Tetrabutylammonium phenoxide induced reaction of silyl nucleophiles

Article abstract of DOI:10.1016/j.tetlet.2009.03.167

Reaction of silyl dithiolanes with electrophiles can be efficiently promoted by catalytic amounts of tetrabutylammonium phenoxide (PhONn-Bu₄), leading to a convenient access to functionalized dithiolanes. PhONn-Bu₄ proved effective a

Full text of DOI:10.1016/j.tetlet.2009.03.167

Tetrahedron Letters 50 (2009) 2808–2810
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Tetrabutylammonium phenoxide induced reaction of silyl nucleophiles
a
b
a,
Antonella Capperucci a, , Caterina Tiberi , Salvatore Pollicino , Alessandro Degl’Innocenti
*
*
a Dipartimento di Chimica Organica and HBL, Università di Firenze, via della Lastruccia, 13, I-50019 Sesto Fiorentino, Italy
b Dipartimento di Chimica Organica A. Mangini, Università di Bologna, viale Risorgimento, 4, 40136 Bologna, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of silyl dithiolanes with electrophiles can be efficiently promoted by catalytic amounts of tetra-
butylammonium phenoxide (PhONn–Bu4), leading to a convenient access to functionalized dithiolanes.
PhONn–Bu4 proved effective also in promoting reactions of silylated sulfides such as PhSTMS and HMDST
as well as silylated selenides such as PhSeTMS and HMDSS toward epoxides. The present reactivity is also
observed on using ILs as reaction media.
Received 5 January 2009
Revised 23 March 2009
Accepted 24 March 2009
Available online 28 March 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Silyldithiolanes
Silylsulfides
Selenosilanes
Phenoxide ion
Fluoride ion-induced reactivity of a carbon silicon bond as a
convenient methodology for the formation, under mild conditions,
of novel carbon–carbon bonds has attracted a great deal of
attention.
In this context, several fluoride ion sources were evaluated,
ranging from CsF, TASF, TBAT, and TBAF, and we found TBAF to
be, at least in our hands, the best choice. Several drawbacks are
nevertheless linked to the use of TBAF, such as the difficulties in
having an anhydrous solution, and its stability along with time.5
This is why we began to look for different catalytic systems. A re-
cent investigation by Mukayama and coworkers6 on the phenox-
ide-catalyzed reactivity of silyldithianes, prompted us to report
our own results in this direction that show how phenoxide ion
can be efficiently used in replacement of TBAF in promoting the
reactions of silyl dithiolanes thus overcoming the mentioned
drawbacks.
Both PhONa and PhONn-Bu4 were used as catalysts in the reac-
tions of silyl dithiolanes 1a,b with aldehydes, and different sol-
vents taken into consideration and we also found the best choice
being PhONn-Bu4 in polar solvents such as DMF (Scheme 1).7 The
use of PhONa generally leads to the formation of variable amounts
of desilylation products, and solvents like THF to low yields of the
expected products. Moreover, reactions in DMF were faster than
those in THF (2–4 h in DMF, 12–24 h in THF).
Our interest in the synthesis and reactivity of organosilanes, in
connection with the very mild functionalization conditions of the
carbon–silicon bond under fluoride ion catalysis,1 led us recently
to disclose a protocol for the dithiolane functionalization through
the 2-silyl-1,3-dithiolane that opened new perspectives in the
chemistry of such heterocyclic rings.2 Direct functionalization of
dithiolane moieties being prevented by the lability of the gener-
ated dithiolane anion, which decompose through a cycloreversion
reaction upon its generation3, we explored different procedures,
and we found that under the influence of fluoride ion, these 2-si-
lyl-1,3- dithiolanes can efficiently transfer the dithiolane moiety
onto electrophiles, such as aldehydes, affording the corresponding
protected
a-hydroxy aldehydes. These results showed that under
the present conditions, silyl dithiolane can be considered as a syn-
thetic equivalent of a dithiolane anion. Furthermore, when using
stereodefined dithiolanes, the stereochemistry of the carbon–sili-
con bond is retained throughout the process and transferred to
the newly formed carbon–carbon bond.4
Such results then outline the peculiarity of the silicon moiety in
promoting these reactions, and evidence the fluoride ion-induced
functionalization of the C–Si bond as a possible general tool for
the functionalization of otherwise not easily functionalizable
heterocycles.
R
R
R1CHO
S
S
S
S
PhONnBu4
R1
OH
SiMe3
2a-g
1a: R = H
1b: R = CH2OiPr
R1 = see Table 1
* Corresponding authors. Tel.: +39 0554573551; fax: +39 055 4573585 (A.D.).
E-mail addresses: antonella.capperucci@unifi.it (A. Capperucci), alessandro.de
glinnocenti@unifi.it (A. Degl’Innocenti).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.167

A. Capperucci et al. / Tetrahedron Letters 50 (2009) 2808–2810
2809
Table 1
Carbodesilylation of silyldithiolanes
Entry
Dithiolane
R1CHO
Catalyst
Solvent
Product
Yield (%)a,b
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1a
1a
1a
1a
1a
PhCHO
PhCHO
PhCHO
PhCHO
Thenyl-CHO
p-Br-C6H4–CHO
E-PhCH@CHCHO
C6H11CHO
(CH3)2CHCH2CHO
PhONa
DMF
THF
2a
2a
2a
2b
2c
2d
2e
2f
42
10
87
49c
88
70
78
60
30d
PhONBu4
PhONBu4
PhONBu4
PhONBu4
PhONBu4
PhONBu4
PhONBu4
PhONBu4
DMF
DMF
DMF
DMF
DMF
DMF
DMF
2g
a
Based on isolated yield.
b
c
All the products were characterized by 1H, 13C NMR and mass spectroscopy.
Mixture of cis and trans isomers.
d
1,3-Dithiolane was recovered (ca. 25%) together with traces of condensation products (<5%).
Results of this investigation are summarized in Table 1.
Reactivity proved general, occurring smoothly with aromatic,
b-hydroxy sulfides, that behave as useful intermediates in different
synthetic transformations.
heteroaromatic, and aliphatic aldehydes. In all reactions no trace
of decomposition of the dithiolane ring was observed, thus show-
ing that also under the influence of phenoxide ion a real carbanion
is not generated in the present conditions. The substituted 2-silyl-
4-(isopropoxymethyl)-1,3-dithiolane 1b was reacted as well with
The efficiency of the methodology is further demonstrated by
the use in such reactions of the much more labile chalcogen deriv-
ative hexamethyldisilathiane [HMDST, (Me3Si)2S], which in turn
reacted smoothly with oxirane 3, affording the b-hydroxythiol 5
in comparable yields with those already reported under fluoride
ion conditions (Scheme 2). Interestingly, epoxide functionalization
reactions could be conveniently performed in THF instead of DMF.
In some cases, products were isolated as their trimethylsilyl ethers.
As a further step, we decided to evaluate the possible extension
to the reactivity of selenosilanes.
benzaldehyde, leading to the formation of the 4-substituted-a-hy-
droxy-dithiolane 2b as a mixture of cis/trans isomers (Table 1, en-
try 4), that can be separated on silica gel. It should be mentioned
that when reacting substituted dithiolanes a greater amount of
protodesilylation was observed.
Usually, dithiolane adducts were obtained as a mixture of hy-
droxy compounds and trimethylsilyl ethers. The use of saturated
aqueous NH4Cl solution during the work-up led to the exclusive
formation of the corresponding alcohols.
To the best of our knowledge, while several papers have re-
ported the reaction of thiosilanes with oxiranes,10 only very few
examples have been described dealing with the reactivity of
selenosilanes.11
Once established the efficiency of phenoxide ion in promoting
the functionalization of silyl dithiolanes, we turned our attention
to different organosilanes, namely those containing an hetero-
atom-silicon bond, such as S–Si.
Very recently we found that bis(trimethylsilyl)selenide
[(TMS)2Se, HMDSS] acts as an efficient reagent in the TBAF-cata-
lyzed reaction with three-membered heterocycles, leading to b-
functionalized diselenides.12
We have in fact recently been interested in the functionaliza-
tion of the S–Si bond in the regio- and stereoselective ring opening
of oxiranes by HMDST, for the synthesis of mercapto alcohols.8
Such investigation showed that sulfurated moieties can easily
and efficiently be transferred onto different electrophiles, such as
epoxides, by using the corresponding silyl derivatives under fluo-
ride ion conditions.
Thus, benzylglycidol 3 was reacted with phenylselenotrimeth-
ylsilane under the catalysis of phenoxide ion, the reaction led to
the isolation of the corresponding b-phenylselenoalcohol 6 in
89% yield (Scheme 3).
Again, when moving to the more intriguing hexamethyldisilase-
lenane (HMDSS) a smooth reaction was observed with benzylglyc-
Thus, when phenylthiotrimethylsilane was reacted with ben-
zylglycidol 3 and a catalytic amount of PhONn-Bu4 (20%),9 a clean
reaction occurred, leading to the isolation in good yield of com-
pound 4, arising from a regioselective attack on the less hindered
side of the oxirane ring (Scheme 2). Then, the above-described
procedure may represent a simple and efficient approach to access
OH
O
Ph
89%
6
SePh
PhONnBu4
THF
PhSeSiMe3
OH
O
O
Ph
O
Ph
PhSSiMe3
Ph
SPh
78%
3
PhONnBu4
HMDST
4
O
PhONnBu4
THF
O
HMDSS
OH
3
OH
OH
PhONnBu4
O
Ph
Ph
O
Se Se
O
Ph
SH
85%
5
7
69%
Scheme 2.
Scheme 3.

2810
A. Capperucci et al. / Tetrahedron Letters 50 (2009) 2808–2810
2. Capperucci, A.; Degl’Innocenti, A.; Nocentini, T. Tetrahedron Lett. 2001, 42,
OH
4557–4559.
O
Ph-X-SiMe3
PhONnBu4
[bmim] [PF6]
O
Ph
3. (a) Wilson, S. R.; Georgiadis, G. M.; Khatri, H. N.; Bartmess, J. E. J. Am. Chem. Soc.
1980, 102, 3577–3583; (b) Wilson, S. R.; Caldera, P.; Jester, M. A. J. Org. Chem.
1982, 47, 3319–3321; (c) Oida, T.; Tanimoto, S.; Terao, H.; Okano, M. J. Chem
Soc., Perkin Trans. 1 1986, 1715–1725.
4. Capperucci, A.; Cerè, V.; Degl’Innocenti, A.; Nocentini, T.; Pollicino, S. Synlett
2002, 1447.
O
Ph
XPh
3
4 X = S (69%)
6 X = Se (78%)
X = S, Se
5. (a) Sharma, R. K.; Fry, J. L. J. Org. Chem. 1983, 48, 2112–2114; (b) Cox, D. P.;
Terpinski, J.; Lawrynowicz, W. J. Org. Chem. 1984, 49, 3216–3219; (c) Majetich,
G.; Casares, A.; Chapman, D.; Behnke, M. J. Org. Chem. 1986, 51, 1745–1753; (d)
Sun, H.; DiMagno, S. G. J. Am. Chem. Soc. 2005, 127, 2050–2051.
6. (a) Michida, M.; Mukaiyama, T. Chem. Lett. 2008, 37, 26–27; (b) Michida, M.;
Mukaiyama, T. Chem. Asian J. 2008, 3, 1592–1600.
7. Typical procedure: A solution of PhONBu4 (30 mg, 0.09 mmol) in dry DMF
(0.2 mL) was added under inert atmosphere dropwise to benzaldehyde (26 mg,
0.24 mmol) and 2-trimethylsilyl-1,3-dithiolane 1a (40 mg, 0.22 mmol).
Progress of the reaction was monitored by TLC (petroleum ether/ethyl
acetate 5:1) and GC/MS, and after 3.5 h the mixture was then diluted with
diethyl ether and washed with water. The aqueous phase was extracted with
diethyl ether and the combined organic phases were washed with brine and
Scheme 4.
idol 3, leading this time to hydroxydiselenide 7, arising from oxida-
tion of the transient selenol obtained in the reaction (Scheme 3).
Attempts to isolate the b-hydroxy silyl selenide (or selenol) inter-
mediate were unsuccessful. It is interesting to note that in the case
of silyl selenides, only a 2% of the catalyst was necessary to achieve
complete transformation of the oxirane. As a consequence, com-
pounds 6 and 7 are recovered from the reaction medium pure en-
ough to undergo subsequent reactions.
Finally, we were interested to evaluate the efficiency of such
protocol also in different reaction media. Due to their peculiar
properties, ionic liquids (ILs) are regarded as eco-friendly novel
and alternative solvents of increasing interest.13
To the best of our knowledge, besides few examples of ring
opening of epoxides with sulfurated14 or silylated15 nucleophiles
in ILs, no example has been described for the reactions of oxiranes
with selenosilanes. Very recently a paper dealing with ring-open-
ing reactions of epoxides with aryselenols has been reported.14e
Thus, we reacted benzylglycidol 3 with phenylthiotrimethylsi-
lane and phenylselenotrimethylsilane under the catalysis of phen-
oxide ion (0.4–0.2 equiv, respectively) in ionic liquids such as
[bmim][PF6] (Scheme 4), and we found that the reaction proved
quite efficient, leading to the b-hydroxy phenylthio- (4) and phe-
nylseleno- (6) derivatives in good yields, thus confirming the ver-
satility of this new catalytic system. Performing the reaction in
ILs, no trimethylsilyl ether formation was observed, but only hy-
droxy compounds were isolated.
dried over Na2SO4. Filtration and evaporation of the solvent gave the crude a-
hydroxy dithiolane 2a as a yellow oil, that can be purified on TLC (petroleum
ether/ethyl acetate 5:1) to afford the pure compound (87%). 1H NMR (200 MHz,
CDCl3) d: 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+À77, 0.5), 107 (18), 105 (100), 79 (15),
77 (22). The reaction was repeated on larger scale (178 mg of silyl-dithiolane
1a (1 mmol), 116 mg of PhCHO (1.09 mmol) and 143 mg of PhONBu4
(0.41 mmol) in 0.9 mL of dry DMF) affording 172 mg of 2a (81%) after
chromatographic purification.
8. Degl’Innocenti, A.; Capperucci, A.; Cerreti, A.; Pollicino, S.; Scapecchi, S.;
Malesci, I.; Castagnoli, G. Synlett 2005, 3063–3066.
9. Typical procedure: A solution of 13 mg of PhONBu4 (0.04 mmol) in dry THF
(0.7 mL) was treated under inert atmosphere with benzylglycidol 3 (30 mg,
0.18 mmol) and phenylthio-trimethylsilane (36 mg, 0.20 mmol). The mixture
was stirred at rt. and progression of the reaction was monitored by TLC. After
quenching with water, the product was extracted with diethyl ether. The
resulting organic phase was washed with brine, dried over Na2SO4 and the
solvent evaporated under vacuum. TLC purification (petroleum ether/ethyl
acetate 9:1) afforded 39 mg (78%) of adduct 4 as a pale yellow oil. 1H NMR
(200 MHz, CDCl3) d (ppm): 7.39–7.17 (m, 10H), 4.5 (br s, 2H), 3.96–3.84 (ap.
pent, 1H), 3.57 (dd, 1H, J = 4 Hz, J = 9.6 Hz), 3.50 (dd, 1H, J = 5.4 Hz, J = 9.6), 3.12
(dd, 1H, J = 6 Hz, J = 13 Hz), 3.02 (dd, 1H, J = 7 Hz, J = 13 Hz), 2.67 (br s, 1H). 13C
NMR (50 MHz, CDCl3) d (ppm): 37.5, 68.9, 72.4, 73.4, 127.4, 127.7, 128.4, 128.9,
129.6, 135.3, 137.7. MS m/z (%): 274 (M+, 13), 165 (12), 123 (51), 109 (29), 91
(100), 77 (25). The reaction was repeated on larger scale (164 mg of
benzylglycidol 3 (1 mmol), 202 mg of PhSSiMe3 (1.11 mmol) and 77 mg of
PhONBu4 (0.22 mmol) in 3.9 mL of dry THF) affording 246 mg of 4 (90%).
10. (a) Abel, E. W.; Walker, D. J. J. Chem. Soc. A 1968, 2338; (b) Rokach, J.; Girard, Y.;
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Synth. Commun. 1981, 11, 391; (d) Trost, B. M.; Scanlan, T. S. Tetrahedron Lett.
1986, 27, 4141; (e) Brittain, J.; Gareau, Y. Tetrahedron Lett. 1993, 34, 3363; (f)
Tanabe, Y.; Mori, K.; Yoshida, Y. J. Chem. Soc., Perkin Trans. 1 1997, 671–676.
11. (a) Detty, M. R. Tetrahedron Lett. 1978, 19, 5087–5090; (b) Miyoshi, N.; Kondo,
K.; Murai, S.; Sonoda, N. Chem. Lett. 1979, 8, 909–912; (c) Miyoshi, N.;
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12. Degl’Innocenti, A.; Capperucci, A.; Castagnoli, G.; Malesci, I.; Tiberi, C.;
Innocenti, B. Phosphorus, Sulfur, Silicon Relat. Elem. 2008, 183, 966–969.
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In conclusion, the use of phenoxide ion in promoting the reac-
tivity of silyl derivatives proved quite efficient and general, thus
disclosing an interesting alternative to the use of tetrabutylammo-
nium fluoride.
The use of different ILs as well as different ring strained hetero-
cyclics as substrates is now under investigation.
Acknowledgments
Financial support from MiUR, National Project PRIN 2007 ‘Ste-
reoselezione in Sintesi Organica. Metodologie ed Applicazioni’ is
gratefully acknowledged. Ente Cassa di Risparmio di Firenze is
acknowledged for granting a 400 MHz NMR spectrometer. Mrs. B.
Innocenti is acknowledged for carrying out GC/MS analyses.
References and notes
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Leriverend, C.; Metzner, P. J. Org. Chem. 1996, 6, 7174–7177; (c) Degl’Innocenti,
A.; Capperucci, A. Eur. J. Org. Chem. 2000, 2171–2186. and references cited
therein; (d) Cerè, V.; Peri, F.; Pollicino, S. Heterocycles 1999, 51, 1025–1034; (e)
Carini, S.; Cerè, V.; Peri, F.; Pollicino, S. Synthesis 2000, 1756–1760; (f)
Degl’Innocenti, A.; Pollicino, S.; Capperucci, A. Chem. Commun. 2006, 4881–4893.
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