Jiang et al.
δ 1.41 (s, 9H), 1.46 (s, 9H), 1.89-1.96 (m, 1H), 2.14-2.21 (m,
1H), 2.43-2.49 (m, 1H), 2.51-2.59 (m, 1H), 2.65-2.70 (m, 1H),
3.16-3.21 (m, 1H), 3.72-3.78 (m, 1H), 4.24-4.28 (m, 1H), 4.48
(t, J ) 4 Hz, 1H), 4.95-5.00 (m, 1H), 5.09-5.24 (m, 4H), 5.28-
5.30 (m, 1H), 7.32-7.35 (m, 5H), 8.62 (s, 1H), 8.73 (s, 1H). 13C
NMR (125 MHz, CDCl3): δ 24.1, 27.9, 28.3, 29.8, 36.5, 43.0, 52.7,
55.0, 65.7, 71.8, 80.5, 82.5, 85.6, 107.3, 127.9, 128.1, 128.6, 128.7,
136.2, 145.8, 150.7, 151.6, 151.9, 155.9, 164.8, 171.5, 171.6. IR
Experimental Section
(S)-1-Benzyl 7-tert-Butyl 6-(tert-Butoxycarbonyl)-2-((1S,4R)-
4-(6-chloro-9H-purin-9-yl)cyclopent-2-enyl)-3-oxoheptanedio-
ate (18). To a solution of keto ester 15 (1.09 g, 2.5 mmol) in THF
(4 mL) was added NaH (0.10 g, 2.51 mmol), and the resultant
mixture was stirred for 20 min. In a separate flask, palladium acetate
(80 mg, 0.35 mmol) was dissolved in THF (2 mL), followed by
addition of PPh3 (0.37 g, 1.43 mmol). The resulting canary yellow
solution was stirred for 5 min. Acetate 17 (0.50 g, 1.79 mmol) was
added, and the reaction was stirred for another 10 min. The enolate
was transferred to the π-allyl complex via cannulation. This mixture
was allowed to stir at 40 °C for 2 h while monitoring the progress
of the reaction by TLC. After completion of the reaction, water (5
mL) was added and the biphasic mixture was extracted thoroughly
with EtOAc (4 × 20 mL). The combined organic extracts were
dried with NaSO4. After filtration and concentration, the residue
was purified by column chromatography, eluting with hexanes/
EtOAc from 5:1 to 1:1 to afford 1.05 g (80%) of compound 18 as
(neat) ν 3332, 2979, 1702, 1639, 1591, 1565, 1368, 1153, 755 cm-1
.
HRMS calcd for C33H4135ClN5O8 (M + H)+, 670.2644; found,
670.2690. The structure of this compound was confirmed by X-ray
analysis.
(S)-tert-Butyl 2-(tert-Butoxycarbonyl)-4-(3aR,5R,6R,6aS)-5-(6-
chloro-9H-purin-9-yl)-2,6-dihydroxyhexahydro-2H-cyclopenta-
[b]furan-2-ylbutanoate (23). The compound was prepared using
1
the same procedure as that for the synthesis of compound 21. H
NMR (300 MHz, CDCl3): δ 1.41 (s, 9H), 1.42 (s, 9H), 1.44 (s,
9H), 1.45 (s, 9H), 1.84-2.61 (m, 14H), 2.81-2.93 (m, 1H), 3.06
(dd, J ) 13.5, 9.9 Hz, 1H), 4.16-4.27 (m, 4H), 4.51 (dd, J ) 9.9,
3.9 Hz, 1H), 4.88-4.97 (m, 2H), 8.50 (s, 1H), 8.67 (s, 1H), 8.68
(s, 1H), 8.82 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 26.0, 26.7,
27.9 (2C), 28.21, 28.24, 35.2, 36.3, 37.9, 38.0, 39.3, 40.3, 40.6,
43.2, 57.9, 58.1, 60.9, 61.6, 70.1, 71.3, 80.5, 81.1, 81.2, 81.4, 81.5,
86.1, 105.2, 105.4, 131.1 (2C), 145.5, 146.0, 150.56, 150.63, 151.4,
151.6, 151.7, 151.8, 152.8, 153.1, 171.2, 171.7. IR (neat, CH2Cl2)
ν 3361, 2978, 2934, 1740, 1697, 1591, 1368, 1158 cm-1. HRMS
(FAB) calcd for C25H3535ClN5O6 (M - H2O), 536.2276; found,
536.2270.
(3aR,5R,6R,6aS)-6-(6-Chloro-9H-purin-9-yl)-2,2-dimethyl-tet-
rahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl Acetate (24). To a
solution of compound 17 (0.24 g, 0.86 mmol) in THF (8 mL) was
added NMO (0.2 g, 1.72 mmol) followed by OsO4 solution in
2-methyl-2-propanol (1.08 mL, 0.086 mmol) dropwise. The mixture
was stirred at room temperature for 1 h and was monitored by TLC.
The reaction was quenched with 10% Na2S2O5 solution (4 mL),
and the mixture was stirred for 10 min. It was diluted with H2O,
extracted with EtOAc. The organic layer was washed with H2O
and brine and dried over Na2SO4. After filtration and concentration,
the residue was dissolved in 2,2-dimethoxypropane followed by
pTSA‚H2O (16 mg, 0.086 mmol). The reaction was stirred at room
temperature overnight. The reaction was quenched with NaHCO3
solution and extracted with EtOAc. The organic layer was washed
with H2O and brine and dried over Na2SO4. After filtration and
concentration, the residue was purified by column chromatography
eluting with 1:1 hexanes/EtOAc to afford 0.13 g (64% for two steps)
of compound 24 as a colorless oil. [R]D ) -8.0° (c ) 0.5, CHCl3).
1H NMR (300 MHz, CDCl3): δ 1.32 (s, 3H), 1.54 (s, 3H), 2.02 (s,
3H), 2.39-2.44 (m, 1H), 2.85-2.95 (m, 1H), 4.77-4.79 (m, 1H),
5.07-5.10 (m, 2H), 5.28-5.30 (m, 1H), 8.22 (s, 1H), 8.77 (s, 1H).
13C NMR (75 MHz, CDCl3): δ 20.9, 24.2, 26.5, 34.5, 61.2, 77.9,
84.1, 84.2, 112.6, 131.8, 143.9, 151.7, 152.0, 169.4. IR (CH2Cl2) ν
1746, 1591, 1562, 1235 cm-1. HRMS calcd for C15H1835ClN4O4
(M + H)+, 353.1017; found, 353.1015.
1
a 1:1 mixture of diastereoisomers. H NMR (300 MHz, CDCl3):
δ 1.31 (s, 9H), 1.39 (s, 18H), 1.41 (s, 9H), 1.52-2.13 (m, 6H),
2.42-2.70 (m, 4H), 2.85-3.03 (m, 2H), 3.55-3.57 (m, 2H), 3.66-
3.71 (m, 2H), 4.04-4.06 (m, 2H), 4.96-4.99 (m, 2H), 5.12 (AB,
J ) 17.4, 12 Hz, 1H), 5.124 (AB, J ) 13.8, 13.8 Hz, 1H), 5.69-
5.76 (m, 2H), 5.83-5.87 (m, 2H), 6.05-6.12 (m, 2H), 7.24-7.33
(m, 10H), 8.10 (s, 1H), 8.13 (s, 1H), 8.69 (s, 2H). 13C NMR (125
MHz, CDCl3): δ 26.2, 26.8, 27.75, 27.78, 28.0, 28.1, 35.6, 36.3,
38.0, 38.6, 43.5, 43.8, 52.5, 53.1, 52.5, 53.1, 59.9, 62.4, 62.6, 67.3,
79.5, 79.6, 82.0, 128.3, 128.4, 128.5, 128.6, 129.0, 129.2, 131.7,
134.66, 134.73, 138.2, 138.5, 143.6, 150.65, 150.68, 151.3, 151.5,
155.3, 155.4, 167.8, 167.9, 171.05, 171.13, 202.1, 202.5. IR (neat)
ν 3332, 2886, 1667, 1641, 1245 cm-1. MS (m/e, rel int.) 654 (25),
326 (20), 189 (25), 136 (100). HRMS calcd for C33H4135Cl N5O7
(M + H)+, 654.2695; found, 654.2670.
(S)-tert-Butyl 2-(tert-Butoxycarbonyl)-6-((1R,4R)-4-(6-chloro-
9H-purin-9-yl)cyclopent-2-enyl)-5-oxohexanoate (19). To a solu-
tion of compound 18 (0.37 g, 0.57 mmol) in THF (3 mL)-H2O (3
mL) was added Na2S‚9H2O (1.1 g, 4.53 mmol). The mixture was
stirred for 60 h and extracted with EtOAc. The combined organic
layers were dried over Na2SO4. After filtration and concentration,
the residue was purified by column chromatography, eluting with
2:3 to 1:2 hexanes/EtOAc to afford 0.21 g (71%) of compound 19
as a colorless oil. [R]D ) +3.4° (c ) 0.45, CHCl3). 1H NMR (300
MHz, CDCl3): δ 1.37 (s, 9H), 1.42 (s, 9H), 1.50-1.59 (m, 1H),
1.74-1.79 (m, 1H), 2.08-2.13 (m, 1H), 2.37-2.75 (m, 5H), 3.02
(dt, J ) 13.8, 8.4 Hz, 1H), 3.26-3.31 (m, 1H), 5.05 (d, J ) 7.8
Hz, 1H), 5.73-5.78 (m, 1H), 5.85-5.88 (m, 1H), 6.17-6.21 (m,
1H), 8.15 (s, 1H), 8.72 (s, 1H). 13C NMR (75 MHz, CDCl3): δ
26.8, 27.9, 28.3, 38.5, 38.6, 40.0, 48.0, 53.1, 60.5, 79.7, 82.1, 127.8,
131.9, 141.1, 143.4, 150.9, 151.5, 151.7, 155.4, 171.4, 207.6. IR
(CH2Cl2) ν 2980, 2927, 1713, 1590, 158, 1480, 1367, 1260 cm-1
.
HRMS calcd for C25H3535ClN5O5 (M + H)+, 520.2327; found,
520.2347.
(3aR,5R,6R,6aS)-Benzyl 2-((S)-4-tert-Butoxy-3-(tert-butoxy-
carbonyl)-4-oxobutyl)-5-(6-chloro-9H-purin-9-yl)-6-hydroxy-
4,5,6,6a-tetrahydro-3aH-cyclopenta[b]furan-3-carboxylate (21).
To a solution of compound 18 (66 mg, 0.1 mmol) in THF (1 mL)
was added NMO (24 mg, 0.2 mmol) followed by an OsO4 solution
in 2-methyl-2-propanol (0.13 mL, 0.01 mmol) dropwise. The
mixture was stirred at room temperature for 4 h, and the reaction
was monitored by TLC. The reaction was quenched with 10%
Na2S2O5 solution (2 mL), and the mixture was stirred for 10 min.
It was diluted with H2O, extracted with EtOAc. The organic layer
was washed with H2O and brine and dried over Na2SO4. After
filtration and concentration, the residue was purified by column
chromatography, eluting with 1:1 hexanes/EtOAc to afford 48 mg
(70%) of compound 20 as an oil. Compound 20 was not stable,
and it was slowly transformed to compound 21. Compound 21 was
(3aR,5R,6R,6aS)-6-(6-Chloro-9H-purin-9-yl)-2,2-dimethyl-tet-
rahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (25). To a solution of
compound 24 (0.18 g, 0.51 mmol) in CH3OH (5 mL) was added
Bu2SnO (13 mg, 0.051 mmol). The mixture was stirred at 70 °C
overnight under an Ar atmosphere. The solvent was removed under
reduced pressure, and the residue was purified by column chro-
matography eluting with 1:3 hexanes/EtOAc to afford 135 mg
(85%) of compound 25 as a white crystalline solid. Mp ) 152-
1
153 °C. [R]D ) -20° (c ) 0.75, CH3OH). H NMR (300 MHz,
CDCl3): δ 1.31 (s, 3H), 1.52 (s, 3H), 2.22-2.28 (m, 1H), 2.85-
2.95 (m, 1H), 3.59 (bs, 1H), 4.53-4.54 (m, 1H), 4.71 (d, J ) 5.7
Hz, 1H), 4.91 (d, J ) 5.7 Hz, 1H), 5.06-5.09 (m, 1H), 8.49 (s,
1H), 8.76 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 24.2, 26.7, 36.9,
62.6, 76.1, 86.2, 87.0, 111.8, 131.5, 145.8, 151.0, 151.3, 151.8. IR
(CH2Cl2) ν 3339, 1592, 1562, 1338, 1211 cm-1. HRMS calcd for
C13H1635ClN4O3 (M + H)+, 311.0911; found, 311.0926.
1
characterized. Mp ) 118-120 °C. H NMR (500 MHz, CDCl3):
4168 J. Org. Chem., Vol. 71, No. 11, 2006