LETTER
Access to 1,2-Mercaptoalcohols
3065
This mild and selective procedure may be usefully applied
also to chiral molecules. When enantiopure epoxides are
reacted under the same conditions, optically active b-hy-
droxy thiols were regioselectively formed (Table 2). Be-
sides glycidol derivatives (Table 2, entries 2 and 3),
pyrrolidine-substituted b-hydroxy thiol 2n was of particu-
lar interest (Table 2, entry 4) as a useful reagent for the
synthesis of 1,3-oxathiolane-derivatives, which have been
recently demonstrated as important molecules in the
pharmacological field.19
References
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1973, 1449. (b) Mullis, J. C.; Weber, W. P. J. Org. Chem.
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(f) Yamashita, H. Bull. Chem. Soc. Jpn. 1988, 61, 1213.
(g) Iqbal, J.; Pandey, A.; Shukla, A.; Srivastava, R. R.;
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therein.
Table 2 Enantioselective Synthesis of 1,2-Mercaptoalcohols
(2) Inter alia: (a) Lalancette, J. M.; Frêche, A. Can. J. Chem.
1971, 49, 4047. (b) Vougioukas, A. E.; Kagan, H. B.
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Pineschi, M. Synlett 1992, 303. (e) Albanese, D.; Landini,
D.; Penso, M. Synthesis 1994, 34. (f) Chou, W.-C.; Chen,
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E. N. J. Org. Chem. 1998, 63, 5252. (i) Wu, J.; Hou, X.-L.;
Dai, L.-X.; Xia, L.-J.; Tang, M.-H. Tetrahedron: Asymmetry
1998, 9, 3431. (j) Yadav, J. S.; Reddy, B. V.; Baishya, G.
Chem. Lett. 2002, 906. (k) Friguelli, F.; Pizzo, F.; Tortoioli,
S.; Vaccaro, L. Tetrahedron Lett. 2003, 44, 6785.
(l) Movassagh, B.; Sobhani, S.; Kheirdoush, F.; Fadaei, Z.
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C.; Blagoev, M.; Linden, A. Phosphorus, Sulfur Silicon
Relat. Elem. 2005, 180, 1309.
1,2-Mercaptoalcohol Yield (%)a [a]D
20,b
Entry Epoxide
1
95c
–5820
HO
O
Ph
Ph
SH
R-(–)-1b
R-(–)-2b
2
84
–5
HO
O
O
Me
MeOCH2
SH
SH
S-(+)-1l
R-(–)-2l
3
65
–9
O
HO
O
Bn
BnOCH2
R-(+)-1m
S-(–)-2m
4
86d
+25
HO
O
SH
N
Cbz
N
Cbz
(3) (a) Luly, J. R.; Yi, N.; Soderquist, J.; Stein, H.; Cohen, J.;
Perun, T. J.; Plattner, J. J. J. Med. Chem. 1987, 30, 1609.
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1S,2S-(+)-1n
1S,2S-(+)-2n
a Refers to isolated products whose spectroscopic data are consistent
with the assigned structure.
b Optical rotation: c 1, THF.
c Yield of regioisomer isolated: 4.6%.
d Traces (3%) of silyl ether were evidenced.
(4) (a) Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, A.;
Mioskowski, C.; Samuelsson, B.; Hammarstrom, S. J. Am.
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In conclusion, we have devised a general and efficient
ring-opening of oxiranes by HMDST, which behaves as
an effective synthetic equivalent of H2S, leading directly
to b-mercaptoalcohols, interesting starting materials of
more complex molecules.
The reactions occur with high regio- and stereoselectivity
and are operationally simple with short reaction times.
The mildness of this procedure should be useful in the
synthesis of sensitive substrates, which preclude the use
of strong reaction conditions.
(8) Hashiyama, T.; Inoue, H.; Takeda, M.; Aoe, K.; Kotera, K.;
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Acknowledgment
Financial support by the National Project ‘Stereoselezione in
Sintesi Organica. Metodologie ed Applicazioni’ (MURST, Roma)
is gratefully acknowledged. Ente Cassa di Risparmio di Firenze is
acknowledged for granting a 400-MHz NMR spectrometer.
(11) Brittain, J.; Gareau, Y. Tetrahedron Lett. 1993, 34, 3363.
Synlett 2005, No. 20, 3063–3066 © Thieme Stuttgart · New York