Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1973–1976
Silyl group deprotection by Pd/C/H2. A facile and selective method
Seongjin Kim,a Sheila Marie Jacobo,a Chih-Tsung Chang,a Sophie Bellone,a
William S. Powellb and Joshua Rokacha,*
aClaude Pepper Institute and Department of Chemistry, Florida Institute of Technology, 150 W. University Blvd., Melbourne,
FL 32901, USA
bMeakins-Christie Laboratories, Department of Medicine, McGill University, 3626 St-Urbain St., Montreal, QC, Canada H2X 2P2
Received 1 December 2003; revised 19 December 2003; accepted 19 December 2003
Abstract—An easy, high yield, RT, short-reaction-time Pd/C hydrogenation of silyl groups is described. This includes TES, TPS,
TBS, TBDMS, TIPS, and TBDPS. The relative selectivity of the process has been investigated and we can show, for example, that
TES, TPS, TBS, and TBDMS removal can be performed in the presence of TIPS and TBDPS.
Ó 2004 Elsevier Ltd. All rights reserved.
A variety of methods are available for the deprotection
of silyl groups.1;2 Among the most widely used are fluo-
rides and acids. Recently, the use of catalysts, palladium
hydroxide,3 PdO,4 and Pd/C5;6 has been reported.
As can be seen, the reactivity of the groups toward
the hydrogenolysis is TES > TPS > TBS ꢀ TBDMS >
TIPS > TBDPS. Entries 1, 10, 11, 14, 15, and 21 show
that the TES group requires only 1–2 min reaction times.
At the other end of the spectrum, the deprotection of
TBDPS derivatives (entries 5 and 8) takes much longer.
Also, the deprotection yields are not as high as the other
silyl groups.
We are describing here a method, which complements the
known procedures and also provides some unique advan-
tages. This method, which is based on the use of Pd/C/H2,
deprotects silyl groups such as TES, TPS, TBS, and the
more resilient, TBDMS, TIPS, and TBDPS. In addition,
remarkable selectivity can be achieved by this procedure,
allowing for the removal of one group in the presence of
others, cleanly and in high to quantitative yield.
As a general rule, the time for the hydrogenolysis is
determined by the amount of catalyst used. TES, TPS,
and TBS are cleaved easily with small amounts of cat-
alyst in 1 or 2 min. On the other hand, TBDMS, TIPS,
and TBDPS are removed with 3–4 times the
amount of catalyst. With smaller quantities of catalyst,
however, TBDMS and TIPS can still be reduced cleanly
and in high yields, albeit in longer reaction times, for
example, entry 4, takes 20 min for complete hydrogen-
olysis under condition c (data not shown). The ease of
hydrogenolysis also depends on the structure of the
silylated molecule; for example, entries 6 and 12 are both
primary TBDMS derivatives. However, it takes longer
to deprotect the bicyclic prostaglandin synthon (entry
12) than the straight chain TBDMS compound (entry 6).
In this case, it is likely that the b-carbon steric effect is
also a factor in the binding of the TBDMS group to the
catalyst.
Perhaps the most attractive features of this procedure
are its simplicity, short reaction times, ease of operation
and the lack of aqueous work-up. The substrate is stir-
red in methanol, 5% Pd/C under H2 at atmospheric
pressure and room temperature for 1 min to a few hours,
depending on the silyl group to be removed. The reac-
tion mixture is filtered through celite and the solvent
evaporated.7 In many cases, a chromatography is not
necessary. Tables 1 and 2 show examples we have
selected. We were particularly interested in the removal
of resistant silyl groups such as TBDMS, TIPS, and
TBDPS (Table 1), and in the selectivity process (Table 2).
As can be seen from the tables, in selected cases we also
carried out the reaction without hydrogen (Method 2).
We wanted to make sure that hydrogenolysis was really
responsible for the cleavage of the silyl protecting group.
Keywords: Hydrogenolysis; TES; TPS; TBS; TBDMS; TIPS; TBDPS.
* Corresponding author. Tel.: +1-321674-7329; fax: +1-6747743; e-mail:
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.12.145