Vijgen et al.
1H NMR (CDCl
) δ 1.52 (s, 6H), 6.17 (s, 2H) ppm; 13C NMR
(M + H)+ 223.0946, found 223.0949. Anal. Calcd (C10
H O ):
16 6
C, 59.98; H, 8.05. Found: C, 59.48; H, 7.93.
3
(
CDCl
3
) δ 24.8, 114.1, 126.6.
(
()-(3aS,4R,7S,7aR)-7-({[tert-Butyl(dimethyl)silyl]oxy}-
methyl)-2,2-dimethyl-3a,4,7,7a-tetrahydro-1,3-benzodioxo-
-ol (14). To a solution of 13 (620 mg, 3.09 mmol) in dry DMF
13 mL) at 0 °C was added imidazole (316 mg, 4.64 mmol, 1.5
4
(
equiv), followed by TBDMSCl (560 mg, 3.72 mmol, 1.2 equiv)
in three portions (after 0.5 h). The reaction was stirred at 0
°
C for 10 min and at room temperature overnight and
quenched with water. The resulting mixture was evaporated
to remove DMF. The residue was absorbed on silica and
chromatographed (hexanes-EtOAc 10:1, 5:1, 1:1, 1:2) to yield
1
4 (580 mg, 59.6%) and unreacted 13 (110 mg, 17.7%) both as
an oil. Spectroscopic data of 14 are given: R 0.57 (hexanes-
) δ 0.084 (s, 6H), 0.91 (s, 9H), 1.36
s, 3H), 1.45 (s, 3H), 2.37 (m, 1H), 2.60 (br-s, 1H), 3.78 (d, 2H,
J ) 1.8 Hz), 4.05-4.21 (m, 3H), 5.73 (ddd, 1H, J ) 9.8, 3.5,
f
1
EtOAc 2:1); H NMR (CDCl
(
3
1
3
2
.0 Hz), 5.93 (dt, 1H, J ) 10.4, 2.6 Hz) ppm; C NMR (CDCl
3
)
δ -5.55, 18.3, 24.7, 25.9, 27.2, 42.9, 64.1, 69.5, 74.1, 80.3, 108.4,
+
+
1
28.3, 130.8 ppm; FAB 337.2 (M + Na) ; HRMS calcd for
+
C
16
H
16
30
O
30
4
Si (M + Na) 337.1811, found 337.1807. Anal. Calcd
Si): C, 61.11; H, 9.61. Found: C, 60.69; H, 9.19.
1
-Bromo-4,4-dimethyl-3,5,8-trioxa-tricyclo[5.2.2.0]undec-
(
C
H
O
4
13,14
1
0-en-9-one (11).
A 15 mL pressure tube (Aldrich) was
(
()-(3aR,7S,7aR)-7-({[tert-Butyl(dimethyl)silyl]oxy}-
charged with 10a (1.28 g, 7.31 mmol), 6 (3.56 g, 35.59 mmol,
methyl)-2,2-dimethyl-7,7a-dihydro-1,3-benzodioxo-4(3aH)-
one (15). A mixture of 14 (120 mg, 0.38 mmol) and activated
4
0
.87 equiv), and H u¨ nig’s base (EtN(i-Pr)
2
, 85.3 mg 0.66 mmol,
.09 equiv). After CH Cl (5.6 mL) was added, the tube was
2
2
MnO
was stirred vigorously. After 12 h, MnO
0 equiv) was added to the mixture. After another 12 h, the
completion of the reaction was checked by TLC. Again, MnO
66 mg, 0.76 mmol, 2 equiv) was added, and stirring was
continued overnight. The reaction mixture was diluted with
CH Cl , filtered through Celite, and concentrated. The residue
was chromatographed on silica gel (hexanes-EtOAc 6:1) to
give 15 (100 mg, 84%) as a white solid: R 0.68 (hexanes-
) δ 0.00 (s, 3H), 0.03 (s, 3H), 0.83
s, 9H), 1.35 (s, 3H), 1.40 (s, 3H), 2.99 (m, 1H), 3.74 (dd, 1H,
2
(332 mg, 3.82 mmol, 10 equiv) in dry CH
2 2
Cl (6 mL)
sealed and placed in an oven (90 °C) for 4 days. After cooling
to room temperature, the resulting brown-yellow solution was
concentrated. The residue was purified by flash chromatog-
2
(332 mg, 3.82 mmol,
1
2
raphy on silica gel (50 g of SiO
hexanes-EtOAc (10:1 + 1% Et
2
, the column was packed with
N) and eluted with hexanes-
(
3
3
EtOAc (1:1 + 1% Et N) in less than 3 min due to the instability
2
2
of 11 on the silica gel). The resulting yellow solution was
concentrated to give an orange-yellow oil as a mixture of the
f
endo and exo isomers. The spectroscopic data of the endo
1
1
EtOAc 2:1); H NMR (CDCl
3
isomer are given: R
CDCl
Hz), 4.77 (dd, H, J ) 7.0, 4.4 Hz), 5.27 (td, 1H, J ) 4.5, 2.2
f
0.68 (hexanes-EtOAc 2:1); H NMR
(
(
3
) δ 1.38 (s, 3H), 1.42 (s, 3H), 4.63 (dd, 1H, J ) 6.9, 1.2
1
J ) 10.1, 3.0 Hz), 3.92 (dd, 1H, J ) 10.0, 4.0 Hz), 4.35 (d, 1H,
J ) 5.0 Hz), 4.51 (dt, 1H, J ) 3.6, 1.65 Hz), 6.19 (d, 1H, J )
1
3
Hz), 6.34-6.48 (m, 2H) ppm; C NMR (CDCl
3
) δ 25.3, 25.4,
0.4, 73.2, 76.7, 79.4, 114.5, 129.1, 135.8, 166.0 ppm.
,4-Dimethyl-3,5,8-trioxa-tricyclo[5.2.2.0]undec-10-en-
1
3
1
0.2 Hz), 6.74 (dddd, 1H, J ) 10.3, 5.2, 1.8 Hz) ppm; C NMR
6
(
CDCl
3
) δ -5.7, 18.1, 25.7, 25.8, 27.4, 41.6, 63.3, 75.7, 77.0,
4
+
+
1
3
108.5, 129.8, 147.2, 196.1 ppm; FAB 335.1 (M + Na) ; HRMS
9
-one (12). A solution of 11 (1.34 g, 4.87 mmol), tributyltin
SnH, 1.94 mL, 7.31 mmol, 1.5 equiv), and AIBN
0.28 g, 0.49 mol, 0.1 equiv) in dry toluene (32 mL) was
+
calcd for C16
Anal. Calcd (C16
H, 8.57.
H
28
O
4
Si (M + Na) 335.1654, found 335.1645.
hydride (n-Bu
3
H O Si): C, 61.50; H, 9.03. Found: C, 61.52;
28 4
(
degassed under nitrogen. The solution was immersed in a
preheated bath (130 °C) and refluxed for 1 h. The reaction
mixture was cooled and concentrated. The residue was purified
on a silica column. The column was eluted with hexane (500
(
()-(3aS,4S,7S,7aR)-7-({[tert-Butyl(dimethyl)silyl]oxy}-
methyl)-2,2-dimethyl-3a,4,7,7a-tetrahydro-1,3-benzodioxo-
-ol (16). To a solution of 15 (110 mg, 0.35 mmol) in MeOH (6
mL) at room temperature was added CeCl ‚7H O (197 mg, 0.53
mmol, 1.5 equiv). The mixture was stirred for 1 h, and a clear
solution was obtained. NaBH (16 mg, 0.42 mmol, 1.2 equiv)
4
mL) (to remove n-Bu
hexanes-Et O 1:2 (600 mL) to afford 12 (690 mg, 72.25%):
0.62 (hexanes-EtOAc 2:1) H NMR (CDCl
.34 (s, 3H), 3.87 (ddd, 1H, J ) 1.8, 4.0, 7.4 Hz), 4.60 (dd, 1H,
J ) 6.9, 3.8 Hz), 4.70 (dd, 1H, J ) 6.8, 4.0 Hz), 5.26 (td, 1H,
3
2
SnH), hexanes-Et O 1:1 (500 mL), and
3
2
2
1
R
f
3
) δ 1.33 (s, 3H),
4
2
was added in portions, and H evolved. The reaction mixture
was stirred for 2 h and quenched with crushed ice. The mixture
was stirred for 0.5 h and concentrated. The residue was diluted
1
1
3
J ) 4.4, 2.2 Hz), 6.40-6.51 (m, 2H) ppm; C NMR (CDCl
3
) δ
5.3, 25.4, 46.4, 72.5, 75.1, 75.8, 113.6, 129.6, 130.3, 170.4 ppm.
()-(3aS,4R,7S,7aR)-7-(Hydroxymethyl)-2,2-dimethyl-
with EtOAc (15 mL), washed with H
Na SO , and concentrated. The residue was chromatographed
on silica gel (hexanes-EtOAc 5:1) to give 16 (80 mg, 72.3%)
2
O and brine, dried over
2
(
2
4
18
3
a,4,7,7a-tetrahydro-1,3-benzodioxo-4-ol (13). To a mix-
as a colorless oil and 14 (10 mg, 9.1%) as a side product: R
f
ture of LiAlH
4
(119 mg, 3.13 mmol, 1.5 equiv) in dry THF (20
1
0
0
.63 (hexanes-EtOAc 2:1); H NMR (CDCl
3
) δ 0.05 (s, 6H),
mL) at 0 °C was added a solution of 12 (410 mg, 2.09 mmol)
.89 (t, 9H, J ) 3.0 Hz), 1.39 (s, 3H), 1.45 (s, 3H), 2.60 (m, 2H,
in THF (8 mL) slowly. The reaction mixture was stirred at 0
H4), 3.61 (dd, 1H, J ) 10.3, 4.7 Hz), 3.69 (dd, 1H, J ) 10.2,
°
C for an additional 15 min and at room temperature over-
5
5
1
1
.0 Hz), 4.33-4.44 (m, 3H), 5.82 (dd, 1H, J ) 10.9, 4.5 Hz),
night. A saturated sodium bisulfite solution was added drop-
wise to the reaction mixture until a precipitate was formed.
EtOAc (3 mL) was added, and the mixture was stirred for an
additional 0.5 h. The precipitate was filtered, and the filtrate
was concentrated. The residue was purified with a silica
13
.92 (dd, 1H, J ) 11.5, 2.6 Hz) ppm; C NMR (CDCl
3
) δ -5.6,
8.3, 24.5, 25.8, 26.4, 42.0, 64.0, 64.6, 74.3, 75.7, 108.5, 129.4,
+
+
31.1 ppm; FAB 337.2 (M + Na) ; HRMS calcd for C16
30 4
H O -
+
Si (M + Na) 337.1811, found 337.1807.
column (the column was eluted with hexanes-EtOAc 1:1) to
(()-9-[(3aS,4R,7S,7aR)-7-({[tert-Butyl(dimethyl)silyl]-
oxy}methyl)-2,2-dimethyl-3a,4,7,7a-tetrahydro-1,3-ben-
zodioxol-4-yl]-9H-purin-6-amine (17). To a mixture of 16
(220 mg, 0.70 mmol), adenine (189 mg, 1.40 mmol, 2 equiv),
1
give 13 (360 mg, 86%): R
CDCl
1
3
f
0.15 (hexanes-EtOAc 1:1); H NMR
(
3
) δ 1.37 (s, 3H), 1.47 (s, 3H), 2.40 (m, 2H), 3.05 (br-s,
H), 3.78 (m, 2H), 4.10-4.52 (m, 3H), 5.68 (ddd, 1H, J ) 9.85,
.7, 2.2 Hz), 5.97 (dt, 1H, J ) 9.6, 2.7 Hz) ppm; 13C NMR
) δ 24.7, 27.1, 42.3, 64.0, 69.7, 75.3, 80.5, 108.7, 127.2,
and PPh
under N
3
(367 mg, 1.40 mmol, 2 equiv) in dry dioxane (11 mL)
at room temperature was added DIAD (278 µL, 1.40
(
CDCl
3
2
+
+
1
31.8 ppm; FAB 223.1 (M + Na) ; HRMS calcd for C10
H
16
O
4
mmol) very slowly. The reaction mixture was stirred at room-
4596 J. Org. Chem., Vol. 70, No. 12, 2005