Efficient trimethylsilylation and tetrahydropyranylation of alcohols in the presence of 1,3-dibromo-5,5-dimethylhydantoin

Article abstract of DOI:10.1055/s-2006-950350

Chemoselective trimethylsilylation and tetrahydropyranylation of benzylic and primary and secondary aliphatic alcohols proceed efficiently in the presence of 1,3-dibromo-5,5-dimethylhydantoin (DBH) under mild and completely heterogeneous reaction conditio

Full text of DOI:10.1055/s-2006-950350

4252
PAPER
Efficient Trimethylsilylation and Tetrahydropyranylation of Alcohols in the
Presence of 1,3-Dibromo-5,5-dimethylhydantoin
T
rimethylsilyl
a
a
tion and
T
r
etrahydr
h
opyranylatio
a
n of Alcoho
d
ls Shirini,*a Mohammad Ali Zolfigol,b Maryam Paktinata
a
Department of Chemistry, College of Science, Guilan University, Rasht 41335, Iran
Fax +98(131)3220066; E-mail: shirini@guilan.ac.ir
b
Department of Chemistry, College of Science, Bu-Ali Sina University, Hamadan 65174, Iran
E-mail: zolfi@basu.ac.ir
Received 31 July 2006; revised 14 August 2006
many synthetic conditions, many of these are associated
with several drawbacks, which include use of strongly
acidic media, expensive reagents, tedious and time-con-
suming work-up procedures, refluxing conditions, long
reaction times, poor selectivity, formation of polymeric
by-products of the dihydropyran and isomerization. Thus
there is still a need for mild and selective methods, espe-
cially using heterogeneous catalysts for this purpose.
Abstract: Chemoselective trimethylsilylation and tetrahydropyra-
nylation of benzylic and primary and secondary aliphatic alcohols
proceed efficiently in the presence of 1,3-dibromo-5,5-dimethylhy-
dantoin (DBH) under mild and completely heterogeneous reaction
conditions in excellent yields.
Key words: alcohols, 1,3-dibromo-5,5-dimethylhydantoin, tri-
methylsilylation, tetrahydropyranylation, heterogeneous reaction
conditions
During the course of our studies on the application of N-
haloamides in organic synthesis,16 we have found that 1,3-
dibromo-5,5-dimethylhydantoin (DBH) is a cheap, stable
and commercially available reagent. 1,3-Dibromo-5,5-
dimethylhydantoin recently have been used as an efficient
reagent for the selective mononitration of phenols,17 oxi-
dation of 1,3,5-trisubstituted pyrazolines,18 thiols,19 and
urazoles20 and acylation of alcohols.21 Herein we wish to
report the use of DBH in the efficient and chemoselective
trimethylsilylation and tetrahydropyranylation of benzyl-
ic and primary and secondary aliphatic alcohols under
mild and completely heterogeneous reaction conditions
(Scheme 1).
Trimethylsilylation and tetrahydropyranylation are popu-
lar methods widely used for the protection of the hydroxyl
group of alcohols. Among the many silylating agents
which have been used for the silylation of alcohols,1 hex-
amethyldisilazane (HMDS), a cheap, stable and commer-
cially available reagent,2 is selected as one of the best
candidates for this purpose. Its handling does not need
special precaution, and the work-up is not time-consum-
ing, as the by-product of the reaction is ammonia, which
is simple to remove from the reaction medium. However,
its poor silylating power is the main drawback of its appli-
cation.3 A variety of catalysts have been used for the acti-
vation of HMDS;4 however, low selectivity, forcing
conditions, tedious work-ups and long reaction times have
been described in many of these reports. Consequently, a
new procedure that addresses these drawbacks is desir-
able.
O
Br
N
N Br
, A or B
O
ROH
ROY
A: HMDS, MeCN, r.t.
B: DHP, n-hexane, r.t.
Due to the remarkable stability of tetrahydropyranyl
ethers towards a variety of reaction conditions such as
Y = TMS, THP
strongly basic media, reactions involving Grignard re- Scheme 1
agents and lithium alkyls, reduction with hydride, oxida-
tion, oxidative alkylation and acylation reactions, and due
Different types of alcohols, were subjected to trimethyl-
silylation using this method at room temperature in MeCN
(Table 1, entries 1–19). Trimethylsilylation of benzylic
alcohols including acid sensitive, electron-donating or
electron-withdrawing groups proceed efficiently with rel-
atively high isolated yields (Table 1, entries 1–13). Prima-
ry and secondary aliphatic alcohols were also successfully
converted to their corresponding trimethylsilyl ethers in
almost quantitative yields under the same reaction condi-
tions (Table 1, entries 14–18). This method was also
found to be useful for the protection of allylic alcohols
(Table 1, entry 19). Tertiary alcohols were resistant to this
reagent system and remained intact during the course of
the reaction (Table 1, entries 20 and 21).
to its low cost and ease with which it can be removed, 3,4-
dihydro-2H-pyran is the reagent of choice for hydroxyl
group protection in multi-step organic synthesis. There
are several reagents available for the tetrahydropyranyla-
tion of alcohols, which include the use of protic5 and
Lewis acids,6 silica-chloride,7 ZrCl4,8 solid silica-based
sulfonic acid,9 LiOTf,10 ionic liquid,11 silica-sulfuric ac-
id,12 trichloroisocyanuric acid,13 K5CoW12O40·3H2O14 and
H-Y zeolite.15 Although these methods are suitable for
SYNTHESIS 2006, No. 24, pp 4252–4256
x
x.
x
x
.
2
0
0
6
Advanced online publication: 02.11.2006
DOI: 10.1055/s-2006-950350; Art ID: Z16206SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Trimethylsilylation and Tetrahydropyranylation of Alcohols
4253
Table 1 Trimethylsilylation and Tetrahydropyranylation of Alcoholsa
Entry
Substrate
Product
Time (min)
Yield (%)b
1
2
3
4
5
6
7
2-BrC6H4CH2OH
2-CIC6H4CH2OH
4-CIC6H4CH2OH
2-NO2C6H4CH2OH
4-NO2C6H4CH2OH
2-MeC6H4CH2OH
4-(t-Bu)C6H4CH2OH
2-BrC6H4CH2OTMS
2-CIC6H4CH2OTMS
4-CIC6H4CH2OTMS
2-NO2C6H4CH2OTMS
4-NO2C6H4CH2OTMS
2-MeC6H4CH2OTMS
4-(t-Bu)C6H4CH2OTMS
<1c
<1c
<1c
5
95
97
95
85
90
95
85
9
<1c
<1c
CH2OTMS
O
CH2OH
O
8
5
95
O
O
9
PhCH(OH)Me
PhCH(OTMS)Me
<1c
<1c
95
90
10
Ph2CHOH
Ph2CHOTMS
11
12
25
15
80
90
N
CH2OH
CH2OH
N
CH2OTMS
CH2OTMS
N
N
13
14
15
16
PhCH(OH)COPh
PhCH(Me)CH2OH
PhCH2CH2CH2OH
PhCH2CH(OH)CH3
PhCH(OTMS)COPh
PhCH(Me)CH2OTMS
PhCH2CH2CH2OTMS
PhCH2CH(OTMS)CH3
<1c
<1c
<1c
<1c
92
95
96
92
17
18
<1c
85
90
OH
OH
OTMS
OSiMe3
<1c
19
20
PhCH=CHCH2OH
PhCH=CHCH2OTMS
<1c
30
80
0d
OH
OTMS
21
22
23
24
25
26
27
28
29
30
Me3COH
Me3COTMS
40
55
20
30
25
7
0d
85
90
85
92
90
85
90
85
80
PhCH2OH
PhCH2OTHP
2-BrC6H4CH2OH
2-CIC6H4CH2OH
4-CIC6H4CH2OH
2-NO2C6H4CH2OH
3-NO2C6H4CH2OH
4-NO2C6H4CH2OH
2-MeC6H4CH2OH
4-(t-Bu)C6H4CH2OH
2-BrC6H4CH2OTHP
2-CIC6H4CH2OTHP
4-CIC6H4CH2OTHP
2-NO2C6H4CH2OTHP
3-NO2C6H4CH2OTHP
4-NO2C6H4CH2OTHP
2-MeC6H4CH2OTHP
4-(t-Bu)C6H4CH2OTHP
22
5
25
35
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4254
F. Shirini et al.
PAPER
Table 1 Trimethylsilylation and Tetrahydropyranylation of Alcoholsa (continued)
Entry
31
Substrate
Product
Time (min)
Yield (%)b
CH2OH
CH2OTHP
O
O
O
35
7
85
90
70
O
32
PhCH(OH)Me
PhCH(OTHP)Me
33
27
N
CH2OH
CH2OH
N
CH2OTHP
CH2OTHP
34
10
80
N
N
35
36
37
PhCH(Me)CH2OH
PhCH2CH2CH2OH
PhCH2CH(OH)CH3
PhCH(Me)CH2OTHP
PhCH2CH2CH2OTHP
PhCH2CH(OTHP)CH3
45
98
60
80
90
80
38
39
30
35
85
85
OTHP
OTHP
OH
OH
40
41
PhCH=CHCH2OH
PhCH=CHCH2OTHP
25
50
85
0d
t-BuOH
t-BuOTHP
42
60
0d
OH
OTHP
2-BrC6H4CH2OH
+
2-BrC6H4CH2OTMS
+
43
<1c
100d + 0d
OH
OH
OTMS
OTHP
44
30
95d + 0d
+
+
t-BuOH
t-BuOTHP
a Products were identified spectroscopically and also by the conversion of the products to their corresponding alcohols.
b Isolated yields.
c Reaction was instantaneous.
d GC yields.
Although the actual role of DBH is not clear, on the basis 40). Tertiary alcohols did not react under the same reac-
of the previously reported mechanism for the silylation of tion conditions (Table 1, entries 41, 42).
alcohols with HMDS in the presence of I2,4d the mecha-
The resistance of tertiary alcohols against trimethylsilyla-
nism that is shown in Scheme 2 is selected as a most prob-
tion and tetrahydropyranylation reactions in the presence
able one.
of DBH, led us to investigate the possibility of the selec-
1,3-Dibromo-5,5-dimethylhydantoin can also be used as tive protection of the different types of alcohols in the
an efficient reagent for the promotion of tetrahydropy- presence of tertiary ones. This is exemplified by the com-
ranylation of benzylic, allylic and primary and secondary petitive reactions between 2-bromobenzyl alcohol and 1-
aliphatic alcohols with 3,4-dihydro-2H-pyran. Reactions adamantanol and between cyclohexanol and tert-BuOH
were carried out in n-hexane at room temperature and un- (Table 1, entries 43,44).
der completely heterogeneous reaction conditions to give
the products in good to high yields (Table 1, entries 22–
pyranylation of alcohols in the presence of trichloroisocy-
According to the selected mechanism for the tetrahydro-
Synthesis 2006, No. 24, 4252–4256 © Thieme Stuttgart · New York

PAPER
Trimethylsilylation and Tetrahydropyranylation of Alcohols
4255
2 ROSiMe3
2 ROH
(Me3Si)2NHBr
NH3
O
O
Br
H3NBr
+
(Me3Si)2NH
N
+
N
(Me3Si)2NH
Scheme 2
anuric acid,13 the mechanism that is shown in Scheme 3 is of 1,3-dibromo-5,5-dimethylhydantoin. Due to the short
proposed for the clarification of the role of DBH in the reaction times, availability and low cost of the reagent,
protection of alcohols as their corresponding THP ethers. heterogeneous reaction conditions, selectivity, easy and
In order to show the efficiency of the proposed method, clean work-up and good to high yields of the products, we
Table 2 compares some of the results with some of those believe it would be a useful addition to the available meth-
reported in the literature.4e,g,13
odologies.
Table 2 Comparison of Trimethylsilylation and Tetrahydropyran-
ylation of Alcohols in the Presence of DBH (I) with Trichloroisocya-
nuric Acid (II) and Al(HSO4)3 (III)
Chemicals were purchased from Fluka, Merck and Aldrich Chemi-
cal Companies. All of the trimethylsilyl and tetrahydropyranyl
ethers are known compounds, and were characterized by spectral
analyses, comparisons with authentic samples (IR and NMR), and
also by regeneration of the corresponding alcohols. All yields refer
to the isolated products. The purity determination of the substrate
and reaction monitoring were accompanied by TLC on silica gel
polygram SILG/UV 254 plates.
Entry Product
Time (min); yield (%)
I
II4e,13
III4g
–
1
2
PhCH(OTMS)COPh
<1a; 92
<1a; 90
600; 96
180; 95
60; 95
OSiMe3
Trimethylsilylation of Alcohols; General Procedure
To a mixture of the substrate (1 mmol) and 1,3-dibromo-5,5-di-
methylhydantoin (0.15 mmol, 0.04 g) in MeCN (30 mL), was added
dropwise HMDS (7 mmol, 1.1 g) within 5 min under stirring at r.t.
After completion of the reaction (TLC or GC), the mixture was fil-
tered through a silica gel pad and the filter cake was washed with
MeCN (2 × 10 mL). Evaporation of the solvent gave almost pure
product(s). Further purification proceeded by bulb-to-bulb distilla-
tion under reduced pressure or recrystallization to afford pure silyl
ether.
3
4
4-CIC6H4CH2OTHP
PhCH2CH2CH2OTHP
25; 92
98; 90
300; 92
330; 94
20; 90
30; 85
a Reaction was instantaneous.
In conclusion, in this study, we have developed an effi-
cient, simple and chemoselective method for trimethyl-
silylation and tetahydropyranylation of benzylic and
Tetrahydropyranylation of Alcohols; General Procedure
A mixture of alcohol (1 mmol), 3,4-dihydro-2H-pyran (1.4 mmol,
primary and secondary aliphatic alcohols in the presence 0.12 g) and 1,3-dibromo-5,5-dimethylhydantoin (0.5 mmol, 0.143
H
RO
O
H
O
Br
ROH
+
R
N
O
H
O
ROH
O
H
Br
OR
+
N
H
O
O
O
Scheme 3
Synthesis 2006, No. 24, 4252–4256 © Thieme Stuttgart · New York

4256
F. Shirini et al.
PAPER
g) in n-hexane (3 mL) was stirred at r.t. The progress of the reaction
was monitored by TLC. After completion of the reaction, the mix-
ture was filtered through a silica gel pad, and the solid residue was
washed with n-hexane (2 × 5 mL). Evaporation of the solvent gave
the desired products in high purity.
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Financial support for this work by the research affair, Guilan
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Synthesis 2006, No. 24, 4252–4256 © Thieme Stuttgart · New York