J. Zhao et al. / Tetrahedron 59 (2003) 9379–9382
9381
reaction mixture was allowed to warm to 258C, stirred at
that temperature for 11 h, diluted with water (15 mL), and
extracted with Et O. The combined organic layers were
2
(5 mL), evaporated, and extracted with CH Cl /2-propanol
2 2
(3:1). The combined organic layers were dried (MgSO4),
filtered and concentrated to give a residue, which was
purified by chromatography (SiO , MeOH/CH Cl , 1:10–
dried (MgSO ), filtered, and concentrated to give a residue,
4
2
2
2
which was chromatographed (SiO2, EtOAc/hexanes,
1:5) to afford 1 (28 mg, 74%) as a colorless solid: mp 1878C
1
1
mp 43–458C; H NMR (CDCl ) d 0.17 (s, 3H), 0.20 (s, 3H),
:3–1:1) to afford 8 (337 mg, 84%) as a colorless solid:
1
dec.; H NMR (CD OD) d 1.47 (s, 3H), 2.09 (dd, J¼12.8,
3
8.2 Hz, 1H), 2.68 (dd, J¼12.4, 7.5 Hz, 1H), 5.06 (t, J¼
7.5 Hz, 1H), 7.45 (d, J¼4.8 Hz, 1H), 8.46 (d, J¼5.1 Hz,
3
0
5
1
8
4
.96 (s, 9H), 2.65–2.72 (m, 1H), 3.09–3.11 (m, 1H), 5.14–
.20 (m, 1H), 5.28 (t, J¼6.6 Hz, 1H), 5.60 (dd, J¼3.3,
.8 Hz, 1H), 7.28–7.31 (m, 1H), 8.51 (d, J¼5.1 Hz, 1H),
1
3
1H), 8.55 (s, 1H); C NMR (CD OD) d 29.3, 53.9, 72.2,
3
77.8, 120.8, 145.4, 145.9, 149.3, 155.0. Anal. calcd for
C H NO : C, 65.44; H, 6.71; N, 8.48. Found: C, 65.25; H,
6.75; N, 8.57.
1
3
.79 (s, 1H); C NMR (CDCl ) d 24.7, 24.5, 18.2, 25.8,
3
9
11
2
3.0, 73.3, 105.6, 119.6, 135.4, 143.2, 143.9, 149.0, 155.4.
Anal. calcd for C H NOSi: C, 68.91; H, 8.87; N, 5.36.
5 23
1
Found: C, 69.07; H, 8.96; N, 5.10.
Method B (Prepared directly from 11). A solution of MeLi
(1.51 M, 0.16 mL, 0.24 mmol) in ether was added to a
4
[
.1.4. 1-((t-Butyldimethylsilyl)oxy)-4-oxocyclopentano-
2,3-c]pyridine (9). A solution of 8 (337 mg, 1.29 mmol)
and acetic acid (74 mL, 1.3 mmol) in CH Cl (15 mL) was
stirred solution of 11 (35 mg, 0.23 mmol) in THF (10 mL) at
2788C. After 30 min, a solution of TMSCl (32 mL,
0.25 mmol) in THF (5 mL) was added at 2788C over
5 min. The reaction mixture was stirred at 2788C for 50 min
before a solution of MeLi (1.51 M, 0.23 mL, 0.35 mmol) in
ether was added. The mixture was stirred at 2788C for 1 h,
allowed to warm to 108C, and stirred at that temperature for
1.5 h. Finally, a solution of TBAF (1 M, 0.26 mL,
0.26 mmol) in THF was added at 08C. The mixture was
stirred at 08C for 30 min, allowed to warm to rt overnight,
2
2
stirred at 2788C as ozone was passed through the solution
until the solution turned blue), which was purged with
oxygen for 15 min. Me S (0.6 mL, 8 mmol) was added at
(
2
2
Saturated aqueous NaHCO solution was added and the
two layers were separated. The aqueous layer was further
extracted with CH Cl /2-propanol (3:1). The combined
organic layers were dried (MgSO ), filtered and concen-
788C and the solution was allowed to warm to rt.
3
2
2
quenched with saturated aqueous NaHCO solution, evapo-
3
4
trated to give a residue, which was purified by chroma-
tography (SiO , EtOAc/hexanes, 1:1–3:1) to afford 9
rated, and extracted with CH Cl /2-propanol (3:1). The
2
combined organic layers were dried (MgSO ), filtered and
4
2
2
1
(
NMR (CDCl ) d 0.20 (s, 3H), 0.24 (s, 3H), 0.96 (s, 9H), 2.63
287 mg, 84%) as a colorless solid: mp 67–698C;
H
concentrated to give a residue, which was purified by
chromatography (SiO , MeOH/CH Cl , 1:10–1:5) to
furnish 1 (28 mg, 72%) as a colorless solid.
3
2
2
2
(
5
(
2
dd, J¼18.3, 3.9 Hz, 1H), 3.08 (dd, J¼18.6, 6.6 Hz, 1H),
.37 (dd, J¼6.6, 3.9 Hz, 1H), 7.57 (d, J¼5.1 Hz, 1H), 8.83
1
3
d, J¼5.1 Hz, 1H), 9.02 (s, 1H); C NMR (CDCl ) d 24.8,
4.1.7. 1-Hydroxy-4-oxocyclopentano[2,3-c]pyridine (11).
A solution of 7 (61 mg, 0.41 mmol) and acetic acid (30 mL,
0.52 mmol) in CH Cl (4 mL) was stirred at 2788C as
3
4.5, 18.0, 25.6, 47.6, 68.5, 120.7, 131.4, 145.8, 154.3,
1
8
63.1, 201.4. Anal. calcd for C H NO Si: C, 63.84; H,
14 21 2
.04; N, 5.32. Found: C, 63.76; H, 8.04; N, 5.15.
2
2
ozone was passed through the solution (until the solution
turned blue), which was purged with oxygen for 15 min.
Me S (0.24 mL, 3.2 mmol) was added at 2788C and the
p
p
4
4
.1.5. (1R ,4S )-1-((t-Butyldimethylsilyl)oxy)-4-hydroxy-
-methylcyclopentano[2,3-c]pyridine (10). To a dry solu-
2
solution was allowed to warm to rt. Saturated aqueous
NaHCO3 solution was added and the two layers were
separated. The aqueous layer was further extracted with
CH Cl /2-propanol (3:1). The combined organic layers
tion of 9 (400 mg, 1.52 mmol) in THF (25 mL) was added
dropwise a solution of MeMgBr (2.4 M, 0.9 mL, 2.2 mmol)
in ether diluted with THF (3 mL) at 108C. The reaction
mixture was stirred at 108C for 3 h, allowed to warm to 308C
2
2
were dried (MgSO ), filtered and concentrated to give a
4
over 0.5 h, quenched with saturated aqueous NH Cl solution
4
residue, which was purified by chromatography (SiO ,
2
4
c
(
5 mL), evaporated, and extracted with CH Cl /2-propanol
2
EtOAc/hexanes, 1:1–3:1) to afford 11 (52.5 mg, 85%) as a
1
2
(
3:1). The combined organic layers were dried (MgSO4),
colorless solid: mp 1048C dec.; H NMR (acetone-d ) d2.52
6
filtered, and concentrated to give a residue, which was
chromatographed (SiO , MeOH/CH Cl , 1:20–1:10) to
afford 10 (325 mg, 77%) as a brownish solid: mp 99–
(dd, J¼18.8, 3.6 Hz, 1H); 3.08 (dd, J¼18.9, 5.4 Hz, 1H);
5.46 (dd, J¼3.6, 3.3 Hz, 1H); 7.77 (d, J¼4.8 Hz, 1H); 8.81
2
2
2
1
(d, J¼5.1 Hz, 1H); 8.85 (s, 1H). H NMR (DMSO-d ) d
6
1
1
008C; H NMR (CDCl ) d 0.16 (s, 3H), 0.18 (s, 3H), 0.92
3
2.39–2.52 (m, 1H), 2.97–3.08 (m, 1H), 5.25 (br, 1H), 5.97
(dd, J¼9.0, 6.6 Hz, 1H), 7.73–7.75 (m, 1H), 8.81 (dd,
J¼5.1, 2.4 Hz, 1H), 8.85 (s, 1H).
(
(
(
s, 9H), 1.54 (s, 3H), 2.14 (dd, J¼13.0, 5.8 Hz, 1H), 2.56
dd, J¼12.9, 6.3 Hz, 1H), 5.04 (t, J¼6.3 Hz, 1H), 7.21
1
3
d, J¼4.8 Hz, 1H), 8.46 (d, J¼5.1 Hz, 1H), 8.58 (s, 1H);
C
NMR (CDCl ) d 24.7, 24.5, 18.0, 25.7, 27.7, 53.4, 72.4,
3
77.5, 119.0, 143.3, 145.0, 148.9, 152.4. Anal. calcd for
C H NO Si: C, 64.47; H, 9.02; N, 5.01. Found: C, 64.42;
H, 8.85; N, 4.79.
Acknowledgements
1
5
25
2
We thank the following agencies for financial support:
Chinese Academy of Sciences (‘Hundreds of Talent’
Program); Science and Technology Commission of
Shanghai Municipality (‘Venus’ Program); National
Natural Science Foundation of China; The Bureau of
Tobacco, PRC.
4.1.6. (6)-Oxerine (1). Method A (Prepared from 10). A
solution of TBAF in THF (1 M, 0.6 mL, 0.6 mmol) was
added to a solution of 10 (64.2 mg, 0.23 mmol) in THF
(
7 mL) at 08C under N . The mixture was stirred at 08C for
2
4
5 min and then at 258C for 3 h, quenched with water