Pellicciari et al.
(23) (6.61 g, 78.6 mmol) in dry dichloromethane (200 mL) was
treated with 4-(dimethylamino)pyridine (9.6 g, 78.6 mmol).
After stirring for 10 min, this mixture was treated with tert-
butyldimethylsilyl chloride (12.15 g, 80 mmol), and the result-
ing solution was stirred overnight at room temperature under
argon. The reaction was quenched with a saturated solution
of sodium bicarbonate. The aqueous phase was extracted with
dichloromethane (3 × 100 mL). The combined extracts were
washed with brine (1 × 50 mL), dried (Na2SO4), and evapo-
rated, and the mixture was purified by flash chromatography
(n-hexane) to give 24 (8.5 g, 55%) as a colorless oil: 1H NMR
(CDCl3) δ 0.01 (6H, s,), 0.83 (9H, s), 1.20 (2H, m), 1.64 (1H,
m), 3.36 (1H, dd, J ) 11 and 7.5 Hz), 3.59 (1H, dd, J ) 11 and
6.8 Hz), 5.3 (1H, m), 5.35 (1H, m).
(()-(pr oxim a l)-4-(ter t-Bu t yld im et h ylsilyloxym et h yl)-
sp ir o[2.2]p en ta n e-1,1-d ica r boxylic Acid Dieth yl Ester
(25) an d (()-(dista l)-4-(ter t-Bu tyldim eth ylsilyloxym eth yl)-
sp ir o[2.2]p en t a n e-1,1-d ica r b oxylic Acid Diet h yl E st er
(26). A solution of diethyldiazomalonate (13.12 g, 70.4 mmol)
in dry dichloromethane (600 mL) was added via syringe pump
over 90 h to a magnetically stirred solution of the olefin 24
(3.5 g, 17.6 mmol) and dirhodium(II) tetraacetate (0.35 g, 0.78
mmol) in dry dichloromethane (200 mL) at reflux under argon.
The reaction mixture was filtered and evaporated to dryness.
The residue was submitted to flash chromatography; elution
with light petroleum ether-EtOAc (98:2) gave a mixture of
25 and 26 as a colorless oil (25/26 ) 1/5, GC-MS). The mixture
of diastereoisomers 25 and 26 was separated by MPLC.
(cyclohexanes-EtOAc, 95:5) to give 25 (0.7 g, 11%) and 26 (3.3
g, 53%). Da ta for 25: 1H NMR (CDCl3) δ 0.10 (6H, bs), 0.94
(9H, bs), 1.14-1.17 (1H, m), 1.27-1.37 (6H, m), 1.73-1.90 (3H,
m), 3.23 (1H, dd, J ) 8.6 and 10.8 Hz),4.02 (1H, dd, J ) 4.5
and 11.4 Hz), 4.19-4.30 (4H, m); 13CNMR (CDCl3) δ 5.25.2
10.114.0 14.218.4 20.6,21.3, 26.0 28.1 32.9, 61.2, 61.2, 64.4,
169.0, 169.4; GC-MS m/z (relative intensity) 355 (M - H+, 1),
299 (100), 225 (32), 181 (16), 75 (38). Da ta for 26: 1H NMR
(CDCl3) δ 0.01 (6H, bs), 0.85 (9H, bs),1.19-1.26 (7H, m), 1.51-
1.98 (3H, 2m,), 3.43 (1H, dd, J ) 2 6.6 and 10.6 Hz), 3.72 (1H,
dd, J ) 5.3 and 11.4 Hz), 4.06-4.19 (4H, m); 13C NMR (CDCl3)
δ 3.9, 3.8, 11.8, 15.6, 19.7, 20.6, 21.2, 27.1, 29.4, 34.4, 62.5,
61.6, 65.7, 170.4, 170.5; GC-MS m/z (relative intensity) 355
(M - H+, 1), 299 (100), 225 (33), 181 (67), 75 (83).
(()-pr oxima l- an d (()-media l-a n ti-4-(ter t-Bu tyldim eth -
ylsilyloxym eth yl)-spir o[2.2]pen tan e-1,1-dicar boxylic Acid
Mon oeth yl Ester s (27a + 27b). A solution of 0.5 M sodium
hydroxyde (8.4 mL, 4.2 mmol) in water was added to a solution
of 25 (1.5 g, 4.2 mmol) in 95% ethanol, and the resulting
mixture was stirred at room temperature for 36 h. The reaction
mixture was evaporated to dryness, water was added to the
residue, and the mixture was neutralized with 10% citric acid
solution and extracted with ethyl acetate (3 × 100 mL). The
combined extracts were dried (Na2SO4) and evaporated to give
the mixture of products 27a and 27b (1.25 g, 90%) as a
colorless oil: 1H NMR (CDCl3) δ 0.04 (6H, bs), 0.79 (9H, bs),
0.95-1.20 (1H, m), 1.27-1.37 (6H, m), 1.73-2.20 (3H, m), 3.50
(1H, m), 3.80 (1H, m), 4.07-4.30 (2H, m).
(()-d ista l- a n d (()-m ed ia l-syn -4-(ter t-Bu tyld im eth yl-
silyloxym eth yl)-sp ir o[2.2]p en ta n e-1,1-d ica r boxylyc Acid
Mon oeth yl Ester s (27c + 27d ). Monohydrolysis of 26 (4.6
g, 13.0 mmol) was performed according to the procedure
described above for 25. The mixture of the isomers 27c + 27d
(3.3 g, 78%) was obtained as a colorless oil: 1H NMR (CDCl3)
δ 0.04 (6H, s), 0.79 (9H, m), 1.05-1.20 (1H, m), 1.21-1.33 (4H,
m), 1.53-1.75 (1H, m), 3.30-3.52 (1H, m), 3.70 (0.5H, dd, J )
8.6 and 10.8 Hz), 3.90 (0.5H, dd, J ) 4.5 and 11.4 Hz), 4.10-
4.30 (2H, m).
g, 0.38 mmol), and freshly distilled ethylchloroformate (0.49
g, 4.54 mmol). The mixture was kept at 0 °C for 30 min and
at room temperature for 90 min. The reaction mixture was
filtered quickly under argon, and the remaining solid was
washed with tetrahydrofurane (2 × 10 mL). A solution of
sodium azide (0.29 g, 4.54 mmol) in water (5 mL) was added
to the filtrate at 0 °C under argon. After 1 h, the reaction
mixture was poured into cold water (100 mL) and extracted
with ethyl acetate (3 × 100 mL). The combined extracts were
dried (Na2SO4) and evaporated. The residue was dissolved in
tert-butyl alcohol (30 mL), and the solution was refluxed
overnight under argon. The reaction mixture was concentrated
under reduced pressure, and the residue was submitted to
flash chromatography; elution with light petroleum ether-
EtOAc (9:1) gave the product 28a + 28b (0.45 g, 30%) as a
mixture of diastereoisomers: 1H NMR (CDCl3) δ 0.04 (6H, s),
0.78 (9H, s), 0.80-1.00 (1H, m), 1.18-1.28 (3H, m), 1.40 (9H,
s), 1.50-1.70 (1H, m), 1.80-1.98 (1H, m), 3.18-3.32 (1H, m),
3.83-3.91 (1H, m), 3.98-4.26 (4H, m).
(()-d ista l- a n d (()-m ed ia l-syn -4-(ter t-Bu tyld im eth yl-
silyloxym eth yl)-1-ter t-bu toxyca r bon yl Am in osp ir o[2.2]-
p en t a n e-1-ca r b oxylic Acid E t h yl E st er s (28c + 28d ).
Starting from the mixture 18c + 18d (2.4 g, 7.32 mmol) the
isomers 19c + 19d were obtained (0.94 g, 32%) according to
the procedure described above for 18a + 18b: 1H NMR (CDCl3)
δ 0.04 (6H, m), 0.82 (9H, m), 1.05-1.35 (4H, m), 1.42 (9H, bs),
1.45-1.90 (3H, m), 3.38 (1H, dd, J ) 6.6 and 10.6 Hz), 3.85
(1H, dd, J ) 5.3 and 11.4 Hz), 4.08-4.22 (4H, m).
(()-pr oxim a l-1-ter t-Bu toxyca r bon yla m in o-4-h yd r oxy-
m eth ylsp ir o[2.2]p en ta n e-1-ca r boxylic Acid Eth yl Ester
(29a ) a n d (()-m ed ia l-a n ti-1-ter t-Bu toxyca r bon yla m in o-
4-h ydr oxym eth ylspir o[2.2]pen tan e-1-car boxylic Acid Eth -
yl Ester (29b). A solution of 28a + 28b (0.44 g, 1.1 mmol) in
distilled tetrahydrofurane (30 mL) was treated with tetra-n-
butylammonium fluoride (0.44 g, 1.1 mmol). The solution was
stirred at room temperature until no starting material was
detected by TLC. Water (150 mL) was added to the mixture,
and the aqueous phase was extracted with ethyl acetate (4 ×
50 mL). The combined extracts were dried (Na2SO4) and
evaporated to give the mixture of derivatives 29a and 29b,
which was separated by MPLC; elution with light petroleum
ether-EtOAc (3:2) gave 29a (0.065 g, 21%) and 29b (0.202 g,
1
65%) as white solids. Da ta for 29a : mp 77-79 °C; H NMR
(CDCl3) δ 0.72 (1H, pt, J ) 4.9 Hz) 1.05 (1H, dd, J ) 5.0 and
8.2 Hz), 1.17 (3H, t, J ) 7.1 Hz), 1.40 (9H, bs), 1.60-1.70 (1H,
m), 2.01 (1H, d, J ) 4.5 Hz), 3.22 (1H, pt, J ) 10.8 Hz) 3.96-
4.19 (3H, m); 13C NMR (CDCl3) δ 10.2, 14.3, 20.8, 23.3, 28.3,
61.1, 64.0, 79.8, 157.4, 172.0. Da ta for 29b: mp 89-81 °C;
1H NMR (CDCl3) δ 0.84 (2H, m), 1.18 (3H, t, J ) 7.1 Hz), 1.37
(10H, m), 1.66-1.80 (1H, m), 1.85 (1H, d, J ) 4.4 Hz), 3.40
(1H, pt, J ) 8.2 Hz), 3.81 (1H, dd, J ) 3.8 and 11.6 Hz), 4.02-
4.22 (2H, m); 13C NMR (CDCl3) δ 7.7, 14.1, 22.4, 24.0, 28.2,
30.9, 38.7, 62.0, 63.6, 80.0, 155.9, 172.4.
(()-dista l-1-ter t-Bu toxycar bon ylam in o-4-h ydr oxym eth -
ylsp ir o[2.2]p en ta n e-1-ca r boxylic Acid Eth yl Ester (29c)
and (()-media -syn-1-tert-Butoxycarbonylamino-4-hydroxy-
m eth ylsp ir o[2.2]p en ta n e-1-ca r boxylic Acid Eth yl Ester
(29d ). Both isomers were prepared as described above for
spiropentanes 29a and 29b from a mixture of 19c + 19d (0.6
g, 2.33 mmol). MPLC in light petroleum ether-EtOAc (3:2)
gave 29c (360 mg, 54%) and 29d (230 mg, 35%) as white solids.
1
Da ta for 29c: mp 84-86 °C; H NMR (CDCl3) δ 0.84 (1H, t,
J ) 5.2 Hz), 1.20 (3H, t, J ) 7.1 Hz), 1.35-1.50 (10H, m), 1.50-
1.72 (1H, m), 1.93-2.10 (2H, 2m), 3.23 (1H, dd, J ) 9.2 Hz,
10.6 Hz), 3.85 (1H, dd, J ) 4.8 and 10.6 Hz), 4.11 (2H, q, J )
7.1 Hz); 13C,NMR (CDCl3) δ 11.3, 14.3, 19.5, 20.2, 20.8, 28.2,
29.2, 29.8, 38.9, 61.2, 65.3, 80.1, 156.1, 172.0. Da ta for 29d :
mp 82-84 °C; 1HNMR (CDCl3) δ 0.78 (1H, t, J ) 5.1 Hz), 1.10
(3H, t, J ) 7.1 Hz), 1.35-1.50 (10H, m), 1.50-1.72 (1H, m),
1.93-2.10 (2H, 2m), 3.62 (2H, m), 4.17 (2H, m); 13C NMR
(CDCl3) δ 10.4, 14.2, 20.6, 21.4, 28.2, 30.5, 38.6, 61.7, 65.1,
80.0, 155.9, 172.9.
(()-pr oxima l- an d (()-media l-a n ti-4-(ter t-Bu tyldim eth -
ylsilyloxym eth yl)-1-ter t-bu toxyca r bon ylAm in osp ir o[2.2]-
p en ta n e-1-ca r boxylic Acid Eth yl Ester s (28a +28b). A
stirred solution of 27a + 27b (1.24 g, 3.78 mmol) in dry
tetrahydrofurane (30 mL) at 0 °C under argon was treated
with potassium carbonate (1.04 g, 7.55 mmol), 18-crown-6 (0.10
5506 J . Org. Chem., Vol. 67, No. 16, 2002