deprotected using sodium methoxide at lower temperature3 and
by using organotin compounds4a–c [tBu2SnOH(Cl)]2 or dibutyltin
oxide, Mg(OMe)2,4d HClO4-SiO2,4e and acetyl chloride.4f As
part of our work on the development of compounds with
potential for the resolution of inflammation, we recently reported
the synthesis and biological evaluation of Lipoxin A4 analogues
of type 1.5 In our synthesis, we prepared (5S,6R)-methyl-5,6-
dihydroxyoct-7-enoate 2a as a key intermediate in a two-step
procedure from (5S,6R)-5,6-diacetoxyoct-7-enoic acid 3 involv-
ing conversion of the acid to the methyl ester 4a using
diazomethane and subsequent diacetate deprotection under basic
conditions at low reaction temperatures. In light of the ability
of ZrCl4 to catalyze a wide range of transformations,6 including
the esterification of acids, and its potential to promote acetate
deprotection, we investigated its use in a one-pot conversion
of (5S,6R)-5,6-diacetoxyoct-7-enoic acid 3 to (5S,6R)-methyl-
5,6-dihydroxyoct-7-enoate 2a.7 We now wish to report in full
the results of this investigation and related protection/depro-
tection studies employing ZrCl4.
ZrCl4 as an Efficient Catalyst for a Novel
One-Pot Protection/Deprotection Synthetic
Methodology
Surendra Singh, Colm D. Duffy, Syed Tasadaque A. Shah,
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
ReceiVed April 30, 2008
Our initial investigation employing ZrCl4 (20 mol %)
demonstrated that the desired one-pot procedure was indeed
(3) Otera, J. Chem. ReV. 1993, 93, 1449.
(4) (a) Orita, A.; Sakamoto, K.; Hamada, Y.; Otera, J. Synlett 2000, 140. (b)
Wang, S.-M.; Ge, W.-Z.; Liu, H.-M.; Zou, D.-P.; Yan, X.-B. Steroids 2004, 69,
599. (c) Wang, S.-M.; Zhang, Y.-B.; Liu, H.-M.; Yu, G.-B.; Wang, K.-R. Steroids
2007, 72, 26. (d) Xu, Y-C.; Bizuneh, A.; Walker, C. J. Org. Chem. 1996, 61,
9086, and references therein. (e) Tiwari, P.; Misra, A. K. Tetrahedron Lett. 2006,
47, 3673. (f) Yeom, C-E.; Lee, S. Y.; Kim, Y. J.; Kim, B. M. Synlett 2005,
1527.
A catalytic quantity of ZrCl4 (20 mol %) was found to be
an efficient catalyst for the one-pot esterification and depro-
tection of (5S,6R)-5,6-diacetoxyoct-7-enoic acid in good
yields (44-62%) with a lactone formed as a minor byprod-
uct. ZrCl4 (10-20 mol %) was also sufficient to deprotect
1,3-dioxalane, bis-TBDMS ethers, and diacetate functional
groups in excellent yields of up to 93%. ZrCl4 (1-10 mol
%) also promoted diol protection as the acetonide in 90%
yield and acted as a trans-esterification catalyst for a range
of esters.
(5) O’Sullivan, T. P.; Vallin, K. S. A.; Shah, S. T. A.; Fakhry, J.; Maderna,
P.; Scannell, M.; Sampaio, A. L. F.; Perretti, M.; Godson, C.; Guiry, P. J. J. Med.
Chem. 2007, 50, 5894.
(6) (a) Review on application of zirconium(IV) chloride in organic
synthesis: Smitha, G.; Chandrasekhar, S.; Reddy, S. C. Synthesis 2008, 6, 829.
(b) Esterification of carboxylic acids: Ishihara, K.; Nakayama, M.; Ohara, S.;
Yamamoto, H. Science 2002, 290, 1140. Ishihara, K.; Nakayama, M.; Ohara,
S.; Yamamoto, H. Tetrahedron 2002, 58, 8179. (c) Deprotection of TBDMS
group: Sharma, G. V. M.; Srinivas, B.; Radha Krishna, P. Tetrahedron Lett.
2003, 44, 4689. (d) Conversion of aldehydes to geminal-diacetates: Smitha, G.;
Reddy, S. C. Tetrahedron 2003, 59, 9571. (e) Preparation of MOM ethers and
their deprotection: Sharma, G. V. M.; Reddy, L. K.; Lakshmi, P. S.; Radha
Krishna, P. Tetrahedron Lett. 2004, 45, 9229. (f) One-pot conversion of TBS
and THP ethers to acetates: Reddy, S. C.; Smitha, G.; Chandrasekhar, S.
TetrahedronLett.2003,44,4693.(g)Openingofepoxideringsbyamines:Chakraborti,
A. K.; Kondaskar, A. Tetrahedron Lett. 2003, 44, 8315. (h) Chemoselective
cleavage of prenyl ethers: Babu, S. K.; Raju, C. B.; Srinivas, P. V.; Rao, M. J.
Tetrahedron Lett. 2003, 44, 2525. (i) Trimethylsilylation of alcohols and
phenols: Shirini, F.; Mollarazi, E. Catal. Commun. 2007, 8, 1393. (j) Fries
rearrangement and isomerisation: Harrowven, D. C.; Dainty, R. F.
Tetrahedron19975315771, andreferencescitedtherein.(k)Biginellireaction:Rodr´ıguez-
Dom´ınguez, J. C.; Bernardi, D.; Kirsch, G. Tetrahedron Lett. 2007, 48, 5777.
(l) Synthesis of tri- and tetra-substitutied imidazoles: Sharma, G. V. M.; Jyothi,
Y.; Sree Lakshmi, P. Synth. Commun. 2006, 36, 2991. (m) Synthesis of
chloromethyl esters: Mudryk, B.; Rajaraman, S.; Soundararajan, N. Tetrahedron
Lett. 2002, 43, 6317. (n) Conversion of sulfide to sulfoxide: Bahrami, K.
Tetrahedron Lett. 2006, 47, 2009. (o) Deoxygenation of heterocyclic N-oxide:
Chary, K. P.; Mohan, G. P.; Iyengar, D. S. Chem. Lett. 1999, 1339. (p) Acylation
of phenol: Chakraborti, A. K.; Gulhane, R. Synlett 2004, 627. (q) Iodination of
alcohols: Firouzabadi, H.; Iranpoor, N.; Jafarpour, M. Tetrahedron Lett. 2004,
45, 7451. (r) Single-step synthesis of pyrano- and furoquinolines: Das, B.; Reddy,
M. R.; Reddy, V. S.; Ramu, R. Chem. Lett. 2004, 1526. (s) Selective tosylation
of alcohol: Das, B.; Reddy, V. S. Chem. Lett. 2004, 1428. (t) Boc-protection of
amines Sharma, G. V. M.; Reddy, J. J.; Sree Lakshmi, P.; Radha Krishna, P.
Tetrahedron Lett. 2004, 45, 6963.
The protection or deprotection of a functional group is one
of the most important and widely carried out synthetic trans-
formations in preparative organic chemistry.1 The use of acidic
or basic conditions or hydrogenolysis are routinely used methods
for the deprotection of phenolic and aliphatic esters.1 Several
catalyst systems are used for the deprotection of phenyl acetate,
but these do not deprotect aliphatic acetates,2 which can be
(1) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic Synthesis,
3rd ed.; John Wiley and Sons: New York, 1999. (b) Kocienski, P. J. Protecting
Groups, 1st ed.; Georg Thieme Verlag: Stuttgart, Germany, 1994.
(2) Bandgar, B. P.; Uppala, L. S.; Sagar, A. D.; Sadavarte, V. S. Tetrahedron
Lett. 2001, 42, 1163. (b) Bandgar, B. P.; Uppalla, L. S.; Sagar, A. D.; Sadavarte,
V. S. New J. Chem. 2002, 26, 1273. (c) Ramesh, C.; Mahender, G.; Ravindranath,
N.; Das, B. Green Chem. 2003, 5, 68. (d) Das, B.; Banerjee, J.; Ramu, R.; Pal,
R.; Ravindranath, N.; Ramesh, C. Tetrahedron Lett. 2003, 44, 5465. (e)
Chakraborti, A. K.; Sharma, L.; Sharma, U. Tetrahedron 2001, 57, 9343. (f)
Ramesh, C.; Mahender, G.; Ravindranath, N.; Das, B. Tetrahedron 2003, 59,
1049.
10.1021/jo800932t CCC: $40.75
Published on Web 07/22/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6429–6432 6429