Rawal et al.
JOCArticle
utilized this method in the preparation of orthogonally
protected β-sugar amino acids.
-7.37 (10H, m, Ar-H); 4.64 (1H, d, J = 11.7 Hz, PhCH); 4.64 (1H,
d, J = 2.4 Hz, H-3); 4.57 (1H, d, J = 12.0, PhCH); 4.50 (1H, d, J =
12.0 Hz, PhCH); 4.45 (1H, d, J = 11.7 Hz, PhCH); 4.37 (1H,
merged dd, J = 6.6, 5.6 Hz, H-5); 3.86 (1H, dd, J = 10.2, 7.1 Hz,
H-6); 3.73 (1H, brs, H-4); 3.64 (1H, dd, J=10.0, 5.4 Hz, H-60);
2.75 (1H, brs, -OH). 13C NMR (100 MHz, CDCl3): δ 190.93,
165.32, 137.58, 137.26, 128.45, 127.98, 127.78, 120.07, 75.97, 75.89,
73.53, 72.71, 72.34, 68.32, 57.73. MSES: m/z 355 [M+1]+, 377
[M+Na]+. Anal. Calcd for C21H22O5: C, 71.17; H, 6.26. Found:
C, 71.13; H, 6.30.
(3S,4R,5R)-4-(Benzyloxy)-5-(benzyloxymethyl)-34-meth-
oxy-3,4-dihydro-2H-pyran-2-carbaldehyde (10a). Yield: 90%. Rf:
0.4 (hexane/ethyl acetate, 4:1). [R]D=-210.0 (c 1.0, DCM), liquid.
1H NMR (400 MHz, CDCl3): δ 9.41 (1H, s, -CHO); 7.43 (1H, s,
H-1); 7.22-7.37 (10H, m, Ar-H); 4.60 (1H, d, J = 11.7 Hz, PhCH);
4.58 (1H, d, J=12.0 Hz, PhCH); 4.50 (1H, d, J=12.0 Hz, PhCH);
4.44 (1H, d, J = 11.7 Hz, PhCH); 4.38 (1H, brt, J = 6.4 Hz, H-5);
4.20 (1H, d, J = 2.4 Hz, H-3); 3.83 (1H, dd, J = 9.8, 7.1 Hz,
H-6); 3.73 (1H, brs, H-4); 3.65 (1H, dd, J=10.0, 5.8 Hz, H-60); 3.37
(3H, s, OMe). 13C NMR (100 MHz, CDCl3): δ 190.38, 166.0,
137.54, 137.09, 128.52, 128.48, 128.18, 128.11, 127.90, 127.87,
117.74, 75.59, 73.55, 72.21, 69.92, 68.22, 64.94, 57.28. MSES: m/z
369 [M+1]+, 391 [M+Na]+. Anal. Calcd for C22H24O5: C, 71.72;
H, 6.57. Found: C, 71.66; H, 6.61.
(3S,4R,5R)-4-(Benzyloxy)-3-(tert-butoxycarbonylamino)-2-
formyl-3,4-dihydro-2H-pyran-5-yl)methyl Acetate (20). Yield:
80%. Rf: 0.3 (hexane/ethyl acetate, 7:3). [R]D = +53.2 (c 1.0,
DCM), oil. IR (neat) νmax/cm-1: 3256, 2926, 2840, 1745, 1690,
1632. 1H NMR (400 MHz, CDCl3): δ 9.36 (1H, s, -CHO); 7.48
(1H, s, H-1); 7.27-7.34 (5H, m, Ar-H); 4.79 (1H, d, J = 11.7 Hz,
PhCH); 4.50-4.65 (3H, m, NH, H-3, PhCH); 4.39 (1H, dd, J =
11.4, 7.3 Hz, H-6); 4.16-4.23 (2H, m, H-5, H-60); 3.85 (1H, brs,
H-4); 2.03 (3H, s, OAc); 1.47 (9H, s, t-Bu). 13C NMR (100 MHz,
CDCl3): δ 189.30, 170.45, 165,31, 154.79, 137.04, 128.35, 127.97,
116.17, 80.23, 74.47, 71.58, 71.24, 60.07, 40.64, 28.25, 20.65. MSES:
m/z 406 [M+1]+, 428 [M+Na]+. Anal. Calcd for C21H27NO7: C,
62.21; H, 6.71; N, 3.45. Found: C, 62.14; H, 6.78; N, 3.42.
(3S,4R,5R)-4-(Benzyloxy)-3-(tert-butoxycarbonylamino)-2-
formyl-3,4-dihydro-2H-pyran-5-yl)methyl Acetate (21). Yield:
78%. Rf: 0.4 (hexane/ethyl acetate, 7:3). [R]D =+71.5 (c 2.3,
DCM), oil. IR (neat) νmax/cm-1: 3270, 2936, 1742, 1631.
1H NMR (400 MHz, CDCl3): δ 7.72 (1H, s, H-1); 7.26 - 7.34
(5H, m, Ar-H); 4.82 (1H, d, J = 11.7 Hz, NH); 4.52-4.63 (3H,
m, 2ꢀPhCH and H-6); 4.34 (1H, dd, J = 11.5, 7.8 Hz, H-60);
3.96-4.12 (2H, m, H-5, H-3); 3.75 (4H, brs, H-4 and OMe); 2.02
(3H, s, OAc); 1.48 (9H, s, t-Bu). 13C NMR (100 MHz, CDCl3): δ
170.51, 166.84, 157.26, 154.80, 137.30, 128.33, 127.90, 103.70,
80.20, 72.62, 71.78, 71.53, 63.20, 51.53, 42.77, 28.31, 20.67.
MSES: m/z 436 [M + 1]+, 458 [M + Na]+. Anal. Calcd for
C22H29NO8: C, 60.68; H, 6.71; N, 3.22. Found: C, 60.73; H, 6.74;
N, 3.19.
Experimental Section
General Procedure for Selective Acetolysis of Tri-O-benzyl-
C-2-formyl Glycals. A mixture of freshly fused ZnCl2 (1.53 g,
11.25 mmol) and Ac2O/AcOH (2:1 ratio, 6 mL) in dry DCM
(4 mL) was cooled to 10 °C using an ice-water bath. A solution
of tri-O-benzyl-C-2-formyl glycal (1 g, 2.25 mmol) in DCM
(4 mL) was quickly added. The reaction was stirred at 25 °C and
monitored at regular intervals (TLC monitoring). At an appro-
priate time (see the main text), the reaction was quenched with
saturated aqueous NaHCO3 solution and was extracted with
DCM (3ꢀ25 mL). The organic layer was washed with water and
brine and dried over anhydrous Na2SO4. Concentration of the
organic phase on a rotary evaporator gave a crude mixture of
products which was purified through column chromatography.
General Procedure for Nucleophilic Substitution Reactions. To
a solution of acetylated derivative (0.5 mmol) in 5 mL of DCM
were added a nucleophile (1.5 mmol) and sodium metal
(1 mmol) at 0-10 °C. After completion of the reaction (TLC
monitoring), the reaction mixture was poured onto crushed ice
(20 g) and extracted with DCM (3ꢀ10 mL). The organic layer
was washed with water and brine and dried over anhydrous
sodium sulfate. Evaporation of the solvent on a rotary evapora-
tor gave a crude product which was purified through column
chromatography. (Note: In the case of azide nucleophile, so-
dium azide was taken in 5 mmol quantity, the solvent used was
DMF, and the reaction mixture was heated at 70 °C for an
appropriate time).
(3S,4R,5R)-4-(Benzyloxy)-5-(benzyloxymethyl)-2-formyl-3,
4-dihydro-2H-pyran-3-yl acetate (2). Yield: 70%. Rf: 0.3 (hexane/
ethyl acetate, 4:1). [R]D=+64.0 (c 1.0, DCM), liquid. IR (neat)
ν
max/cm-1: 3061, 3031, 2924, 2871, 1739, 1676, 1629, 1369, 1269,
1
1101, 1024, 739. H NMR (400 MHz, CDCl3): δ 9.38 (1H, s,
-CHO); 7.54 (1H, s, H-1); 7.25-7.37 (10H, m, Ar-H); 5.76 (1H,
d, J=2.2 Hz, H-3); 4.76 (1H, d, J=12.0 Hz, PhCH); 4.55 (1H, d,
J=12.0 Hz, PhCH); 4.50 (1H, d, J=11.7 Hz, PhCH); 4.43 (1H, d,
J=11.7 Hz, PhCH); 4.20 (1H, merged dd, J=5.9, 5.8 Hz, H-5);
3.80 (1H, dd, J = 10.0, 6.8 Hz, H-6); 3.71 (1H, brs, H-4); 3.51 (1H,
dd, J=10.0, 5.4 Hz, H-60); 2.06 (3H, s, OAc). 13C NMR (100 MHz,
CDCl3): δ 188.97, 169.79, 165.82, 137.32, 136.97, 128.43, 128.39,
128.11, 127.92, 127.88, 127.61, 115.59, 76.14, 73.67, 71.89,
71.80, 69.96, 68.28, 58.83, 21.01. MSES: m/z 397 [M+1]+, 419
[M+Na]+. Anal. Calcd for C23H24O6: C, 69.68; H, 6.10. Found:
C, 69.60; H, 6.17.
(3S,4R,5R)-3-Acetoxy-4-(benzyloxy)-2-formyl-3,4-dihydro-
2H-pyran-5-yl)methyl Acetate (3). Yield: 60%. Rf: 0.25 (hexane/
ethyl acetate, 4:1). [R]D =+115.0 (c 2.0, DCM), oil. IR (neat)
ν
max/cm-1: 3061, 2924, 2853, 1746, 1673, 1625, 1371, 1194, 1113,
1045, 738. 1H NMR (400 MHz, CDCl3): δ 9.39 (1H, s, -CHO);
7.55 (1H, s, H-1); 7.29-7.37 (5H, m, Ar-H); 5.79 (1H, d, J=
2.2 Hz, H-3); 4.76 (1H, d, J = 12.2 Hz, PhCH); 4.57 (1H, d, J=
12.0 Hz, PhCH); 4.35 (1H, dd, J = 11.5, 7.3 Hz, H-6); 4.22 (1H,
merged dd, J = 6.6, 5.4 Hz, H-5); 4.13 (1H, dd, J = 11.4, 4.9 Hz,
H-60) 3.68 (1H, brs, H-4); 2.06 (3H, s, OAc); 1.99 (3H, s, OAc). 13C
NMR (100 MHz, CDCl3): δ180.92, 170.39, 169.84, 165.44, 136.56,
128.61, 128.52, 128.31, 115.58, 74.75, 71.67, 69.34, 62.56, 58.50,
21.04, 20.66. MSES: m/z349 [M+1]+, 371 [M+Na]+. Anal. Calcd
for C18H20O7: C, 62.06; H, 5.79. Found: C, 62.00; H, 5.84.
Acknowledgment. We thank the Department of Science
and Technology, New Delhi, for financial support in the
form of Ramanna Fellowship to Y.D.V. (Grant No. SR/S1/
RFOC-04/2006). We also thank the CSIR, New Delhi for
fellowships to G.K.R. and S.R. N.K. thanks the U.G.C.,
New Delhi for a fellowship.
(3S,4R,5R)-4-(Benzyloxy)-5-(benzyloxymethyl)-3-hydroxy-
3,4-dihydro-2H-pyran-2-carbaldehyde (9). Yield: 55%. Rf: 0.3
(hexane/ethyl acetate, 7:3). [R]D=+110.0 (c 1.5, DCM), solid. Mp:
80 °C. IR (neat) νmax/cm-1: 3358, 3065, 3013, 1678, 1627. 1H NMR
(400 MHz, CDCl3): δ 9.37 (1H, s, -CHO); 7.44 (1H, s, H-1); 7.22
Supporting Information Available: General experimental
procedures and characterization data for all of the compounds,
1H and 13C NMR, COSY, and NOE spectra, and CIF files of
compounds 6, 9, and 21. This material is available free of charge
J. Org. Chem. Vol. 74, No. 15, 2009 5355