R. Miethchen et al. / Tetrahedron Letters 46 (2005) 831–833
833
(d, 1H, J ꢀ 8.0 Hz, NH), 4.40–4.26 (m, 2H, H-5, H-6), 5.52–5.46 (m, 2H, H-3, H-1), 5.41 (ÔqÕ, J6,F ꢀ J1,6
ꢀ
ꢀ
3.69 (ÔtÕ, 1H, J3,4 ꢀ J4,5 ꢀ 8.5 Hz, H-4), 3.56 (s, 3H,
OCH3), 3.55–3.40 (m, 2H, H-3, cyclohexyl–CH), 2.68
(br, 1H, OH), 1.96–1.11 (m, 10H, cyclohexyl–CH2), 1.36
(d, 3H, J ꢀ 5.0 Hz, CH3CH); 13C NMR (125.7 MHz,
CDCl3): d 154.1 (C(O)NH), 100.8 (CHCH3), 90.9 (d,
JC,F ꢀ 182.2 Hz, C-2), 81.6 (d, JC,F ꢀ 23.8 Hz, C-3), 78.2
(C-5), 75.1 (d, JC,F ꢀ 6.5 Hz, C-6), 71.4 (d, JC,F ꢀ 7.5 Hz,
C-4), 69.5 (d, JC,F ꢀ 17.5 Hz, C-1), 59.6 (OCH3), 50.3
(cyclohexyl–CH), 33.2 (2·), 25.4, 24.7 (2·) (cyclohexyl–
CH2), 20.1 (CHCH3); 19F{1H} NMR (235 MHz, CDCl3):
d ꢁ199.9 (s). LC–MS (M+H): m/z = 348.
J5,6 ꢀ 3.5 Hz, 1H, H-6), 5.36 (ÔtÕ, 1H, J4,F ꢀ J3,4 ꢀ J4,5
10.2 Hz, H-4), 5.21 (dd, 1H, J4,5 ꢀ 10.2, J5,6 ꢀ 3.5 Hz,
H-5), 4.97 (ddd, 1H, J2,F ꢀ 46.4, J1,2 ꢀ 3.5, J2,3 ꢀ 9.8 Hz,
H-2), 2.18, 2.15, 2.06, 2.01, 1.95 (s, 15H, 5 · CH3). 13C
NMR (62.9 MHz, CDCl3): d 171.4, 171.4, 171.4, 170.7,
170.5 (5 C@O), 88.9 (d, JC,F ꢀ 188.6 Hz, C-2), 71.7 (d,
JC,F ꢀ 21.0 Hz, C-3), 70.4 (s, C-5), 70.4 (d, JC,F ꢀ 10.2 Hz,
C-4), 68.8 (d, JC,F ꢀ 17.7 Hz, C-1), 68.1 (d, JC,F ꢀ 6.7 Hz,
C-6), 20.5 (CH3); 19F{1H} NMR (235 MHz, CDCl3): d
ꢁ207.5. Anal. Calcd for C16H21FO10 (392.34): C, 48.98;
H, 5.40. Found: C, 49.23; H, 5.57.
1
5 (endo-H form): H NMR (500 MHz, CDCl3): d 5.38 (t,
(3): To a stirred suspension of aluminia supported caesium
fluoride24 (150 mg, c = 1.533 mmol CsF/g support, 1/
15 mol equiv fluoride per acetyl group) in MeOH
(10 mL), the mixture of 6 and 7 (200 mg) was added and
stirring was continued at rt overnight. After filtration and
evaporation of the solvent, the residue was column
chromatographically (CHCl3/MeOH 20:1 ! 5:1) purified.
92 mg (75%) of 8 related to 3 were isolated. The colourless
crystals were recrystallized from acetone/MeOH (10:1), Rf
1H, J ꢀ 4.0 Hz, ClCH2CH), 5.18 (ddd, 1H, J1,F ꢀ 22.5,
J1,2 ꢀ 3.0, J1,6 ꢀ 6.3 Hz, H-1), 4.81 (ddd, 1H, J2,F ꢀ 48.5,
J1,2 ꢀ 3.0, J2,3 ꢀ 5.0 Hz, H-2), 4.72 (d, 1H, J ꢀ 8.0 Hz,
NH), 4.40–4.26 (m, 2H, H-5, H-6), 3.73 (ÔtÕ, 1H,
J3,4 ꢀ J4,5 ꢀ 8.5 Hz, H-4), 3.54 (s, 3H, OCH3), 3.55–3.40
(m, 4H, H-3, cyclohexyl–CH, CHCH2Cl), 2.68 (br, 1H,
OH), 1.96–1.11 (m,10H, cyclohexyl–CH2); 13C N MR
(125.7 MHz, CDCl3):
d
153.9 (C(O)NH), 102.1
21
(CHCH2Cl), 90.8 (d, JC,F ꢀ 183.4 Hz, C-2), 81.0 (d,
JC,F ꢀ 21.2 Hz, C-3), 79.0 (C-5), 74.0 (d, J C,F ꢀ 6.5 Hz,
C-6), 70.7 (d, JC,F ꢀ 7.5 Hz, C-4), 69.5 (d, JC,F ꢀ 17.5 Hz,
C-1), 59.2 (OCH3), 50.2 (cyclohexyl–CH), 44.6 (CH2Cl),
33.2 (2·), 25.4, 24.7 (2·) (5C, cyclohexyl–CH2); 19F{1H}
NMR (235 MHz, CDCl3): d ꢁ202.4 (s). LC–MS (M+H):
m/z = 382.
0.48 (CHCl3/MeOH 1:1); ½aꢂD +46.2 (c 0.66, MeOH); LC–
MS [M]: m/z 182. On heating compound 8 loses from 163–
164 ꢁC and up water by polycondensation; the polycon-
1
densate melts finally at 212–213 ꢁC. H NMR (250 MHz,
CD3OD):
d
4.52 (ddd, 1H, J2,F ꢀ 48.8, J1,2 ꢀ 3.3,
J2,3 ꢀ 9.5 Hz, H-2), 4.11 (ddd, 1H, J1,F ꢀ 6.9, J1,6
ꢀ
4.0 Hz, H-1), 3.93 (ddd, 1H, J6,F ꢀ 4.4, J5,6 ꢀ 3.3 Hz,
H-6), 3.82 (ddd, 1H, J3,F ꢀ 12.3, J3,4 ꢀ 9.4 Hz, H-3), 3.71
(dd, 1H, J4,5 ꢀ 9.7 Hz, H-5), 3.55 (dd, 1H, H-4); 13C N MR
(62.9 MHz, CD3OD): d 94.2 (d, JC,F ꢀ 179.0 Hz, C-2),
74.2 (d, JC,F ꢀ 11.0 Hz, C-4), 73.4 (d, JC,F ꢀ 8.4 Hz, C-6),
72.8 (d, JC,F ꢀ 18.2 Hz, C-3), 72.2 (s, C-5), 71.6 (d,
JC,F ꢀ 17.1 Hz, C-1); 19F{1H} NMR (235 MHz, CD3OD):
d ꢁ206.5.
(2): The 1.3:1 mixture of 4 and 5 (208 mg) was refluxed in
2 mL of 57% aqueous HI for 2 h. After concentration of
the solution under reduced pressure, the residue was
peracetylated with acetic acid anhydride/pyridine at rt
(8 h). Then it was again concentrated. Compounds 6
(Rf = 0.27, 2:1 heptane/EtOAc) and 7 (Rf = 0.37, 2:1
heptane/EtOAc) were column chromatographically sepa-
rated as mixed fraction (200 mg); LC–MS (6: [M+H]: m/z
393; 7: [M]: m/z 368.4). 7: 1H NMR (500 MHz, CDCl3): d
24. Ando, T.; Yamawaki, J.; Kawate, T.; Sumi, S.; Hanafusa,
T. Bull. Chem. Soc. Jpn. 1982, 55, 2504–2507.