Zinc mediated reactions in organic synthesis: Efficient synthesis of silyl ethers under mild conditions

Article abstract of DOI:10.1002/jccs.200500019

General and practical method for the syn the sis of silyl ethers in the presence of zinc powder under mild conditions has been described.

Full text of DOI:10.1002/jccs.200500019

Journal of the Chinese Chemical Society, 2005, 52, 125-128
125
Zinc Mediated Reactions in Organic Synthesis: Efficient Synthesis of Silyl
Ethers under Mild Conditions
a
a
b
Babasaheb Pandurang Bandgar, * Satish Navnath Chavare and Shivaji Sandu Pandit
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth
a
Marathwada University, Vishnupuri, Nanded-431 606, India
b
P.G. Department of Chemistry. P. V. P. College Pravaranagar, (Loni kd.) Tal. Rahata. Dist. Ahmednagar.
13713 (M. S.) India
4
General and practical method for the synthesis of silyl ethers in the presence of zinc powder under mild
conditions has been described.
Keywords: Silyl ethers; Selectivity; Protection; Zinc powder; Alcohol; TMSCl.
Scheme I
INTRODUCTION
The protection of alcohols as a trimethylsilyl group has
o
Zn, 25 C
R
OH
R OSiMe3
Me SiCl
3
1
-3
been frequently and widely used in organic synthesis, and
this derivatization is also applicable to increase volatility for
analysis in liquid or gas-chromatography and mass spectrom-
RESULTS AND DISCUSSION
4
etry. A number of methods have been reported for this pur-
pose, using for example trimethylsilyl chloride (TMSCl) or
Trace of HCl in TMSCl reacted with zero-valent zinc to
1
-8
hexamethyldisilazane (HMDS) pyridine or triethyl amine,
generate a trace amount of ZnCl , which activates silyl chlo-
2
ride in a halophilic manner to make silylchloride much more
electrophilic.
9
10
TMSCl/Et
CO /phase transfer catalyst, trimethylsilyl azide, allyl-
trimethylsilane, ethyl trimethylacetate, N-trimethylsilyl-
3
N/catalyst, TMSCl/lithium sulfide, TMSCl/
11
12
K
2
3
1
3
14
1
5
16
2
-oxazolidinone, N-(trimethylsilyl)imidazoles N,N-bis-
1
7
18
(
triethylsilyl)urea, ketene methyltrialkylsilyl acetals, and
1
9
hexamethyldisilyloxane. Sterically hindered tertiary alco-
hols are in general not or only partly transformed into their
O-trimethylsilylated derivatives by most of these methods.
Thus-generated HCl is again trapped by zinc.
Exceptions among them are the reactions using TMSCl/Et
3
N/
9
15
Zn + 2 HCl
ZnCl + H2
2
catalyst, N-trimethylsilyl-2-oxazolidinone, N-(trimethyl-
1
6
silyl)imidazoles, and N,N-bis(trimethylsilyl)trifluoroace
In order to confirm this mechanism, the reaction is per-
2
0
tamide. Some difficulties may be, however, sometimes en-
countered because of the basic conditions for the first method
and expensiveness of the reagents for the latter three cases.
The method which allows O-silylation under mild conditions
should heighten the synthetic potentiality of the reaction. We
now report here for the first time a zinc mediated efficient and
general method of O-silylation of a variety of alcohols
formed in the presence of a trace amount of base, triethyl-
2 3
amine or Na CO , and it was observed that the corresponding
O-silylated product is not formed even after stirring the mix-
ture for a longer time (10 h). This indicates that a trace amount
of HCl in trimethylsilyl chloride plays an important role in
initiating the reaction.
Use of readily available and inexpensive reagents, fac-
ile procedure, mild conditions and easy and selective applica-
(
Scheme I).
*
Corresponding author. E-mail: bandgar_bp@yahoo.com

1
26 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Bandgar et al.
bility for alcohols having other substituents which may be la-
bile under basic conditions are important features of this
method.
(Table 2 entry 5). Other silylating reagents are also equally
effective for silylation of benzyl alcohols (equations 1 and 2).
It is also important to note that tertiary alcohols (equations 3
and 4) efficiently silylated even by using sterically hindered
reagents such as t-butyl/phenyl dimethylsilyl chloride.
Under these reaction conditions, primary, secondary,
tertiary, benzylic, allylic and propargylic alcohols were effi-
ciently and conveniently transformed into the corresponding
silyl ethers (Table 1) in excellent yields. Using less than a
stoichiometric amount of zinc powder resulted in a decrease
in the yield of O-silylated product. When attempts were made
to carry out O-silylation in the absence of zinc powder, it re-
sulted in almost a quantitative recovery of the starting alco-
hols. It is important to note that O-silylation of benzylic alco-
hols (Table 1, entries 1-4), allylic alcohols (Table 1, entry 5)
and propargylic alcohols (Table 1, entries 6, 12) is very fast as
compared to O-silylation of primary, secondary and tertiary
alcohols (Table 1, entries 7-11).
OH
Zn
O
Si
----1
+
+
+
Si Cl
2
5 0C,10 min.
9
7%
OH
Zn
Si
O
Ph ----2
Ph
Si Cl
2
5 0C,10 min.
9
7%
O
Zn
Ph3C OH
Ph3C OH
Si
Cl
Ph3C
Ph3C
Si
Si
-----3
-----4
2
2
5 0C,10 min.
8
3%
O
Zn
5
+ Ph
Si Cl
Ph
0C,10 min.
7
7%
It may also be quite interesting that the presence of a
carbonyl group (Table 2, entry 3), halogen atoms (Table 2, en-
tries 1, 2, 6, 7 and 10) or a ester group, (Table 2, entry 4)
which may show some reactivity under the basic conditions
of conventional methods, did not give any disturbance to the
present reaction. It is worth noting that various other func-
tional groups such as C=C, CºC, methoxy, methylenedioxy
remain unaltered during silylation under these reaction con-
ditions.
In conclusion, mild conditions tolerance of other sensi-
tive functional groups and chemo selectivity using inexpen-
sive zinc dust are important features of this method.
EXPERIMENTAL SECTION
Activation of Zinc
4 g of commercial Zinc powder was stirred with 1.5 mL
of 10% HCl for 2 minutes, filtering and washing with 30 mL
of water followed by 10 mL acetone.
One of the most noteworthy features of this method is
that chemoselective o-silylation of benzylic primary alcohols
occurred in the presence of primary alkanols (Table 2 entries
6
-7). Similarly benzylic primary alcohols are chemoselec-
A typical procedure
tively O-silylated in the presence of secondary alkanols (Ta-
ble 2, entry 8), tertiary alkanols (Table 2, entry 9) and phenols
A mixture, activated zinc dust (5 mmol) and tri-methyl
silyl chloride (5 mL) was stirred at room temperature (25 °C)
Table 1. Zinc mediated O-silylation of alcohols
a,b
Time
Yield
(%)
Entry
Substrate
Benzyl alcohol
4-chloro benzyl alcohol
4-methoxy benzyl alcohol
3,4-dioxymethylene benzyl
alcohol
Product
(
min)
1
2
3
4
TMS benzyl ether
5
5
10
10
91
96
94
91
TMS 4-chloro benzyl ether
TMS 4-methoxy benzyl ether
TMS 3,4-dioxymethylene
benzyl ether
5
6
Cinnamyl alcohol
3-methyl-1-pentyn-3-ol
TMS cinnamyl ether
5
10
94
91
TMS 3-(trimethyl silyl)-3-
methyl-1-pentyne ether
TMS t-Butyl ether
TMS triphenyl methyl ether
TMS menthyl ether
TMS tetrahydrofurfuryl ether
TMS 3-methyl-1-butyl ether
TMS propargyl ether
7
8
9
1
1
1
a
t-Butyl alcohol
Triphenyl carbinol
Menthol
Tetrahydro furfuryl alcohol
3-methyl-1-butanol
Propargyl alcohol
120
150
90
600
420
5
88
82
82
91
98
92
0
1
2
Yields of isolated products.
Products are characterised by spectral analysis and comparision with authentic samples.
b

Synthesis of Sily Ethers under Zinc Mediated Conditions
Table 2. Zinc mediated selective O-silylation of alcohols
J. Chin. Chem. Soc., Vol. 52, No. 1, 2005 127
ab
Yield
Entry
Substrate
6-chloro-1-hexanol
5-bromo-1-pentanol
Benzoin
Product
Time
(
%)
1
2
3
TMS 6-chloro-1-hexyl ether
TMS 5-bromo-1-pentyl ether
TMS-benzoin ether
8 h
7 h
2 h
91
87
97
OH
OTMS
4
5
3
h
85
87
COOET
COOET
4-hydroxy-3-methoxy benzyl
alcohol
TMS 4-hydroxy-3-methoxy
benzyl ether
10 min
0 min
1
77
+
OH
OTMS
Cl
Cl
6
7
00
+
+
CH
3 2 4
(CH ) OH
CH
3 2 4
(CH ) OH
OH
OH
OTMS
OTMS
Br
Br
5 min
90
+
00
+
+
CH
3
(CH
2
)
6
OH
CH (CH ) OH
3
2 6
NC
NC
8
10 min
92
+
+
+
0
0
OH
OTMS
OH
OTMS
O
N
2
O N
2
9
10 min
93
+
+
+
0
0
3
Ph COH
3
Ph COTMS
Cl
Cl
N
OTMS
N
OH
1
0
O2N
O
N
5 h
82
2
N
N
a
Yields of isolated products.
Products are characterised by spectral analysis and comparision with authentic samples.
b
22
1-8
for one minute and then benzyl alcohol (5 mmol) was added
in it. Spontaneous and exothermic reaction took place which
was controlled by cooling the reaction mixture in an ice bath.
After completion of the reaction (TLC) the mixture was di-
vacuum to afford the crude product, which was further puri-
fied by column chromatography on silica gel (hexane: ethyl
acetate = 9:1). A large excess of TMSCl is used because it is
highly volatile and acted as a solvent for the reaction. A
stoichiometric amount of TMSCl under this reaction condi-
2 2
luted with CH Cl and filtered. Solvent was removed under

1
28 J. Chin. Chem. Soc., Vol. 52, No. 1, 2005
Bandgar et al.
tion resulted in lowering the yield of product. However, a
stoichiometric amount of TMSCl in dichloromethane or
acetonitrile as a solvent worked well for this reaction.
PaysBas 1980, 99, 70.
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