LETTER
CAN-Catalysed Highly Chemoselective Deprotection of Ketals and THP Ethers
2197
Table 2 CAN-Catalysed Deprotection of Bifunctional Substratesa
Entry
1
Substrate
Product
Temperature, time
40 °C, 2 h
Yield (%)b
90
O
OTf
O
OTf
O
1
3
13a
2
OTf
OTf
60 °C, 2 h
94
O
O
O
1
4a
1
1
1
1
4
5
6
6
3
4
5
OTf
OTf
60 °C, 3 h
60 °C, 3 h
60 °C, 3 h
76c
OTHP
OH
OH
15a
80c
OTf
OTf
OTf
OTBDMS
OTBDPS
15a
–
NRd
a
All deprotection reactions were performed using 3 mol% CAN in buffered (pH = 8) MeCN.
Unless otherwise stated, yields are for pure, isolated products.
Yield of crude product (see text).
b
c
d
No reaction.
In summary, we have shown that the enol triflate function
(3) Maulide, N.; Vanherck, J.-C.; Markó, I. E. Eur. J. Org.
Chem. 2004, 3962; and references cited therein.
is compatible with our CAN-catalysed deprotection con-
ditions. Using this mild procedure, ketals, THP- and
TBDMS-ethers could be chemoselectively and efficiently
unmasked without affecting the acid-labile enol triflate
(
4) The successful Fe(III)-catalysed coupling of 2 with MeMgI
was initially observed when an impure sample of 1,
containing some ketone 2, was found to afford 3 and
recovered substrate 1.
1
1
functionality. To the best of our knowledge, this is the
first report on such chemoselective deprotections. Further
studies are aimed at expanding the scope of this unique
cerium-catalysed protocol and applying it to the synthesis
of relevant natural products.
(
5) (a) Markó, I. E.; Ates, A.; Gautier, A.; Leroy, B.; Plancher,
J.-M.; Quesnel, Y.; Vanherck, J.-C. Angew. Chem. Int. Ed.
1999, 38, 3207. (b) Ates, A.; Gautier, A.; Leroy, B.;
Plancher, J.-M.; Quesnel, Y.; Vanherck, J.-C.; Markó, I. E.
Tetrahedron 2003, 59, 8989. For similar uses of CAN, see:
(
c) Barone, G.; Bedini, E.; Iadonisi, A.; Manzo, E.; Parrilli,
M. Synlett 2002, 1645. (d) Manzo, E.; Barone, G.; Bedini,
E.; Iadonisi, A.; Mangoni, L.; Parrilli, M. Tetrahedron 2002,
Acknowledgment
58, 129.
Financial support of this work by the Université catholique de
Louvain, the Fonds pour la Recherche dans l’Industrie et l’Agricul-
ture (F.R.I.A., studentship to N.M.) and the Actions de Recherche
Concertées (convention 96/01-197) is gratefully acknowledged.
I.E.M. is grateful to Merck for receiving the Merck Academic
Development Program Award and to Merck Frosst for the Merck
Frosst Lectureship.
(6) For deprotection of other functions using CAN, see:
(a) DattaGupta, A.; Singh, R.; Singh, V. K. Synlett 1996, 69.
(b) Schreiber, S. L.; Kiesling, L. L. Tetrahedron Lett. 1989,
30, 433. (c) Matsumoto, T.; Katsuki, M.; Jona, H.; Suzuki,
K. J. Am. Chem. Soc. 1991, 113, 6982. (d) Cotelle, P.;
Catteau, J.-P. Tetrahedron Lett. 1992, 33, 3855. (e) Nair,
V.; Nair, L. G.; Balagopal, L.; Rajan, R. Indian J. Chem.,
Sect. B: Org. Chem. Incl. Med. Chem. 1999, 38, 1234.
(
f) Hwu, J. R.; Jain, M. L.; Tsai, F.-Y.; Tsay, S.-C.;
Balakumar, A.; Hakimelahi, G. H. J. Org. Chem. 2000, 65,
077. (g) Roy, S. C.; Banerjee, B. Synlett 2002, 1677.
h) Hwu, J. R.; Jain, M. L.; Tsai, F.-Y.; Balakumar, A.;
Hakimelahi, G. H.; Tsay, S.-C. ARKIVOC 2002, (ix), 29.
i) For the removal of ketals using CeCl , see: Marcantoni,
References
5
(
(
1) For beautiful illustrations of the skilful use of protecting
groups in synthesis, see: (a) Nicolaou, K. C.; Sorensen, E. J.
Classics in Total Synthesis; VCH: Weinheim, 1996.
(
3
(
b) Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis
E.; Nobili, F.; Bartoli, G.; Bosco, M.; Sambri, L. J. Org.
Chem. 1992, 62, 4183.
II; VCH: Weinheim, 2003.
(
2) (a) Kocienski, P. J. Protecting Groups; Georg Thieme: New
York, 1994. (b) Greene, T. W.; Wuts, P. G. M. Protecting
Groups in Organic Chemistry; Wiley: New York, 1991.
Synlett 2005, No. 14, 2195–2198 © Thieme Stuttgart · New York