HF-Pyridine: A versatile promoter for monoacylation/sulfonylation of phenolic diols and for direct conversion of t-butyldimethylsilyl ethers to the corresponding acetates

Article abstract of DOI:10.1246/cl.2012.138

Monoacylation and trifluoromethanesulfonylation of phenolic diols were achieved by the aid of HF-pyridine, whereas diacylation occurred with pyridine alone. Furthermore, HF-pyridine was found to promote the direct conversion of t-butyldimethylsilyl ethers to the corresponding acetates.

Full text of DOI:10.1246/cl.2012.138

doi:10.1246/cl.2012.138
138
Published on the web January 28, 2012
HF-Pyridine: A Versatile Promoter for Monoacylation/Sulfonylation of Phenolic Diols
and for Direct Conversion of t-Butyldimethylsilyl Ethers to the Corresponding Acetates
Kyosuke Michigami, Kazuya Yoshimoto, and Masahiko Hayashi*
Department of Chemistry, Graduate School of Science, Kobe University, Kobe, Hyogo 657-8501
(Received October 19, 2011; CL-111029; E-mail: mhayashi@kobe-u.ac.jp)
Table 1. Monoacetylation of phenolic diolsa
Monoacylation and trifluoromethanesulfonylation of phe-
nolic diols were achieved by the aid of HF-pyridine, whereas
diacylation occurred with pyridine alone. Furthermore, HF-
pyridine was found to promote the direct conversion of t-
butyldimethylsilyl ethers to the corresponding acetates.
Conditions
Yieldb/%
Mono- Di-
Entry
Substrate
Promoter
Temp/°C Time/h
acetate
acetate
OH
1
2
0
0.5
1.5
0
96
12
pyridine
OH
HF−pyridine
27
70
Monoprotection of diols is an important problem in organic
synthesis,1 and several methods to achieve this have been
reported to date. For example, Babler and Coghlan reported
monoacetylation of symmetric diols using an AcOH-H2SO4-
H2O system.2 Nishiguchi and Taya reported selective mono-
acylation of 1,n-diols catalyzed by metallic sulfates supported
on silica gel.3 Nishiguchi’s group also reported monoacylation
of 1,n-diols catalyzed by ion-exchange resins.4 More recently,
monoacylation of multi-hydroxy groups of a carbohydrate was
accomplished using an elegantly designed acylation catalyst
developed by Kawabata.5
With respect to operational simplicity, direct conversion of
one protective group into another protective group is desirable.6
Oriyama revealed a variety of one-step conversions of one
protective group to another group, such as the direct conversion
of p-methoxybenzyl ethers into silyl ethers.7
Herein, we will describe HF-pyridine-promoted monopro-
tection of phenolic diols, which is in contrast to the pyridine-
promoted reaction, and direct conversion of t-butyldimethylsilyl
ethers into the corresponding acetates by the aid of HF-pyridine.
During the course of our study of HF-pyridine-promoted
aryl C-glycosidation of glycals,8 we found that HF-pyridine also
promoted the acetylation of phenolic hydroxy groups. Therefore,
we turned our attention to the monoacetylation of phenolic diols.
We first examined the reactions of catechol (1), resorcinol (2),
hydroquinone (3), and 2,7-naphthalenediol (4) with 5 equiv of
acetic anhydride (Ac2O) in the presence of pyridine or 70% HF-
pyridine (Table 1). In all cases examined, when using pyridine
as a promoter, only diacetates were obtained in high yields (96-
98%). When HF-pyridine was used as the promoter, mono-
acetates were predominantly obtained. There was little differ-
ence in reactivity among the substitution patterns of the hydroxy
groups (ortho, meta, and para) (Entries 2, 4, and 6).9 We
confirmed HF-pyridine retarded both the first and the second
acetylation step. It should be mentioned that the separation of the
monoacetates and diacetates was easily carried out by silica gel
column chromatography using a mixture of hexane and ethyl
acetate (3:1) as an eluent.
1
HO
3
4
pyridine
0.5
1.0
0
0
97
16
OH
20
63
HF−pyridine
2
3
5
6
pyridine
0.5
1.5
0
0
98
13
HO
HO
OH
HF−pyridine
20
74
OH
7
8
pyridine
0.5
2.0
0
0
96
28
HF−pyridine
27
64
4
aAll reactions were carried out using 5 equiv of Ac2O in the
presence of 1.5 equiv of pyridine (Entries 1, 3, 5, and 7) or 15
equiv of HF-pyridine (Entries 2, 4, 6, and 8). CH2Cl2 was used
as a solvent in the case of pyridine. bIsolated yield by silica gel
column chromatography using a mixture of hexane and ethyl
acetate (3:1).
Tf2O
(5 equiv)
promoter
+
HO
OH
HO
OTf
TfO
OTf
30 °C
1.5 h
pyridine
HF-pyridine
0%
81%
84%
6%
Scheme 1. Monotrifluoromethanesulfonylation of 3.
ditriflate, and recovery of starting material were 23%, 0%, and
62%, respectively.
For benzoylation instead of acetylation, the tendency of
pyridine and HF-pyridine was also the same. In the case of
pyridine, dibenzoate was produced predominantly (but not
exclusively), whereas HF-pyridine gave the monobenzoate
selectively. Little difference was observed between BzCl and
Bz2O as benzoylating reagents (Table 2).
In the trifluoromethanesulfonylation of hydroquinone (3),
similar phenomena were observed as shown in Scheme 1. The
reaction of hydroquinone (3) with Tf2O (Tf: -SO2CF3) promoted
by pyridine gave only the ditriflate, whereas the reaction in the
presence of HF-pyridine afforded predominantly the monotri-
flate. In the absence of promoter, the yields of monotriflate,
In the acetylation of 2- and 4-aminophenol (Scheme 2),10
only the diacetate was obtained in the presence of pyridine,
whereas only N-acetylated product was obtained in the presence
of HF-pyridine.
Chem. Lett. 2012, 41, 138-139
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

139
Table 2. Benzoylation of catechol (1), resorcinol (2), and
hydroquinone (3)a
Table 3. HF-pyridine-promoted direct conversion of t-butyldi-
methylsilyl ethers to the corresponding acetate
OBz
OBz
OH
promoter
Conditions
Yieldc/%
+
HF−pyridineb
+
+ diol
BzCl
Entry Substratea
Temp/°C Time/h
OH
OBz
OH
OTBS
Conditions
Temp Time Mono-
/°C /h benzoate benzoate
Yieldb/%
Di-
1
5.0
19
20
19
5
88
Entry Substrate Promoter
OTBS
2
1
2
3c
4c
5
6
7
8
1
1
1
1
2
2
3
3
pyridine
HF-pyridine 25
pyridine 26
HF-pyridine 26
pyridine 28
HF-pyridine 28
pyridine 30
HF-pyridine 30
25
15
15
24
24
2
2
1
1
18
71
16
68
16
60
18
64
71
22
75
22
60
16
65
20
4.5
4.7
2.5
3
97
91
OTBS
3
4
OTBS
4.8
2.5
92
19
aAll reactions were carried out using 5 equiv of BzCl in the
presence of 1.5 equiv of pyridine (Entries 1, 3, 5, and 7) or 15
equiv of HF-pyridine (Entries 2, 4, and 8). bIsolated yield.
cBz2O (5 equiv) was used.
aTBS: t-butyldimethylsilyl. b(mL of HF-pyridine)/(g of
c
substrate). Isolated yield.
References and Notes
Ac2O
NH2
OH
NHAc
NH2
OAc
NHAc
OAc
1
P. G. M. Wuts, T. W. Greene, Greene’s Protective Groups in Organic
Synthesis, 4th ed., John Wiley & Sons, Inc, 2007.
(5 equiv)
promoter
+
+
OH
2
3
4
J. H. Babler, M. J. Coghlan, Tetrahedron Lett. 1979, 20, 1971.
T. Nishiguchi, H. Taya, J. Am. Chem. Soc. 1989, 111, 9102.
T. Nishiguchi, S. Fujisaki, Y. Ishii, Y. Yano, A. Nishida, J. Org.
Chem. 1994, 59, 1191.
0 °C
20 min
pyridine
HF-pyridine
0%
86%
0%
0%
96%
0%
5
a) T. Kawabata, W. Muramatsu, T. Nishio, T. Shibata, H. Schedel,
J. Am. Chem. Soc. 2007, 129, 12890. b) Y. Ueda, W. Muramatsu, K.
Mishiro, T. Furuta, T. Kawabata, J. Org. Chem. 2009, 74, 8802.
Review: T. Oriyama, J. Synth. Org. Chem., Jpn. 1996, 54, 490.
T. Oriyama, K. Yatabe, Y. Kawada, G. Koga, Synlett 1995, 45.
M. Hayashi, S. Nakayama, H. Kawabata, Chem. Commun. 2000,
1329.
Ac2O
(5 equiv)
promoter
6
7
8
+
H2N
AcHN
AcHN
OH
OH
OAc
0 °C
20 min
pyridine
HF-pyridine
0%
94%
87%
0%
9
When one equiv of Ac2O was used for 1, 2, and 3, monoacetylated
products were predominantly obtained approximately equally in both
case of pyridine and HF-pyridine (monoacetate:diacetate = 63:13 for
1).
Scheme 2. Monoacetylation of 2- and 4-aminophenol.
10 In the reactions promoted by pyridine described in Schemes 1 and 2,
CH2Cl2 was used as a solvent.
11 B. Ganem, V. R. Small, Jr., J. Org. Chem. 1974, 39, 3728.
12 S. J. Danishefsky, N. Mantlo, J. Am. Chem. Soc. 1988, 110, 8129.
13 S. Kim, W. J. Lee, Synth. Commun. 1986, 16, 659.
Unfortunately, monoacetylation of aliphatic diols was
unsuccessful. In all cases examined such as trans- and cis-1,2-
cyclohexanediol and 1,8-octanediol using either pyridine or HF-
pyridine as promoters, monoacetylated products were obtained
predominantly with only moderate selectivities.
14 T. Oriyama, M. Oda, J. Gono, G. Koga, Tetrahedron Lett. 1994, 35,
2027.
15 Other examples: a) K. L. Chandra, P. Saravanan, V. K. Singh,
Tetrahedron Lett. 2001, 42, 5309. b) Ch. S. Reddy, G. Smitha, S.
Chandrasekhar, Tetrahedron Lett. 2003, 44, 4693. c) A. Brar, Y. D.
Vankar, Tetrahedron Lett. 2006, 47, 5207. d) T.-J. Du, Q.-P. Wu,
H.-X. Liu, X. Chen, Y.-N. Shu, X.-D. Xi, Q.-S. Zhang, Y.-Z. Li,
Tetrahedron 2011, 67, 1096.
In 1974, Ganem and Small reported an FeCl3-Ac2O system
for the direct conversion of t-butyldimethylsilyl ethers to
acetates.11 Danishefsky and Mantlo used this method for the
synthesis of («)-heptelidic acid.12 Kim and Lee reported the
reaction of silyl ethers with acid chlorides in the presence of
zinc chloride to give the corresponding carboxylic esters
including acetates.13 Oriyama reported that a stoichiometric
amount of acyl bromide and a catalytic amount of tin(II)
promoted the conversion of silyl ethers into acetates.14,15
We examined the reactions of several t-butyldimethylsilyl
ethers with HF-pyridine as shown in Table 3. In all cases
examined, the corresponding acetates were obtained in high
yields.
16 Experimental procedure for acetylation using HF-pyridine: To a
polyethylene vessel containing phenolic diol, HF-pyridine (15 equiv)
was added, followed by addition of Ac2O (5 equiv). After stirring at
the indicated temperature for the indicated amount of time, the
mixture was poured into a solution of saturated aqueous KF solution.
The mixture was extracted by ethyl acetate, then the organic layer
was washed with 1 M HCl, saturated NaHCO3, and brine. After
evaporation, the residue was purified by silica gel column chroma-
tography to give the monoacetylated and diacetylated products.
17 Experimental procedure for t-butyldimethylsilyl ethers to acetates
using HF-pyridine: In a polyethylene vessel was placed the t-
butyldimethylsilyl ether. The amount was described in Table 3.
Addition of Ac2O (5 equiv) followed by confirmation of completion
of the reaction, the usual workup was performed as described above to
give the corresponding acetate.
In summary, we have discovered the HF-pyridine-pro-
moted monoacylation of phenolic diols and direct conver-
sion of t-butyldimethylsilyl ethers to the corresponding
acetates.16,17
Chem. Lett. 2012, 41, 138-139
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/