give the bromide 14. In contrast to the tosylate analogue,32
compound 14 did not undergo spontaneous cyclization to form
the desired bicyclic sulfonium salt. Treatment of compound 14
with AgOTf in CH2Cl2 to promote cyclization gave the
undesired product 13 once again. However, when the same
reaction was carried out using CH3CN as solvent, the reaction
proceeded smoothly to give the desired sulfonium salt 15 as a
stable, colorless oil. Compound 15 was remarkably stable even
after long-term storage at room temperature. The ring junction
of this bicyclic compound 15 was cis as expected because of
the strain in the trans isomer, in agreement with the work of
Izquierdo and co-workers.32 The stereochemistry was further
confirmed with the aid of 1D-NOESY experiments, which
showed a correlation between H-3 and H-8ax, and the config-
uration at C-5 of compound 15 was also assigned by means of
a 1D-NOESY experiment, which showed a correlation between
H-3 and H-5; the stereochemistry of compound 10 was thus
assigned by inference. The benzyl protecting groups were
removed with boron trichloride at -78 °C to give the desired
bicyclic sulfonium salt 8. During the course of deprotection,
some of the triflate counterion was exchanged with the chloride
ion. Hence, the deprotected bicyclic sulfonium salt was treated
with Amberlyst A-26 (chloride form) to completely exchange
the triflate counterion with chloride ion.
Hz, H-1b), 3.61 (m, 1H, H-8eq), 3.29 (ddd, 1H, J7ax,8ax ) J8ax,8eq
)
12.8 Hz, J7eq,8ax ) 3.6 Hz, H-8ax), 1.92 (m, 1H, H-7ax), 1.74
(ddddd, 1H, J7ax7eq ) 15.3 Hz, J6eq,7eq ) J6ax,7eq ) J7eq,8eq ) 4.1
Hz, H-7eq), 1.60 (dddd, 1H, J6ax,6eq ) 13.9 Hz, J6eq,7ax ) 4.4 Hz,
H-6eq), 1.34 (dddd, 1H, J6ax,7ax ) 11.7 Hz, H-6ax). 13C NMR
(CDCl3): δ 137.0, 136.6, 136.4 (3Cipso), 130.0-128.2 (15CAr),
120.9 (q, 1C, JC,F ) 318.8 Hz, OTf), 84.8 (C-3), 83.6 (C-2), 72.9,
72.7, 71.0 (3CH2Ph), 69.0 (C-5), 55.4 (C-4), 43.9 (C-1), 35.4 (C-
8), 23.3 (C-6), 16.7 (C-7). MALDI-TOF MS: m/e 460.99 (M+
OTf). Anal. Calcd for C30H33F3O6S2: C, 59.00; H, 5.45. Found:
C, 58.92; H, 5.49.
-
Procedure for the Synthesis of (2S,3S,4R,5R)-2,3,5-Tri-
hydroxy-cis-1-thioniabicyclo[4.3.0]nonane Triflate (8). BCl3 gas
was bubbled vigorously through a solution of 15 (100 mg, 0.16
mmol) in CH2Cl2 (6 mL) at -78 °C under N2 atmosphere for 10
min. The mixture was stirred at -78 °C for 2 h and a stream of
dry air was blown vigorously over the solution to remove excess
BCl3. The reaction was quenched with MeOH (2 mL) and the
solvent was removed. The residue was coevaporated with MeOH
(2 × 2 mL) and then washed with CH2Cl2 (2 × 2 mL) to give a
white solid. The solid was dissolved in MeOH (5 mL) and a freshly
washed ion-exchange resin (Amberlyst A-26 (chloride form), 100
mg) was added. The mixture was stirred at room temperature for
1 h and filtered. The filtrate was concentrated and recrystallized
from MeOH:CH2Cl2 to give compound 8 as white crystals (29 mg,
78%): mp 195-197 °C; [R]D - 38.00° (c 0.45, CH3OH). 1H NMR
(CD3OD): δ 4.49 (dd, 1H, J2,3 ) 6.0 Hz, J3,4 ) 8.6 Hz, H-3), 4.42
(m, 1H, H-5), 4.37 (ddd, 1H, J1a,2 ) 7.4 Hz, J1b,2 ) 5.9 Hz H-2),
3.86 (dd, 1H, J1a,1b ) 13.8 Hz, H-1a), 3.69 (dd, 1H, J4,5 ) 4.3 Hz,
H-4), 3.58 (ddd, 1H, J8ax,8eq ) 12.3 Hz, J7ax,8eq ) J7eq,8ax ) 4.0 Hz,
H-8eq), 3.52, (ddd, 1H, J7eq,8ax ) 3.6 Hz, J7ax,8ax ) 12.1 Hz, H-8ax),
In conclusion, the preparation of 8, a bicyclic sulfonium ion
analogue of the glycosidase inhibitor swainsonine (1), has been
achieved.
Experimental Section
3.18 (dd, 1H, H-1b), 2.19 (ddddd, 1H, J6ax,7ax ) 11.9 Hz, J7ax,7eq
)
15.4 Hz, J6eq,7ax ) 3.6 Hz, H-7ax), 2.06-1.81 (m, 3H, H-6ax, H-6eq,
H-7eq). 13C NMR (CD3OD): δ 78.0 (C-3), 77.2 (C-2), 62.4 (C-5),
59.3 (C-4), 44.1 (C-1), 36.7 (C-8), 25.7 (C-6), 16.2 (C-7). MALDI-
TOF MS: m/e 191.22 (M+ - Cl). Anal. Calcd for C8H15ClO3S:
C, 42.38; H, 6.67. Found: C, 42.31; H, 6.72.
Procedure for the Synthesis of (2S,3S,4R,5R)-2,3,5-Tribenz-
yloxy-cis-1-thioniabicyclo[4.3.0]nonane Triflate (15). A solution
of compound 14 (110 mg, 0.20 mmol) in CH3CN (4 mL) was
treated with AgOTf (104 mg, 2 equiv) for 20 h at ambient
temperature. The solvent was removed and the crude product was
purified by flash chromatography [CH2Cl2/MeOH, 1:0 to 20:1] to
give compound 15 as a colorless oil (88 mg, 71%): [R]D -14.40°
Acknowledgment. We thank Dr. B. D. Johnston for helpful
discussion. We also thank the Natural Sciences and Engineering
Research Council of Canada for financial support and the
Michael Smith Foundation for Health Research for a trainee
fellowship (to N.S.K.).
1
(c 0.75, CH2Cl2). H NMR (CDCl3): δ 7.29-7.03 (m, 15H, Ar),
4.53 and 4.34 (2d, each 1H, Ja,b ) 11.5 Hz, CH2Ph), 4.51 and 4.35
(2d, each 1H, Ja,b ) 12.1 Hz, CH2Ph), 4.49 (m, 1H, H-2), 4.47 and
4.43 (2d, each 1H, Ja,b ) 12.0 Hz, CH2Ph), 4.25 (dd, 1H, J2,3
)
3.8 Hz, J3,4 ) 7.8 Hz, H-3), 4.04 (dd, 1H, J4,5 ) 4.4 Hz, H-4),
3.89 (dd, 1H, J1a,1b )14.8 Hz, J1a,2 ) 6.6 Hz, H-1a), 3.76 (ddd,
1H, J5,6eq ) 4.9 Hz, J5,6ax ) 1.9 Hz, H-5), 3.66 (dd, 1H, J1b,2 ) 3.0
Supporting Information Available: Experimental procedures
and characterization data for compounds 10-14. This material is
(32) Izquierdo, I.; Plaza, M. T.; Aragon, F. Tetrahedron: Asymmetry
1996, 7, 2567-2575.
JO052111S
1264 J. Org. Chem., Vol. 71, No. 3, 2006