Reduction of trihalomethyl carbinols and their acetates, mesylates and tosylates by indium metal

Article abstract of DOI:10.1016/S0040-4039(02)01262-5

A study of reduction of trihalomethyl carbinols and their derivatives by indium metal shows that while trichloromethyl carbinols produce a mixture of the corresponding dichloromethyl carbinol and vinylidene dichloride, the acetates, mesylates and tosylate

Full text of DOI:10.1016/S0040-4039(02)01262-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5993–5995
Reduction of trihalomethyl carbinols and their acetates,
mesylates and tosylates by indium metal
Brindaban C. Ranu,* Sampak Samanta and Arijit Das
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India
Received 17 April 2002; revised 12 June 2002; accepted 27 June 2002
Abstract—A study of reduction of trihalomethyl carbinols and their derivatives by indium metal shows that while trichloromethyl
carbinols produce a mixture of the corresponding dichloromethyl carbinol and vinylidene dichloride, the acetates, mesylates and
tosylates of the trichloro- and tribromomethyl carbinols undergo clean reduction to provide the respective vinylidene dichloride
only. © 2002 Elsevier Science Ltd. All rights reserved.
In recent times, indium metal has been the subject of
growing interest because of its unique properties and
great synthetic potential.1 Because of the close resem-
blance of indium to magnesium and zinc in several
respects including the first ionization potential (5.8 eV),
we envisioned indium to be a potential reducing agent
and initiated a systematic investigation into reduction
by indium metal.2 Interestingly, although considerable
activities have been observed in indium-mediated car-
bonyl addition reactions during the last decade, its
capability as a reducing agent has only been explored
quite recently.2,3 As part of our continuing program we
have already reported the selective reduction of termi-
nal alkynes,2a highly activated conjugated alkenes,2b
a-halocarbonyl compounds,2c vic-dibromides,2d and
gem-vinyl dibromides2e and we now disclose our results
on the reduction of gem-trihalides in trihalomethyl
carbinols and their derivatives.
rial. So, we considered the possibility of a more facile
reaction by derivatization of the hydroxy functionality.
Thus, the corresponding acetates, mesylates and tosy-
lates of trichloromethyl carbinols when treated with
indium in DMF resulted in the corresponding vinyli-
dene dichlorides being obtained as single products in
high yields (Scheme 2).
In a typical experimental procedure,4 an acetate, mesy-
late or tosylate of the trihalomethyl carbinol (1 mmol)
was heated under reflux in DMF with indium metal (1
mmol, cut into small pieces) for the period of time
required to complete the reaction (TLC). The usual
workup and purification by column chromatography
furnished the pure product. The results are reported in
Table 1.
The reduction of trichloromethyl carbinols by indium
metal is not very clean. Upon reflux with indium in
aqueous ethanolic ammonium chloride a mixture of the
corresponding dichloromethyl carbinols and vinylidene
dichlorides are obtained in rather low yield (30–40%)
(Scheme 1). Even after prolonged periods (16–20 h) of
reflux the conversion was never complete, with unre-
acted starting material remaining. The use of other
solvents such as DMF or AcOH made the situation
worse producing considerable amounts of tarry mate-
Scheme 1.
Scheme 2.
Keywords: indium metal; reduction; trihalomethyl carbinols and
derivatives; vinylidene dichloride.
* Corresponding author. Fax: +91-33-4732805; e-mail: ocbcr@
mahendra.iacs.res.in
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01262-5

5994
B. C. Ranu et al. / Tetrahedron Letters 43 (2002) 5993–5995
Table 1. Reduction of trihalomethyl carbinol derivatives by indium metal
A wide range of structurally varied acetates, mesylates
and tosylates of trichloro- and tribromomethyl
carbinols underwent reductions by this procedure to
provide the corresponding vinylidene dihalides. It was
observed that reductions of mesylates and tosylates
were more facile and relatively clean compared to those
of acetates. Presumably, this was due to -OMs and
-OTs being better leaving groups. The reduction of a

B. C. Ranu et al. / Tetrahedron Letters 43 (2002) 5993–5995
5995
non-aromatic derivatives was rather complex giving a
comparatively low yield of vinylidene dichloride along
with some unidentified side products (entry 6). This is
not unusual for non-aromatic substrates and we
obtained similar results in our earlier observations dur-
ing the reduction of vic- and gem-dibromides.2d,2e It
may be assumed that these reductions occur through a
SET process and thus the intermediate radical species
are more stabilized in the aryl-substituted derivatives.
When 2 equiv. of indium were used, the tribro-
momethyl sulphonates underwent two consecutive
reductions to produce the corresponding vinyl bromides
as final products (entries 20–22). This is to be expected
as we have observed earlier that indium reduces vinyli-
dene dibromides to vinyl bromides.2e However, the
trichloromethyl derivatives did not undergo any further
reduction beyond vinylidene dichlorides even with 3
equiv. of indium and longer periods of reflux. These
reductions are very selective not reducing Cl (entries 9,
10, 21) or Br (entry 19) functionalities attached to the
aromatic rings. Moreover, double bonds (CꢀC) (entries
2, 4) also remained unaffected during these reductions.
11149; (e) Chauhan, K. K.; Frost, C. G. J. Chem. Soc.,
Perkin Trans. 1 2000, 3015; (f) Ranu, B. C. Eur. J. Org.
Chem. 2000, 2343.
2. (a) Ranu, B. C.; Dutta, J.; Guchhait, S. K. J. Org. Chem.
2001, 66, 5624; (b) Ranu, B. C.; Dutta, J.; Guchhait, S. K.
Org. Lett. 2001, 3, 2603; (c) Ranu, B. C.; Dutta, P.;
Sarkar, A. J. Chem. Soc., Perkin Trans. 1 1999, 1139; (d)
Ranu, B. C.; Guchhait, S. K.; Sarkar, A. Chem. Commun.
1998, 2113; (e) Ranu, B. C.; Samanta, S.; Guchhait, S. K.
J. Org. Chem. 2001, 66, 4102.
3. (a) Moody, C. J.; Pitts, M. R. Synlett 1998, 1028; (b)
Moody, C. J.; Pitts, M. R. Synlett 1998, 1029; (c) Reddy,
G. V.; Rao, G. V.; Iyenger, D. S. Tetrahedron Lett. 1999,
40, 3937; (d) Chae, H.; Cho, S.; Keum, G.; Kang, S. B.;
Pae, A. N.; Kim, Y. Tetrahedron Lett. 2000, 41, 3899; (e)
Pitts, M. R.; Harrison, J. R.; Moody, C. J. J. Chem. Soc.,
Perkin Trans. 1 2001, 955 and References cited therein.
4. General experimental procedure for the reduction of
acetates, mesylates and tosylates of trichloro- and tribro-
momethyl carbinols. Representative procedure for the reduc-
tion
of
2-phenyl-2-tosyloxy-1,1,1,-trichloroethane
to
1,1-dichloro-2-phenylethene. A solution of 2-phenyl-2-tosy-
loxy-1,1,1-trichloroethane (380 mg, 1 mmol) in DMF (2
mL) was heated under reflux at 150–160°C with indium
metal (115 mg, 1 mmol, cut into small pieces) under
nitrogen for 3 h (TLC). The reaction mixture was then
quenched with a saturated solution of ammonium chloride
and extracted with ether (3×10 mL). The ether extract was
washed with brine, dried (Na2SO4) and evaporated to
leave the crude product which was purified by column
chromatography over silica gel [eluted with hexane–ether
(9:1) solvent system] to furnish 1,1-dichloro-2-
phenylethene as a colourless oil (163 mg, 94%). The IR, 1H
and 13C NMR spectral data of this compound were found
to be identical with those reported.7 This procedure has
been followed for the reduction of all the other trihalides
listed in Table 1. All the products have been characterized
by IR, 1H and 13C NMR spectroscopy and elemental
analyses.
In conclusion, the present procedure using indium
metal provides a highly selective reduction of acetates,
mesylates and tosylates of aryl-substituted tri-
halomethyl carbinols to the corresponding vinylidene
dihalides which are useful intermediates in organic syn-
thesis.5 The high yield, considerably fast reaction and
compatibility with other reducible functional groups
make this procedure a practical alternative to existing
ones.6,7 Furthermore, this procedure also broadens the
scope of reductions by indium metal.
Acknowledgements
We are pleased to acknowledge the financial support
from CSIR, New Delhi, India [Grant No. 01(1739)/02]
for this investigation. S.S. and A.D. are also thankful
to CSIR for their fellowships.
5. (a) Ramirej, F.; Desai, N. B.; McKelvie, N. J. Am. Chem.
Soc. 1962, 84, 1745; (b) Corey, E. J.; Fuchs, P. L. Tetra-
hedron Lett. 1972, 13, 3769.
6. (a) Takai, K.; Kokumai, R.; Nobunaka, T. Chem. Com-
mun. 2001, 1128; (b) Wang, Z.; Campagna, S.; Xu, G.;
Pierce, J. M. F.; Confalone, P. N. Tetrahedron Lett. 2000,
41, 4007 and References cited therein; (c) Hosomi, A.;
Inaba, M.; Sakurai, H. Tetrahedron Lett. 1983, 24, 4727.
7. Aggarwal, V. K.; Merell, A. J. Org. Chem. 2000, 65, 7211.
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