for Monothioacetalization
1583
(4) (a) Pushin, A. N.; Tkachenko, S. E.; Martynov, I. V. Dokl.
Akad. Nauk SSSR 1988, 299, 154. (b) Chem. Abstr. 1989,
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(5) The following procedure is representative (Table 1, entry 1).
A mixture of LiBr (34.7 mg, 0.4 mmol), benzaldehyde
dimethyl acetal (304 mg, 2.0 mmol), benzenethiol (286 mg,
2.6 mmol), and dry toluene (0.5 cm3) was stirred at 25 °C.
The progress of the reaction was followed by TLC. After
completion of the reaction (25 h), ether (40 cm3) was added
and the mixture was successively washed with 1M NaOH
solution (10 cm3) and brine (10 cm3). The organic layer was
dried (Na2SO4) and concentrated. GC analysis showed that
the crude product consisted of methoxyphenyl(phenyl-
thio)methane (99%) and [phenyl(phenylthio)methyl-
thio]benzene (1%). Purification was achieved by column
chromatography on silica gel (1% ethyl acetate-hexane) to
give the desired product (415 mg, 90%).
(6) These results are consistent with the facts that the cleavage
of exocyclic carbon-oxygen bond is the favored process
when this type of acetals are treated with common Lewis
acids.3e,f,h,l-p
(7) When , -unsaturated acetals were treated with PhSH under
similar reaction conditions, not , -unsaturated mono-
thioacetals but other type of compounds were obtained.
The details of this result will be communicated later.
(8) Selective monothioacetalization of benzaldehyde dimethyl
acetal vs. octanal dimethyl acetal with benzenethiol; typical
procedure (Table 2, entry 1). A mixture of LiBr (17.4 mg,
0.2 mmol), benzaldehyde dimethyl acetal (152 mg, 1.0
mmol), octanal dimethyl acetal (174 mg, 1.0 mmol),
benzenethiol (110 mg, 1.0 mmol), and dry toluene (0.5 cm3)
was stirred at 25 °C for 25 h. GC analysis of the reaction
mixture indicated the formation of methoxyphenyl(phenyl-
thio)methane (98%) and 1-methoxy-1-(phenylthio)octane
(2%).
Synlett 2001, No. 10, 1581–1583 ISSN 0936-5214 © Thieme Stuttgart · New York