TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7699–7701
Cleavage of the THP protecting group under Pd/C-catalyzed
hydrogenation conditions
Leena H. Kaisalo* and Tapio A. Hase
Department of Chemistry, Laboratory of Organic Chemistry, University of Helsinki, PO Box 55, FIN-00014 Helsinki, Finland
Received 30 May 2001; revised 17 August 2001; accepted 30 August 2001
Abstract—Alcohol and phenol THP or ethoxyethyl ether protecting groups may be cleaved in high yield under Pd/C-catalyzed
hydrogenation conditions in EtOH, owing to the inadvertent presence of small quantities of HCl in the reaction mixture. MOM
ethers are not cleaved under these conditions. © 2001 Elsevier Science Ltd. All rights reserved.
1
Prompted by recent reports by Hattori and co-workers
of TBDMS ether cleavages under hydrogenolytic condi-
tions, we wish to report that analogous protecting
group cleavage occurs in THP and ethoxyethyl ethers.
In contrast to the Japanese workers, we do not visualise
any of these reactions as truly hydrogenolytic but
ascribe them to the presence of small quantities of HCl
It is obvious that a prime candidate responsible for
these unexpected acetal cleavages is an acidic impurity
in the reaction mixture, capable of catalysing a trans-
acetalization reaction between the THP ether and the
ethanol solvent. However, rinsing the catalyst with aq.
NaHCO before hydrogenation did not prevent depro-
3
tection of 4 (entry 6), while addition of a small amount
of pyridine to the reaction mixture (entry 7) did. No
in the reaction mixture, generated from residual PdCl2
in the commercial Pd/C catalyst. A hydroxylic solvent,
normally ethanol, appears to be essential in all these
cleavages.
reaction was detected in the absence of H (entry 4).
2
Interestingly, when 2-(dec-9-en-1-yloxy)tetrahydro-
pyran 4 was treated with Pd/C in the absence of H the
2
terminal double bond migrated to give a mixture of
decenol THP ether isomers (entry 8). As expected, the
Pd/C-catalyzed hydrogenation of the benzylic THP–
ether 6 gave the hydrogenolysis product p-cymene 6a
During recent studies concerning the synthesis and
reactions of certain macrolides, reduction of the THP-
2
protected macrolide 1 under standard conditions unex-
pectedly gave the g-hydroxylactone 1a as the sole
(
entry 10).
3
product instead of the THP ether of 1a (Scheme 1). In
4
the literature there are a few reports of complete or
In a comparison of various commercial Pd/C catalysts
Table 2), complete cleavage of the THP group took
5
partial deprotections of THP groups under hydrogena-
(
tion conditions but no comments were offered to
explain such phenomena. A study of a variety of alco-
hol or phenol THP ethers established that this is a
general deprotection method for THP ethers (Table 1).
7
place in 24 h only when Pd/C (Aldrich) was used in an
equal amount to the substrate (entry 3). Pd/C catalysts
from other suppliers (entries 4–6) were less effective in
promoting the THP cleavage. As expected, the THP
8
moiety ends up as EtOTHP, confirming an acid-cata-
lyzed acetal exchange with the solvent ethanol. In keep-
ing with this, the reaction fails completely in
cyclohexane solution (entry 7).
Pd/C
H2
O
O
O
O
EtOH
Pd/C catalysts are usually prepared by the reduction of
THPO
HO
9
PdCl in the presence of activated charcoal. If some
2
1
1a
residual PdCl remains in the catalyst it will liberate
2
HCl first during the hydrogenation (cf. Table 1, entries
Scheme 1.
10
6
and 8). Electron spectroscopic analysis ESCA of
Pd/C (10%, Fluka) showed that the palladium on the
surface layer of the catalyst was ca. 1:1 Pd(0):Pd(2 ) but
+
*
0
Corresponding author.
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01630-6
Kaisalo, Leena
