C. Portella et al.
FULL PAPER
3J(H,H) 6.1 Hz, 1H; H1), 5.28 (dm, 3J(H,H) 9.1 Hz, 1H; H4), 5.93 ±
6.02 (m, 2H; H2, H3); 13C NMR (CDCl3): d 14.0 (CH3), 20.6 (CH3), 20.8
(CH3), 22.4, 22.6, 28.9, 29.0, 29.3, 31.8, 38.4 (CH2), 62.7 (C6), 64.5 (C4), 74.1
(C5), 74.6 (dd, 2J (C,F) 31.5, 27.6 Hz, C1), 114.2 (dd, 1J (C,F) 261.9,
general procedure with BF3 ´ Et2O activation of the glycosyl donor from tri-
O-acetyl-d-glucal (1.5 mmol). Purification by flash chromatography (PE/
EtOAc 80:20) gave compound 10a (60%) a mixture of anomers a:b
75:25 (determined by 19F NMR) as an oil. 1H NMR (250 MHz, CDCl3):
major a anomer: d 2.00 (s, 3H; COCH3), 2.06 (s, 3H; COCH3), 4.01 ± 4.20
254.0 Hz, CF2), 123.8 (C2), 129.0 (C3), 170.0 (C O acetyl), 170.5 (C O
2
acetyl), 200.9 (dd, J (C,F) 29.5, 25.6 Hz, C O); 19F NMR (CDCl3): d
3
3
(m, 3H, H5, H6, H'6), 4.91 (ddd, J(H,F) 18.8, 7.2 Hz, J(H,H) 1.8 Hz,
1H; H1), 5.18 (dm, 3J(H,H) 6.9 Hz, 1H; H4), 6.01 ± 6.11 (m, 2H; H2,
H3), 7.43 ± 8.10 (m, 5H, Ph); 13C NMR (CDCl3): major a anomer, d 20.5
(CH3), 20.8 (CH3), 62.6 (C6), 64.4 (C4), 74.0 (C5), 74.8 (dd, 2J (C,F) 30.5,
26.6 Hz, C1), 115.8 (dd, 1J (C,F) 259.4, 251.3 Hz, CF2), 123.9 (C3), 128.6 ±
124.4 (dd, 2J(F,F) 261.1, 3J(H,F) 15.5 Hz, 1F), 114.2 (d, 2J(F,F)
261.1 Hz, 1F); MS (70 eV, EI): m/z (%): 213 (30) [M 191] , 141 (100), 111
(78).
2-(3,5-Di-O-benzoyl-2-deoxy-a-d-erythro-pentofuranosyl)-2,2-difluoro-1-
(3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-d-xylo-pentofuranosyl)-
ethanone (13): The reaction was performed according to the general
procedure with SnCl4 activation from 5 (0.5 mmol). The reaction mixture
was kept to 208C. Purification by flash chromatography (PE/EtOAc
85:15) gave a mixture of anomers a:b 92:8 (determined by 19F NMR) as a
solid (0.13 g, 37%). M.p. 45 ± 478C; [a]D24 21.1 (c 0.45 in chloroform);
1H NMR (500 MHz, CDCl3): d 1.33 (s, 3H, CH3), 1.50 (s, 3H, CH3), 2.47
(ddd, J(H,H) 14.9, 5.2, 3.2 Hz, 1H; H9a), 2.78 (ddd, J(H,H) 14.9, 8.8,
7.6 Hz, 1H; H9b), 3.30 (d, J(H,H) 6.8 Hz, 2H; H5, H'5), 4.10 (d,
3J(H,H) 3.2 Hz, 1H; H3), 4.35 (dd, J(H,H) 11.7, 3.8, 1H; H12), 4.41 ±
4.49 (m, 3H; H11, H'12, H-benzyl), 4.59 ± 4.75 (m, 4H; H2, H4, H8, H'-
benzyl), 5.50 (dt, 3J(H,H) 7.6, 3.2 Hz, 1H; H10), 5.88 (d, 3J(H,H)
3.8 Hz, 1H; H1), 7.12 ± 8.03 (m, 15H; 3Ph); 13C NMR (CDCl3): d 26.2
(CH3), 26.8 (CH3), 31.7 (C9), 37.3 (C5), 64.3 (C12), 72.0 (CH2 benzyl), 74.9
(C10), 75.3 (C4), 77.6 (dd, 2J (C,F) 32.1, 25.5 Hz, C1), 81.7 (C3), 82.4 (C2),
83.0 (C11), 104.5 (C1), 111.7 (C-acetal), 114.6 (dd, 1J(C,F) 261.8,
129.0 (C2, C-arom), 170.1 (C O acetyl), 170.5 (C O acetyl), 188.8 (t, 2J
(C,F) 27.6 Hz, C O); minor b anomer, d 20.5 (CH3), 20.8 (CH3),62.4
(C6), 63.9 (C4), 71.2 (C5), 71.6 (dd, 2J (C,F) 26.6, 22.6 Hz, C1), 116.9 (dd,
1J (C,F) 264.8, 258.9 Hz, CF2), 123.2 (C3), 128.6 ± 129.0 (C2, C-arom),
2
170.1 (C O acetyl), 170.5 (C O acetyl), 189.8 (t, J (C,F) 27.6 Hz, C O);
19F NMR (CDCl3): major a anomer, d 112.5 (dd, 2J(F,F) 275.8,
3J(H,F) 18.8 Hz, 1F), 105.0 (dd, 2J(F,F) 275.8 Hz, 3J(H,F) 7.2 Hz,
1F); minor b anomer, d 115.3 (dd, 2J(F,F) 270.8, 3J(H,F) 15.3 Hz,
1F);
108.5 (dd, 2J(F,F) 270.8 Hz, 3J(H,F) 7.6 Hz, 1F); elemental
analysis calcd (%) for C18H18O6F2 (368.11): C 58.68, H 4.93; found C
58.69, H 4.70.
1-(4,6-Di-O-acetyl-2,3-dideoxy-d-erythro-hex-2-enopyranosyl)-1,1-difluoro-
propan-2-one (10b): The reaction was performed according to the general
procedure with BF3 ´ Et2O activation of the glycosyl donor from tri-O-
acetyl-d-glucal (1.5 mmol). Purification by flash chromatography (PE/
EtOAc 85:15) gave compound 10b (60%) a mixture of anomers a:b
77:23 (determined by 19F NMR) as an oil. 1H NMR (250 MHz, CDCl3):
major a anomer: d 2.00 (s, 3H; COCH3), 2.02 (s, 3H; COCH3), 2.33 (d,
4J(H,F) 1.9 Hz, 3H; CH3), 3.95 ± 4.15 (m, 3H, H5, H6, H'6), 4.59 (ddd,
3J(H,F) 18.9, 5.0 Hz, 3J(H,H) 2.7 Hz, 1H; H1), 5.07 (dm, 3J(H,H)
7.2 Hz, 1H; H4), 5.86 (dm, 3J(H,H) 10.7 Hz, 1H; H3), 6.04 (dt,
3J(H,H) 10.7, 2.3 Hz, 1H; H2); 13C NMR (CDCl3): major a anomer:
d 20.5 (CH3), 20.7 (CH3), 25.4 (CH3), 62.5 (C6), 63.8 (C4), 70.8 (dd, 2J
254.0 Hz, CF2), 127.5 ± 137.8 (C-arom), 166.0, 166.1 (C O benzoyl), 198.5
2
(dd, J(C,F) 32.5, 26.5 Hz, C O); 19F NMR (CDCl3): a anomer, d
125.2 (dd, 2J(F,F) 270.5, 3J(H,F) 19.2 Hz, 1F), 112.7 (dd, 2J(F,F)
270.5, 3J(H,F) 6.0 Hz, 1F); b anomer, d 127.6 (dd, 2J(F,F) 268.3,
3J(H,F) 18.5 Hz, 1F), 105.0 (dd, 2J(F,F) 268.3, J(H,F) 3.3 Hz, 1F);
3
1
IR: nÄ 1730 cm (C O); MS (70 eV, EI): m/z (%): 665 (2) [M H] , 651
(13) [M 15] , 501 (29), 447 (58), 428 (33), 337 (26), 325 (100), 277 (93);
1
elemental analysis calcd (%) for C36H36O10F2 (666.67): C 64.86, H 5.41;
found C 64.61, H 5.24.
(C,F) 31.3, 26.2 Hz, C1), 71.3 (C5), 115.1 (dd, J (C,F) 163.9, 257.7 Hz,
CF2), 122.9 (C3), 129.0 (C2), 170.0 (C O acetyl), 170.4 (C O acetyl), 197.9
2
(dd, J (C,F) 31.5, 25.6 Hz, C O); minor b anomer: d 20.4 (CH3), 20.7
2-(4,6-Di-O-acetyl-2,3-dideoxy-d-erythro-hex-2-enopyranosyl)-2,2-difluo-
ro-1-(3-O-benzyl-5-deoxy-1,2-O-isopropylidene-a-d-xylo-pentofurano-
syl)-ethanone (14): BF3 ´ Et2O (1.3 equiv, 0.39 mmol) was added dropwise
at 408C under dry argon to a solution of tri-O-acetyl-d-glucal (1.1 equiv,
0.33 mmol) in CH2Cl2 (3 mL). After 15 min stirring at 408C, a solution of
the difluoroenoxysilane 12 (0.30 mmol) was slowly added and the reaction
was monitored by TLC (PE/EtOAc 4:1). After stirring 3 h at 408C, the
reaction was quenched by a saturated NaHCO3 solution (30 mL). After
extraction with CH2Cl2 (4 Â 30 mL), the organic layer was washed with
brine, dried over MgSO4 and the solvent was evaporated under reduced
pressure. The crude product was purified by silicagel column chromato-
graphy. Purification by flash chromatography (PE/EtOAc 4:1) gave 14 as a
mixture of anomers (a:b 80:20, 19F NMR) (0.13g, 75%). The two
diastereoisomers were separated by HPLC on silica gel (hexane/EtOAc
3:1) and were fully characterized. Major a anomer: white solid; m.p. 83 ±
848C; [a]D22 23.9 (c 0.36 in chloroform); 1H NMR (250 MHz, CDCl3):
d 1.32 (s, 3H, CH3), 1.50 (s, 3H, CH3), 2.04 (s, 3H, COCH3), 3.29 (d,
3J(H,H) 6.9 Hz, 2H; H5, H'5), 4.00 ± 4.08 (m, 3H, H12, H13, H'13), 4.13
(d, 3J(H,H) 3.4 Hz, 1H; H3), 4.45 (d, 2J(H,H) 11.8 Hz, 1H; H-benzyl),
(CH3), 26.0 (CH3), 61.8 (C6), 64.3 (C4), 74.0 (C5), 114.0 (dd, 1J (C,F)
260.0, 254.2 Hz, CF2), 123.5 (C3), 129.7 (C2), 169.8 (C O acetyl), 170.2
(C O acetyl); 19F NMR (CDCl3): major a anomer: d 120.8 (dd,
2J(F,F) 261.3, J(H,F) 18.9 Hz, 1F), 110.8 (d, J(F,F) 261.3 Hz, 1F);
3
2
minor b anomer: d 123.2 (dd, 2J(F,F) 265.1, 3J(H,F) 15.2 Hz, 1F),
114.5 (d, 2J(F,F) 265.1 Hz, 1F); IR: nÄ 1726 cm (C O); MS (70 eV,
1
EI): m/z (%): 445 (28) [M] , 201 (24), 105 (100), 77 (27); elemental analysis
calcd (%) for C13H16O6F2 (306.09): C 68.00, H 4.36; found C 67.64, H 4.26.
1-(4,6-Di-O-acetyl-2,3-dideoxy-d-erythro-hex-2-enopyranosyl)-1,1-difluoro-
decan-2-one (10c): The reaction was performed according to the general
procedure with BF3 ´ Et2O activation of the glycosyl donor from tri-O-
acetyl-d-glucal (1.5 mmol). Purification by flash chromatography (PE/
EtOAc 85:15) gave compound 10c (63%). The a and b isomers were
obtained in proportions 80:20, respectively. a Isomer was isolated by
recrystallisation in n-pentane and a fraction of pure b-anomer was obtained
by flash chromatography. a Anomer: white solid; m.p. 48 ± 498C; [a]2D4
73.0 (c 1.0 in chloroform); 1H NMR (250 MHz, CDCl3): d 0.88 (t,
3J(H,H) 6.5 Hz, 3H; CH3), 1.29 (m, 10H; 5CH2), 1.65 (tm, 3J(H,H)
7.2 Hz, 2H; CH2), 2.06 (s, 3H; COCH3), 2.10 (s, 3H; COCH3), 2.72 (t,
3J(H,H) 7.2 Hz, 2 H ; CH2), 4.01 ± 4.23 (m, 3H; H5, H'6, H6), 4.68 (ddd,
3J(H,F) 21.6, 5.3 Hz, 3J(H,H) 2.3 Hz, 1H; H1), 5.16 (dm, 3J(H,H)
6.9 Hz, 1H; H4), 5.99 (dm, 3J(H,H) 10.7 Hz, 1H; H3), 6.09 (ddd,
3J(H,H) 10.7 Hz, 4J(H,H) 2.3 Hz, 1H; H2); 13C NMR (CDCl3): d
14.0 (CH3), 20.6 (CH3), 20.9 (CH3), 22.5, 22.6, 28.9, 29.0, 29.3, 31.8, 37.8
(CH2), 62.6 (C6), 63.9 (C4), 71.0 (dd, 2J (C,F) 29.5, 25.6 Hz, C1), 71.4
2
3
4.59 (d, J(H,H) 11.8 Hz, 1H; H-benzyl), 4.60 (d, J(H,H) 3.8 Hz, 1H;
H2), 4.56 ± 4.68 (m, 2H; H4, H8), 5.11 (m, 1H; H11), 5.85 (d, 3J(H,H)
3.8 Hz, 1H; H1), 5.98 (dm, 3J(H,H) 10.7 Hz, 1H; H10), 6.09 (dt,
J(H,H) 10.7, 2.3 Hz, 1H; H9), 7.20 ± 7.35 (m, 5H; Ph); 13C NMR (CDCl3):
d 20.5 (COCH3), 20.9 (COCH3), 26.2 (CH3), 26.8 (CH3), 37.2 (C5), 62.6
2
(C13), 63.9 (C11), 70.9 (dd, J (C,F) 29.5, 25.2 Hz, C8), 71.5 (C12), 72.2
(CH2 benzyl), 75.4 (C4), 81.7 (C3), 82.4 (C2), 104.4 (C1), 111.0 (C-acetal),
115.2 (dd, 1J (C,F) 263.8, 257.9 Hz, CF2), 123.0 (C10), 127.8 ± 128.4 (C-
(C5), 115.4 (dd, 1J (C,F) 263.8, 257.9 Hz, CF2), 123.2 (C2), 129.0 (C3),
2
2
arom), 129.2 (C9), 137.2 (C-arom), 170.1, 170.6 (C O acetyl), 197.9 (dd, J
170.2 (C O acetyl), 170.5 (C O acetyl), 200.3 (dd, J (C,F) 30.5, 24.6 Hz,
(C,F) 29.5, 25.6 Hz, C O); 19F NMR (CDCl3): d 120.7 (dd, 2J(F,F)
C O); 19F NMR (CDCl3): d 121.6 (dd, 2J(F,F) 267.2, 3J(H,F)
263.8, 3J(H,F) 20.8 Hz, 1F), 111.1 (dd, 2J(F,F) 263.8, 3J(H,F) 5.0 Hz,
2
21.6 Hz, 1F), 110.4 (d, J(F,F) 267.2 Hz, 1F); MS (70 eV, EI): m/z (%):
1
213 (30) [M 191] , 141 (100), 111 (78). b-anomer: colourless oil; [a]2D4
1F); IR: nÄ 1744 cm (C O); MS (70 eV, EI): m/z (%): 554 (0.1) [M
28.0 (c 0.3; chloroform); 1H NMR (250 MHz, CDCl3): d 0.89 (t,
3J(H,H) 6.7 Hz, 3H; CH3), 1.28 (m, 10H; 5CH2), 1.60 (tm, 3J(H,H)
7.1 Hz, 2H; CH2), 2.06 (s, 3H; COCH3), 2.10 (s, 3H; COCH3), 2.67 (t,
3J(H,H) 7.1 Hz, 2 H ; CH2), 3.72 (dt, 3J(H,H) 9.1, 4.2 Hz, 1H; H5), 4.18
(d, 3J(H,H) 4.2 Hz, 2H; H6, H'6), 4.66 (ddm, 3J(H,F) 15.5 Hz,
H] , 539 (9) [M 15] , 329 (27), 275 (95), 215 (66), 153 (100); HRMS (EI):
calcd for C27H32O10F2 554.1963, found 554.1956; C27H32O10F2 (554.20): calcd
for C 58.46, H 5.82; found C 58.18, H 5.59. Minor b anomer: [a]2D2
12.7
(c 0.30 in chloroform); 1H NMR (250 MHz, CDCl3): d 1.32 (s, 3H,
CH3), 1.51 (s, 3H, CH3), 2.08 (s, 3H, COCH3), 3.19 (d, 3J(H,H) 6.9 Hz,
908
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0704-0908 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 4