Highly atom economical uncatalysed and I2-catalysed silylation of phenols, alcohols and carbohydrates, using HMDS under solvent-free reaction conditions (SFRC)

Article abstract of DOI:10.1016/j.tet.2012.03.040

An uncatalysed silylation of phenols, regardless on the aggregate state and nature of the substituents with 0.55 equiv of HMDS under solvent-free reaction conditions (SFRC) at room temperature is reported. Sterically hindered phenols, carbohydrates and most of the alcohols additionally required a catalytic amount (up to 2 mol %) of iodine. The reaction protocol is very simple; obtaining a pure product, particularly of uncatalysed reactions, was frequently a completely solvent-free process.

Full text of DOI:10.1016/j.tet.2012.03.040

Tetrahedron 68 (2012) 3861e3867
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly atom economical uncatalysed and I2-catalysed silylation of phenols,
alcohols and carbohydrates, using HMDS under solvent-free reaction conditions
(SFRC)
*
Marjan Jereb
ꢀ
ꢀ
Faculty of Chemistry and Chemical Technology, Askerceva 5, 1000 Ljubljana, Slovenia
a r t i c l e i n f o
a b s t r a c t
Article history:
An uncatalysed silylation of phenols, regardless on the aggregate state and nature of the substituents
with 0.55 equiv of HMDS under solvent-free reaction conditions (SFRC) at room temperature is reported.
Sterically hindered phenols, carbohydrates and most of the alcohols additionally required a catalytic
amount (up to 2 mol %) of iodine. The reaction protocol is very simple; obtaining a pure product, par-
ticularly of uncatalysed reactions, was frequently a completely solvent-free process.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 13 December 2011
Received in revised form 22 February 2012
Accepted 12 March 2012
Available online 20 March 2012
Keywords:
Solvent-free
Atom economy
Waste minimization
Iodine
HMDS
1. Introduction
Trimethylsilyloxy moiety is very attractive in the chemistry of
the protecting groups, due to its selective introduction and mild
Clean and environmentally friendly synthesis is an increasingly
important hot topic in chemistry.1 Sustainable development has
become one of the central demands in both academic and in-
dustrial research.2 Consideration of environmental impact is im-
portant both for the final product and, increasingly, its means of
production. Solvent-free reaction conditions3 (SFRC) represent one
of the most efficient contributions to the minimization of waste;
further advantages include reduction of health hazards, improved
cost efficiency and operational simplicity. Highly atom economical
processes are also a noteworthy part of the overall process effi-
ciency.4 A generally desirable process is the uncatalysed trans-
formation of neat reactants under mild reaction conditions due to
their simplicity and cost efficiency. Reactions with product isolation
and purification without any solvent deserve a special mention.
Iodine is an extremely versatile catalyst5 and reagent6 in organic
chemistry; it is mild, air and moisture tolerant, compatible with
a broad range of functional groups, and (in numerous cases) it is an
effective substitute for expensive and sensitive metallic Lewis acid
catalysts. It was demonstrated to be efficient in a solution, under
highly concentrated reaction conditions and also under SFRC.5d
and selective removal. TMS derivatisation of polar and non-volatile
molecules enhances their volatility, making them suitable for
the GC and MS analysis. This is particularly important for the
analysis of different natural products. HMDS is a very popular
transfer agent of the TMS group into organic molecules; however,
it often needs activation. Thus, the introduction of the TMS group is
usually accomplished using TMSCl and HMDS in the presence
of different catalysts, i.e., Aliquat 336,7 MgBr2$Et2O,8 NH4SCN,9
12
LiClO4,10 LaCl3,11 Mg(HSO4)2, trichloroisocyanuric acid,13 ZrCl4,14
ZnO,15 Fe(ClO4)3$6H2O,16 tungstophosphoric acid,17 zirconium sul-
fophenyl phosphonate,18 poly(4-vinylpyridinium tribromide),19
cerium-containing polyoxometalate,20 H-
b
zeolite,21 zirconyl tri-
flate,22 montmorillonite K-10,23 superparamagnetic iron oxide,24
a porous nanocomposite Nafion SAC-13,25 a solid supported sul-
fate,26 FeCl3 and ZnCl2,28 sulfonic acid-functionalised silica,29
27
Bu4NBr30 in combination with TMSN3 and 1,3-dibromo-5,5-
dimethylhydantoin31 and others. The main drawbacks of the
known methods are metal-based catalysts, the use of organic sol-
vents and the presence of different bases for neutralisation of HCl,
elevated temperature, long reaction times, tedious workup and
considerable excess of the silylating agent.
A recent report showed uncatalysed protection of phenols and
alcohols; however, the reaction took place in nitromethane using
50 mol % excess of HMDS.32 Iodine was also showed to be an
* Tel.: þ386 1 241 9248; fax: þ386 1 241 9220; e-mail address: marjan.jereb@
fkkt.uni-lj.si.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.040

3862
M. Jereb / Tetrahedron 68 (2012) 3861e3867
Table 1
effective catalyst for trimethylsilylation of phenols and alcohol;
nevertheless, the reaction proceeded in halogenated solvents and
with a considerable excess of HMDS33 and TMSCl.34 Our goal was
the protection of hydroxyl derivatives using an as-low-as-possible
excess of HMDS in the absence of solvent. We report on uncata-
lysed and iodine-catalysed trimethylsilylation of phenols, alcohols
and carbohydrates under SFRC.
Protection of phenols with HMDS under SFRC
Yielda (%)
2. Results and discussion
C
2
t (h)
Initially, 4-bromophenol 1a was functionalised with 0.8 equiv of
HMDS under SFRC, and full conversion to 2a was noted in 10 min. A
decrease in the amount of HMDS to 0.6 equiv resulted in the full
conversion of 1a into 2a within 15 min. Full conversion could also
be achieved with 0.55 and 0.53 equiv of HMDS only. Unfortunately,
the latter threshold amount appears not to be general; for conve-
nience, 0.55 equiv of HMDS was used. The evaluation of the po-
tential new method was performed on a series of structurally
different phenols; the results are summarised in Table 1. Phenol 1b
was fully transformed to 2b, using 0.55 equiv of HMDS (entry 2); 4-
chlorophenol 1c exhibited similar reactivity to 1a. Electron de-
ficient phenols 1deg were effectively transformed into their TMS
derivatives 2deg (entries 4e7), even though the opposite might
have been be expected, since 4-nitrophenol 1d failed to react in an
uncatalysed reaction in nitromethane. Moreover, the reactivity of
1deg was surprisingly high. Naphthols 1h and 1i produced de-
rivatives 2h and 2i in high yields (entries 8 and 9).
1
2
3
A
A
A
2a
2b
2c
0.25
91
77
85
PhOTMS
4
0.25
CI
4
5
A
A
2d
2e
1.5
1
92
87
6
7
A
A
2f
1
9
93
90
2g
Indane and tetraline derivatives 1jel efficiently provided their
TMS analogues 2jel (entries 10e12), though phenol 1l required
iodine (2 mol %) as a catalyst. 3- and 4-Alkylphenols could be suc-
cessfully derivatised with HMDS, without a catalyst (entries
13e15), while the uncatalysed protection of 2-alkylphenols took
a longer time and was not complete. The functionalisation of 1per
in the presence of iodine effectively furnished derivatives 2per
(entries 16e18). Electron-rich phenols 1seu were transformed to
the corresponding TMS derivatives 2seu (entries 19e21) without
8
9
A
A
2h
2i
4
3
89
91
a
catalyst. Trisubstituted phenols 1v and 1w were efficien-
tly protected in the presence of iodine under SFRC (entries 22
and 23). Sterically hindered phenols 1xez required iodine for
successful transformation (entries 24e26). Functionalisation of 4-
methylcatechol 1aa and pyrogallol 1bb proceeded effectively in
the presence of iodine under SFRC giving 2aa and 2bb in good
yields (entries 27 and 28). 4-Hydroxybenzyl alcohol 1cc was con-
verted to its 2cc analogue, showing that alcohols and phenols
could be protected under SFRC (entry 29). Oestrone 1dd was
transformed to its TMS derivative 2dd; no difficulties due to the
heterogeneous reaction mixture were noted (entry 30). Phenol-
phthalein 1ee was converted into its di-OTMS ether 2ee in an
iodine-catalysed reaction using 10 mol % excess of HMDS (entry
31). A highly viscous reaction mixture was obtained after approx-
imately 30 min of stirring, and a stronger stirring bar was needed
for effective stirring.
10
11
A
A
2j
1.5
4
90
88
2k
12
B
2l
2.5
86
An interesting feature of the transformation is the unexpected
reactivity of activated and deactivated phenols with HMDS without
a catalyst; known methods usually work either with one or the
other type of phenol.23 4-Nitrophenol was much more reactive
than 4-methoxyphenol, indicating the proton transfer as the key
step in the reaction.
13
14
A
A
2m
2n
12
90
85
2.5
Scale-up of the uncatalysed protection of phenols with HMDS
was exemplified on solid 4-nitrophenol 1d. 50 mmol of 1d and
0.55 equiv of HMDS were stirred at room temperature for 170 min,
and pure product 2d was obtained in high yield after distillation of
the crude reaction mixture in a completely solvent-free process.
Next, we examined the reactivity of different alcohols; the re-
sults are presented in Table 2. Benzyl alcohol 3a was smoothly
derivatised with HMDS in an uncatalyzed reaction under SFRC
15
16
A
B
2o
2p
2
4
85
86

M. Jereb / Tetrahedron 68 (2012) 3861e3867
3863
Table 1 (continued )
Table 2
Protection of alcohols with HMDS under SFRC
C
2
t (h)
Yielda (%)
78
17
18
B
B
2q
2r
3.5
C
4
t (h)
Yielda (%)
1
2
3
4
5
6
A
A
A
B
A
A
PhCH2OTMS
4a
4b
4c
4d
4e
4f
12
20
20
0.17
16
6
73
84
4-MeOC6H4CH2OTMS
2,4-diMeOC6H3CH2OTMS
4-NO2C6H4CH2OTMS
PhCH]CHCH2OTMS
PhC^CCH2OTMS
83b
78c
80
10
83
86
19
20
A
A
2s
2t
1.5
22
96
88
7
A
4g
0.7
79
8
9
B
B
n-C16H23OTMS
c-C12H23OTMS
4h
4i
0.17
0.33
77
84
21
22
23
24
A
B
B
B
2u
2v
2w
2x
2.2
95
90
86
85
10
11
B
B
4j
0.33
0.25
87
76d
10
4k
12
B
4l
0.17
78
0.5
0.5
13
14
B
B
(þ)-Menthol-OTMS
(ꢀ)-Menthol-OTMS
4m
4n
0.17
0.17
83
92
15
16
17
B
B
B
4o
4p
4q
0.25
0.25
0.25
76
75
72
25
B
2y
4
86
CI
18
19
20
B
B
B
4r
4s
4t
0.5
74e
78e
79
26
27
B
B
2z
0.4
87
0.5
2aa
12
83b
0.17
28
29
B
B
2bb
2cc
15
81c
21
22
B
B
4u
4v
0.42
0.17
83
88
PhCH2CH2C(Me)2OTMS
1.2
48b
23
B
4w
0.17
72
30
31
B
B
TMSO-oestrone
Di-OTMS-phenolphthalein
2dd
2ee
3.5
0.8
72d
88e
Reaction conditions C: A: 1 mmol 1 and 0.55 mmol HMDS stirred at room tem-
perature. B: 1 mmol 1, 0.55 mmol HMDS and 0.02 mmol I2 stirred at room
temperature.
24
25
B
B
4x
4y
0.17
0.17
79
82
a
Isolated yield.
1 mmol 1aa, 1.1 mmol HMDS and 0.04 mmol I2.
1 mmol 1bb, 1.65 mmol HMDS and 0.039 mmol I2.
0.2 mmol 1dd, 0.24 mmol HMDS and 0.004 mmol I2.
b
c
d
(continued on next page)
e
0.3 mmol 1ee, 0.33 mmol HMDS and 0.012 mmol I2.

3864
M. Jereb / Tetrahedron 68 (2012) 3861e3867
Table 2 (continued )
and after quenching of iodine and filtration of solids, the distillation
Yielda (%)
54
afforded pure 4n in an excellent yield.
C
4
t (h)
The heterogeneous reaction mixtures were dealt with to
a great extent in this study. Consequently, the role of iodine was
examined in a competitive silylation of the selected couples; the
results are summarised in Table 3. Benzyl alcohol exhibited higher
reactivity than 1-hexadecanol in an uncatalyzed reaction, while in
the presence of I2 the situation was reversed (entries 1 and 2). A
primary alcohol was much more reactive than a secondary
one (entry 3), and the situation changed in the presence of I2
(entry 4).
26
27
B
B
4z
0.17
4aa
0.17
67
28
29
B
B
1-Adamantyl-OTMS
TMSO-cholesteryl
4bb
4cc
0.7
3.33
82
93f
Reaction conditions C: A: 1 mmol 1 and 0.55 mmol HMDS stirred at room tem-
perature. B: 1 mmol 1, 0.55 mmol HMDS and 0.02 mmol I2 stirred at room
temperature.
Table 3
a
Isolated yield.
1 mmol 1 and 0.67 mmol HMDS.
1 mmol 1, 0.65 mmol HMDS and 0.02 mmol I2.
1 mmol 1, 1.1 mmol HMDS and 0.04 mmol I2.
Competitive silylation with HMDS with and without I2 under SFRC
b
c
d
e
1 mmol 1, 083 mmol HMDS and 0.026 mmol I2.
f
5 mmol 1cc, 3.90 mmol HMDS and 0.1 mmol I2.
Couplea A-OH/B-OH
C
Relative ratiob
A-OTMS/B-OTMS
(Table 2, entry 1). Similarly, activated benzylic alcohols 3b and 3c
yielded products 4b and 4c (entries 2 and 3) in good yield. In
contrast, 4-nitrobenzyl alcohol 3d required iodine as catalyst; the
reaction was completed in 10 min (entry 4).
1
2
3
4
5
6
7
8
PhCH2OH/C16H33OH
PhCH2OH/Ph2CH(OH)
PhCH2OH/Ph2C(OH)Me
Ph2CH(OH)/Ph2C(OH)Me
PhCH2OH/PhOH
/
I2
/
I2
/
I2
/
I2
/
I2
/
I2
/
I2
65/33
47/51
100/0
50/50
100/0
100/0
100/0
100/0
65/35
65/35
81/21
50/50
100/0
100/0
Unsaturated alcohols 3e and 3f were converted into products
4e and 4f and isolated in good yields (entries 5 and 6). 9-
Fluorenylmethanol 3g formed a highly viscous reaction mixture
with HMDS, and furnished derivative 4g without iodine (entry 7).
1-Hexadecanol 3h and cyclododecanol 3i were fully converted into
silyl ethers 4h and 4i in the presence of iodine (entries 8 and 9).
Alcohols 1jel were silylated under SFRC by means of iodine in
a short reaction time (entries 10e12). (þ)-Menthol 3m and
(ꢀ)-menthol 3n were functionalised without the loss of stereo-
chemical integrity, furnishing analogues 4m and 4n (entries 13 and
14). Homoallylic alcohols 3oeq smoothly yielded the correspond-
ing derivatives 4oeq (entries 15e17). BayliseHillman adducts 3r
and 3s gave the related silyl ethers 4r and 4s, though 0.75 equiv of
HMDS was used for effective transformation (entries 18 and 19).
Sterically hindered tertiary alcohols 3tew could be easily silylated
in the presence of iodine as catalyst giving products 4tew in good
yields (entries 20e23). Tertiary propargyl alcohols 3xez also fur-
nished the desired products 4xez in a short reaction time and good
yields (entries 24e26). exo-Norborneol 3aa smoothly gave non-
rearranged product 4aa, thus indicating that carbocationic in-
termediates were not intermediates of the prime importance in this
transformation (entry 27). Sterically more hindered 1-adamantanol
3bb effectively produced its silylated derivative 4bb in good yield
(entry 28).
Cholesterol 3cc was taken to demonstrate the feasibility of
scaling up the present iodine-catalysed SFRC method in the case of
solid substrates. Numerous solid substrates dissolved during the
reaction, while 3cc remained solid and, in this sense, it can be
regarded as ‘tough’ substrate. Nevertheless, the transformation of
5 mmol of 3cc using 0.78 equiv of HMDS and 2 mol % of I2 was
completed in 200 min, and the pure product 4cc was obtained in
excellent yield by crystallisation.
Scale-up of uncatalysed silylation of alcohols was performed on
liquid 4-methoxybenzyl alcohol 3b. 20 mmol of 3b and 0.6 equiv of
HMDS were stirred for 22 h at room temperature, and an almost
pure product 4b was obtained in an excellent yield only with the
distillation of excess of HMDS. Distillation of the crude 4b only
slightly improved its purity.
9
10
11
12
13
14
PhOH/Ph2CH(OH)
PhOH/Ph2C(OH)Me
Reaction conditions, C.
a
0.3 mmol A-OH, 0.3 mmol B-OH and 0.165 mmol HMDS stirred 14 h at room
temperature with and without 0.006 mmol I2.
Relative distribution of products determined from 1H NMR spectra.
b
Tertiary alcohol exhibited the lowest reactivity among alcohols;
primary and secondary ones were more reactive (entries 5e8).
Reaction of benzyl alcohol and phenol with HMDS obviously took
place uncatalyzed, and the former showed higher reactivity (en-
tries 9 and 10). Phenol was more reactive than secondary and ter-
tiary benzylic alcohols (entries 11e14), thus revealing that
importance of sterical hindrance and acidity on the reactivity. Io-
dine had a substantial impact on the reactivity of the secondary
alcohol and no impact on the reactivity of the tertiary alcohol in the
combination with phenol (entries 11e14). It can be concluded that
seemingly simple systems are rather complex, mainly because of
the heterogeneity.
Carbohydrates and polyols possess several hydroxy groups
that often need to be protected in a simple way during the multi-
step transformation. Derivatisation of polyols into fully silylated
analogues is of practical value in analytical chemistry. The re-
activity of some of the polyols with HMDS and catalytic amount
of iodine under SFRC was examined, and the results are presented
in Scheme 1. A variable excess of HMDS was needed in these
examples; no general threshold was noted, and low amount of
iodine was required.
5a, consisting of a mixture of
of 1:0.42. -Galactose 6 was fully converted into
alogue 6a; no -anomer was detected. Xylose 7 gave fully sily-
lated product 7a, consisting of almost an equimolar mixture of
and -anomer. -Fructose 8 furnished its fully protected de-
mixture of stereoisomeric furanoses and
D
-Glucose 5 was transformed into derivative
- and -anomer in a relative ratio
-anomeric an-
a
b
D
a
b
Scale-up of the I2-catalysed silylation under SFRC was man-
ifested on (ꢀ)-menthol 3n. 25 mmol of 3n, 2 mol % of I2 and
0.55 equiv of HMDS were stirred at room temperature for 15 min;
the crude reaction mixture was diluted with small amount of TBME,
a-
b
D
rivative 8a as
pyranoses.
a

M. Jereb / Tetrahedron 68 (2012) 3861e3867
3865
Scheme 1. Protection of carbohydrate derivatives with HMDS/I2 under SFRC.
D
-Mannitol 9 was fully protected, giving derivative 9a. Saccha-
rose 10 was successfully protected, i.e., all eight hydroxy groups
were silylated, and product 10a was isolated in high yield. -Cy-
Products can be purified with column chromatography and/or
distillation.
b
clodextrin 11 and its derivatives are gaining importance in the
chemical, pharmaceutical, agricultural and food industries. Due to
its very high polarity and sparing solubility,10 was anticipated to be
a difficult substrate for protection with HMDS/I2 under SFRC. Al-
though a considerable excess of HMDS was needed, the reaction
took place surprisingly well, and the partly protected derivative 11a
was isolated in an excellent yield. The reaction exhibited excellent
selectivity and furnished a product with two-thirds of the hydroxy
groups protected.
4.2. Representative procedure of I2-catalysed reaction of
phenols, alcohols and carbohydrates with HMDS under SFRC
(small scale)
Iodine (5.1 mg, 0.02 mmol) was added to phenol 1l (0.148 g,
1 mmol) or alcohol 3h (0.242 g, 1 mmol), followed by addition of
HMDS (0.089 g, 0.55 mmol); the mixture was stirred at room
temperature until the complete consumption of the starting ma-
terial (TLC check). The crude reaction mixture was dissolved in 4 mL
of hexane/TBME and stirred with the finely powdered Na2S2O3
until the disappearance of iodine. From this point on, two different
scenarios are possible:
3. Conclusions
In this paper, we describe environmentally friendly synthesis of
trimethylsilyl ethers from phenols, alcohols and carbohydrates
using a small excess of HMDS, thus contributing to a high atom
economy and a reduced amount of waste. The procedure is very
simple, performed in the presence of air with untreated substrates
and HMDS at room temperature. Numerous substrates, mainly
phenols, required no catalyst, while, sterically hindered phenols,
carbohydrates and most of the alcohols required a catalytic
amount of iodine. A noteworthy feature of the method is the re-
activity of activated and deactivated phenols, and benzylic alco-
hols. Reactions were performed strictly without solvent, also in
the case of highly polar and insoluble substrates. The crude
products exhibited high purity, and could be directly used further.
Isolation and purification in numerous cases were completely
solvent-free. We have demonstrated the feasibility of the scale-up
regardless on the aggregate state of the substrate and presence of
the catalyst.
a) The solids were filtered off and the solvent evaporated under
the reduced pressure, yielding the crude product. In numerous
cases, such products were practically pure; column chroma-
tography and/or distillation improved their quality only
slightly.
b) A solution of a product in hexane/TBME mixture could be di-
rectly subjected to the column chromatography, without fil-
tration of the solids.
Caution: Although we experienced no problems when per-
forming these reactions, care should taken due to the potential
formation of NI3.
4.3. Representative procedure of the non-catalysed reaction
of the solid phenols and alcohols with HMDS under SFRC
(scale-up)
4. Experimental
To 4-nitrophenol 1d (6.95 g, 50 mmol), HMDS (4.43 g,
27.5 mmol) was added; the mixture was stirred at room tem-
perature for 170 min (full conversion). A slight evolution of am-
monia accompanied the transformation. Solid phenol began
dissolving during stirring and a homogenous, oily reaction mix-
ture was finally obtained. The excess of HMDS was distilled
off and 10.4 g of the crude product (light brown) was obtained;
no impurities were observed in the 1H NMR spectrum.
Distillation of the crude product yielded yellow oily product 2d
(8.84 g, 84%).
4.1. Representative procedure of the non-catalysed reaction
of phenols and alcohols with HMDS under SFRC (small scale)
To phenol 1a (0.173 g, 1 mmol) or alcohol 3a (0.108 g, 1 mmol)
HMDS (0.089 g, 0.55 mmol) was added, and the mixture was stirred
at room temperature until the complete consumption of the
starting material (TLC check). The excess of HMDS was distilled off
under reduced pressure and nearly pure products were obtained.

3866
M. Jereb / Tetrahedron 68 (2012) 3861e3867
4.4. Representative procedure of the non-catalysed reaction
of the liquid phenols and alcohols with HMDS under SFRC
(scale-up)
211.0790, found 211.0789 (Mþ1). Anal. Calcd for C10H14O3Si: C,
57.11; H, 6.71. Found: C, 56.98; H, 7.14.
3,3-Bis(4-trimethylsilyloxyphenyl)-1(3H)-isobenzofuranone
(2ee). Colourless, highly viscous liquid; column chromatography Rf
(25% Et2O/hexane) 0.30; (0.3 mmol of phenolphthalein, 0.33 mmol
of HMDS (0.55 equiv), 0.012 mmol of I2 (2 mol %)): IR (neat) 2958,
To 4-methoxybenzyl alcohol 3b (2.76 g, 20 mmol), HMDS
(1.94 g, 12 mmol) was added; the mixture was stirred at room
temperature for 22 h (full conversion). At the beginning, two sep-
arate phases slowly turned into one homogenous oily phase, an oily
reaction mixture was obtained. The excess of HMDS was distilled
off and 4.06 g of the crude product (transparent) was obtained; in
the 1H NMR spectrum, no impurities were observed. Distillation of
the crude product yielded transparent oily product 4b (3.92 g, 93%).
1770, 1607, 1506, 1260, 1240, 1171, 906, 846, 709 cmꢀ1 1H NMR:
;
d
0.25 (s, 18H), 6.77 (d, J¼8.7 Hz, 4H), 7.18 (d, J¼8.7 Hz, 4H),
7.48e7.58 (m, 2H), 7.62e7.72 (m, 1H), 7.88e7.96 (m, 1H); 13C NMR:
0.2, 91.7, 119.7, 124.1, 125.6, 125.9, 128.5, 129.1, 133.7, 134.0, 152.7,
d
155.4, 169.9; Anal. Calcd for C26H30O4Si2: C, 67.49; H, 6.54. Found: C,
67.64; H, 6.40.
2-Cyano-1-phenyl-1-trimethylsilyloxypropene (4s). Colourless
liquid; column chromatography Rf (20% Et2O/hexane) 0.48;
(1 mmol of alcohol, 0.83 mmol of HMDS (0.83 equiv), 0.026 mmol
of I2 (2.6 mol %)): IR (neat): 2958, 2227, 1253, 1090, 1071, 876, 837,
4.5. Representative procedure of I2-catalysed reaction of the
solid phenols and alcohols with HMDS under SFRC (scale-up)
To (ꢀ)-menthol 3n (3.9 g, 25 mmol) iodine (127 mg, 0.5 mmol)
was added, followed by the dropwise addition of HMDS (2.22 g,
13.75 mmol); the mixture was stirred at room temperature for
15 min (full conversion). A vigorous evolution of ammonia began
approx. 1 min after beginning of the stirring, and it almost com-
pletely ceased in a few minutes. After completion, the reaction
mixture was dissolved in 7 mL of TBME, and stirred in the presence
of a finely powdered Na2S2O3 until the disappearance of iodine. The
solids were filtered off, the solvent was distilled off and 5.61 g of
crude product (yellow) was obtained. As can be judged from the 1H
NMR spectrum, the crude product was almost pure. Distillation
of the crude product yielded slightly yellow, oily product 4n
(5.22 g, 92%).
760, 700 cmꢀ1; 1H NMR:
d
0.11 (s, 9H), 5.18e5.22 (m, 1H), 5.91e5.94
(m, 1H), 5.96e6.00 (m, 1H), 7.28e7.40 (m, 5H); 13C NMR:
d
ꢀ0.2,
74.6, 117.1, 126.5, 127.6, 128.4, 128.5, 128.6, 139.8. Anal. Calcd for
C13H17NOSi: C, 67.49; H, 7.41; N, 6.05. Found: C, 67.51; H, 7.52; N,
6.02.
Acknowledgements
ꢀ
ꢀ
Dr. D. Zigon at the Mass Spectroscopy Centre at the ‘Jozef Stefan’
ꢀ
Institute in Ljubljana for HRMS, Mrs. T. Stipanovic and Prof. B.
Stanovnik for the elemental combustion analyses and Ministry of
Higher Education, Science and Technology (P1-0134) for financial
support are gratefully acknowledged.
4.6. Representative procedure of I2-catalysed reaction of the
solid phenols and alcohols with HMDS under SFRC (scale-up)
Supplementary data
Compound characterization and copies of 1H NMR and 13C NMR
spectra of new products and products derived from polyols 5ae11a.
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2012.03.040. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
To cholesterol 3cc (1.93 g, 5 mmol) iodine (25 mg, 0.1 mmol)
was added, followed by the dropwise addition of HMDS (0.63 g,
3.90 mmol); the mixture was stirred at room temperature for
200 min (full conversion). No visible evolution of ammonia was
noted. In spite of a heterogeneous reaction mixture (solid always
present), the reaction progress took place smoothly. After com-
pletion, the crude reaction mixture was dissolved in approx. 85 mL
of boiling acetone and cooled. Pure product 4cc (2.13 g, 93%) as
white crystals was obtained.
References and notes
1. (a) Handbook of Green Chemistry and Technology; Clark, J., Macquarrie, D., Eds.;
Blackwell Science: Oxford, 2002; (b) Lancaster, M. Green Chemistry: An In-
troductory Text; RSC: Cambridge, 2002; (c) Green Chemical Reactions; Tundo, P.,
Esposito, V., Eds.; Springer: Dordrecht, 2008; (d) Green Chemical Syntheses and
Processes; Anastas, P. T., Heine, L. G., Williamson, T. C., Eds. ACS Symposium
Series; ACS: Washington, DC, 2000; Vol. 767; (e) Green Reaction Media in Or-
ganic Synthesis; Mikami, K., Ed.; Oxford: Blackwell, 2005; (f) Nelson, W. M.
Green Solvents for Chemistry: Perspectives and Practice; Oxford University Press:
New York, 2003; (g) Li, C.-J.; Trost, B. M. Proc. Natl. Acad. Sci. U.S.A. 2008, 105,
13197e13202.
2. (a) Green Chemistry: Designing Chemistry for the Environment; Anastas, P. T.,
Williamson, T. C., Eds. ACS Symposium Series; ACS: Washington, DC, 1996; Vol.
626; (b) Green Chemistry Metrics: Measuring and Monitoring Sustainable Pro-
cesses; Lapkin, A., Constable, D. J. C., Eds.; Wiley-Blackwell: Chichester, 2009; (c)
Green Chemistry for Environmental Sustainability; Sharma, S. K., Mudhoo, A.,
Eds.; CRC: Boca Raton, 2011; (d) Sheldon, R. A. Green Chem. 2005, 7, 267e278.
3. (a) Tanaka, K. Solvent-free Organic Synthesis, 2nd ed.; Wiley-VCH: Weinheim,
2009; (b) Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025e1074; (c) Metzger, J. O.
Angew. Chem., Int. Ed. 1998, 37, 2975e2978; (d) Varma, R. S. Green Chem. 1999, 1,
43e55; (e) Cave, G. W. V.; Raston, C. L.; Scott, J. L. Chem. Commun. 2001,
2159e2169; (f) Rothenberg, G.; Downie, A. P.; Raston, C. L.; Scott, J. L. J. Am.
Chem. Soc. 2001, 123, 8701e8708; (g) Correa, W. H.; Edwards, J. K.; McCluskey,
A.; McKinnon, I.; Scott, J. L. Green Chem. 2003, 5, 30e33; (h) Martins, M. A. P.;
Frizzo, C. P.; Moreira, D. N.; Buriol, L.; Machado, P. Chem. Rev. 2009, 109,
4140e4182; (i) Walsh, P. J.; Li, H.; de Parrodi, C. A. Chem. Rev. 2007, 107,
2503e2545.
4.7. Spectral data for new products
(5,6,7,8-Tetrahydronaphthen-1-yloxy)trimethylsilane (2l). Col-
ourless liquid; column chromatography Rf (20% Et2O/hexane) 0.71;
IR (neat): 2930, 1459, 1266, 1250, 1075, 1037, 975, 924, 838,
770 cmꢀ1; 1H NMR:
d 0.27 (s, 9H), 1.73e1.81 (m, 4H), 2.57e2.65 (m,
2H), 2.71e2.79 (m, 2H), 6.58 (d, J¼8.1 Hz,1H), 6.68 (d, J¼8.1 Hz, 1H),
6.94 (dd, J¼8.1, 8.1 Hz, 1H); 13C NMR:
d 0.5, 23.0, 23.8, 29.6, 115.5,
122.0, 125.4, 128.5, 138.9, 153.3; HRMS: (CI) calcd for C13H21OSi
221.1362, found 221.1359 (Mþ1).
(4-Phenoxyphenoxy)trimethylsilane (2s). Colourless liquid;
column chromatography Rf (20% Et2O/hexane) 0.64; IR (neat): 1499,
1227, 920, 756, 679 cmꢀ1
;
1H NMR:
d
0.28 (s, 9H), 6.74e6.82 (m,
2H), 6.86e6.97 (m, 4H), 6.98e7.06 (m, 1H), 7.24e7.32 (m, 2H); 13C
NMR: 0.2, 117.8, 120.5, 120.9, 122.5, 129.6, 150.8, 151.2, 158.2;
d
HRMS: (CI) calcd for C15H19O2Si 259.1154, found 259.1150 (Mþ1).
Anal. Calcd for C15H18O2Si: C, 69.72; H, 7.02. Found: C, 69.78; H, 7.14.
(3,4-Methylenedioxyphenoxy)trimethylsilane (2u). Colourless
liquid; column chromatography Rf (17% Et2O/hexane) 0.60; IR
(neat): 2961, 1483, 1250, 1181, 1130, 1038, 957, 877, 800 cmꢀ1 1H
;
4. (a) Trost, B. M. Science 1991, 254, 1471e1477; (b) Trost, B. M. Angew. Chem., Int.
Ed. Engl. 1995, 34, 259e281.
5. (a) Banerjee, A. K.; Vera, W.; Mora, H.; Laya, M. S.; Bedoya, L.; Cabrera, E. V. J. Sci.
Ind. Res. 2006, 65, 299e308; (b) Vaino, A. R.; Szarek, W. A. Adv. Carbohydr. Chem.
Biochem. 2001, 56, 9e63; (c) Das, S.; Borah, R.; Devi, R. R.; Thakur, A. J. Synlett
NMR:
d
0.24 (s, 9H), 5.90 (s, 2H), 6.22 (dd, J¼8.4, 2.4 Hz, 1H), 6.34 (d,
J¼2.4 Hz, 1H), 6.60 (d, J¼8.4 Hz, 1H); 13C NMR:
d 0.1, 101.1, 102.5,
107.9, 111.6, 142.0, 147.9, 149.9; HRMS: (CI) calcd for C10H15O3Si

M. Jereb / Tetrahedron 68 (2012) 3861e3867
3867
ꢀ ꢀ
2008, 2741e2762; (d) Jereb, M.; Vrazic, D.; Zupan, M. Tetrahedron 2011, 67,
1355e1387.
20. Yadollahi, B.; Mirkhani, V.; Tangestaninejad, S.; Karimian, D. Appl. Organomet.
Chem. 2011, 25, 83e86.
6. (a) French, A. N.; Bissmire, D.; Wirth, T. Chem. Soc. Rev. 2004, 33, 354e362; (b)
Mphahlele, M. J. Molecules 2009,14, 4814e4837; (c) Togo, H.; Iida, S. Synlett 2006,
2159e2175; (d) Stavber, S.; Jereb, M.; Zupan, M. Synthesis 2008, 1487e1513.
7. Lissel, M.; Weiffen, J. Synth. Commun. 1981, 11, 545e549.
8. Mojtahedi, M. M.; Abbasi, H.; Abaee, M. S. J. Mol. Catal. A: Chem. 2006, 250, 6e8.
9. Jadhav, V. H.; Kumar, K. S. A.; Chaudhari, V. D.; Dhavale, D. D. Synth. Commun.
2007, 37, 1363e1370.
21. Tillu, V. H.; Jadhav, V. H.; Borate, H. B.; Wakharkar, R. D. Arkivoc 2004, xiv,
83e88.
22. Moghadam, M.; Tangestaninejad, S.; Mirkhani, V.; Mohammadpoor-Baltork, I.;
Chahardahcheric, S.; Tavakoli, Z. J. Organomet. Chem. 2008, 693, 2041e2046.
23. Zhang, Z.-H.; Li, T.-S.; Yang, F.; Fu, C.-G. Synth. Commun. 1998, 28, 3105e3114.
24. Mojtahedi, M. M.; Abaee, M. S.; Eghtedari, M. Appl. Organomet. Chem. 2008, 22,
529e532.
10. Azizi, N.; Saidi, M. R. Organometallics 2004, 23, 1457e1458.
11. Narsaiah, A. V. J. Organomet. Chem. 2007, 692, 3614e3618.
12. Shaterian, H. R.; Doostmohammadi, R.; Khorami, F.; Ghashang, M. Phosphorus,
Sulfur Silicon Relat. Elem. 2010, 185, 171e180.
13. Khazaei, A.; Zolfigol, M. A.; Rostami, A.; Choghamarani, A. G. Catal. Commun.
2007, 8, 543e547.
14. Shirini, F.; Mollarazi, E. Catal. Commun. 2007, 8, 1393e1396.
15. Shaterian, H. R.; Ghashang, M. Phosphorus, Sulfur Silicon Relat. Elem. 2008, 183,
194e204.
16. Oskooie, H. A.; Heravi, M. M.; Tehrani, M. H.; Behbahani, F. K.; Heravi, O. M.
Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184, 1729e1737.
17. Firouzabadi, H.; Iranpoor, N.; Amani, K.; Nowrouzi, F. J. Chem. Soc., Perkin Trans. 1
2002, 2601e2604.
25. Rajagopal, G.; Lee, H.; Kim, S. S. Tetrahedron 2009, 65, 4735e4741.
26. Jin, T.-S.; Tian, R.-F.; Liu, L.-B.; Zhao, Y.; Li, T.-S. Synth. Commun. 2006, 36,
1823e1828.
27. Shaterian, H. R.; Ghashang, M.; Hosseinian, A. Phosphorus, Sulfur Silicon Relat.
Elem. 2008, 183, 2108e2118.
28. Shaterian, H. R.; Khorami, F.; Doostmohammadi, R.; Amirzadeh, A.; Ghashang,
M. Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184, 2227e2237.
29. Zareyee, D.; Karimi, B. Tetrahedron Lett. 2007, 48, 1277e1280.
30. Amantini, D.; Fringuelli, F.; Pizzo, F.; Vaccaro, L. J. Org. Chem. 2001, 66,
6734e6737.
31. Rostami, A.; Khazaei, A.; Mahboubifar, M.; Rahmati, S. Org. Prep. Proced. Int.
2008, 40, 303e306.
32. Kadam, S. T.; Kim, S. S. Green Chem. 2010, 12, 94e98.
33. (a) Karimi, B.; Golshani, B. J. Org. Chem. 2000, 65, 7228e7230; (b) Mamaghani,
M.; Badrian, A. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 1181e1186.
34. Saxena, I.; Deka, N.; Sarma, J. C.; Tsuboi, S. Synth. Commun. 2003, 33,
4005e4011.
18. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Constantino, U. Synth.
Commun. 1999, 29, 541e546.
19. Ghorbani-Choghamarani, A.; Zolfigol, M. A.; Hajjami, M.; Darvishi, K.; Gho-
lamnia, L. Collect. Czech. Chem. Commun. 2010, 75, 607e615.