ZrCl4 as a mild and efficient catalyst for the one-pot conversion of TBS and THP ethers to acetates

Article abstract of DOI:10.1016/S0040-4039(03)01078-5

A mild, efficient and chemoselective method has been developed for the direct transformation of tert-butyldimethylsilyl and tetrahydropyranyl protected alcohols into the corresponding acetates with acetic anhydride and zirconium(IV) chloride as the catalyst in acetonitrile, in a one-pot reaction with high yields and short reaction times. This method has been applied to a variety of substrates.

Full text of DOI:10.1016/S0040-4039(03)01078-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4693–4695
ZrCl4 as a mild and efficient catalyst for the one-pot conversion
of TBS and THP ethers to acetates
Ch. Sanjeeva Reddy,a,* G. Smithaa and S. Chandrasekharb
aDepartment of Chemistry, Kakatiya University, Warangal-506009, India
bIndian Institute of Chemical Technology, Hyderabad-500007, India
Received 8 February 2003; revised 14 April 2003; accepted 25 April 2003
Abstract—A mild, efficient and chemoselective method has been developed for the direct transformation of tert-butyldimethylsilyl
and tetrahydropyranyl protected alcohols into the corresponding acetates with acetic anhydride and zirconium(IV) chloride as the
catalyst in acetonitrile, in a one-pot reaction with high yields and short reaction times. This method has been applied to a variety
of substrates. © 2003 Elsevier Science Ltd. All rights reserved.
Selective protection and deprotection of functional
groups is a commonly used process in multistep organic
synthesis and the interconversion of one protecting
group into another is also an important transformation
in synthetic organic chemistry. Thus, development of
new methods for such interconversions in one-step
avoiding the intermediate step of going back to the
parent functionality has gained importance in recent
times.1 Amongst protecting groups for alcohols, tert-
butyldimethylsilyl (TBS) and tetrahydropyranyl (THP)
ethers are most frequently used due to their reasonable
stability and compatibility to various reaction condi-
tions and reagents such as strongly basic media, alkyl
lithiums, metal hydrides, and catalytic hydrogenation.2
However, they are not stable under strongly acidic
conditions. On the other hand, acetates serve as effec-
tive hydroxyl blocking groups, which are stable to
acidic conditions. Thus the conversion of TBS and
THP ethers to the corresponding acetates is an impor-
tant transformation in organic synthesis. The methods
available for this transformation are limited and include
AcCl/ZnCl2,3 AcBr/SnBr2,4 FeCl3/Ac2O5 or AcOH6 and
Cu(OTf)2/Ac2O7 (for the conversion of TBS and THP
ethers to acetates), AcOH/AcCl,8 TiCl4/Ac2O,9 In/I2–
EtOAc10 and recently In(OTf)3/Ac2O11 (for the conver-
sion of THP ethers to acetates). However, these
procedures suffer from some disadvantages such as
elevated reaction temperatures, long reaction times, and
incompatibility with other protecting groups.12 Despite
all these methods, an efficient and practical method for
this transformation is desired. Toward this goal, our
experience in protecting group interconversion9,13
prompted us to explore new methods for this useful
transformation. We found that the zirconium(IV) chlo-
ride (5 mol%) and acetic anhydride reagent system
converts TBS and THP ethers to the corresponding
acetates under mild conditions, in one-pot and in short
reaction times (Scheme 1).
A wide range of structurally diverse TBS and THP
ethers were subjected to this protocol to produce the
corresponding acetates. The results are summarized in
Table 1. In the first case, 3-phenyl-1-propanol TBS
ether was treated with catalytic ZrCl4 (5 mol%) and
acetic anhydride in CH3CN at room temperature to
give the corresponding acetate in 94% yield within 5
min (entry 1).14 Primary and secondary benzylic alcohol
TBS ethers also gave the corresponding acetates in
short reaction times, in 93 and 90% yields, respectively
(entries 2 and 3). Entries 4 and 5 clearly demonstrate
that the TBS ethers of aliphatic alcohols can be selec-
tively converted to acetates in the presence of phenolic
TBS and TIPS (triisopropylsilyl) ethers. This conver-
sion is also effective in the presence of an acid labile
Keywords: zirconium(IV) chloride; one-pot reaction.
* Corresponding author. Tel./fax: +91-870-243-8833; e-mail: chsrkuc
@yahoo.co.in
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01078-5

4694
Ch. S. Reddy et al. / Tetrahedron Letters 44 (2003) 4693–4695
Table 1. Conversion of TBS and THP ethers to acetates
functionalities were also found to be unaffected under
the present reaction conditions.
In summary, we have developed a rapid and efficient
method for the one-pot conversion of TBS and THP
ethers to the corresponding acetates in the presence of
a catalytic amount of ZrCl4. The advantages of this
protocol such as mild reaction conditions, chemoselec-
tivity, shorter reaction times and high yields of the
desired products are worthy of mention and make this
method an attractive and useful contribution to present
methodologies.
General experimental procedure: To a stirred solution of
the substrate (1 mmol) in CH3CN (10 mL), Ac2O (1
mmol)16 followed by ZrCl4 (5 mol%) was added and the
reaction mixture was stirred at room temperature for
the given time (see Table 1). After completion of the
reaction, the solvent was evaporated in vacuo, extracted
with EtOAc, washed with 10% NaHCO3 solution. The
combined organic layers were dried (Na2SO4) and evap-
orated to give the corresponding acetate17 which was
purified by column chromatography.
References
1. (a) Yang, G.; Ding, X.; Kong, F. Tetrahedron Lett. 1997,
38, 6725; (b) Oriyama, T.; Yatabe, K.; Sugauttra, S.;
Machiguchi, Y.; Koga, G. Synlett 1996, 523; (c) Oriyama,
T.; Kimura, M.; Koga, G. Bull. Chem. Soc. Jpn. 1994, 67,
885.
2. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999; (b)
Kocienski, P. J. Protective Groups; Georg Thieme: Stutt-
gart, 1994.
3. Kim, S.; Lee, W. J. Synth. Commun. 1986, 16, 659.
4. Oriyama, T.; Oda, M.; Gono, J.; Koga, G. Tetrahedron
Lett. 1994, 35, 2027.
5. Ganem, B.; Small, V. R. J. Org. Chem. 1974, 39, 3728.
6. Sharma, G. V. M.; Mahalingam, A. K.; Nagarajan, M.;
Ilangoan, A.; Radhakrishna, P. Synlett 1999, 1200.
7. Chandra, K. L.; Saravanan, P.; Singh, V. K. Tetrahedron
Lett. 2001, 42, 5309.
8. Schwarz, M.; Waters, R. M. Synthesis 1972, 567.
9. Chandrasekhar, S.; Ramachander, T.; Reddy, M. V.;
Takhi, M. J. Org. Chem. 2000, 65, 4729.
10. Ranu, B. C.; Hajra, A. J. Chem. Soc., Perkin Trans. 1
2001, 355.
11. Mineno, T. Tetrahedron Lett. 2002, 43, 7975.
12. (a) Benzyl ethers were cleaved under AcBr/SnBr2 condi-
tions; (b) Benzyl and methyl ethers are also cleaved with
the FeCl3/Ac2O reagent system.
13. (a) Chandrasekhar, S.; Babu, B. N.; Reddy, Ch. R.
Tetrahedron Lett. 2003, 44, 2057 (for NBn, NDPM and
NTr to NHBoc) (for NHCbz to NHBoc); (b) Chan-
drasekhar, S.; Chandraiah, L.; Reddy, Ch. R.; Reddy, M.
V. Chem. Lett. 2000, 780.
N-tbutyl carbamate group within 30 min (entry 6). To
check the compatibility and prove the mildness of the
reagent system, we have studied a series of 1,6-hexane
diol diether substrates having a TBS ether at one end
and a hydroxyl-protecting group at the other end.
Interestingly, the TBS ether was selectively converted to
acetate even though a TBDPS ether was located at the
other end (entry 7). Furthermore, the benzyl and allyl
ethers and tosylates were stable to the present protocol
(entries 8, 9 and 10). However, aliphatic TIPS (entry
12) and THP (entry 13) ethers were not stable, being
smoothly converted to the corresponding acetates. A
brief literature search showed that, there was no report
presenting the conversion of THP ethers to acetates
with ZrCl4.15 This result has encouraged us to extend
the generality of the direct conversion of THP ethers to
acetates to a few other substrates. Accordingly, the
primary and secondary alcohol THP ethers (entries
14–18) were prepared and subjected to the ZrCl4–Ac2O
system to afford the corresponding acetates rapidly and
in good yields. During this study, olefinic (entries 15
and 16), halo (entry 17) and methyl ether (entry 18)
14. The same reaction was tested with ZrCl4 (5 mol%) in the
absence of Ac2O, wherein we observed that TBS ether
cleavage occurred in 10 h.

Ch. S. Reddy et al. / Tetrahedron Letters 44 (2003) 4693–4695
4695
15. There is one method reported for THP deprotection
with ZrCl4 in MeOH, where the reaction time was 2–6
h. See: Rezai, N.; Alsadat, M.; Salehi, P. Synth. Com-
mun. 2000, 30, 1799.
16. For entries 11–13, 2 equiv. of Ac2O were used.
17. Spectroscopic data for selected products: Entry 4: 1H
NMR (400 MHz, CDCl3): l 7.1 (d, J=7.6 Hz, 2H), 6.8
(d, J=8 Hz, 2H), 4.25 (t, J=6.8 Hz, 2H), 2.88 (t,
J=2.8 Hz, 2H), 2.06 (s, 3H), 1.0 (s, 9H), 0.2 (s, 6H);
EIMS (m/z): 294 (M+). Entry 5: 1H NMR (CDCl3): l
7.07 (d, J=8 Hz, 2H), 6.83 (d, J=8 Hz, 2H), 4.25 (t,
J=7.2 Hz, 2H), 2.88 (t, J=7.2 Hz, 2H), 2.05 (s, 3H),
1.31–1.21 (m, 3H), 1.1 (d, J=7.2 Hz, 18H); EIMS (m/
z): 336 (M+). Entry 6: 1H NMR (CDCl3): l 4.14 (t,
J=6 Hz, 2H), 3.2 (t, J=5.6 Hz, 2H), 2.07 (s, 3H),
1.84–1.8 (m, 2H), 1.45 (s, 9H); EIMS (m/z): 116 (M+−
101). Entry 8: 1H NMR (CDCl3): l 7.36–7.24 (m, 5H),
4.5 (s, 2H), 4.06 (t, J=3.2 Hz, 2H), 3.46 (t, J=6.8 Hz,
2H), 2.04 (s, 3H), 1.68–1.58 (m, 4H), 1.45–1.35 (m, 4H);
EIMS (m/z): 250 (M+).