2,3-Anhydrosugars in Glycoside Bond Synthesis
A R T I C L E S
132 (151 mg, 91%) as oils. The Rf values for 11 and 13 (10:1, hexane:
EtOAc) are 0.30 and 0.40, respectively.
was placed in the position favored by the exo-anomeric effect,24 and
no significant change in the orientation about this bond was seen upon
optimization.
B. Probing the Interconversion of Glycosides 12 and 14 under
the Reaction Conditions. The experiments done with 11 and 13 were
also carried out with 12 and 14, using the protocol described above.
Following the reaction and workup, the products were purified by
chromatography (10:1, hexane:EtOAc) to provide 121 (83%) and
recovered 141 (90%) as oils. The Rf values for 12 and 14 (10:1, hexane:
EtOAc) are 0.45 and 0.27, respectively.
NMR Experiments. All NMR experiments were performed in
duplicate in 5-mm NMR tubes dried under a stream of argon and
1
stoppered with septa under a positive pressure of argon. The H and
13C spectra were recorded at 500 and 125 MHz, respectively; the 19F
NMR spectra were recorded at 235 MHz. Chemical shifts are in ppm
and are referenced to the solvent for 1H and 13C spectra (1H, CHDCl2,
δH 5.32 ppm; 13C, CD2Cl2, δC 53.8 ppm). 19F spectra were referenced
to external trifluoroacetic acid (δF 0.00 ppm).
C. 5-O-Benzoyl-2,3-anhydro-r-D-lyxofuranose (28). To a solution
of 11 (1.1 g, 3.22 mmol) in CH3CN/H2O (5:1, 15 mL) at 0 °C was
added NIS (0.86 g, 3.85 mmol). The solution was allowed to stir for
10 min followed by the addition of AgOTf (21 mg, 0.38 mmol). After
the solution was stirred for 10 min, triethylamine (2 mL) was added
and the solution was diluted with CH2Cl2 and filtered through Celite.
The filtrate was washed with a saturated aqueous Na2S2O3 solution,
water, and brine. The organic layer was dried, filtered, and concentrated,
and the residue was purified by chromatography (hexanes/EtOAc, 4:1)
yielding 28 (0.68 g, 90%) as a white solid: Rf 0.14 (hexanes/EtOAc,
2:1); 1H NMR (500 MHz, CD2Cl2, δH) 8.06 (d, 2 H, J ) 7.2 Hz), 7.57
(t, 1 H, J ) 7.5, 7.5 Hz), 7.44 (dd, 2 H, 7.5, 7.5 Hz), 5.32 (d, 1 H, J
) 4.1 Hz), 4.37-4.27 (m, 3 H), 3.67 (d, 1 H, J ) 2.8 Hz), 3.56 (d, 1
H, J ) 2.8 Hz), 3.30 (br d, 1 H, J ) 4.0 Hz); 13C NMR (125 Hz,
CD2Cl2, δC) 166.2, 133.1, 129.6, 129.4, 128.3, 95.6, 73.9, 62.9, 56.7,
A. Following the Formation of Intermediates Produced from 2
and 4 by NMR Spectroscopy. The sulfoxide (60 mg, 0.17 mmol) and
DTBMP (40 mg, 0.20 mmol) were dissolved in CD2Cl2 (1.1 mL) in an
NMR tube, and a spectrum was recorded at -78 °C. The tube was
removed and kept at -78 °C, and then Tf2O (23 µL, 1.8 mmol) was
added. The tube was then quickly returned to the cooled spectrometer,
and spectra were taken over 60 min, while warming the probe from
-78 to -40 °C.
B. Synthesis of an Authentic Sample of 17. A solution of 28 (36
mg, 0.15 mmol) and DTBMP (62 mg, 0.30 mmol) in CD2Cl2 (1.0 mL)
was cooled to -78 °C in a 5-mm NMR tube. To this solution was
added Tf2O (26 µL, 0.17 mmol). The solution stirred for 20 min at
-78 °C and was vortexed periodically to allow for efficient mixing.
The 1H spectrum of the product (obtained at -78 °C) matched that of
the intermediate formed upon treatment of sulfoxide donor 2 with Tf2O.
C. Synthesis of an Authentic Sample of Sulfenate 24. To a solution
of lactol 28 (40 mg, 0.17 mmol) and DTBMP (40 mg, 0.20 mmol) in
CD2Cl2 (1.1 mL) in an NMR tube cooled to -78 °C was added
p-TolSCl16 (14 µL, 0.18 mmol). The progress of the reaction was
1
54.1. JC-1,H-1 ) 175.6. HRMS (ESI) calcd for (M + Na+) C12H12O5
259.0582, found 259.0571.
Computational Methods. Ab initio molecular orbital20 and density
functional theory (DFT)21 calculations were performed using Gaussian
98.22 The optimized geometries were calculated at the HF/6-31G* level
of theory,20 and single-point energies of these optimized geometries
were calculated at the B3LYP/6-31+G** level of theory23 (Tables 1
and S1). To obtain a better understanding of the potential energy surface
of the glycosyl triflates, all possible combinations of anomers and
rotamers about the C4-C5 bond and the C1-O1 bonds were explored
(a total of 18 conformers; see Tables 1 and S1). The optimization
process did not lead to significant changes in rotamer orientation. For
the methyl glycosides (Tables 2 and S2), only the rotamers about only
the C4-C5 bond were explored; the C1-O1 bond in these molecules
1
monitored by H spectroscopy while warming from -78 °C to -40
°C over the course of 60 min. After a single product was formed, the
probe was again cooled to -78 °C and the spectrum provided in the
Supporting Information was recorded.
Acknowledgment. The National Institutes of Health (AI44045-
01) and the National Science Foundation (CHE-9875163)
supported these investigations. C.S.C.’s contributions to this
work were supported first by a GAANN fellowship from the
U.S. Department of Education and later by an American
Chemical Society Division of Organic Chemistry Fellowship
sponsored by Aventis Pharmaceuticals. We also acknowledge
support from the Ohio Supercomputer Center where some of
the calculations were performed.
(20) Hehre, W. J.; Radom, L.; Schyeyer, P. V. R.; Pople, J. A. Ab initio
Molecular Orbital Theory; John Wiley & Sons: New York, 1986.
(21) (a) Labanowski, J. W.; Andzelm, J. Density Functional Methods in
Chemistry; Springer: New York, 1991. (b) Parr, R. G.; Yang, W. Density
Functional Theory in Atoms and Molecules; Oxford University Press: New
York, 1989.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M.
A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann,
R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin,
K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi,
R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz,
J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-
Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.9;
Gaussian, Inc.: Pittsburgh, PA, 1998.
Supporting Information Available: Results of computational
and NMR investigations involving sulfoxide 4 (relative energies
of triflates and methyl glycosides, NMR spectra), Cartesian
coordinates of all optimized geometries, NMR spectra of
sulfenate 24. This material is available free of charge via the
(23) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098. (b) Becke, A. D. J. Chem.
Phys. 1993, 98, 5648. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B
1988, 37, 785.
JA0349610
(24) Lemieux, R. U.; Koto, S. Tetrahedron 1974, 30, 1933.
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