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M. Gascon-Lopez et al. / Tetrahedron 59 (2003) 9349–9360
9356
1/2£OCH2Ph), 4.54 (1H, d, J¼12.2 Hz, 1/2£OCH2Ph),
4.60 (1H, d, J¼12.2 Hz, 1/2£OCH2Ph), 4.62 (1H, ddd,
J¼10.3, 4.7, 1.8 Hz, H-7), 4.61 (1H, d, J¼11.7 Hz,
1/2£OCH2Ph), 4.67 (1H, d, J¼11.9 Hz, 1/2£OCH2Ph),
4.69 (1H, d, J¼11.9 Hz, 1/2£OCH2Ph), 5.67 (1H, s, 2-H),
5.93 (1H, d, J¼1.8 Hz, H-4), 7.14–7.16 (2H, m, Ph), and
7.24–7.36 (18H, m, Ph); dC (151.0 MHz, CDCl3) 51.0,
68.7, 69.4, 70.8, 71.0, 72.3, 73.3, 74.9, 77.7, 80.5, 100.3,
127.5, 127.6, 127.79, 127.82, 127.87, 128.25, 128.36, 137.3,
137.7, 137.9, 138.0, 165.9 and 167.9; m/z (FAB) MþþH
595.2708 [C37H39O7 requires 595.2696].
J¼11.3, 1.8 Hz, H-8a), 3.97 (1H, dd, J¼4.1, 1.7 Hz, H-5),
4.43 (1H, d, J¼11.3 Hz, 1/2£OCH2Ph), 4.47 (1H, d,
J¼11.5 Hz, 1/2£OCH2Ph), 4.55 (1H, d, J¼12.2 Hz,
1/2£OCH2Ph), 4.58 (1H, d, J¼11.5 Hz, 1/2£OCH2Ph),
4.60–4.63 (1H, m, H-7), 4.62 (1H, d, J¼12.1 Hz,
1/2£OCH2Ph), 4.64 (1H, d, J¼11.8 Hz, 1/2£OCH2Ph),
4.70 (1H, d, J¼11.3 Hz, 1/2£OCH2Ph), 4.71 (1H, d,
J¼11.7 Hz, 1/2£OCH2Ph), 5.63 (1H, s, H-2, irradiation of
this signal gave no significant nOe at H-4), 5.96 (1H, d,
J¼1.7 Hz, H-4), 7.17–7.38 (20H, m, 4£Ph); dH (250 MHz,
t
C6D6) 1.46 (9H, s, Bu), 3.70 (2H, d, J¼2.9 Hz, H-8aþH-
8b), 4.06 (1H, dd, J¼10.3, 4.2 Hz, H-6), 3.97 (1H, dd,
J¼4.2, 1.6 Hz, H-5), 4.31–4.86 (8H, m, 4£OCH2Ph), 4.92
(1H, dt, J¼10.3, 2.9 Hz, H-7), 6.04 (1H, s, H-2), 6.43 (1H,
br s, H-4) and 7.09–7.44 (20H, m, 4£Ph); dC (62.9 MHz,
CDCl3) 28.3 (CH3), 68.9, 69.5, 70.7, 71.1, 72.4, 73.4, 74.8,
77.9, 79.6, 80.9, 102.8 (CvCH), 127.5, 127.6, 127.8, 128.3,
128.4, 137.5 (C-ipso), 137.9 (C-ipso), 138.2 (C-ipso), 138.2
(C-ipso), 164.3 (CvCH) and 166.8 (CvO); m/z (FAB)
MþþNa 659.2985 [C40H44O7Na requires 659.2985].
More polar product: (Z)-3,7-anhydro-4,5,6,8-tetra-O-
benzyl-2-deoxy-D-gluco-oct-2-enonic acid, methyl ester
(Z)-4a (3.23 g, 92%), obtained as a waxy syrup;
[a]2D5¼þ47.0 (c 2.85, CHCl3); nmax (film)/cm21 1720
(CvO), 1701, and 1651; dH (400 MHz, CDCl3) 3.70 (3H,
s, CO2Me), 3.82 (1H, dd, J¼11.5, 3.8 Hz, H-8a), 3.82–3.84
(1H, m, H-5 or H-6), 3.84 (1H, d, J¼3.2 Hz, H-4), 3.85–
3.89 (1H, m, H-6 or H-5), 3.89 (1H, dd, J¼11.5, 2.1 Hz,
H-8b), 4.34 (1H, ddd, J¼9.7, 3.5, 2.0 Hz, H-7), 4.50 (1H, d,
J¼12.0 Hz, 1/2£OCH2Ph), 4.53 (1H, d, J¼11.5 Hz,
1/2£OCH2Ph), 4.53 (1H, d, J¼12.8 Hz, 1/2£OCH2Ph),
4.61 (1H, d, J¼11.7 Hz, 1/2£OCH2Ph), 4.64 (1H, d,
J¼12.4 Hz, 1/2£OCH2Ph), 4.65 (1H, d, J¼11.1 Hz,
1/2£OCH2Ph), 4.71 (1H, d, J¼11.8 Hz, 1/2£OCH2Ph),
4.76 (1H, d, J¼12.3 Hz, 1/2£OCH2Ph), 5.19 (1H, s, H-2)
and 7.11–7.39 (20H, m, 4£Ph); dH (400 MHz, C6D6) 3.56
(3H, s, CO2Me), 3.83 (1H, dd, J¼11.8, 3.6 Hz, H-8a), 3.86
(1H, d, J¼3.6 Hz, 4-H), 3.93 (1H, d, J¼11.8, 1.9 Hz, H-8b),
3.96 (1H, dd, J¼5.7, 3.6 Hz, H-5), 4.10 (1H, dd, J¼10.2,
5.7 Hz, H-6), 4.25 (1H, d, J¼11.8 Hz, 1/2£OCH2Ph), 4.37
(1H, d, J¼11.9 Hz, 1/2£OCH2Ph), 4.45 (1H, d, J¼11.9 Hz,
1/2£OCH2Ph), 4.50 (1H, d, J¼11.8 Hz, 1/2£OCH2Ph),
4.56 (1H, ddd, J¼10.1, 3.5, 1.9 Hz, H-7), 4.59 (1H, d,
J¼11.6 Hz, 1/2£OCH2Ph), 4.70 (1H, d, J¼11.6 Hz,
1/2£OCH2Ph), 4.71 (1H, d, J¼12.3 Hz, 1/2£OCH2Ph),
4.84 (1H, d, J¼12.3 Hz, 1/2£OCH2Ph), 5.44 (1H, s, H-2),
7.02–7.29 (18H, m, Ar-H) and 7.51–7.53 (2H, m, Ar-H);
dC (62.9 MHz, CDCl3) 50.9, 68.3, 71.4, 72.7, 73.4, 73.6,
77.4, 77.7, 82.7, 99.4 (CvCH), 127.4, 127.7, 127.8, 127.9,
128.3, 128.4, 128.5, 137.1 (C-ipso), 137.6 (C-ipso), 137.8
(C-ipso), 138.4 (C-ipso), 161.9 (CvCH) and 165.1 (CvO);
m/z (FAB) MþþNa 617.2540 [C37H38O7Na requires
617.2515].
More polar product: (Z)-3,7-anhydro-4,5,6,8-tetra-O-ben-
zyl-2-deoxy-D-gluco-oct-2-enonic acid, tert-butyl ester (Z)-
4b (1.20 g, 92%) as a waxy syrup; [a]2D5¼þ41.4 (c 5.4,
CHCl3); nmax (film)/cm21 1713 (CvO) and 1647 (CvC);
dH (600 MHz, CDCl3) 1.48 (9H, s, tBu), 3.81–3.82 (1H, m,
H-5 or H-6), 3.83 (1H, d, J¼8.6, 3.5 Hz, H-8a), 3.86 (1H, d,
J¼4.1 Hz, H-4), 3.86–3.88 (1 H, m, H-6 or H-5), 3.88 (1H,
dd, J¼11.1, 2.0 Hz, H-8b), 4.26 (1H, ddd, J¼10.0, 3.5,
2.0 Hz, H-7), 4.51 (1H, d, J¼11.8 Hz, 1/2£OCH2Ph), 4.54
(1H, d, J¼11.2 Hz, 1/2£OCH2Ph), 4.55 (1H, d, J¼11.6 Hz,
1/2£OCH2Ph), 4.61 (1H, d, J¼12.3 Hz, 1/2£OCH2Ph),
4.63 (1H, d, J¼11.6 Hz, 1/2£OCH2Ph), 4.67 (1H, d,
J¼11.2 Hz, 1/2£OCH2Ph), 4.72 (1H, d, J¼11.8 Hz,
1/2£OCH2Ph), 4.73 (1H, d, J¼12.3 Hz, 1/2£OCH2Ph),
5.14 (1H, s, H-2, irradiation of this signal gave 6.1% nOe at
H-4), 7.15–7.40 (20H, m, 4£Ph); dC (151.0 MHz, CDCl3)
28.3 (CH3), 68.4 (CH2), 71.6 (CH2), 73.0 (CH2), 73.6 (CH2),
76.7 (CH2), 77.2 (CH), 77.4 (CH), 78.1 (CH), 79.7 (C), 83.2
(CH), 101.9 (CvCH), 127.5, 127.7, 127.8, 127.9, 128.0,
128.3, 128.5, 128.5, 137.3 (C-ipso), 137.7 (C-ipso), 138.0 (C-
ipso), 138.4 (C-ipso), 160.7 (CvCH), and 164.2 (CvO); m/z
(FAB) MþþNa 659.2985 [C40H44O7Na requires 659.2985].
4.3.3. (Z)- and (E)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-2-
solution of
3c (0.67 g,
deoxy-D-gluco-oct-2-enononitrile 4c.
(cyanomethylene)tri-n-butylphosphorane
A
4.3.2. (E)- and (Z)-3,7-Anhydro-4,5,6,8-tetra-O-benzyl-2-
deoxy-D-gluco-oct-2-enonic acid, tert-butyl ester 4b. A
solution of (tert-butoxycarbonylmethylene)tri-n-butyl-
phosphorane 3b (1.29 g, 4.08 mmol) in dry toluene
(10 mL) was added to a solution of 2,3,4,6-tetra-O-benzyl-
D-glucono-1,5-lactone 1 (1.10 g, 2.04 mmol) in dry toluene
(10 mL) at 808C under N2. The reaction mixture was stirred
for 12 h and concentrated under reduced pressure. The
yellow residue was subjected to flash chromatography using
petroleum spirit/AcOEt (8:1) to give the following products.
2.77 mmol) in dry CH2Cl2 (3 mL) was added to a solution
of 2,3,4,6-tetra-O-benzyl-D-glucono-1,5-lactone 1 (0.75 g,
1.39 mmol) in dry CH2Cl2 (2 mL) at 408C under N2. The
reaction mixture was stirred 20 h and concentrated under
reduced pressure. The Z/E isomer ratio of this crude product
1
was 6.5:1 as determined by H NMR. The yellow residue
(1.56 g) was subjected to flash chromatography using
petroleum spirit/Et2O (5:2) to give firstly (E)-3,7-anhydro-
2-deoxy-4,5,6,8-tetra-O-benzyl-D-gluco-oct-2-enononitrile
(E)-4c (0.081 g, 10%) as a colourless oil and from the later
fractions (Z)-3,7-anhydro-2-deoxy-4,5,6,8-tetra-O-benzyl-
D-gluco-oct-2-enononitrile (Z)-4c (0.58 g, 1.04 mmol,
75%) as a white solid.
Less polar product: (E)-3,7-anhydro-4,5,6,8-tetra-O-benzyl-
2-deoxy-D-gluco-oct-2-enonic acid, tert-butyl ester (E)-4b
(45 mg, 3%), [a]D24¼þ22.2 (c 0.95, CHCl3); nmax (film)/
cm21 1695 (CvO) and 1645 (CvC); dH (600 MHz,
t
CDCl3) 1.49 (9H, s, Bu), 3.70 (1H, dd, J¼11.3, 4.6 Hz,
Less polar product: (E)-3,7-anhydro-4,5,6,8-tetra-O-benzyl-
2-deoxy-D-gluco-oct-2-enononitrile (E)-4c; [a]2D0¼þ30.5 (c
H-8b), 3.72 (1H, dd, J¼10.4, 4.1 Hz, H-6), 3.78 (1H, dd,