An easy conversion of the Baylis-Hillman adducts into tert- butyldimethylsilyl ethers with tert-butyldimethylsilyl chloride and Li 2S

Article abstract of DOI:10.1080/10426500490485291

The hydroxy group of the Baylis-Hillman adducts is protected with the t-butyldimethylsilyl (TBDMS) group using the reaction of adducts 1a-h with tert-butyldimethylsilyl chloride (TBDMSCl) in the presence of lithium sulfide under nearly acidic reaction con

Full text of DOI:10.1080/10426500490485291

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AN EASY CONVERSION OF THE
BAYLIS-HILLMAN ADDUCTS INTO
tert-BUTYLDIMETHYLSILYL
ETHERS WITH tert-
BUTYLDIMETHYLSILYL
CHLORIDE AND Li S
2
a
a
Manouchehr Mamaghani & Abed Badrian
a
Department of Chemistry, Faculty of Sciences,
Guilan University, Rasht, Iran
Published online: 16 Aug 2010.
To cite this article: Manouchehr Mamaghani & Abed Badrian (2004): AN EASY
CONVERSION OF THE BAYLIS-HILLMAN ADDUCTS INTO tert-BUTYLDIMETHYLSILYL
ETHERS WITH tert-BUTYLDIMETHYLSILYL CHLORIDE AND Li S, Phosphorus, Sulfur, and
2
Silicon and the Related Elements, 179:12, 2429-2435
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Phosphorus, Sulfur, and Silicon, 179:2429–2435, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490485291
AN EASY CONVERSION OF THE BAYLIS-HILLMAN
ADDUCTS INTO tert-BUTYLDIMETHYLSILYL
ETHERS WITH tert-BUTYLDIMETHYLSILYL
CHLORIDE AND Li S
2
Manouchehr Mamaghani and Abed Badrian
Department of Chemistry, Faculty of Sciences,
Guilan University, Rasht, Iran
(
Received February 20, 2004; accepted April 20, 2004)
The hydroxy group of the Baylis-Hillman adducts is protected with the
t-butyldimethylsilyl (TBDMS) group using the reaction of adducts 1a–
h with tert-butyldimethylsilyl chloride (TBDMSCl) in the presence of
lithium sulfide under nearly acidic reaction conditions.
Keywords: Baylis-Hillman adducts; tert-butyldimethylsilyl ethers;
TBDMSCl; protecting group
INTRODUCTION
1
Recently, the key role of the Baylis-Hillman reaction in the preparation
of a variety of important products has been recognized by many organic
2
chemists.
The Baylis-Hillman adducts 1, containing chemospecific functional
groups in close proximity, have been extensively used in a number
of transformation methodologies often involving a high level of stere-
oselectivity. These adducts are versatile building blocks for the syn-
thesis of several important compounds3 and have been exploited
4
in the preparation of natural products such as kijanolid, myces-
5
6
7
tericin E, terpenticin, insect pheromons and nitrogen-containing
8
,9
heterocycles.
The authors are grateful to Guilan University Research Council for financial support
of our research program.
Address correspondence to Manouchehr Mamaghani, Department of Chemistry,
Faculty of Sciences, Guilan University, P.O. Box 41335-1914 Rasht, Iran. E-mail:
m-chem41@guilan.ac.ir
2
429

2
430
M. Mamaghani and A. Badrian
However, due to vital importance of the Baylis-Hillman adducts 1a–h
as very interesting acceptor reactants in many types of transformations,
the protection of the hydroxy group may be essential in some of the
reactions.
Chemists are often faced with the problem of having to use one
or more protecting groups as part of a synthetic sequence. Factors
that must be taken into account for identification of the most appro-
priate protecting groups are (1) the protecting group must withstand
the reaction conditions, including those used to protect and depro-
tect other functional groups; (2) the protecting group must be eas-
ily introduced selectively at the desired site and in high yield; and
(
3) the protecting group must be easily removed selectively and in high
yield.
Identification of the best protecting groups and the most appropriate
conditions for performing the protection and deprotection steps becomes
a relatively straightforward task. The role of silyl group has already
been recognized of late as an important part of organic chemistry from
both analytical and synthetic point of view, especially as protecting
1
1
group in many synthesis of reasonable complexity.
The popularity of silylation reagents is enhanced by their ease of
use and formation of derivatives. In silylation, an active hydrogen is
replaced by an alkylsilyl group such as trimethylsilyl (TMS) or TB-
DMS. Both TMS and TBDMS reagents are suitable for a wide variety
of compounds, offer excellent thermal stability, and can be used un-
der a variety of conditions and applications. Compared to their par-
ent compounds, silyl derivatives are more volatile, less polar, and more
thermally stable. The derivatives of TMS reagents are generally mois-
ture sensitive, requiring them to be sealed to prevent deactivation. In
response to this difficulty TBDMS reagents were introduced, which en-
abled the formation of derivatives 10,000 times more stable to hydrol-
ysis than the TMS ethers.12
RESULTS AND DISCUSSION
TBDMS ethers are stable to aqueous or alcoholic base under the normal
conditions for acetate saponification, and are also stable to hydrogenol-
ysis (H2 Pd) and mild chemical reduction (e.g., Zn CH3OH).13 The
specific reactions, which are outlined immediately below, provide an il-
lustration of the stability and applicability of the TBDMS group in the
protection of alcohols.
In continuation of our interest for the Baylis-Hillman adducts and
1
4
transforming into a variety of natural and unnatural compounds and

tert-Butyldimethylsilyl Ether
2431
organosilicon compounds,15 herein we wish to report our results for the
protection of the hydroxy group of these adducts with the TBDMS group
using the reaction of adducts 1a–h with TBDMSCl and lithium sulfide
(
Scheme 1).
SCHEME 1
The procedure generally used for the preparation of TBDMS ethers
involves treatment of alcohols with TBDMSCl in the presence of im-
idazole in dimethylformamide solution. The silylation of tertiary and
1
6
allylic alcohols were, however sluggish under these conditions. In the
case of Baylis-Hillman type allylic alcohols used in this study, after ad-
dition of the silylating reagent and Li2S in acetonitrile, the reactions
were completed in 5–8 h in all the cases studied (1a–h). The results are
summarized in Table I.
Silylation of the Baylis-Hillman adducts took place very smoothly at
ambient temperature when a mixture of alcohol, TBDMSCl, and Li2S
(
in a 1:2:1.5 molar ratio) in dry acetonitrile was stirred overnight. Yields
were generally high, and the method provided an extremely mild, sim-
ple, and inexpensive way of tert-butyldimethylsilylation under weakly
acidic conditions.17
The proposed mechanism of this reaction and the role of Li2S is not
clear, but a proposed mechanism of this transformation is depicted in
Scheme 2. The reaction is initiated through the formation of a com-
plex with the sulfide and TBDMSCl, resulting in in situ formation of
a disilathiane-type equivalent 3, which would be responsible for the
1
8
remarkable silylating power of the reagent. A rapid reaction with
SCHEME 2 A proposed mechanism of the silylation with t-BuMe
2
SiCl and
2
Li S.

2
432
M. Mamaghani and A. Badrian
TABLE I Product Distribution Data and the Yield of the Products
Entry
Alcohols (1)
Products (2)a
Time (h)
6
% yieldb
88c
a
b
c
d
e
f
7
85
84
90
82
79
78
80
7.5
5
6
6.5
7
g
h
8
aAll compounds have been fully characterized spectroscopically by 1H NMR, IR, and
elemental analyses.
b
Isolated yields.
c
1
Analyzed by comparition of its spectroscopic data ( H NMR, IR) with those of an
9
authentic sample (Annunziata et al. ).
alcohol then ensues, leading to the hydrogensulfide silylating species
4
and concomitant release of the corresponding TBDMS ether and
H2S.
In conclusion,
a
practical, highly efficient, and convenient
◦
protocol with mild conditions (25 C) has been developed for tert-
butyldimethylsilylation of the Baylis-Hillman adducts. This reaction
can be applied to the protection of hydroxy groups and the syn-
thesis of multiple-point pharmacophores of natural and unnatural
compounds.

tert-Butyldimethylsilyl Ether
2433
EXPERIMENTAL
General
Chemicals were purchased from Merck and Fluka. Melting points were
measured on an Electrothermal 9100 apparatus. Elemental analyses
were performed using a Heraeus CHN O-Rapid analyzer. IR spectra
1
were determined on a Shimadzu IR-470 spectrometer. H NMR spectra
were recorded on a 500 MHz Bruker DRX-500 instrument in CDCl3
as solvent and TMS as internal standard. Preparative thin layer chro-
matography (TLC) was prepared from Merck Kieselgel 60 H, F254, Art
No 7730. GC was carried out using Buck Scientific 910 (capillary col-
umn, MXT-5, 15 m). All solvents used were dried and distilled according
to standard procedures.
General Procedure for tert-Butyldimethylsilylation
of Baylis-Hillman Adducts
To a well-stirred suspension of lithium sulfide (0.345 g, 7.5 mmol) in
dry acetonitrile (15 ml) was added tert-butyldimethylsilylchloride (1.5 g,
1
0 mmol) under a nitrogen atmosphere. To this mixture was then added
a solution of the corresponding alcohol 1 (5.0 mmol) in acetonotrile
5 ml), and the stirring continued until the reaction was completed.
(
The reaction mixture was diluted with ether (20 ml), washed succes-
sively with water (2 × 20 ml) and brine (10 ml), and dried over anhy-
drous sodium sulfate. Evaporation of the ethereal extract afforded pure
TBDMS ethers, which were further purified by vacuum distillation or
recrystalization to afford pure silyl ether 2. The isolated yield for each
1
product is given in parentheses, and the IR and HNMR data for the
compounds 2b–h are given below.
◦
2
b: yellow solid, m.p. 85–87 C, 85%. Found: C, 67.46; H, 8.81.
−
1
C18H28O3Si requires: C, 67.50; H, 8.75%. IR (film, cm ): 3100, 2900,
1
2
0
1
800, 1722, 1610, 1254. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 3.62 (s, 3H), 5.63 (t, br., 1H), 6.13 (t, br., 1H), 6.26 (t, br.,
H), 6.77 (d, 2H, J = 7.6 Hz), 7.11 (d, 2H, J = 7.6 Hz).
◦
2
c: yellow solid, m.p. 89–91 C, 84%. Found: C, 64.20; H, 8.35.
−
1
C18H28O4Si requires: C, 64.28; H, 8.33%. IR (film, cm ): 3100, 2900,
1
2
0
6
800, 1720, 1612, 1253. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 3.62 (s, 3H), 3.7 (s, 3H), 5.61 (t, br., 1H), 6.11 (t, br., 1H),
.24 (t, br., 1H), 6.8 (d, 2H, J = 7.7 Hz), 7.13 (d, 2H, J = 7.7 Hz).
◦
2
d: white solid, m.p. 99–101 C, 90%. Found: C, 59.80; H, 7.44.
−
1
C17H25ClO3Si requires: C, 59.91; H, 7.34%. IR (film, cm ): 3100, 2900,
800, 1721, 1613, 1250. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
1
2

2
434
M. Mamaghani and A. Badrian
0.99 (s, 9H), 3.66 (s, 3H), 5.65 (t, br., 1H), 6.15 (t, br., 1H), 6.26 (t, br.,
1
H), 7.12 (d, 2H, J = 7.9 Hz), 7.23 (d, 2H, J = 7.9 Hz).
◦
2
e: white solid, m.p. 96–98 C, 82%. Found: C, 59.83; H, 7.35.
−
1
C17H25ClO3Si requires: C, 59.91; H, 7.34%. IR (film, cm ): 3109, 2900,
1
2
0
1
800, 1722, 1615, 1253. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 3.66 (s, 3H), 5.65 (t, br., 1H), 6.15 (t, br., 1H), 6.26 (t, br.,
H), 7.12–7.25 (m, 4H).
◦
2f: green solid, m.p. 110–112 C, 79%. Found: C, 62.55; H, 8.27.
−
1
C16H25NO3Si requires: C, 62.54; H, 8.14%. IR (film, cm ): 3150, 2900,
1
2
0
1
800, 1725, 1625, 1256. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 3.66 (s, 3H), 5.65 (t, br., 1H), 6.15 (t, br., 1H), 6.26 (t, br.,
H), 7.45–8.70 (m, 4H).
◦
2g: green solid, m.p. 101–103 C, 78%. Found: C, 65.25; H, 8.97.
−
1
C19H31NO3Si requires: C, 65.32; H, 8.88%. IR (film, cm ): 3100, 2900,
1
2
0
6
800, 1720, 1621, 1252. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 2.9 (s, 6H), 3.69 (s, 3H), 5.63 (t, br., 1H), 6.12 (t, br., 1H),
.23 (t, br., 1H), 6.70 (d, 2H, J = 7.8 Hz), 7.11 (d, 2H, J = 7.8 Hz).
◦
2
h: yellow solid, m.p. 89–91 C, 80%. Found: C, 68.87; H, 9.30.
−
1
C20H32O3Si requires: C, 68.96; H, 9.19%. IR (film, cm ): 3100, 2900,
1
2
0
6
800, 1720, 1612, 1252. H NMR (CDCl3, δ): −0.1 (s, 3H), 0.00 (s, 3H),
.99 (s, 9H), 1.3 (d, 6H), 3.10 (m, 1H), 3.62 (s, 3H), 5.63 (t, br., 1H),
.13 (t, br., 1H), 6.26 (t, br., 1H), 7.10 (d, 2H, J = 7.6 Hz), 7.19 (d, 2H,
J = 7.6 Hz).
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