9
120 J . Org. Chem., Vol. 63, No. 24, 1998
Notes
2
1
1
4
H), 4.84 (s, 2H), 3.56 (s, 2H). 13C NMR (50 MHz, CDCl
62.8, 151.4, 139.0, 137.3, 136.8, 135.3, 131.6, 130.5, 129.0, 128.3,
27.8, 127.6, 120.4, 113.6, 52.1, 44.7, 32.7. MS (EI): 462 (21),
3
): δ
(s, 3H), 3.59 (s, 2H). 13C NMR (50 MHz, CDCl
151.4, 139.8, 139.1, 136.9, 135.5, 129.6, 129.0 (2), 128.4, 128.3,
127.8, 127.5, 121.2, 114.3, 112.2, 55.1, 52.2, 44.7, 33.2. MS
(EI): 413 (16), 412 (533), 321 (53), 91 (100). HRMS: calcd for
3
): δ 162.9, 159.8,
60 (20), 371 (20), 369 (2), 91 (100). Anal. Calcd for C25
21
H -
BrN
.90.
,3-Dib en zyl-5-[4-(t r iflu or om et h yl)b en zyl]u r a cil (1e).
Compound 1e was prepared according to the typical procedure
starting from 4-(trifluoromethyl)phenyl iodide (272 mg, 1.0
2
O
2
: C, 65.08; H, 4.59; N, 6.07, found C, 64.81; H, 4.55; N,
C
26
H
24
N
2
O
3
: 412.1787, found 412.1780.
5
1
,3-Dib e n zyl-5-[3-(n on a flu or ob u t ylsu lfon yl)b e n zyl]-
1
u r a cil (1j). Compound 1j was prepared according to the typical
procedure starting from 3-(nonafluorobutylsulfonyl)phenyl iodide
(351 mg, 0.7 mmol), Pd(dba)
2
(11.5 mg, 0.02 mmol), tfp (9.2 mg,
2
mmol), Pd(dba) (115 mg, 0.02 mmol), tfp (9.2 mg, 0.04 mmol),
0
.04 mmol), and zinc reagent 2 (5.8 mL, 1.8 mmol, 0.31 M in
and zinc reagent 2 (11.4 mL, 4 mmol, 0.35 M in THF). Reaction
time: 12 h at room temperature. After purification by flash
chromatography (pentane/EtOAc 3:1), the product 1e was
obtained as a yellow oil (388 mg, 86%). IR (neat): 1699 (s), 1664
THF). Reaction time: 12 h at room temperature. After puri-
fication by flash chromatography (pentane/EtOAc 4:1), the
product 1j was obtained as a colorless oil (450 mg, 95%). IR
(neat): 1699 (m), 1663 (m), 1643 (s), 1458 (m), 1450 (m), 1430
-
1
1
(s), 1453 (s), 1324 (s), 1160 (m), 1119 (s), 1065 (m) cm
.
H
-1
1
(
6
(
m) cm
.83 (s, 1H), 5.14 (s, 2H), 4.87 (s, 2H), 3.66 (s, 2H). C NMR
50 MHz, CDCl ): δ 162.9, 151.5, 149.9, 141.7, 139.4, 136.9,
.
H NMR (300 MHz, CDCl ): δ 7.46-7.11 (m, 14H),
3
NMR (200 MHz, CDCl
3
): δ 7.41-7.08 (m, 14H), 6.70 (s, 1H) 5.04
13
1
3
(s, 2H), 4.74 (s, 2H), 3.55 (s, 2H). C NMR (50 MHz, CDCl
3
):
3
δ 162.8, 151.5, 142.7, 139.2, 136.8, 135.3, 129.1, 128.5, 127.9,
1
4
35.4, 130.4, 129.1, 128.5, 128.0, 127.7, 121.8, 119.5, 113.1, 52.3,
4.9, 33.1. MS (EI): 680 (40), 590 (13), 589 (39), 91 (100).
1
3
6
27.7, 125.6, 113.3, 52.2, 44.8, 33.2. MS (EI): 450 (31), 360 (12),
59 (35), 316 (16), 91 (100). Anal. Calcd for C26 : C,
9.33; H, 4.70; N, 6.22, found C, 68.89; H, 4.62; N, 6.13.
,3-Diben zyl-5-(4-m eth oxyben zyl)u r a cil (1f). Compound
f was prepared according to the typical prodecure starting from
-methoxyphenyl iodide (187 mg, 0.8 mmol), Pd(dba) (11.5 mg,
21 3 2 2
H F N O
HRMS: calcd for C29
,3-Diben zyl-5-[(2)-2-h ep ten yl]u r a cil (1k ). Compound 1k
was prepared according to the typical procedure starting from
Z)-1-iodohexene (210 mg, 1.0 mmol), Pd(dba) (11.5 mg, 0.02
21 9 2 5
H F N O S 680.1028, found 680.1039.
1
1
1
4
0
1
(
2
2
mmol), tfp (9.2 mg, 0.04 mmol), and zinc reagent 2 (11.4 mL, 4
mmol, 0.35 M in THF). Reaction time: 12 h at room tempera-
ture. After purification by flash chromatography (pentane/
EtOAc 5:1), the product 1k was obtained as a yellow oil (330
mg, 85%). IR (neat): 2956 (s), 2929 (s), 1701 (s), 1665 (s), 1452
.02 mmol), tfp (9.2 mg, 0.04 mol), and zinc reagent 2 (6 mL,
.94 mmol, 0.32 M in THF). Reaction time: 12 h at room
temperature. After purification by flash chromatography (pen-
tane/EtOAc 4:1), the product 1f was obtained as a white solid
(
330 mg, 62%). Mp: 95 °C. IR (KBr): 1709 (s), 1665 (s), 1510
-1
1
-
1
1
(s), 1382 (s), 1350 (s) cm
.25 (m, 10H), 6.88 (s, 1H), 5.59-5.32 (m, 2H), 5.16 (s, 2H), 4.89
(s, 2H), 3.07 (d, J ) 7.2, 2H), 1.97 (m, 2H), 1.23 (m, 4H), 0.85
tr, J ) 6.8 Hz, 3Η). 13C NMR (50 MHz, CDCl
): δ 163.2, 151.6,
. H NMR (200 MHz, CDCl ): δ 7.70-
(m), 1461 (m), 1243 (m) cm
.
H NMR (200 MHz, CDCl
3
): δ
3
7
7
2
.47-7.05 (m, 12Η), 6.82-6.78 (m, 2H), 6.71 (s, 1H), 5.14 (s,
1
3
H), 4.80 (s, 2H), 3.76 (s, 3H), 3.56 (2H). C NMR (50 MHz,
): δ 163.0, 158.3, 151.5, 138.9, 136.9, 135.5, 130.0, 129.0,
28.4, 127.8, 127.5, 114.8, 114.0, 55.2, 52.2, 44.7, 32.4. MS
EI): 413 (11), 412 (57), 321 (29), 278 (10), 91 (100). Anal. Calcd
for C26 : C, 75.71; H, 5.86; N, 6.79, found C, 75.50; H,
(
3
CDCl
1
(
3
137.9, 137.0, 135.6, 133.6, 129.1, 128.4, 127.8, 127.5, 124.2, 113.3,
112.9, 52.2, 44.7, 31.6, 26.8, 24.6, 22.3, 13.9. MS (EI): 388 (15),
305 (22), 91 (100). HRMS: calcd for C25
388.2157.
H
24
N
2
O
3
28 2 2
H N O 388.2151, found
5
.80; N, 6.44.
,3-Diben zyl-5-(2-m eth oxyben zyl)u r a cil (1g). Compound
g was prepared according to the typical procedure starting from
-methoxyphenyl iodide (187 mg, 0.8 mmol), Pd(dba) (11,5 mg,
.02 mmol), tfp (9.2 mg, 0.04 mmol), and zinc reagent 2 (6.2 mL,
.4 mmol, 0.39 M in THF). Reaction time: 12 h at room
1
Hyd r ogen a tion P r oced u r e. P r ep a r a tion of 3-Ben zyl-5-
(3,5-d im eth ylben zyl)u r a cil (8). To a stirred suspension of 1b
(140 mg, 0.34 mmol) and an equal weight of 10% Pd-C in dry
methanol (2 mL) was added anhydrous formate (108 mg, 1.7
mmol) in a single portion under argon. The resulting mixture
was stirred at reflux, and the reaction was monitored by TLC.
After completion of the reaction (24 h), the catalyst was removed
by filtration through a Celite pad, which was washed with
chloroform (20 mL). The filtrate after evaporation under
reduced pressure afforded the pure uracil derivative 8 as a
colorless solid (84 mg, 77%). Mp: 149-152 °C. IR (KBr): 3217
1
2
0
2
2
temperature. After purification by flash chromatrography (pen-
tane/EtOAc 5:1), the product 1g was obtained as a colorless solid
(
219 mg, 66%). Mp: 80 °C. IR (KBr): 1696 (s), 1638 (s), 1656
-
1
1
(s), 1450 (s), 1246 (m) cm
.
H NMR (300 MHz, CDCl
3
): δ
7
2
1
1
.50-7.48 (m, 12H), 6.88-6.79 (m, 3H), 5.14 (s, 2H), 4.82 (s,
1
3
3
H), 3.60 (s, 5H). C NMR (50 MHz, CDCl ): δ 163.1, 157.3,
51.5, 139.0, 137.0, 135.7, 131.0, 129.1, 128.9, 128.3, 128.2, 128.0,
27.9, 127.5, 126.2, 120.6, 113.0, 110.2, 54.9, 51.9, 44.6, 28.0.
-1
1
(m), 3076 (m), 2944 (m), 1713 (s), 1648 (s), 1447 (m) cm
.
H
NMR (200 MHz, CDCl
3
): δ 10.21 (s, 1Η), 7.36-7.17 (m, 5Η),
MS (EI): 413 (11), 412 (57), 321 (29), 278 (10), 91 (100).
HRMS: calcd for C26 412.1787, found 412.1789.
,3-Diben zyl-5-(2-cya n oben zyl)u r a cil (1h ). Compound 1h
was prepared according to the typical procedure starting from
-cyanophenyl iodide (206 mg, 0.9 mmol), Pd(dba) (11.5 mg, 0.02
13
6
.79-6.63 (m, 4Η), 5.02 (s, 2Η), 3.48 (s, 2Η), 2.20 (s, 6Η).
C
24 2 3
H N O
3
ΝΜR (50 MHz, CDCl ): δ 163.5, 153.3, 138.3, 138.0, 136.7, 135.8,
1
1
28.8, 128.5, 127.7, 127.0, 114.7, 44.1, 33.0, 21.4. MS (EI): 321
(10), 320 (40), 229 (56), 186 (40), 143 (11), 91 (100). HRMS: calcd
2
2
for C20 320.1525, found 320.1523.
20 2 2
H N O
mmol), tfp (9.2 mg, 0.04 mmol), and zinc reagent 2 (7.4 mL, 2.3
mmol, 0.31 M in THF). Reaction time: 12 h at room tempera-
ture. After purification by flash chromatography (pentane/
EtOAc 4:1), the product 1h was obtained as a white solid (278
mg, 76%). Mp: 131 °C. IR (KBr): 1700 (m), 1661 (s), 1452 (m)
Typ ica l P r oced u r e for t h e P d (0)-Ca t a lyzed Cr oss-
Cou p lin g of th e Zin ca ted Th ym in e Der iva tive (2) a n d
1
7
Resin -Atta ch ed o-, m - or p-Iod oben zoa tes (9a -c). Resin
80 mg, ca. 0.6 mmol/g substitution) was placed into a Schlenk
flask. THF (2 mL) containing Pd(dba) (1.4 mg, 2.5 µmol) and
tfp (1.2 mg, 5.0 µmol) and zinc reagent 2 (1.7 mL, 0.5 mmol,
(
-
1
1
2
cm
s, 2H), 4.89 (s, 2H), 3.82 (s, 2H). C NMR (75 MHz, CDCl
δ 162.8, 151.4, 142.5, 140.3, 136.8, 135.3, 132.9 (2), 131.1, 129.1,
.
H NMR (300 MHz, CDCl ): δ 7.58-7.25 (m, 15H), 5.10
3
13
(
3
):
0
4
.30 M in THF) were added, and the reaction mixture was stirred
8 h at room temperature. The resin was then treated with
1
4
29.0, 128.4 (2), 128.3, 127.6, 127.2, 119.0, 112.2, 111.6, 52.6,
4.8, 32.4. MS (EI): 408 (14), 407 (38), 317 (20), 316 (68), 273
MeOH and washed with DMF and repeatedly with MeOH and
CH Cl (four times). The desired compound was cleaved from
the resin by treatment with a CF CO H/H O/CH Cl (9:1:1)
solution for Wang resin or a CF CO H/H O (1:1) solution for
2
2
21 3 2
(13), 91 (100). HRMS: calcd for C26H N O 407.1634, found
3
2
2
2
2
4
07.1639.
,3-Diben zyl-5-(3-m eth oxyben zyl)u r a cil (1i). Compound
i was prepared according to the typical procedure starting from
-methoxyphenyl iodide (187 mg, 0.8 mmol), Pd(dba) (11.5 mg,
.02 mmol), tfp (9.2 mg, 0.04 mmol), and zinc reagent 2 (6.3 mL,
.4 mmol, 0.33 M in THF). Reaction time: 12 h at room
3
2
2
1
Rink resin and evaporated under reduced pressure.
1
3
0
2
2-(3-Ben zyl-2,4-d ioxo-1-p h en eth yl-1,2,3,4-tetr a h yd r o-5-
p yr im id in ylm eth yl)ben zoic a cid (11a ). Compound 11a was
prepared according to the typical procedure starting from Wang-
2
1
7
temperature. After purification by flash chromatography (pen-
tane/EtOAc 4:1), the product 1i was obtained as a colorless oil
resin-attached o-iodobenzoate (92% HPLC purity, UV 254 nm).
1
H NMR (300 MHz, DMSO): δ 7.64-7.00 (m, 15H), 4.79 (s, 2H),
1
3
(
cm
7
265 mg, 80%). IR (neat): 1699 (s), 1642 (s), 1602 (m), 1452 (s)
4.71 (s, 2H), 3.77 (s, 2H). C NMR (75 MHz, DMSO): δ 167.9,
161.8, 150.2, 140.75, 139.0, 136.4, 135.9, 130.9, 129.6, 129.5,
127.9, 127.6, 126.9, 126.7, 126.6, 126.4, 125.6, 111.1, 50.9, 43.1,
-
1
1
.
3
H NMR (200 MHz, CDCl ): δ 7.60-7.47 (m, 2H), 7.32-
.18 (m, 9H), 6.75-6.72 (m, 4H), 5.14 (s, 2H), 4.80 (s, 2H), 3.71