1041s; δH (CDCl3) 0.96–1.04 (2 H, m, CHAHB), 1.33–1.45 (1 H,
m, CHX), 2.08 (3 H, s, CH3), 2.53 (1 H, s, OH ), 3.78 (1 H, m,
CHEHFOH), 3.85 (1 H, m, CHEHFOH), 4.07 (ddd, J 11.7, 7.9
and 1.3, 1 H, CHCHDOAc), 4.32 (1 H, ddd, J 11.7, 6.9 and 1.5,
CHCHDOAc); δC (CDCl3) 13.4 (dt, J 11.4, CHAHB), 19.3 (dd,
J 11.4, CHX), 20.9 (q, CH3), 62.5 (dt, J 8.9, CHCHDOAc), 65.6
(dt, J 22.9, CHEHFOH), 81.9 (ds, J 222.5, C-F), 171.2 (s, C(O)-
CH3); δF (CDCl3) Ϫ203.6 (m); m/z 145 (9%), 119 (1), 102 (5), 86
(11), 82 (4), 73 (17), 69 (12), 61 (5), 59 (7), 55 (7), 53 (9), 43
(100).
which was synthesized as described in the literature.41 The reac-
tion mixture was purified twice by column chromatography
(ethyl acetate/cyclohexane, 1 : 1 and ethyl acetate/cyclohexane,
3 : 2). After HPLC (ethyl acetate/cyclohexane 3 : 1) 9a (106 mg,
53%) was isolated as a viscous oil. (Found: C, 59.7; H, 4.6;
N, 7.7. Calc. for C18H17FN2O5: C, 60.0; H, 4.8; N, 7.8%);
νmax(KBr)/cmϪ1 1750s (aliph. C᎐O), 1707m (arom. C᎐O), 1663s
᎐
᎐
(arom. C᎐O), 1386s (C–O), 1242s (CF); δ (CDCl3) 0.91 (1 H,
᎐
H
ddd, J 10.3, 10.3 and 7.4, CHAHB), 1.38 (1 H, dddd, J 18.8,
10.3, 7.4 and 1.3, CHAHB), 1.78–1.99 (1 H, m, CHX), 2.05 (3 H,
s, CH3), 3.54–3.75 (1 H, m, CHCHDOAc), 4.08–4.41 (3 H, m,
CHCHDOAc and CHEHFN), 5.85 (1 H, d, J 8.1, Ar), 7.45–7.50
(3 H, m, Ar), 7.62–7.68 (2 H, m, Ar), 7.91–7.94 (2 H, m, Ar);
δC (CDCl3) 14.7 (dt, J 11.4, CHAHB), 20.7 (q, CH3), 21.8 (dd,
J 12.7, CHX), 49.2 (dt, J 20.3, CHEHFN), 62.7 (t, CHCHDOAc),
80.7 (ds, J 218.7, C-F), 102.4 (d), 129.1 (d), 130.4 (d), 131.4 (s),
General procedure for Mitsunobu reactions
Under argon the alcohols 6a or 6b (162 mg, 1.0 mmol), PPh3
(525 mg, 2.0 mmol) and the corresponding nucleobase
(2.0 mmol) were suspended in anh. 1,4-dioxane (10 cm3). A
solution of diethyl azodicarboxylate (DEAD) (351 mg,
2.0 mmol) in anh. 1,4-dioxane (15 cm3) was added within 3–4 h.
After stirring overnight at room temperature all volatiles were
removed under vacuum. The residue was absorbed to SiO2 and
purified by column chromatography.
135.1 (d), 144.2 (dd, J 2.5, Ar), 150.1 (s, C ᎐O), 162.2 (s,
᎐
Ar
C ᎐O), 168.4 (s, C᎐O), 170.5 (s, C(O)-CH ); δ (CDCl ) Ϫ175.6
᎐
᎐
Ar
3
F
3
(m); m/z 361 (1%), 332 (1), 317 (2), 301 (15), 273 (9), 255 (2), 217
(5), 197 (6), 189 (2), 145 (7), 122 (2), 105 (100), 85 (7), 77 (92),
51 (18), 43 (56).
9-{[cis-1Ј-Fluoro-2Ј-(acetoxymethyl)cycloprop-1Ј-yl]methyl}-
adenine (7a). According to the general procedure for the
Mitsunobu reaction, 6a (122 mg, 0.75 mmol) was reacted with
adenine (203 mg, 1.5 mmol). After column chromatography
(ethyl acetate/methanol, 10 : 1) 7a (68 mg, 52%) was isolated as
an amorphous, white powder; mp 183 ЊC; (Found: C, 51.1; H,
4.6; N, 24.3. Calc. for C12H14FN5O2: C, 51.6; H, 5.0; N, 25.1%);
δH (MeOH-d4) 1.02–1.12 (1 H, m, CHAHB), 1.30–1.43 (1 H, m,
CHAHB), 1.79–2.01 (1 H, m, CHX), 1.88 (3 H, s, CH3), 3.84
(1 H, dd, J 12.0 and 9.9, CHCHDOAc), 4.38 (1 H, ddd, J 12.0,
6.2 and 2.7, CHCHDOAc), 4.60–4.88 (2 H, m, CHEHF-N), 8.18–
8.21 (2 H, m, Ar); δC (MeOH-d4) 15.1 (dt, J 10.2, CHAHB), 20.5
(q, CH3), 22.7 (dd, J 12.7, CHX), 45.9 (dt, J 22.9, CHEHF-N),
64.2 (t, CHCHDOAc), 81.7 (ds, J 218.7, C-F), 119.6 (s),
3-Benzoyl-1-{[trans-1Ј-fluoro-2Ј-(acetoxymethyl)cycloprop-
1Ј-yl]methyl}uracil (9b). According to the procedure described
above, 9b was prepared from 6b (105 mg, 0.648 mmol). After
column chromatography (ethyl acetate/cyclohexane, 1 : 1) and
HPLC (ethyl acetate/methanol, 1 : 1) 9b (95 mg, 41%) was iso-
lated as a viscous oil. (Found: C, 59.7; H, 4.8; N, 7.5. Calc. for
C18H17FN2O5: C, 60.0; H, 4.8; N, 7.8%); νmax(KBr)/cmϪ1 1749s
(aliph. C᎐O), 1707s (arom. C᎐O), 1666s (arom. C᎐O), 1386s
᎐
᎐
᎐
(C–O), 1245s (CF); δH (CDCl3) 0.94–1.24 (2 H, m, CHAHB),
1.43–1.55 (1 H, m, CHX), 1.98 (3 H, s, CH3), 3.88 (1 H, ddd,
J 11.7, 9.1 and 1.3, CHCHDOAc), 4.01–4.10 (2 H, m, CHEHFN),
4.31 (1 H, ddd, J 11.7, 5.8 and 1.5, CHCHDOAc), 5.75 (1 H, d,
J 7.9, Ar), 7.35 (1 H, dd, J 7.9 and 1.1, Ar), 7.26 (2 H, m, Ar),
7.55–7.61 (1 H, m, Ar), 7.84–7.88 (2 H, m, Ar); δC (CDCl3) 14.4
(dt, J 11.4, CHAHB), 20.4 (dd, J 10.2, CHX), 20.8 (q, CH3), 52.1
(dt, J 20.3, CHEHFN), 61.9 (dt, J 8.9, CHCHDOAc), 80.4 (ds,
J 222.5, C-F), 102.2 (d), 129.1 (d), 130.3 (d), 131.4 (s), 135.1 (d),
142.6 (d), 151.0 (s), 153.9 (d), 157.3 (s, Ar), 172.2 (s, C᎐O);
᎐
δF (MeOH-d4) Ϫ174.8 (m); m/z 279 (2%), 259 (9), 236 (6), 220
(45), 216 (45), 200 (85), 183 (4), 173 (3), 148 (17), 135 (100), 119
(5), 108 (38), 85 (18), 65 (6), 54 (5), 43 (55); m/z (ESI) 280.1210
(M ϩ Hϩ, C12H14FO2 requires 280.1241); 302.1065 (M ϩ Naϩ,
NaC12H13FO2 requires 302.1029).
144.2 (d), 150.2 (s, C ᎐O), 162.2 (s, C ᎐O), 168.4 (s, C᎐O),
᎐
᎐
Ar
᎐
Ar
170.7 (s, C(O)-CH3); δF (CDCl3) Ϫ198.7 (m); m/z 360 (3%), 328
(3), 317 (6), 301 (100), 290 (9), 287 (4), 255 (2), 217 (8), 206 (13),
197 (15), 189 (10), 145 (28), 122 (6), 105 (100), 95 (30), 77 (100),
51 (43), 43 (100).
9-{[trans-1Ј-Fluoro-2Ј-(acetoxymethyl)cycloprop-1Ј-yl]methyl}-
adenine (7b). According to the procedure described above, 7b
was prepared from 6b (98 mg, 0.60 mmol). After column
chromatography (ethyl acetate, ethyl acetate/methanol, 20 : 1)
7b (110 mg, 66%) was isolated as a white, amorphous powder;
mp 161 ЊC; (Found: C, 51.2; H, 5.2; N, 24.7. Calc. for C12H14-
FN5O2: C, 51.6; H, 5.1; N, 25.1%); δH (MeOH-d4, 360 MHz,
50 ЊC) 1.09 (1 H, ddd, 20.4, 7.4 and 7.4, CHAHB), 1.32 (1 H,
ddd, J 10.2, 10.2 and 7.4, CHAHB), 1.70–1.79 (1 H, m, CHX),
1.82 (3 H, s, CH3), 3.84 (1 H, ddd, J 11.5, 9.4 and 1.2, CHCHD-
OAc), 4.38 (1 H, ddd, J 11.5, 5.9 and 1.4, CHCHDOAc), 4.49
(1 H, dd, 25.3 and 15.4, CHEHFN), 4.75 (1 H, dd, 18.3 and
15.4, CHEHFN), 8.16 (1 H, d, J 1.1, Ar), 8.22 (1 H, s, Ar);
δC (MeOH-d4, 90.57 MHz, 50 ЊC) 15.2 (dt, J 11.1, CHAHB),
20.7 (q, CH3), 22.0 (dd, J 9.6, CHX), 49.2 (dt, J 20.7,
CHEHFN), 63.6 (dt, J 9.1, CHCHDOAc), 81.9 (ds, J 222.8,
C-F), 120.2 (s), 143.0 (d), 151.4 (s), 154.2 (d), 157.7 (s, Ar),
172.7 (s, C᎐O); δ (MeOH-d4) Ϫ198.4 (m); m/z 279 (17%),
3-Benzoyl-1-{[cis-1Ј-fluoro-2Ј-(acetoxymethyl)cycloprop-
1Ј-yl]methyl}thymine (11a). According to the general procedure
for the Mitsunobu reaction, cis alcohol 6a (84 mg, 0.519 mmol)
was reacted with N 3-benzoylthymine (14) (239 mg, 1.038
mmol), which was synthesized as described.41 After column
chromatography (ethyl acetate/cyclohexane, 3 : 2) a mixture of
11a and ethyl NЈ-(2-ethoxyacetyl)hydrazine carboxylate (30%)
was isolated. The latter compound was removed by crystalliz-
ation from ethyl acetate at Ϫ20 ЊC. After further purification of
the mother liquor by column chromatography (ethyl acetate/
cyclohexane, 3 : 2), 11a (142 mg, 73%) was isolated as a white
solid. For elemental analysis the product was recrystallized
from CH2Cl2/pentane (1 : 2) at Ϫ20 ЊC; mp 87 ЊC (from CH2Cl2/
pentane); (Found: C, 60.4; H, 4.9; N, 7.5. Calc. for C19H19-
FN2O5: C, 61.0; H, 5.1; N 7.5%); νmax(KBr)/cmϪ1 1749s (aliph.
C᎐O), 1699m (arom. C᎐O), 1656s (arom. C᎐O), 1251m (CF),
᎐
F
᎐
᎐
᎐
236 (8), 220 (100), 200 (22), 173 (3), 152 (2), 135 (100), 119 (3),
108 (30), 85 (17), 81 (7), 59 (4), 43 (50); m/z (ESI) 280.1210
(M ϩ Hϩ, C12H14FO2 requires 280.1257); 302.1029 (M ϩ Naϩ,
NaC12H13FO2 requires 302.1088).
1231m; δH (CDCl3) 0.92 (1 H, ddm, J 10.3 and 7.5, CHAHB),
1.25–1.43 (1 H, ddm, J 10.3 and 1.5, CHAHB), 1.76–1.93 (1 H,
m, CHX), 1.98 (3 H, s, CH3), 2.05 (3 H, s, C(O)-CH3), 3.73 (1 H,
dd, J 12.2 and 9.4, CHCHDOAc), 4.11–4.25 (2 H, dm, J 1.5,
CHEHFN), 4.30–4.40 (1 H, dm, J 12.2, CHCHDOAc), 7.30 (1 H,
t, J 1.2, Ar), 7.46–7.52 (2 H, m, Ar), 7.64 (1 H, tt, J 7.4 and 1.3,
Ar), 7.89–7.94 (2 H, m, Ar); δC (CDCl3) 12.4 (q, CH3), 14.7 (dt,
J 11.0, CHAHB), 20.7 (q, C(O)-CH3), 21.9 (dd, J 12.7, CHX),
49.0 (dt, J 20.3, CHEHFN), 62.7 (t, CHCHDOAc), 80.9 (ds,
3-Benzoyl-1-{[cis-1Ј-fluoro-2Ј-(acetoxymethyl)cycloprop-1Ј-yl]-
methyl}uracil (9a). According to the general procedure for the
Mitsunobu reaction, cis alcohol 6a (90 mg, 0.556 mmol) was
reacted with N 3-benzoyluracil (13) (240 mg, 1.112 mmol),
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 2 2 9 – 2 3 7
233