H. Miyake et al. / Tetrahedron Letters 47 (2006) 6247–6250
6249
1
2
H
R
R
S
S
R
R
HOOC-COOH
1
2
1
2
+
R
R
S
R
R
R
O
C(=O)COOH
R
R
+
S
S
1
CH O CH
2
3
CH OCH
2
3
+
CH S
R
2
CH O
3
4
+
H
CH O
3
5
H
H
O
1
2
R
R
CH
3
1
RS CH SR
2
+
O
R
O
C
COOH
R
O
R
2
+
R
S
2
3
CH S
2
6
Scheme 4.
and the additional use of DMM and oxalic acid was not
effective. In these cases, yields can be improved using
DEM instead of DMM. For example, although the
DMM mediated reaction of 1i gave 2a in 67% yield,
the corresponding DEM mediated reaction gave 2a in
90% yield. The deprotection of 1,3-dithiolane derivative
1k also proceeded in 86% yield. Although large excesses
of DMM or DEM were present in the reaction mixture,
we did not obtain a monothioacetal such as (dodecyl-
thio)methyl methyl ether, although we did obtain
bis(dodecylthio)methane (3a) in excellent yield. How-
ever, the corresponding reaction of bis(phenylthio)acetal
1h gave only small amount of bis(phenylthio)methane
(2b), and monothioacetal PhSCH2OC2H5 was obtained
in 78% yield. The reasons for these unexpected results
are under investigation. 1.3-Dithiane (3b) was obtained
only in poor yield, probably because it has relatively
low boiling point, and a considerable amount of 3b
was lost from the reaction mixture during the course
of purification with other compounds with a low boiling
point. The recovered 3a can be used as a new acyl cation
equivalent. This means that the recycling of dithioacetal,
shown in Scheme 2, is possible. Some dithioacetals like 1
are often prepared from 3 using stepwise alkylation.
acetalization, and an acetal of 2 was not obtained. The
methoxy group or ethoxy group of an acetal may be
converted into an ester of oxalic acid. The plausible mech-
anism in our experiment was as follows (Scheme 4).
Initially, a protonation of acetal occurred, and a nucleo-
philic attack of the sulfur atom to the methylene carbon
caused a substitution that gave a sulfonium ion (4). The
following nucleophilic attack of oxalic acid caused the
elimination of monothioacetal. The nucleophilic attack
of the remaining sulfur atom of the substrate to a proton-
ated monothioacetal (5) gave a sulfonium ion (6). The
following elimination of dithioacetal (3) gave a carbonyl
compound (2).
The general procedure we used was as follows. We added
a powdered oxalic acid (6.0 mmol) to a mixture of nitro-
methane (5 ml), dimethoxymethane (or diethoxy-
methane) (20 mmol), and dithioacetal (1) (2.0 mmol).
The mixture was stirred at 60 °C. After the reaction
was completed, the reaction mixture was poured into
water. After usual workup, we purified the mixture using
column chromatography on a silica gel to give carbonyl
compound (2) and dithioacetal (3).
Selecting the appropriate solvent is very important in this
transformation. So far in our studies, we have found
nitromethane to be the most effective. Other solvents such
as DMF, THF, CHCl3, CH2Cl2, and acetonitrile, are not
as effective as nitromethane. Concerning the acid catalyst,
some carboxylic acids are also effective to a certain extent.
Trichloroacetic acid is especially effective as oxalic acid.
When three equivalents of trichloroacetic acid and
DME (10 equiv) were used instead of oxalic acid, the
deprotection of dithioacetal 1i proceeded in excellent
yield (Scheme 3). However, it is often difficult to remove
trichloroacetic acid from a reaction mixture without
treatment using a base such as an aqueous solution of
NaHCO3, whereas oxalic acid can be removed very easily
by aqueous workup without the addition of a base.
References and notes
1. (a) Gro¨bel, B. T.; Seebach, D. Synthesis 1977, 357; (b)
Page, P. C. B.; van Niel, M. B.; Prodger, J. C. Tetrahedron
1989, 45, 7643.
2. Sneddon, H. F.; van den Heuvel, A.; Booth, R. A.; Gaunt,
M. J.; Hirsch, A. K. H.; Shaw, D. M.; Ley, S. V. J. Org.
Chem. 2006, 71, 2715.
3. Greene, T. W.; Wuts, P. G. M. Protective Group in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999; pp
329–333.
4. (a) Amoo, V. E.; De Bernardo, D.; Weigele, M. Tetra-
hedron Lett. 1988, 29, 2401; (b) Norris, P.; Horton, D.;
Levine, B. R. Tetrahedron Lett. 1995, 36, 7811.
5. Mukaiyama, T.; Kobayashi, S.; Kamio, K.; Takei, H.
Chem. Lett. 1972, 237.
6. (a) Fuji, K.; Ichikawa, K.; Fujita, E. Tetrahedron Lett.
1978, 3561; (b) Olah, G. A.; Narang, S. C.; Salem, G. F.;
Gupta, B. G. B. Synthesis 1979, 273; (c) Mehta, G.; Uma,
In this reaction, we convert an acetal into a corresponding
dithioacetal. On the other hand, we did not observe trans-