2-Trimethylsilyl-1,3-dithiolane as a masked dithiolane anion

Article abstract of DOI:10.1016/S0040-4039(01)00771-7

2-Trimethylsilyl-1,3-dithiolane, easily obtainable through transthioacetalization of corresponding silylated acetals, can be efficiently reacted, under fluoride-ion catalysis, with different organic electrophiles, leading to a general and mild functionalization protocol. This reactivity discloses the ability of compound 3 to act as a masked dithiolane anion.

Full text of DOI:10.1016/S0040-4039(01)00771-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4557–4559
2-Trimethylsilyl-1,3-dithiolane as a masked dithiolane anion
Alessandro Degl’Innocenti,* Antonella Capperucci* and Tiziano Nocentini
Centro CNR Composti Eterociclici, Dipartimento di Chimica Organica, via G. Capponi, 9, I-50121 Florence, Italy
Received 1 February 2001; revised 27 April 2001; accepted 10 May 2001
Abstract—2-Trimethylsilyl-1,3-dithiolane, easily obtainable through transthioacetalization of corresponding silylated acetals, can
be efficiently reacted, under fluoride-ion catalysis, with different organic electrophiles, leading to a general and mild functionaliza-
tion protocol. This reactivity discloses the ability of compound 3 to act as a masked dithiolane anion. © 2001 Elsevier Science
Ltd. All rights reserved.
1,3-Dithiane anions have been extensively used in the
last decades as masked acyl carbanions in umpolung
reactivity, and have had substantial impact on synthetic
organic chemistry.1 In contrast, 1,3-dithiolanes, upon
treatment with bases, have been reported to undergo
either deprotonation at C-2 with subsequent cycloelimi-
nation to dithiocarboxylate anions and ethylene
derivatives2 or at C-4 to afford products derived from
thiocarbonyl derivatives and vinyl thiolate anion,3 thus
preventing the possibility of further functionalization of
the dithiolane moiety and consequently their use in
umpolung reactivity. Although in fact two examples of
functionalization under basic conditions of dithiolanes
bearing an electron-withdrawing group are reported in
the literature, there is still the need for a general
protocol for their functionalization.4
BF3 catalysis6 as a possible way to access dithiolane 3
(Scheme 1). This procedure was indeed able to afford
for the first time the desired molecule, albeit in an
unsatisfactory yield, due to the poor conversion of the
silyl dithiane 1 into the corresponding silylated 1,3-
dioxane 2.
To overcome these problems an alternative procedure
has
been
devised,
through
bromination
of
methoxymethyltrimethylsilane 4,7 followed by reaction
with alcohols or phenols, to afford the open chain
acetals 6, which can then be efficiently subjected to
BF3·Et2O-catalyzed transthioacetalization to the desired
compound (Scheme 2).8
HgCl2
HgO
HS
SH
S
S
SiMe3
3
S
S
O
O
Our interest in the synthesis and the reactivity of
organosilanes, in connection with the very mild func-
tionalization conditions of the carbonꢀsilicon bond
under fluoride-ion catalysis,5 led us to point our atten-
tion to 2-trimethylsilyl-1,3-dithiolane, as a possible
masked dithiolane anion.
BF3.Et2O
SiMe3
SiMe3
1
2
Scheme 1.
CH3O
Br2
CH3O
SiMe3
SiMe3
Direct functionalization of the parent 1,3-dithiolane
under basic conditions being prevented, an alternative
access to such molecule had to be devised. We envis-
aged the transthioacetalization reaction of 2-
trimethylsilyl-1,3-dioxane 2, in turn obtained by
reaction of the silyl dithiane 1 with 1,3-propanediol in
the presence of Hg2+ salts, with ethanedithiol, under
4
Br
5 (73%)
ROH
iPr2NEt
HS
SH
CH3O
SiMe3
S
S
BF3.Et2O
OR
SiMe3
(88%)
R = n-Bu, PhCH2, Ph
6
(70%-84%)
3
Keywords: organosilanes; dithiolanes; fluoride-ion catalysis; hydroxy-
aldehydes.
* Corresponding authors. Tel.: +39 055 2757609; fax: +39 055
2476964; e-mail: degli@chimorg.unifi.it
Scheme 2.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00771-7

4558
A. Degl’Innocenti et al. / Tetrahedron Letters 42 (2001) 4557–4559
ketone 9 will undergo reaction as well. With a,b-unsat-
urated aldehydes 7e and 7f only 1,2-adducts have been
isolated, whereas reaction with methyl vinyl ketone 9
afforded a 3:1 mixture of 1,2- and 1,4-adducts (10a and
10b, respectively). Examples of this reactivity are sum-
marized in Table 1.
Then, taking advantage of the well-known reactivity of
organosilanes under fluoride-ion catalysis, we evaluated
the possibility of dithiolane functionalization in such
conditions.
Thus, when the silyl dithiolane 3 is treated with benz-
aldehyde in the presence of different sources of
fluoride ion (TBAF, TBAT, TASF), a smooth reaction
occurs, leading to the corresponding functionalized a-
hydroxy dithiolane 8a (together with desilylated dithio-
lane, ca. 20%), so disclosing the possibility of an
effective transfer of a ‘dithiolane anion’ onto elec-
trophiles under mild conditions (Scheme 3).9 This reac-
tivity appears not to be restricted to benzaldehyde 7a,
but may be conveniently extended to aliphatic 7g, het-
eroaromatic 7c,d and a,b-unsaturated aldehydes 7e,f,
affording in all cases protected a-hydroxy aldehydes.
The low yields observed for 7d may be attributed to
steric hindrance of the N-methyl group. Reactive halo
derivatives such as allyl bromide 11 and methyl vinyl
Furthermore, the hydroxydithiolanes obtained can be
easily and efficiently transformed into hydroxy alde-
hydes 13 upon treatment with Tl(NO3)3, as shown in
Scheme 4,10 thus disclosing a novel synthetic route to
an interesting class of compounds.
OH
HO
Ph
S
S
Tl(NO3)3
H
Ph
13
O
8a
Scheme 4.
O
Ph
S
F
S
S
+
Ph
H
HO
S
SiMe3
7a
8a
3
S
S
S
S
SiMe3
Scheme 3.
Table 1.
Yield (%)a,b
Aldehyde
Product
Yield (%)a,b
Aldehyde
CHO
Product
OH
S
S
Ph-CHO
C
Ph
H
79
7a
OH
CH
S
24
8a
S
CHO
8f
7f
OH
CH
S
S
Br
Br
78
83
7b
OH
80
S
8b
OH
CH
CHO
S
S
S
CHO
8g
7g
S
C
H
S
7c
CH3
HO
S
S
8c
C
O
OH
S
30c
CHO
CHO
10a
10b
N
C
H
12
S
9
CH3
S
N
7d
Me
8d
S
O
OH
S
S
S
30
Br
C
H
Ph
7e
S
81
11
Ph
12
8e
a Yields refer to chromatographically pure material. b All spectroscopic and analytical data were consistent with
the assigned structure. c 3 : 1 mixture of 1,2 : 1,4 adducts.

A. Degl’Innocenti et al. / Tetrahedron Letters 42 (2001) 4557–4559
4559
In conclusion we have presented a novel protocol for
the generation of unreported 2-trimethylsilyl-1,3-dithio-
lane 3, whose fluoride-ion-catalyzed reactivity allows
the development of an efficient and mild protocol for
the general functionalization of the dithiolane moiety.
These results show that, under the present conditions, 3
can behave as a masked dithiolane anion. Further work
in this direction is currently underway in our
laboratory.
7. Christiansen, M. L.; Benneche, T.; Undheim, K. Acta
Chem. Scand. Ser. B 1987, 40, 536.
8. Recent results show that 3 can also be efficiently obtained
from 5 under basic conditions.
9. Typical procedure: To a solution of 88 mg (0.28 mmol) of
anhydrous TBAF (dried over 250 mg of activated molec-
11
,
ular sieves 4 A, following Majetich’s procedure ), in 1.5
mL of dry DMF, a solution of benzaldehyde (0.28 mmol,
28 mL) and 2-trimethylsilyl-1,3-dithiolane (50 mg, 0.28
mmol) in 1 ml of dry DMF was added at room tempera-
ture, under an inert atmosphere. The reaction was moni-
tored by GC/MS, then the mixture was diluted with
diethyl ether, washed with water, brine and dried over
Na2SO4. Purification by TLC (hexanes/ethyl acetate 5:1)
References
1. (a) Seebach, D. Synthesis 1969, 17; (b) Seebach, D.;
Corey, E. J. J. Org. Chem. 1975, 40, 231; (c) Bulman
Page, P. C.; van Niel, M. B.; Prodger, J. C. Tetrahedron
1989, 45, 7643.
1
afforded 47 mg of pure product 8a (79%). H NMR (200
MHz, CDCl3): l 3.14–3.32 (m, 4H), 4.62 (d, 1H, J=7.0
Hz), 4.79 (d, 1H, J=7.0 Hz), 7.30–7.46 (m, 5H). MS m/z
(%): 135 (M+−77, 0.5), 107 (18), 105 (100), 79 (15), 77
(22). Reaction with TBAT as catalyst gave comparable
results.
2. Oida, T.; Tanimoto, S.; Terao, H.; Okano, M. J. Chem.
Soc., Perkin Trans. 1 1986, 1715.
3. (a) Wilson, S. R.; Georgiadis, G. M.; Khatri, H. N.;
Bartmess, J. E. J. Am. Chem. Soc. 1980, 102, 3577; (b)
Wilson, S. R.; Caldera, P.; Jester, M. A. J. Org. Chem.
1982, 47, 3319.
10. Typical procedure. To a solution of (1,3-dithiolane-2-yl)-
phenyl methanol 8a (15 mg, 0.071 mmol) in 0.5 ml of
THF was added at room temperature, under an inert
atmosphere, 31 mg (0.071 mmol) of Tl(NO3)3·3H2O in 1
mL of methanol. After 5 min a white precipitate was
formed, then the reaction mixture was treated with
diethyl ether, washed with water and brine, and dried
over Na2SO4. Evaporation of the solvent afforded 7.2 mg
of product 13 (75%). 1H NMR (200 MHz, CDCl3): l 5.24
(s, 1H), 7.31–7.43 (m, 5H), 9.64 (s, 1H). MS m/z (%): 136
(M+, 3), 105 (91), 77 (100), 51 (73). Upon standing,
partial dimerization of the a-hydroxyaldehyde was
4. (a) Paulsen, H.; Koebernick, W.; Koebernick, H. Tetra-
hedron Lett. 1976, 27, 2297; (b) Yamashita, M.; Suemitsu,
R. J. Chem. Soc., Chem. Commun. 1977, 691.
5. (a) Capperucci, A.; Degl’Innocenti, A.; Metzner, P.; Bar-
toletti, L.; Checcacci, C. Phosphorus Sulfur Silicon 1997,
120–121, 333–334; (b) Capperucci, A.; Degl’Innocenti,
A.; Scafato, P. Recent Res. Devel. Synth. Org. Chem.
1998, 1, 171–197; (c) Degl’Innocenti, A.; Capperucci, A.
Eur. J. Org. Chem. 2000, 2171.
1
6. Spectroscopic data of 2-trimethylsilyl-1,3-dithiolane 3: H
1
observed. H NMR of the dimer (CDCl3): l 4.30 (d, 2H,
NMR (200 MHz, CDCl3): l 0.18 (s, 9H), 3.06–3.29 (m,
4H), 3.53 (s, 1H). 13C NMR (50 MHz, CDCl3): l −2.3,
37.6, 39.4. MS m/z (%): 178 (M+, 51), 150 (74), 135 (98),
105 (84), 91 (34), 77 (68), 75 (69), 73 (100), 59 (88).
J=6.4 Hz), 4.62 (d, 2H, J=6.4 Hz), 7.28–7.40 (m, 10).
11. Majetich, G.; Casares, A.; Chapman, D.; Behnke, M. J.
Org. Chem. 1986, 51, 1745.
.