FIGURE 1. 1H NMR spectra showing formation of glycosyl triflate at -60 °C. (A) A decrease in the anomeric signal of 2 is
observed upon addition of 0.6 equiv of Tf2O to a solution of donor 2, BSP, and TTBP (a), with concomitant appearance of signals
correlating to the anomeric proton of R-triflate (b) and â-triflate (c) intermediates. (B) Further addition of Tf2O affords a continued
increase in signals for the anomeric triflates with a concomitant decrease in the anomeric signal for thioglycoside 2.
Coupling of 2 with 3j To Give Methyl (4,6-Di-O-acetyl-
2-deoxy-2-N-acetyl-R-D-glucopyranosid[2,3-d]-1,3-oxazoli-
din-2-one)-(1-4)-3,6-di-O-benzyl-2-deoxy-2-N-phthalimido-
â-D-glucopyranoside (4j). The reaction was quenched after 48
h and separated by flash chromatography (ethyl acetate/hexanes,
1:1.5): yield ) 81%; Rf ) 0.41 (ethyl acetate/hexanes ) 1:1); 1H
NMR (CDCl3) δ 7.72-7.66 (m, 4H, Ar-H), 7.43-7.34 (m, 5H, Ar-
H), 7.08-6.90 (m, 5H, Ar-H), 6.27 (d, 1H, H-1, 2.7 Hz), 5.28 (dd,
1H, H-4), 5.02 (d, 1H, H-1′), 4.83 (d, 1H, -PhCH2), 4.74 (d, 1H,
-PhCH2), 4.68 (d, 1H, -PhCH2), 4.64 (dd, 1H, H-3) 4.44 (dd,
1H, H-3′), 4.32 (d, 1H, -PhCH2), 4.26 (dd, 1H, H-2′), 4.18 (t,
1H, H-4′), 4.14 (m, 1H, H-6a), 4.06 (m, 1H, H-5), 4.02 (t, 1H,
H-6b), 3.98 (t, 1H, H-6a′), 3.86(m, 1H, H-2), 3.82 (m, 1H, H-6b′),
3.64 (dd, 1H, H-5′), 3.40 (s, 3H, -OCH3), 2.36 (s, 3H, -COCH3),
2.15 (s, 3H, -COCH3), 2.10 (s, 3H, -COCH3); 13C NMR (CDCl3)
δ 171.3, 170.5, 169.2, 152.8, 137.9, 137.8, 133.9, 131.6, 128.4,
128.1, 127.8, 127.6, 127.3, 127.1, 123.4, 99.1, 95.2, 79.9, 75.6,
74.9, 74.6, 73.8, 73.6, 70.5, 68.4, 68.1, 60.3, 56.6, 55.6, 29.7, 23.5,
20.7; HRESI MS calcd for C42H44N2O15 [M + Na]+ 839.2639,
found 839.2626.
Representative Procedure for NMR-Scale Activation of
Thioglycoside 2 with BSP, TTBP, and Tf2O at -60 °C. To
a solution of thioglycoside 2 (4.4 mg, 0.01 mmol), BSP (2.1 mg,
0.01 mmol), and TTBP (5.0 mg, 0.02 mmol) in CD2Cl2 (0.8 mL)
in a 5 mm NMR tube at -60 °C, under an argon atmosphere,
was added 1.1 equiv of Tf2O (0.011 mmol, 1.9 µL). The NMR
tube was immediately transferred to the precooled NMR probe
(-60 °C), and the 1H and 19F spectra were recorded. The
R-glucosyl triflate [major component,1H NMR δ 6.91 (H-1, d, J1,2
) 2.4 Hz,); 19F NMR δ 0.69] and â-glucosyl triflate [minor
component,1H NMR δ 6.41 (H-1, d, J1,2 ) 7.2 Hz,); 19F NMR δ
0.69] were formed immediately. Other signals at δ -3.08
(TTBPH+OTf-) and δ 4.26 (Tf2O) were observed in the 19F NMR
spectrum.
oxazolidinone-protected glucosaminyl donors with PST
(e.g., 1) rapidly affords N-sulfenylated R-linked glycosides
with sterically hindered alcohols. Future studies are
anticipated to reveal how donor reactivity and stereose-
lectivity of glycosylation might be more stringently
controlled by altering the steric and electronic nature of
the N-substituent on the oxazolidinone ring of this
exciting new type of donor. Future studies evaluating
different substituents on the oxazolidinone ring are also
expected to reveal orthogonal protection/deprotection
strategies for 2N,3O-oxazolidinonyl-protected sugars,
which will facilitate synthesis of glycoconjugates contain-
ing variably substituted D-glucosamine residues.
Experimental Section
General Procedure for BSP/Tf2O Glycosylation Reac-
tions. Tf2O (1.3 equiv) was added to a stirred solution of 2 (1.2
equiv), BSP (1.3 equiv), TTBP (2.4 equiv), and activated,
powdered 3 Å molecular sieves in CH2Cl2 (5 mL) at -60 °C under
nitrogen atmosphere. The reaction mixture was stirred for 5 min,
after which time a solution of the acceptor alcohol 3a-j (1 equiv)
in CH2Cl2 (3 mL) was added. The mixture was stirred at -60
°C for 1-48 h and then quenched by the addition of saturated
aqueous NaHCO3. The organic layer was washed with brine,
dried, and concentrated. Glycosides were purified by silica gel
chromatography.
Separation and characterization data for representative gly-
cosidations reported in Table 1 are presented below. Data for
the remaining reactions in Table 1 are provided in the Support-
ing Information.
Coupling of 2 with 3a To Give 4,6-di-O-acetyl-1-O-
benzyl-2-deoxy-2-N-acetyl-â-D-glucopyranosid[2,3-d]-1,3-
oxazolidin-2-one (4a). The reaction was quenched after 1 h
and separated by flash chromatography (ethyl acetate/hexanes,
1:1.5): yield ) 90%; Rf ) 0.58 (ethyl acetate/hexanes ) 1:1); 1H
NMR (CDCl3) δ7.41-7.28 (m, 5H, Ar-H) 5.20 (d, 1H, H-1, J )
6.6 Hz), 5.14 (dd, 1H, H-4), 4.88 (d, 1H, -CH2Ph), 4.68 (d, 1H,
-CH2Ph), 4.55 (dd, 1H, H-3), 4.28 (m, 2H, H-5, H-6a), 4.15-
3.95 (m, 2H, H-6b, H-2), 2.52 (s, 3H, -COCH3), 2.15 (s, 3H,
-COCH3), 2.10 (s, 3H, -COCH3); 13C NMR (CDCl3) δ 170.4,
170.3, 169.6, 153.1, 136.5, 128.4, 128.1, 128.0, 99.6, 77.6, 74.9,
Acknowledgment. This research was supported by
the Department of Defense (DAMD17-01-1-0452).
Supporting Information Available: Experimental de-
tails and glycoside characterization for remaining glycosida-
tions reported in Table 1. 1H and 13C NMR spectra for all new
compounds. Additional spectra for low-temperature 1H and 19
F
NMR studies on glycosyl triflate intermediates. This material
71.0, 70.2, 64.1, 60.5, 24.5, 20.7; HRESI MS calcd for C20H23
-
NO9 [M + Na]+ 444.1271, found 444.1261.
JO047812O
4198 J. Org. Chem., Vol. 70, No. 10, 2005