J. Karban, J. Kroutil, M. Budeˇsˇínský, J. Sýkora, I. Císarˇová
FULL PAPER
means of comparison with authentic samples: 70% of 3a, 15% of
the unreacted 1, 4% of the unsaturated tosylamino derivative 5 (see
below) and 10% of an unidentified compound, probably chloride
4a; the percentages in Table 1 are recalculated as yields from 1.
NMR analysis of the mixture confirmed this composition.
Reaction of 1 with Benzyl Alcohol: Sodium benzyl alcoholate
(1.22 in benzyl alcohol, 0.7 mL, 0.85 mmol) was added to a mix-
ture of the epimine 1 (100 mg, 0.355 mmol) and benzyl alcohol
(2 mL), and the resulting solution was stirred for 7 h at 105 °C. The
reaction mixture was diluted with water and neutralized with aq.
Crystallization from anhydrous EtOH afforded 3a (63 mg, 47%) in HCl (5%). The common workup afforded 1,6-anhydro-3-O-benzyl-
1
approximately 90% purity according to H NMR and GC/MS.
2,4-dideoxy-2-(tosylamino)-β--xylo-hexopyranose (3g, 100 mg,
72%); m.p. 174–176 °C (methanol/water), [α]2D5 = –103 (c = 0.21,
CHCl3). C20H23NO5S (389.47): calcd. C 61.68, H 5.95, N 3.60, S
8.23; found C 61.45, H 5.93, N 3.55, S 8.53.
X = Br: A mixture of the epimine 1 (100 mg, 0.355 mmol), Bu4NBr
(226 mg, 0.70 mmol) and NH4Br (171 mg, 1.75 mmol) was refluxed
in dry toluene (10 mL) for 4 h. The reaction mixture was worked
up as described above for X = Cl. Chromatography (13 g) in hep-
tane/ethyl acetate (12:5) gave: 1) 70 mg (54%) of an inseparable
mixture of 1,6-anhydro-3-bromo-2,3,4-trideoxy-2-(tosylamino)-β-
-ribo-hexopyranose (4b) and 1,6-anhydro-3-bromo-2,3,4-trideoxy-
2-(tosylamino)-β--xylo-hexopyranose (3b) in a 72:28 ratio (deter-
Reaction of 1 with Potassium tert-Butoxide: A solution of the epim-
ine 1 (100 mg, 0.355 mmol) in THF (5 mL) was added to a suspen-
sion of potassium tert-butoxide (400 mg, 3.56 mmol) in THF
(5 mL), and the resulting mixture was stirred for 18 h at r.t. The
reaction mixture was worked up as described above for 3g.
Chromatography (10 g) in S1 gave 1,6-anhydro-2,3,4-trideoxy-2-
(tosylamino)-β--erythro-hex-2-enopyranose (5, 52 mg, 52%); m.p.
180–184 °C (acetone/heptane), [α]2D5 = –131 (c = 0.20, CHCl3).
C13H15NO4S (281.33): calcd. C 55.50, H 5.37, N 4.98, S 11.40;
found C 55.46, H 5.37, N 4.89, S 11.02.
1
mined by H NMR); the percentages in Table 1 were recalculated
as yields from 1, 2) 18 mg (18%) of 1,6-anhydro-2,3,4-trideoxy-2-
(tosylamino)-β--erythro-hex-2-enopyranose (5), and 3) 13 mg of
an unresolved mixture of 4b, 3b and 5.
X = I: A mixture of epimine 1 (100 mg, 0.355 mmol), Bu4NI
(259 mg, 0.70 mmol) and NH4I (254 mg, 1.75 mmol) was refluxed
in dry toluene (10 mL) for 1.5 h. The reaction mixture was then
concentrated to ca. 1 mL, diluted with ethyl acetate, washed with
aq. sodium thiosulfate and concentrated. Chromatography (13 g)
in heptane/ethyl acetate (2:1) gave: 1) 108 mg (74%) of a mixture
of 1,6-anhydro-3-iodo-2,3,4-trideoxy-2-(tosylamino)-β--ribo-hexo-
pyranose (4c) and 1,6-anhydro-3-iodo-2,3,4-trideoxy-2-(tosylam-
Reactions of 2 with Halo Acids: A mixture of the epimine 2 (100 mg,
0.355 mmol), EtOH (10 mL) and hydrohalogenic acid (320 µL,
3.41–3.62 mmol) was stirred at 50 °C for a given time until 2 was
consumed (TLC in S1). The reaction mixture was diluted with
brine, and the common workup followed by column chromatog-
raphy afforded the ring-cleavage products.
HCl: Reaction with HCl (35%, 320 µL, 3.62 mmol) for 21 h.
Chromatography (10 g) afforded: 1) 1,6-anhydro-3-chloro-2,3,4-tri-
deoxy-2-(tosylamino)-β--arabino-hexopyranose (6a, 75 mg, 66%);
1
ino)-β--xylo-hexopyranose (3c) in a 91:9 ratio (determined by H
NMR); recrystallization gave 4c [15 mg, 10%, m.p. 179–182 °C
(ethyl acetate/heptane) for X-ray analysis], 2) 16 mg (16%) of 1,6-
anhydro-2,3,4-trideoxy-2-(tosylamino)-β--erythro-hex-2-enopyr-
anose (5), and 3) 15 mg of an unresolved mixture of 4c, 3c and 5.
m.p. 174–176 °C (EtOH), [α]2D5
= –107 (c = 0.21, CHCl3),
C13H16ClNO4S (317.79): calcd. C 49.13, H 5.07, N 4.41, Cl 11.16;
found C 48.99, H 5.00, N 4.27, Cl 11.07 and 2) 1,6-anhydro-3-
O-ethyl-2,4-dideoxy-2-(tosylamino)-β--arabino-hexopyranose (6h,
31 mg, 27%), identical to 6h prepared by the ethanolysis of 2.
Reaction of 1 with Azide: A mixture of the epimine 1 (100 mg,
0.355 mmol), sodium azide (100 mg, 1.54 mmol), 2-methoxy-
ethanol (5 mL) and water (1 mL) was stirred for 2.5 h at 110 °C
until 1 was consumed (TLC in S1). The reaction mixture was di-
luted with water, and the common workup afforded 1,6-anhydro-
3-azido-2,3,4-trideoxy-2-(tosylamino)-β--xylo-hexopyranose (3d,
94 mg, 82%); m.p. 114–116 °C (ethyl acetate/heptane), [α]2D5 = –96
(c = 0.21, CHCl3). C13H16N4O4S (324.36): calcd. C 48.14, H 4.97,
N 17.27, S 9.88; found C 48.05, H 4.95, N 17.13, S 9.96.
HBr: Reaction with HBr (46%, 400 µL, 3.41 mmol) for 6 h.
Chromatography (20 g) afforded: 1) 1,6-anhydro-3-bromo-2,3,4-tri-
deoxy-2-(tosylamino)-β--arabino-hexopyranose
(6b,
106 mg,
82%); m.p. 170–172 °C (EtOH), [α]2D5 = –104 (c = 0.21, CHCl3);
C15H22BrNO5S (408.31, M + EtOH): calcd. C 44.12, H 5.43, N
3.43, S 7.85; found C 43.81, H 5.47, N 3.37, S 7.60; HRMS: calcd.
for C13H17BrNO4S [M + H]+ 362.0056; found 362.0057 and 2) 1,6-
anhydro-3-O-ethyl-2,4-dideoxy-2-(tosylamino)-β--arabino-hexo-
pyranose (6h, 14 mg, 12%), identical to 6h prepared by the etha-
nolysis of 2.
Reaction of 1 with Benzylamine: A solution of the epimine 1
(100 mg, 0.355 mmol) in benzylamine (600 µL, 5.69 mmol) was
stirred for 3 h at 140 °C. The reaction mixture was then poured
into ice, and the resulting crystalline precipitate was filtered off to
afford 1,6-anhydro-3-benzylamino-2,3,4-trideoxy-2-(tosylamino)-
β--xylo-hexopyranose (3e, 121 mg, 88%); m.p. 161–163 °C, [α]2D5
= –67 (c = 0.24, CHCl3). C20H24N2O4S (388.49): calcd. C 61.83, H
6.23, N 7.21, S 8.25; found C 62.31, H 6.21, N 7.11, S 8.40. HRMS:
calcd. for C20H25N2O4S [M + H]+ 389.1529; found 389.1513.
HI: Reaction with HI (57%, 470 µL, 3.56 mmol) for 6 h. The reac-
tion mixture was decolorized by the addition of aq. sodium thiosul-
fate before workup. Chromatography (20 g) afforded: 1) the epim-
ine 2 (23 mg, 23%), formed by aziridine back-closure during
workup according to TLC, 2) 1,6-anhydro-3-iodo-2,3,4-trideoxy-2-
(tosylamino)-β--arabino-hexopyranose (6c, 88 mg, 60%); m.p.
176–181 °C (EtOH), [α]2D5 = –108 (c = 0.21, CHCl3); C13H16INO4S
(409.24): calcd. C 38.15, H 3.94, N 3.42, S 7.83, I 31.01; found C
38.14, H 3.97, N 3.29, S 7.66, I 30.87, and 3) 1,6-anhydro-3-O-
Reaction of 1 with Phenylmethanethiol: Sodium methoxide (1 in
methanol, 0.3 mL, 0.3 mmol) was added to a solution of the epim-
ine
1 (100 mg, 0.355 mmol) and phenylmethanethiol (80 µL,
ethyl-2,4-dideoxy-2-(tosylamino)-β--arabino-hexopyranose
7 mg, 7%), identical to 6h prepared by the ethanolysis of 2.
(6h,
0.68 mmol) in methanol (5 mL). The resulting solution was stirred
at 70 °C for 3 h and then poured into ice. The crystalline precipitate
was filtered off to afford 1,6-anhydro-3-benzylsulfanyl-2,3,4-trid-
eoxy-2-(tosylamino)-β--xylo-hexopyranose (3f, 135 mg, 94%;
79% after recrystallization); m.p. 202–204 °C (ethyl acetate/meth-
anol), [α]2D5 = –214 (c = 0.22, CHCl3). C20H23NO4S2 (405.54): calcd.
C 59.23, H 5.72, N 3.45, S 15.81; found C 59.27, H 5.70, N 3.43,
S 16.08.
Reactions of 2 with Bu4NX + NH4X
X = Cl: A suspension of the epimine 2 (100 mg, 0.355 mmol),
Bu4NCl (195 mg, 0.70 mmol), NH4Cl (264 mg, 4.93 mmol) and
molecular sieves (4 Å) was refluxed in toluene (10 mL) for 6 h. The
reaction mixture was then diluted with dichloromethane, filtered,
washed with water, and the water was re-extracted with dichloro-
6404
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 6399–6406