744
Spotlight 85
This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and
preparation of the reagent in
current research
Chemistry of Tetrathiomolybdate and
Tetraselenotungstate: Applications in
Carbohydrate and Peptide Chemistry
Compiled by Perali Ramu Sridhar
Perali Ramu Sridhar was born in Andhra Pradesh, India in 1977. He
received his M.Sc from Sri Venkateswara University, Tirupathi,
Andhra Pradesh, India, in 1999. Then he joined in the Department
of Organic Chemistry, Indian Institute of Science, Bangalore, India
for graduate studies in 1999. Currently he is completing his Ph.D
thesis on the utility of tetrathiomolybdate and tetraselenotungstate
in carbohydrate chemistry under the supervision of Prof. S.
Chandrasekaran. His research interest includes synthesis of carbohydrate based therapeutics, sugar amino acids, combinatorial
peptide and nucleotide synthesis and glycobiology.
Department of Organic Chemistry, Indian Institute of Science,
Bangalore – 560012, India
Introduction
The reagents, benzyltriethylammonium tetrathiomolybdate, [BnNEt3]2MoS4 11 and tetraethylammonium tetraselenotungstate [Et4N]2WSe4 2 have been shown to be
useful for sulfur and selenium transfer reactions respectively in organic synthesis. Preparation of disulfides from
alkyl halides,2 ring opening of epoxides,3 tandem sulfur
transfer-reduction-Michael addition4 in one step, reduction of aryl azides to amines5 and alkyl azides to imines5
have been reported from our laboratory using the reagent
tetrathiomolybdate 1. Tetrathiomolybdate 1 is also used
for the selective deprotection of propargyloxycarbonyl
(Poc) protective group for amines6 in peptides and for
alcohols7 in carbohydrate chemistry. Recently, regioselective reduction of anomeric azides8 to amines using
the reagent 1 has been reported. Reagent 1 has also been
used, as a sulfur transfer reagent, for the synthesis of phosphorothioate oligonucleotides.9 Large quantities of 1 can
be prepared from ammonium tetrathiomolybdate and benzyltriethylammonium chloride.2a
On the other hand tetraselenotungstate 2 has been used for
the formation of diselenides10 form alkyl halides and in
the synthesis of diselenides of several amino acid
deirvatives11 from the corresponding halides or activated
alcohols. The reagent 2 can be prepared from K2Se3 and
W(CO)6 in DMF.10,12
Abstracts
(A) The first report on the application of tetrathiomolybdate,
MoS42,- 1 in carbohydrate chemistry appeared in 1997 towards the
synthesis of sugar disulfides. More recently use of tetraselenotungstate, WSe42,- 2 towards the synthesis of sugar diselenides has been
published. The reagents 1 or 2 work very well for the synthesis of
disulfides and diselenides respectively from the corresponding
sugar halides.
OAc
OAc
MoS42–, 1, CH3CN
O
AcO
AcO
r.t., 6 h, 95%
AcO
O
AcO
AcO
AcO
Br
OAc
WSe42–, 2, CH3CN
r.t., 6 h, 91%
AcO
AcO
AcO
Br
(B) The formation of disulfides and diselenides has been applied in
the efficient synthesis of cystine, selenocystine, and their higher
homologues like homo and bis-homo amino acid derivatives from
natural amino acids. The generality of the reaction has been studied
by capping various groups to amino and carboxyl components of
canonical amino acids.11
SYNLETT 2004, No. 4, pp 0744–074509.03204
Advanced online publication: 10.02.2004
DOI: 10.1055/s-2004-817757; Art ID: V08603ST
© Georg Thieme Verlag Stuttgart · New York
MoS42–, 1 /CH3CN (or)
WSe42–, 2 /CH3CN, r.t.
X
n
R1HN
2
OAc
O
AcO
AcO
S
CO2
X = -OTs, -Br
R2
76–95%
O
AcO
Y
n
R1HN
Se
2
Y
n
1
CO2R2 R HN
Y = S, Se
n = 1, 2
CO2R2
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SYNLETT
SPOTLIGHT
SPOTLIGHT
745
O
O
(D) Polymer supported tetrathiomolybdate has been used for the
deprotection of propargyloxycarbonyl in the synthesis of small
peptides and it has also been shown that the protective group is stable under peptide coupling reaction conditions using acid chlorides.6b
N
H
O
O
COOMe
H
Me
N
Me
O
O
RO
PocO
H 2N
84%
MeHN
O
A, Aq. Na2CO3,
O
Me
A
H
COOMe
Me
Me
N
N
Me
Ph
COOMe
H
O
MoS42–, 1, CH3CN
OMe
COOMe
H
)))))), 20 KHz, 1 h
COCl CH Cl , 0 °C,
2 2
15 min
O
SCH3
Resin bound MoS42–
MeOH, r.t.,
Me
N
Me
O
Ph
COOMe
H
O
(E) Tetrathiomolybdate 1 selectively deprotects propargyloxycarbonyl (Poc) protective group in the case of alcohols in carbohydrate chemistry under neutral conditions at room temperature.7
MoS42–, 1, CH3CN
r.t., )))), 1 h
SCH3
O
O
RO
Me
O
r.t., 1.5 h, >90 %
HO
OMe
R = Ac, Cbz, Alloc, Levulinoyl
Poc = Propargyloxycarbonyl
(F) Tetrathiomolybdate 1 reduces the aryl azides to the corresponding amines and alkyl azides to the corresponding imines.
Moreover it selectively reduces the anomeric azides to the corresponding anomeric amines with excellent regioselecitvity.8
AcO
MoS42–, 1,
CH3CN:EtOH (1:1),
O
AcO
AcO
N3
OAc
R = Ac,Bz, Bn, Allyl
N3
AcO
AcO
N3
r.t., 3 h, 90%
r.t., 3 h, 90%
O
AcO
AcO
OAc
MoS42–, 1,
CH3CN:EtOH (1:1),
O
OAc
(G) Tetrathiomolybdate 1 react with 1, 6 diactivated carbons in
hexoses to give the corresponding epithio derivatives (1,6-anhydro
derivatives) as the only products in excellent yield.13
OAc
N3
O
AcO
AcO
OAc
OTs
AcO
AcO
NH2
NH2
S
O
MoS42–, 1, CHCl3,
AcO
Br
r.t., 24 h, 88%
OAc
O
OAc
OAc
References
(1) Prabhu, K. R.; Devan, N.; Chandrasekaran, S. Synlett 2002,
1762.
(2) (a) Remesha, A. R.; Chandrasekaran, S. Synth. Commun.
1992, 22, 3277. (b) Ramesha, A. R.; Chandrasekaran, S. J.
Org. Chem. 1994, 59, 1354. (c) Bhar, D.; Chandrasekaran,
S. Carbohydr. Res. 1997, 301, 221.
(3) Devan, N.; Ramu Shridhar, P.; Prabhu, K. R.;
Chandrasekaran, S. J. Org. Chem. 2002, 67, 9417.
(4) Prabhu, K. R.; Sivanand, P. S.; Chandrasekaran, S. Angew.
Chem. Int. Ed. 2000, 31, 4316.
(5) Ramesha, A. R.; Bhat, S.; Chandrasekaran, S. J. Org. Chem.
1995, 60, 7683.
(6) (a) Sinha, S.; Ilankumaran, S.; Chandrasekaran, S.
Tetrahedron Lett. 1999, 40, 771. (b) Bhat, R. G.; Sinha, S.;
Chandrasekaran, S. Chem. Commun. 2002, 8, 812.
(7) Ramu Sridhar, P.; Chandrasekaran, S. Org. Lett. 2002, 4,
4731.
(8) Ramu Sridhar, P.; Prabhu, K. R.; Chandrasekaran, S. J. Org.
Chem. 2003, 68, 5261.
(9) Rao, M. V.; Macfarlane, K. Tetrahedron Lett. 1994, 35,
6741.
(10) Saravanan, V.; Emmanuel, P.; Chandrasekaran, S.
Tetrahedron Lett. 2003, 44, 2257.
(11) Bhat, R. G.; Emmanuel, P.; Saravanan, V.; Chandrasekaran,
S. Tetrahedron Lett. 2003, 44, 5251.
(12) O’ Neal, S.; Kolis, J. W. J. Am. Chem. Soc. 1988, 110, 1971.
(13) Driguez, H.; McAuliffe, C.; Stick, R. V.; Tilbrook, D.;
Matthew, G.; Wiliams, S. J. Aust. J. Chem. 1996, 49, 343.
Synlett 2004, No. 4, 744–745
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(C) Tetrathiomolybdate 1 deprotects propargyloxy carbonyl (Poc)
group, a protective group for amines, which has been developed in
our laboratory. The preliminary results on the highly selective deblocking of Poc group from sulfur containing amino acids and peptides using tetrathiomolybdate 1 has been reported recently.6a