TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7153–7154
Indium-mediated chemoselective deprotection of
trichloroethoxycarbonyl and trichloroacetyl groups
Muralikrishna Valluri,a Tomoko Mineno,a Rama M. Hindupura and Mitchell A. Averya,b,c,
*
aDepartment of Medicinal Chemistry, School of Pharmacy, University of Mississippi, PO Box 1848, University,
MS 38677-1848, USA
bDepartment of Chemistry, University of Mississippi, PO Box 1848, University, MS 38677-1848, USA
cNational Center for National Products Research, University of Mississippi, PO Box 1848, University, MS 38677-1848, USA
Received 21 June 2001; accepted 3 August 2001
Abstract—A new, mild, and chemoselective method for the deprotection of trichloroethoxylcarbonyl and trichloroacetyl groups
is described. © 2001 Elsevier Science Ltd. All rights reserved.
Protecting groups play an important role in chemical
synthesis, particularly for the total synthesis of natural
products. Various protecting groups and deprotection
methods have been developed to achieve chemoselective
transformations.1 2,2,2-Trichloroethoxycarbonyl (Troc)
and trichloroacetyl groups have been widely used as
protecting groups in organic synthesis.2–8 Though they
are very useful protecting groups, only a few deprotec-
tion methods are available for their removal. The Troc
group can be removed by zinc reduction,2–4 electroly-
sis,5 or alkenolysis.6 In contrast, the trichloroacetyl
group can be removed by ammonia7 and alkali bases.8
Since these conditions are not mild enough to accom-
modate several other functionalities, the development
of a new mild method seemed worthwhile.
derivatives by refluxing the protected alcohols in the
presence of indium powder and aq. NH4Cl in
methanol.
To determine the general applicability of this methodol-
ogy, various substrates having diverse functionality and
protecting groups were prepared and subjected to
deprotection. The reaction conditions were very mild
and gave the corresponding alcohols in excellent yields
(Table 1). Under these reaction conditions, chiral sub-
strates did not undergo any racemization (entries 1, 4,
5, and 9). Deprotection of silyl-protected 1,2- and 1,3-
diols (entries 3 and 4) led to the formation of the
desired silyloxy alcohols, and migration of silyl group
was not observed. It was possible to carry out the
deprotection without affecting olefins (entries 1 and 3),
alkyne (entry 6), alkoxy group (entry 7), or halogen
(entry 8). This method is highly chemoselective in that
many protecting groups, such as benzoyl, t-butyl-
dimethylsilyl, t-butyldiphenylsilyl, ethyl ester, and
amide are stable to these reaction conditions. This
method is also very effective in the unmasking of
protected sterically hindered alcohol (entry 10).
There has been growing interest in the use of metallic
elements in synthetic chemistry.9 Recent research using
metallic indium10,11 stimulated us to investigate its use
in the deprotection of these chlorinated protecting
groups.
indium, aq. NH4Cl
R OP
R OH
MeOH
In a typical experimental procedure, the Troc or
trichloroacetyl protected alcohol (1 mmol) was com-
bined with indium powder12 (2 mmol), aqueous NH4Cl
(5N, 1 mL), and methanol (5 mL). The mixture was
refluxed and monitored for completion by TLC. The
solvent was removed by rotary evaporation under vac-
uum, and the residue was extracted with ethyl acetate
(3×25 mL), washed with brine (50 mL), and dried over
Na2SO4. The mixture was filtered, and the solvent was
P = Cl3CH2OCO- or Cl3CCO-
Herein, we describe a mild, chemoselective, and general
method for the release of alcohols from the correspond-
ing trichloroethoxycarbonate and trichloroacetate
* Corresponding author. Tel.: 1-662-915-5880; fax: 1-662-915-5638;
e-mail: mavery@olemiss.edu
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01489-7
Valluri, Muralikrishna
