Highly efficient and chemoselective cleavage of prenyl ethers using ZrCl4/NaBH4

Article abstract of DOI:10.1016/S0040-4039(03)00330-7

An efficient and chemoselective deprotection of prenyl ethers of phenols and alcohols with ZrCl₄/NaBH₄ in DCM was achieved in high yields. The selectivity of prenyl ether deprotection is well demonstrated by carrying out the reaction

Full text of DOI:10.1016/S0040-4039(03)00330-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2525–2528
Highly efficient and chemoselective cleavage of prenyl ethers
ꢀ
using ZrCl /NaBH
4
4
K. Suresh Babu, B. China Raju, P. V. Srinivas and J. Madhusudana Rao*
Natural Products Laboratory, Organic Chemistry Division-1, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 12 December 2002; revised 24 January 2003; accepted 31 January 2003
Abstract—An efficient and chemoselective deprotection of prenyl ethers of phenols and alcohols with ZrCl /NaBH in DCM was
4
4
achieved in high yields. The selectivity of prenyl ether deprotection is well demonstrated by carrying out the reaction in the
presence of several other ether and ester functionalities. © 2003 Elsevier Science Ltd. All rights reserved.
Protection of hydroxyl and acid groups plays an impor-
1
tant role in organic synthesis. Selective deprotection of
a particular functionality in the synthesis of complex
natural products having a multitude of functionalities is
often a challenging task for organic chemists. The allyl
group has been used frequently for protecting various
functionalities especially alcohols and phenols due to its
stability towards acidic and basic conditions. Several
methods are available for the deprotection of the allyl
Scheme 1.
2
group and these have been reviewed. Currently much
attention has been given to the 2-methylbut-2-enyl
groups. The cleavage was effected by ZrCl /NaBH in
4
4
(
prenyl) group as protection for phenols and acids.
DCM at room temperature and the reaction is clean
9
Recently a few methods have been developed for the
cleavage of prenyl ethers under different conditions
which include TiCl –nBu NI, I and DDQ. In addi-
and complete within 1.5–4 h.
3
4
5
4
4
2
The deprotection of prenyl ethers was achieved in high
yields with high chemoselectivity. The results are tabu-
lated in Table 1, which clearly show the chemoselectiv-
ity in the deprotection of prenyl ethers. This is the first
report of selective deprotection of prenyl ethers in the
presence of prenyl esters.
tion two more methods are known in the literature for
the deprotection of prenyl esters, these are I in
2
6
7
cyclohexane and CeCl ·7H O/NaI.
3
2
However, many of these methods have limited synthetic
scope due to lack of selectivity. Moreover, the yields of
deprotection of prenyl ethers in substrates containing a
carbonyl functional group in the position para to the
ether are very low, and some of the above methods
require cumbersome experimental procedures.
In summary, the present methodology offers attractive
features such as high chemoselectivity, high yields and
simple reaction conditions. It may find extensive appli-
cations in organic synthesis where the selective depro-
9
tection of prenyl ethers is required.
Herein, we wish to report ZrCl /NaBH as an efficient
4
4
8
reagent for the selective removal of prenyl ether groups
Scheme 1) over a wide range of other functional
(
Acknowledgements
Keywords: deprotection; prenyl ethers; zirconium tetrachloride;
The authors are thankful to the Director IICT and
Head, Organic Chemistry Division-1 for their constant
encouragement. K.S.B. thanks CSIR for providing
financial support.
sodium borohydride.
ꢀ
IICT Communication No. 030116.
*
Corresponding author. Tel.: 091-40-27193166; fax: +91-40-
7160512; e-mail: janaswamy@iict.ap.nic.in
2
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00330-7

2
526
K. Suresh Babu et al. / Tetrahedron Letters 44 (2003) 2525–2528
Table 1. Selective cleavage of prenyl ethers catalyzed by ZrCl /NaBH4
4

K. Suresh Babu et al. / Tetrahedron Letters 44 (2003) 2525–2528
2527
Table 1. (Continued)
References
mmol, 1 equiv.) was placed into a two necked round
bottom flask equipped with a magnetic bead, and dry
DCM (5 ml) was syringed into the flask. The contents were
1
. (a) Kocienski, P. J. Protecting Groups; Thieme: Stuttgart,
1
994; (b) Greene, T. W.; Wuts, P. G. M. Protecting Groups
cooled to 0°C and NaBH (0.054 g, 1.45 mmol, 4 equiv.)
4
in Organic Synthesis, 3rd ed.; John Wiley and Sons: New
York, 1999.
. Guibe, F. Tetrahedron 1997, 53, 13509.
. Tsuritani, T.; Shinokubo, H.; Oshima, K. Tetrahedron
Lett. 1999, 40, 8121.
. Vatele, J. M. Synlett 2001, 1989.
. Vatele, J. M. Synlett 2002, 507.
. Cossy, J.; Albouy, A.; Scheloske, M.; Pardo, G. Tetra-
hedron Lett. 1994, 35, 1539.
. Yadav, J. S.; Subba Reddy, B. V.; Rao, C. V.; Chand, P.
K.; Prasad, A. R. Synlett 2002, 137.
. (a) Itsuno, S.; Sakurai, Y.; Shimizu, K.; Ito, K. J. Chem.
Soc., Perkin Trans. 1 1990, 1859; (b) Itsuno, S.; Sakurai,
Y.; Shimizu, K.; Ito, K. J. Chem. Soc., Perkin Trans. 1
was added to the solution. The substrate (0.1 g, 0.364
mmol, 1 equiv., entry 1) in DCM (5 ml) was then added at
the same temperature. After the complete addition the ice
bath was removed and the contents brought to room
temperature. The progress of the reaction was monitored
by TLC which clearly indicated the disappearance of the
starting material. After completion of the reaction, the
reaction mixture was quenched with cold water (10 ml)
and diluted with DCM (20 ml). The organic layer was
separated and dried with anhydrous Na SO . The solvent
2
3
4
5
6
7
2
4
was removed under vacuum and the product was purified
by column chromatography on silica gel (60–120) to give
8
pure product in 96% yield (entry 1, 2a).
1
Compound 1e: H NMR (CDCl , 200 MHz): 1.68 (br s,
3
1
1
989, 1548; (c) Itsuno, S.; Sakurai, Y.; Ito, K. Synthesis
988, 995.
12H, 4×CH ), 4.60 (d, 2H, J=7 Hz, CH -CH), 4.90 (d,
3
2
2H, J=7 Hz, CH -CH), 5.28–5.38 (br t, 2H, 2 CH -CH),
2
2
9. Typical experimental procedure: ZrCl4 (0.085 g, 0.364
7.2–7.48 (m, 3H), 7.62–7.82 (m, 3H). Mass: m/z 324.

2
528
K. Suresh Babu et al. / Tetrahedron Letters 44 (2003) 2525–2528
CH -CH), 4.78 (d, 2H, J=7 Hz, CH -CH), 5.38–5.46 (br t,
1
Compound 2e: H NMR (CDCl , 200 MHz): 1.64 (br s,
3
2
2
6
7
1
1
H, 2×CH ), 5.02 (d, 2H, J=7 Hz, CH -CH), 5.58 (t, 1H,
2H, 2 CH - CH), 6.82 (d, 1H, J=10 Hz), 7.46 (s, 1H), 7.62
(d, 1H, J=8 Hz). Mass: m/z 304.
3
2
2
.0 Hz, CH -CH), 7.18 (d, 1H, J=8 Hz), 7.32–7.38 (m,
2
1
H), 7.42–7.58 (m, 1H), 7.72 (d, 1H, J=8 Hz), 7.92 (d,
H, J=8 Hz), 8.80 (d, 1H, J=8 Hz), 12.38 (s, 1H, OH).
Compound 1i: H NMR (CDCl
3
, 200 MHz): 1.64 (br s,
-CH), 4.52 (d,
-CH), 5.32 (s, 2H, -OCH ), 5.4–5.60 (b
-CH), 6.38–6.48 (m, 2H), 7.24–7.48 (m, 5H),
7.80 (d, 1H, J=8 Hz). Mass: m/z 380.
12H, 4×CH
2H, J=7 Hz, CH
t, 2H, 2 CH
), 3.98 (d, 2H, J=7 Hz, CH
3
2
Mass: m/z 256.
Compound 1d: H NMR (CDCl , 200 MHz): 1.64 (br s,
2
2
1
3
2
1
2H, 4×CH ), 3.90 (s, 3H, OMe), 4.60 (d, 2H, J=7 Hz,
3