TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7755–7757
A facile method for deprotection of trityl ethers using
column chromatography
Ashish K. Pathak, Vibha Pathak, Lainne E. Seitz, Kamal N. Tiwari, Mohammad S. Akhtar and
Robert C. Reynolds*
Division of Organic Chemistry, Southern Research Institute, PO Box 55305, Birmingham, AL 35255-5305, USA
Received 31 July 2001; accepted 28 August 2001
Abstract—A mild, efficient and inexpensive detritylation method is reported that uses trifluoroacetic acid on a silica gel column
to obtain pure, detritylated compounds in one-step. This method is applicable to acid stable as well as acid sensitive compounds
with only slight alterations in the procedure. Nineteen examples are given. © 2001 Elsevier Science Ltd. All rights reserved.
Triphenyl (Tr), monomethoxytriphenyl (MMTr) and
dimethoxytriphenyl (DMTr) methylethers continue to be
utilized as protecting groups for hydroxyl moieties in
saccharide and nucleoside chemistry even after 50 years.
Their utility is attributed to the high selectivity for
primary hydroxyl groups in polyols as well as the ease
and mildness in preparing and removing the trityl func-
tion.1–4 These functionalities are typically removed using
protic acids, Lewis acids or catalytic hydrogenation. The
use of sodium involving strong reducing conditions
destroy ester and benzyl ethers5 and hydrogenation6 of
tritylated nucleosides proceeds sluggishly, often giving
unsatisfactory results. In certain cases, the standard
deprotection conditions are not suitable due to acid
sensitivity of the starting material, resulting, for example,
in deglycosylation. Classically, acids such as formic acid,7
acetic acid and trifluoroacetic acid (TFA),8 and acid-cat-
alyzed reactions such as 1% methanolic solution of
iodine9 have been employed for deprotection, but in acid
sensitive compounds such as deoxynucleosides and pen-
toses, several methods have been reported using ZnBr2,10
reaction is limited only by available column sizes. Trityl
and monomethoxytrityl deoxynucleosides are depro-
tected in excellent yields (77% to quantitative) using
trifluoroacetic acid in chloroform:methanol solvent sys-
tems on a silica gel column using two different methods
(A and B) as shown in Table 1 (entries 1–15). Method
B typically gives better yields. This method uses less TFA
for deprotection, and is useful for the deprotection of
more acid sensitive molecules. For example, method B
was applied to the dimer nucleosides 3a16 and 4a16 and
gave excellent yields of detritylated products from the
column (Fig. 1). A further modification has been adapted
for extremely acid sensitive molecules (method C) such
as certain pentoses (arabinofuranoside23 and galacto-
furanoside24) (Fig. 1), resulting in further improvements
in yields. The starting materials in Table 1 and Fig. 1 were
either purchased commercially or were prepared by
reported methods. As an example of a comparative yield
see entry 15; an 88% yield of the deprotected product
(method B) was obtained as compared to a 55% yield22
using the conventional detritylation method (80% glacial
acetic acid solution in water under reflux). The pure,
detritylated products were compared to authentic sam-
ples using TLC and mass spectrometry (FAB-MS).
AlClEt2,11 Yb(OTf)3,12 BCl3 and Ce(NH4)2(NO3)6 as
Lewis acids.
13
14
Generally, even when a substrate deprotects efficiently,
the product must be purified via crystallization or column
chromatography. Herein, we report an efficient detrityla-
tion method that combines deprotection under acidic
conditions with chromatography to supply a pure
product in high yield in one simple process. For sub-
strates that are acid labile, this technique can easily be
adapted to further improve yields. The scale of the
Three variations have been adapted for this process, and
typical procedures are as follows: Method A: The sample
(50 mg) was dissolved in CHCl3 (5 mL) containing 5%
TFA, and was promptly loaded onto a prepared silica gel
column [silica gel (5.0 g) in CHCl3 or hexane]. The
detritylated product was eluted with the appropriate
solvent system. Method B: The sample (50 mg) was
dissolved in 5 mL of CHCl3 and loaded onto a column
of silica gel (5.0 g) first prepared in CHCl3 or hexane to
* Corresponding author. Tel.: +1-205-581-2454; fax: +1-205-581-2877;
e-mail: reynolds@sri.org
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01645-8