yielded 79% of the monotosylate along with 15% of the
ditosylate. The reaction was slightly exothermic and complete
within 5 min. When the reaction was achieved at 0 °C, the
monotosylate was obtained in 92% accompanied with only
5% of the ditosylate15 (Table 2). Note that in both 3 and 13
the hydoxy groups are separated by five atom units; however,
better selectivity was achieved in the case of 13 (vide infra).
Other commercially available OEGs (12, 14-17) were
subjected to the described conditions and gave good to
excellent yields of the monotosylate ester except for 12,
which afforded moderate selectivity. Remarkably, treatment
of the synthetic glycol derivatives 18, where the two hydroxy
groups are separated by 20 atom units, gave a good yield of
the corresponding monotosylate (Table 2). Moderate selec-
tivity, however, was obtained in the case of 19 and 20.
Scheme 1
within 40 min the monosulfonate ester in 91% yield, while
the ditosylate byproduct was isolated in only 6% yield (Table
1, entry 2).
Table 1. Monotosylation of Symmetrical Diols
We next took advantage of this reaction to prepare in one
step polysubstituted cyclic ethers from the corresponding
diols. For example, when diol 67 was treated with TsCl (1.2
equiv) and an excess of Ag2O (3 equiv) for 15 h (Table 3,
conditions A), disubstituted tetrahydrofuran 23 was obtained
in 75% yield. Treatment of diol 2116 under similar conditions
(6) (a) General Procedure for the Monotosylation of Symmetrical
Diols. To a stirred solution of diol (1 mmol) in CH2Cl2 or toluene (10 mL)
were added fresh Ag2O (350 mg, 1.5 mmol), TsCl (210 mg, 1.1 mmol),
and KI (33 mg, 0.2 mmol). The reaction mixture was stirred at room
temperature for alkanediols and at 0 °C for OEGs for 5 min to 8 h and then
filtered through a small pad of silica gel and washed with EtOAc.
Evaporation of the solvent, followed by column chromatography, gave the
desired monotosylate product. (b) The use of fresh Ag2O is recommended
because on standing for a few months on bench, Ag2O became less active
due to its oxidation to AgO and its decomposition to metallic silver: L’vov,
B. V. Thermochim. Acta 1999, 333, 13-19. (c) Ag2O can be easily prepared
by reacting AgNO3 with NaOH, Tanabe, M.; Peters, R. H. Organic
Syntheses; Wiley: New York, 1990; Collect. Vol. VII, pp 386-392.
(7) (a) Nemto, H.; Takamatsu, S.; Yamamoto, Y. J. Org. Chem. 1991,
56, 1321-1322. (b) Kalinovski, H. O.; Crass, G.; Seebach, D. Chem. Ber.
1981, 114, 477. We found that diol 6 can be prepared readily in good yield
from dimethyl L-tartrate without isolating the intermediate. Reaction of
dimethyl L-tartrate with Ag2O in the presence of BnBr at reflux of CH2Cl2;
after filtration and evaporation of the solvent, the crude was treated with
LiAlH4 in THF to afford 6 in 88% overall yield after purification.
(8) (a) Burgess, K.; Henderson, I. Tetrahedron Lett. 1991, 32, 5701-
5704. (b) Burgess, K.; Chaplin, D. A.; Henderson, I. J. Org. Chem. 1992,
57, 1103-1109.
(9) 8 was prepared in three steps from commercially available 3,4-O-
isopropylidene-D-mannitol: (i) Bu2SnO, CsF, p-methoxybenzyl chloride
(PMBCl), (ii) BnBr, NaH, DMF, (iii) SnCl2, EtSH, CH2Cl2.
(10) Zuccarello, G.; Bouzide, A.; Kvarnstro¨m, I.; Niklasson, G.; Svens-
son, S. C. T.; Brisander, M.; Danielsson, H.; Nillroth, U.; Karle´n, A.;
Hallberg, A.; Classon, B.; Samuelsson, B. J. Org. Chem. 1998, 63, 4898-
4906.
(11) 11 was prepared readily from commercially available 3,4-O-
isopropylidene-D-mannitol: (i) Bu2SnO, Toluene, (ii) 4F-BnBr, CsF, DMF.
(12) (a) Dietrich, B.; Viout, P.; Lehn, J.-M. Macrocyclic Chemistry;
VCH: Weinheim, 1993. (b) Pederson, C. J. J. Am. Chem. Soc. 1967, 89,
7017-7036. (c) Izzat, R. M.; Pawlak, K.; Bradshaw, J. S. Chem. ReV. 1995,
95, 2529-2586 and references therein.
(13) (a) Roberts, C.; Chen, C. S.; Mrksich, M.; Martinochonok, V.;
Ingeber, D. E.; Whitesides, G. M. J. Am. Chem. Soc. 1998, 120, 6548-
6555. (b) Wittman, V.; Takayama, S.; Gong, K. W.; Weitz-Schmidt, G.;
Wong, C.-H. J. Org. Chem. 1998, 63, 5137-5143. (c) Valiokas, R.;
Svedhem, S.; Svensson, S. C. T.; Lieberg, B. Langmuir 1999, 15, 3390-
3394.
(14) (a) Gravert, D. J.; Janda, K. D. Chem. ReV. 1997, 97, 489-509. (b)
Houseman, B.; Mrksich, M. J. Org. Chem. 1998, 63, 7552-7555. (c)
Bettinger, T.; Remy, J.-S.; Erbacher, P.; Behr, J.-P. Bioconjugate Chem.
1998, 9, 842-846.
(15) Only 54% of the monotosylate was obtained when stoichiometric
amount of TsCl and pyridine were employed; see: MacMahon, S.; Fong,
R., II; Baran, P. S.; Safonov, I.; Wilson, S. R.; Schuster, D. I. J. Org. Chem.
2001, 66, 5449-5455. Bertozzi, C. R.; Bednarski, M. D. J. Org. Chem.
1991, 56, 4326-4329.
a Isolated yield.
As illustrated in Table 1, other primary as well as
secondary symmetrical diols underwent selective monoto-
sylation in high yields.6
Monosulfonation of OEGs, which is often the first step in
the preparation of crown ether type derivatives,12 hydrophilic
tethers for linkage of bio-molecules,13 and spacers in solid-
phase synthesis,14 was undertaken. Thus, treatment of di-
(ethylene glycol) 13 under the conditions described above
2330
Org. Lett., Vol. 4, No. 14, 2002