Armstrong et al.
combined organic extracts were washed with saturated sodium
hydrogen carbonate solution (50 mL), dried over MgSO , and
evaporated to dryness under reduced pressure to give a yellow
oil (456 mg). Flash chromatography over silica using 50%
give a pale yellow oil (260 mg). Flash chromatography over
silica using 50% ether/50% petrol as eluent gave the acetate
7 (174 mg, 74%) as a colorless oil, which crystallized on
4
storage: mp 53-54 °C (Et
2
O/petrol); IR (CHCl
cm ; H NMR (400 MHz, CDCl ) δ 4.82-4.57 (m, 3H), 4.27-
4.11 (m, 2H), 3.01 (br, 1H), 2.37 (1H, d, J ) 15 Hz), 2.14-2.00
3
) 1748, 1732
-
1 1
ether-50% petrol as eluent gave the chloro ketone 5 (241 mg,
3
1
5
6%) as a colorless oil: IR (film) 1724, 1698 cm-1; H NMR
1
3
(
250 MHz, CDCl
3
) δ 4.82-4.57 (m, 2H), 4.20 (m, 2H), 3.96 (s,
(m, 2H), 2.06 (s, 3H), 1.66-1.61 (m, 2H), 1.29 (m, 3H); C NMR
(67.5 MHz, CDCl ) δ 202.8 (C), 169.2 (C), 154.0 (C), 78.3 (CH),
61.3 (CH ), 55.1 (CH), 52.8 (CH), 46.7 (CH), 27.3 (CH ), 24.3
(CH ), 20.5 (CH ); MS m/z (EI) 255 (M , 1%), 213
(MH - OAc, 8%); HRMS calcd for C12
found 255.1115. Anal. Calcd for C12
N, 5.49. Found: C, 56.70; H, 6.65; N, 5.40.
1R ,2R ,5S )-(+)-2-Ace t oxy-3-oxo-8-a za b icyclo[3.2.1]-
1
2
H), 3.18 (br d, J ) 15.5 Hz, 1H), 2.29 (d, J ) 15.5 Hz, 1H),
3
.25-1.95 (m, 2H), 1.75-1.55 (m, 2H), 1.29 (t, J ) 7.0 Hz, 3H);
2
2
1
3
+
C NMR (100 MHz, CDCl
1.6 (CH ), 58.1 (CH), 53.0 (CH), 44.6 (CH
7.1 (br CH ), 14.5 (CH ); MS m/z (FAB+) 232 (MH , Cl,
3
) δ 201.1 (C), 154.0 (C), 62.1 (CH),
2
3 3
), 14.5 (CH
+
6
2
3
2
2
2
), 27.5 (br CH ),
2
H
17NO
17NO
5
(M ) 255.1107,
5
: C, 56.46; H, 6.71;
+
35
2
3
H
3
5
+
5%); HRMS calcd for C10
32.0735.
3
H15 ClO N (MH ) 232.0740, found
(
(
1R,2R,5S)-(+)-2-Ch lor o-3-oxo-8-azabicyclo[3.2.1]octan e-
octa n e-8-ca r boxylic Acid Eth yl Ester (7). This compound
was prepared as described above for the racemate, starting
from nonracemic 4, giving material spectroscopically identical
with the racemic sample. The material was shown by chiral
HPLC (Chiralcel OD, 1/100 iPrOH/hexane, 1 mL/min flow rate,
detection at 221 nm) to be of 80% ee, with retention times of
8
-ca r boxylic Acid Eth yl Ester (5). The above procedure
using nonracemic 4 followed by flash chromatography twice
over silica using first 40% ether/60% petrol and then 0.5%
MeOH/99.5% CH Cl as eluent gave nonracemic 5 (45%) as a
2 2
yellow solid, shown by chiral HPLC (Chiralcel OJ , 1/100
i
PrOH/hexane with 0.1% TFA added as eluent, flow rate 1 mL/
2
7.4 min (minor enantiomer) and 30.0 min (major enantiomer).
min, detection at 221 nm) to be of 78% ee, with elution times
of 24.4 min (minor enantiomer) and 28.4 min (major enanti-
omer), which were spectroscopically identical with those of the
racemic sample prepared previously. A single recrystallization
from petrol gave pale brown needles of >98% ee: mp 52.0-
24
Additional data; [R]
1R*,5S*)-2-Meth ylen e-3-oxo-8-a za bicyclo[3.2.1]octa n e-
-ca r boxylic Acid Eth yl Ester (9). (a ) Cyclop r op a n a tion
D
) +48.4 (c 1.00, CHCl
3
) at 80% ee.
(
8
of Silyl En ol Eth er 4. To a stirred solution of the silyl enol
ether 4 (683 mg, 2.55 mmol) in dry ether (15 mL) at 0 °C under
2
5
5
NO
3.0 °C; [R]
3
D
) +152 (c 1.11, CHCl
3 14
). Anal. Calcd for C10H -
nitrogen was added dropwise Et
solution in hexanes, 2.55 mmol) followed by CH
.06 mmol). The reaction mixture was stirred at room tem-
2
Zn (2.55 mL of a 1.0 M
Cl: C, 51.84; H, 6.06; N, 6.05. Found: C, 51.84; H, 6.03;
2 2
I
(248 µL,
N, 6.06.
3
(
1R*,2R*,5S*)-(()-2-Hyd r oxy-3-oxo-8-a za bicyclo[3.2.1]-
perature for 20 h, quenched with saturated ammonium
chloride solution (25 mL), and diluted with ether (50 mL), and
the phases were separated. The organic phase was washed
with saturated sodium hydrogen carbonate solution (25 mL)
and H O (25 mL). The organic phase was dried over MgSO
2 4
and evaporated to dryness under reduced pressure to give a
pale yellow oil (718 mg). Flash chromatography over silica
octa n e-8-ca r boxylic Acid Eth yl Ester (6). To a stirred
solution of the racemic silyl enol ether 4 (0.402 g, 1.5 mmol)
2 2
in dry CH Cl (20 mL) at room temperature under nitrogen
4
0
was added dimethyldioxirane (30 mL of a 0.075 M solution
in acetone, 2.25 mmol). The reaction mixture was stirred at
room temperature for 2 h, and then the solvent was removed
under reduced pressure to give a colorless oil (375 mg). Flash
chromatography over silica using 50% ether/50% petrol and
then 100% ether as eluent yielded the alcohol 6 (196 mg, 63%)
(previously washed with 1% Et
3
N/99% eluent) using 25% ether/
7
5% petrol as eluent gave the cyclopropane (300 mg, 42%) as
-1
1
a colorless oil: IR (CHCl
CDCl
2
1
3
) 1681 cm
) δ 4.29 (br, 1H), 4.10-4.07 (m, 3H), 2.51 (br, 1H), 2.09-
.04 (m, 1H), 1.97-1.92 (m, 1H), 1.85-1.74 (m, 3H), 1.25-
.21 (m, 3H), 1.14 (br, 1H), 0.87 (br, 1H), 0.23 (br, 1H), 0.11
; H NMR (400 MHz,
-
1 1
as a colorless oil: IR (CHCl
3
) 3550, 2982, 1724, 1683 cm ; H
) δ 4.62-4.58 (m, 2H), 4.22 (q, J ) 7
3
NMR (400 MHz, CDCl
3
Hz, 2H), 3.84 (s, 1H), 3.06 (d, J ) 15 Hz, 1H), 2.26 (d, J ) 15
Hz, 1H), 2.12-2.02 (m, 2H), 2.00 (br, 1H), 1.65-1.52 (m, 2H),
13
(s, 9H); C NMR (67.5 MHz, CDCl
3
) δ 154.0 (C), 60.8 (CH
1.9 (CH), 51.6 (C), 49.3 (CH), 41.6 (br, CH ), 30.0 (br, CH
8.8 (br, CH ), 26.0 (CH), 17.9 (CH ), 14.7 (CH
), 1.3 (3 × CH
2
2
3
),
),
);
1
1
.30 (t, J ) 7 Hz, 3H); 13C NMR (67.5 MHz, CDCl
3
) 206.5 (C),
2
), 58.7 (CH), 53.8 (CH), 46.3
5
2
2
55.4 (C), 79.3 (CH), 62.3 (CH
), 28.1 (CH ), 24.4 (CH ), 15.1 (CH
7%), 140 (M - CO Et, 100%); HRMS calcd for C10
13.1001, found 213.0991.
1R,2R,5S)-(+)-2-H yd r oxy-3-oxo-8-a za b icyclo[3.2.1]-
2
2
3
+
(CH
2
2
2
3
); MS m/z (EI) 213 (M ,
+
+
MS m/z (EI) 283 (M , 6%). HRMS calcd for C14
83.1604, found 283.1611.
b) F or m a tion of En on e 9. To a stirred solution of the
cyclopropane silyl ether (300 mg, 1.06 mmol) in dry CH Cl
15 mL) under nitrogen was added dropwise SnCl (127 µL,
.1 mmol). The reaction mixture was stirred at room temper-
3
H25NO Si (M )
+
2
2
2
4
H15NO (M )
2
(
(
2
2
octa n e-8-ca r boxylic Acid Eth yl Ester (6). The above
procedure using nonracemic silyl enol ether 4, followed by flash
chromatography on silica using 10% EtOAc/90% petrol to 100%
EtOAc as eluent gave nonracemic 6 (55%) as a colorless oil,
(
1
4
ature for 2 h and then the solvent removed under reduced
pressure to give the crude stannane as an oily yellow solid.
The crude stannane was redissolved in dry CH Cl (15 mL),
2 2
dry DMSO (270 µL, 3.18 mmol) was added dropwise, and the
reaction mixture was stirred at room temperature for 20 h.
The resultant white precipitate was removed by filtration and
2
5
[R]
D
3
) +20.4 (c 0.83, CHCl ), at 80% ee (shown by subsequent
chiral HPLC analysis of the derived acetate). NMR data agreed
with those of the previously prepared racemic sample.
(
1R*,2R*,5S*)-(()-2-Acetoxy-3-oxo-8-a za bicyclo[3.2.1]-
octa n e-8-ca r boxylic Acid Eth yl Ester (7). To a stirred
solution of alcohol 6 (196 mg, 0.92 mmol), in dry CH CN (10
mL) under nitrogen, were added acetic anhydride (347 µL, 3.7
3
mmol) and a solution of Sc(OTf) (5 mg, 0.01 mmol) in dry CH -
washed with CH
washings were washed with saturated ammonium chloride
, and evaporated to
2 2
Cl (10 mL). The combined filtrate and
3
solution (2 × 30 mL), dried over MgSO
4
3
dryness under reduced pressure to give a colorless oil (314 mg).
Flash chromatography over silica using 50% ether/50% petrol
as eluent yielded the enone 9 (177 mg, 80%) as a colorless oil:
CN (100 µL). The reaction mixture was stirred at room
temperature for 1 h, quenched by addition of saturated sodium
hydrogen carbonate solution (10 mL), and extracted into ether
-
1
1
IR (CHCl
H), 5.24 (s, 1H), 4.90 (br, 1H), 4.57 (br, 1H), 4.16 (q, J ) 7
Hz, 2H), 2.77 (br, 1H), 2.46 (d, J ) 17 Hz, 1H), 2.29-2.17 (m,
3 3
) 1690 cm ; H NMR (250 MHz, CDCl ) δ 5.92 (s,
(
4 × 20 mL). The combined organic extracts were dried over
1
MgSO and evaporated to dryness under reduced pressure to
4
2
H), 1.81-1.66 (m, 2H), 1.26 (t, J ) 7 Hz, 3H); 13C NMR (67.5
(
40) Adam, W.; Bialas, J .; Hadjiarapoglou, L. Chem. Ber. 1991, 124,
377.
41) 1-(Chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-
tetrafluoroborate).
42) Details of this X-ray crystal structure are given in the Sup-
porting Information.
MHz, CDCl
6
2
3
) δ 198.3 (C), 153.8 (C), 146.1 (C), 119.4 (br, CH
), 58.2 (CH), 52.4 (CH), 47.5 (CH ), 31.2 (br, CH
8.8 (br, CH ), 14.6 (CH
2
),
),
2
1.4 (CH
2
2
2
(
+
2
3
); MS m/z (EI) 209 (M , 11%), 181
(
+
+
(
MH - Et, 100%); HRMS calcd for C11
3
H15NO (M ) 209.1052,
(
found 209.1057.
8
616 J . Org. Chem., Vol. 67, No. 24, 2002