SCHEME 1
A Novel, Chemoselective and Efficient
Microwave-Assisted Deprotection of Silyl Ethers
with Selectfluor
Syed Tasadaque A. Shah, Surendra Singh, and
Patrick J. Guiry*
Centre for Synthesis and Chemical Biology, School of
Chemistry and Chemical Biology, UCD Conway Institute,
UniVersity College Dublin, Belfield, Dublin 4, Ireland
alcohols and examples from the recent literature include the
following: BF3,5 BCl3,6 sulfated SnO2,7 silica triflate,8 CuBr2,9
ZnBr2,10 NIS,11 TMSBr,12 and TMSCl.13 Many of these reagents
provide the added advantage of promoting selective desilylation
of bis-silyl ethers.14,15
ReceiVed NoVember 07, 2008
We recently reported the chemoselective and efficient depro-
tection of silyl ethers using catalytic quantities of TMSBr.16a
We have also reported the use of ZrCl4 as an efficient catalyst
for one-pot protection/deprotection synthetic methodology.16b
Considering the electrophilic and oxidative characters of
Selectfluor, we envisioned that this reagent could be used in
the cleavage of more commonly used, electron-rich silyl ether
protecting groups. In this communication, we wish to report
the desilylation of a wide range of silyl-protected primary,
secondary, and aromatic hydroxy and acid groups using
microwave irradiation in the presence of a substoichiometric
amount of Selectfluor in organic solvents such as acetonitrile,
methanol, and ethanol without any added reagent (Scheme 1).
A novel microwave-assisted, chemoselective and efficient
method for the cleavage of silyl ethers (aliphatic and
aromatic) catalyzed by Selectfluor is reported. A wide range
of TBS-, TIPS-, and TBDPS-protected alkyl silyl ethers can
be chemoselectively cleaved in high yield in the presence
of aryl silyl ethers. The chemoselective deprotection of
phenolic TBS ethers, and not the TIPS- or TBDPS-protected
phenolic ethers, and the deprotection of silyl esters were also
achieved under these reaction conditions. In addition, the
transetherification and etherification of benzylic hydroxy
groups in alcoholic solvents is observed.
(4) (a) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart, Germany, 1994.
(b) Green, T. W.; Wuts, P. G. M. Protecting Groups in Organic Synthesis, 3rd
ed.; John Wiley and Sons: New York, 1999. (c) Jarowicki, K.; Kocienski, P.
J. Chem. Soc., Perkin Trans. 1 1999, 1589. (d) Nelson, T. D.; Crouch, R. D.
Synthesis 1996, 1031.
(5) Toshima, K.; Takai, S.; Maeda, Y.; Takano, R.; Matsumura, S. Angew.
Chem., Int. Ed. 2000, 39, 3656.
(6) Yang, Y.-Y.; Yang, W.-B.; Teo, C.-F.; Lin, C.-H. Synlett 2000, 1634.
(7) Bhure, M. H.; Kumar, I.; Natu, A. D.; Rode, C. V. Synth. Commun. 2008,
38, 346.
(8) Shirini, F.; Marjani, K.; Nahzomi, H. T.; Zolfigol, M. A. Phosphorus,
Sulfur Silicon Relat. Elem. 2008, 183, 168.
(9) Bhatt, S.; Nayak, S. K. Tetrahedron Lett. 2006, 48, 8395.
(10) McGarvey, G. J. Zinc Bromide. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; John Wiley: New York, 1995; Vol. 8, p 5539.
(11) Karimi, B.; Zamani, A.; Zareyee, D. Tetrahedron Lett. 2004, 45, 9139.
(12) Friedrich, E. C.; Delucca, G. J. Org. Chem. 1983, 48, 1678.
(13) Peng, Y.; Li, W.-D. Z. Synlett 2006, 1165.
(14) (a) Yeom, C.-E.; Kim, H. W.; Lee, S. Y.; Kim, B. M. Synlett 2007,
146. (b) Nelson, T. D.; Crouch, R. D. Synthesis 1996, 1031. (c) Grieco, P. A.;
Markworth, C. J. Tetrahedron Lett. 1999, 40, 665.
Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-
[2.2.2]octane bis(tetrafluoroborate)) is a commercially avail-
able, user-friendly electrophilic fluorinating reagent for a wide
variety of electron-rich carbon centers.1,2 Due to its electro-
philic and oxidative characteristics Wong has reported its use
in the cleavage of electron-rich protecting groups, such as
p-methoxybenzylidene (PMP) and tetrahydropyranyl (THP)
ethers and 1,3-dithianes.3
Silyl esters and ethers are among the most frequently used
protecting groups for acid and alcohol functionalities.4 A number
of Lewis acids and other reagents have been reported to be
effective in promoting cleavage of silyl-protected acids and
(1) (a) Banks, R. E.; Besheesh, M. K.; Mohialdin, S. N.; Sharif, I. J. Chem.
Soc., Perkin Trans. 1 1996, 2069. (b) Nyffeler, P. T.; Duron, S. G.; Burkart,
M. D.; Vincent, S. P.; Wong, C.-H. Angew. Chem., Int. Ed. 2005, 44, 192.
(2) Bluck, G. W.; Carter, N. B.; Smith, S. C.; Turnbull, M. D. J. Fluorine
Chem. 2004, 125, 1873.
(15) (a) Oriyama, T.; Kobayashi, Y.; Noda, K. Synlett 1998, 1047. (b) Bartoli,
G.; Cupone, G.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Procopio, A.; Sambri,
L.; Tagarelli, A. Tetrahedron Lett. 2002, 43, 5945.
(16) (a) Shah, S. T. A.; Guiry, P. J. Org. Biomol. Chem. 2008, 6, 2168. (b)
Singh, S.; Duffy, C. D.; Shah, S. T. A.; Guiry, P. J. J. Org. Chem. 2008, 73,
6429.
(3) Liu, J.; Wong, C.-H. Tetrahedron Lett. 2002, 43, 4037.
10.1021/jo802494t CCC: $40.75
Published on Web 01/27/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2179–2182 2179