Taber et al.
40.7, 37.7, 34.2, 33.6, 21.6, 20.7; d 74.9, 46.8, 32.2, 31.3, 26.2,
23.4, 22.0, 20.9, 16.3; IR 2950, 1735, 1454, 1384, 1311 cm-1; MS
m/z 279 (M + H, 100), 263 (49), 141 (98), 123 (79); HRMS calcd
for C17H27O3 (M + H) 279.1960, obsd 279.1967.
Rayonet apparatus (300 nm) set for autocooling. The reaction was
halted every hour to agitate the tube inside the larger tube, after
which photolysis was restarted. At the end of the irradiation, DBU
(304 mg, 2.0 mmol) was added, and the mixture was stirred at room
temperature for 1 h under nitrogen. The mixture was diluted with
40 mL of EtOAc and filtered through a small pad of packed silica
gel. The eluate was concentrated and the residue was chromato-
graphed to give 152 mg of unreacted 3 and 90 mg of 4 (98% yield
Ketal 9. 2,2-Dimethyl-1,3-propanediol (2.11 g, 24 mmol),
p-toluenesulfonic acid monohydrate (5 mg, 0.02 mmol), and
cyclopentanone 2 (3.33 g, 12 mmol) were combined in 24 mL of
dry toluene. The solution was maintained at reflux for 8 h. The
reaction was concentrated, and the residue was chromatographed
to give the ketal 6 (3.89 g, 89% yield) as a white solid: mp )
based on 3 not recovered) as an oil: [R]20 +102.5 (c ) 1.0,
D
CH2Cl2); TLC Rf ) 0.30 (8:2 petroleum ether/MTBE); 1H NMR δ
6.45 (s, 1H), 3.45 (m, 4H), 2.95 (br s, 1H), 2.64 (m, 1H), 2.41 (m,
2H), 2.17 (m, 2H), 1.70- 1.97 (m, 3H), 1.35 (m, 1H), 0.95 (m,
6H), 0.85 (m, 3H); 13C NMR δ u 198.4, 140.7, 108.2, 71.4, 70.7,
39.9, 30.5, 29.3, 25.0, 21.7; d 138.9, 45.0, 33.1, 21.5, 21.3, 12.1;
IR 2952, 1672, 1493, 1312, 1153 cm-1; HRMS calcd for C16H24O3
264.1725, obsd 264.1731.
97-99 °C; [R]20 +32.1 (c ) 1.0, CH2Cl2); TLC Rf ) 0.49 (8:2
D
1
petroleum ether/MTBE); H NMR δ 4.69 (dt, J ) 4.9, 11.5 Hz,
1H), 3.62 (d, J ) 11.2 Hz, 1H), 3.47 (m, 3H), 2.43 (dd, J ) 8.2,
13.6 Hz, 1H) 1.87-2.10(m, 4H), 1.66-1.74 (m, 3H), 1.39-1.48
(m, 5H), 1.14 (m, 2H), 1.06 (m, 3H), 0.868-1.05 (m, 7H), 0.74
(m, 6H); 13C NMR δ u 170.6, 107.1, 73.2, 71.7, 40.7, 37.0, 34.5,
30.2, 25.2, 23.6, 23.3, 23.0, 16.8; d 74.3, 47.0, 31.4, 26.0, 24.6,
22.1, 22.0, 20.8, 16.4; IR 2950, 1705, 1455, 1384, 1309 cm-1; MS
m/z 365 (M + H, 87), 279 (7), 227 (100), 209 (63), 182 (36), 141
(65), 128 (60); HRMS calcd for C22H36O4 364.2614, obsd 364.2623.
(1S,5R)-5′,5′-Dimethyl-1H-spiro[bicyclo[3.1.0]hexane-2,2′-[1,3]di-
oxane]-1-carbaldehyde 10. LiAlH4 (1.0 M solution in THF, 12 mL,
12 mmol) was added over 10 min to ketal 9 (3.64 g, 10 mmol) in
10 mL (1.0 M) of dry THF at rt. The solution was stirred at rt for
2 h. Ethyl acetate (5 mL) was added dropwise over 30 min followed
by sodium sulfate decahydrate (3.2 g, 10 mmol). The mixture was
stirred at rt for 2 h and then filtered through a pad of silica gel
with ethyl acetate (20 mL) and concentrated. The residue was
chromatographed to give the crude alcohol. Dess-Martin perio-
dinane (4.24 g, 11 mmol) was added to the alcohol in 10 mL of
dry dichloromethane at rt. The mixture was concentrated, and the
residue was chromatographed to give the aldehyde 10 (1.62 g, 77%
yield from 9) as an oil: TLC Rf ) 0.34 (8:2 petroleum ether/MTBE);
[R]20D -59.1 (c ) 1.0, CH2Cl2); 1H NMR δ 10.36 (s, 1H), 3.72 (d,
J ) 11.2 Hz, 1H), 3.54 (d, J ) 11.2 Hz, 1H), 3.48 (s, 2H), 2.47
(dd, J ) 8.6, 14.3 Hz, 1H), 2.07 (m, 1H), 1.90 (m, 1H), 1.79 (m,
1H), 1.49 (dd, J ) 5.2, 13.0 Hz, 1H), 1 30 (m, 3H), 1.17 (m, 2H),
0.77 (s, 3H); 13C NMR δ u 107.7, 73.3, 71.6, 44.8, 30.0, 25.6,
24.2, 18.6; d 201.1, 30.5, 22.9, 22.0; IR 2953, 1700, 1467, 1335,
1116 cm-1; MS m/z 211 (M + H, 58), 181 (55), 141 (67), 123
(100); HRMS calcd for C12H18O3 210.1256, obsd 210.1262.
(1S,5R)-1-[(1Z)-But-1-en-1-yl]-5′,5′-dimethylspiro[bicyclo[3.1.0]-
hexane-2,2′-[1,3]dioxane] 3. Potassium tert-butoxide (1.0 M solution
in THF, 20 mL, 20 mmol) was added over 20 min to a suspension
of propyltriphenylphosphonium bromide (3.50 g, 9 mmol) in 20
mL of dry THF at 0 °C. The external cooling was removed, and
the mixture was stirred for 30 min. The aldehyde 10 (1.57 g, 7.5
mmol) was added, and the mixture was stirred at rt for 1 h. The
mixture was quenched with water (50 mL) and then partitioned
between water and EtOAc. The combined organic extract was dried
(MgSO4) and concentrated. The residue was chromatographed to
(3a′R,6′R,7a′S)-6′-Ethyl-5,5-dimethylhexahydrospiro[1,3-dioxane-
2,1′-inden]-5′(4′H)-one 14. Pd/C (5 wt%, 10 mg) was added to the
bicyclic enone 4 (85 mg, 0.32 mmol) in 5 mL of methanol. The
reaction vessel was purged with hydrogen, a hydrogen balloon was
attached, and the mixture was stirred at rt for 4 h until the TLC
indicated disappearance of the UV absorbent spot. The mixture was
filtered through a plug of Celite and concentrated. The residue was
chromatographed to give 11 (81 mg, 95% yield) as an oil: [R]20
D
+124.6 (c ) 1.0, CH2Cl2), TLC Rf ) 0.30 (8:2 petroleum ether/
1
MTBE); H NMR δ 3.48 (m, 4H), 2.62 (m, 1H), 2.51 (m, 2H),
2.25 (dd, J ) 5.6, 14.4 Hz, 1H), 2.15 (m, 1H), 2.00 (m, 3H), 1.82
(m, 2H), 1.46 (m, 1H), 1.24 (m, 2H), 1.04 (m, 3H), 0.91 (m, 6H);
13C NMR δ u 214.2, 109.6, 72.4, 71.5, 43.8, 30.7, 30.0, 28.3, 26.6,
22.3; d 49.2, 44.3, 37.1, 22.5, 11.6; HRMS calcd for C16H26O3
266.1882, obsd 266.1880.
Methyl (3a′S,5′S,6′R,7a′S)-6′-Ethyl-5′-hydroxy-5,5-dimethyloc-
tahydrospiro[1,3-dioxane-2,1′-indene]-4′-carboxylate 15. Sodium
hydride (60%, 24 mg, 0.6 mmol) and dimethyl carbonate (3 mL,
35 mmol) were heated to reflux for 20 min. A drop of methanol
was added via an addition funnel over a condenser and stirred at
reflux for 5 min. Bicyclic ketone 14 (80 mg, 0.3 mmol) in 1 mL
dry toluene was added via an addition funnel over a condenser,
and the mixture was stirred at reflux for 3 h. The mixture was cooled
to rt and quenched with saturated aqueous NH4Cl and then
partitioned between water and EtOAc. The combined organic extract
was dried (MgSO4) and concentrated. The residue was dissolved
in methanol (5 mL), and NaBH4 (19 mg, 0.5 mmol) was added.
The mixture was stirred at rt for 2 h. The mixture was concentrated
and the residue was chromatographed to give alcohol 15 (44 mg,
45% yield) as an oil: [R]20 +10.4 (c ) 1.0, CH2Cl2); TLC Rf )
D
1
0.19 (8:2 petroleum ether/MTBE); H NMR δ 4.17 (s, 1H), 3.72
(s, 3H), 3.50 (s, 2H), 3.42 (s, 2H), 2.64 (m 1H), 2.56 (m, 1H), 2.21
(m, 2H), 2.01 (m, 1H), 1.92 (m, 1H), 1.56 (m, 3H), 1.38 (m, 4H),
0.95 (m, 9H); 13C NMR δ u 176.1, 109.5, 72.7, 71.0, 31.6, 30.1,
30.0, 25.3, 22.3; d 67.6, 51.7, 46.8, 44.5, 42.0, 36.5, 22.5, 11.7; IR
3488, 2913, 1713, 1289, 1152 cm-1; MS m/z 327 (M + H, 6), 141
(100); HRMS calcd for C18H30O5 326.2093, obsd 326.2095.
Methyl (3a′S,6′R,7a′S)-6′-Ethyl-5,5-dimethyl-2′,3′,3a′,6′,7′,7a′-
hexahydrospiro[1,3-dioxane-2,1′-indene]-4′-carboxylate 16. Meth-
anesulfonyl chloride (60 mg, 0.36 mmol) was added slowly to
alcohol 12 (40 mg, 0.12 mmol) and triethylamine (1 mL, 7.2 mol)
in 1 mL of dichloromethane at 0 °C. The solution was stirred to rt
over 2 h. DBU (2 mL, 2.04 g, 14 mmol) was added, and the solution
was stirred at rt for 18 h. The solution was filtered through a pad
of silica gel with EtOAc and concentrated. The residue was
chromatographed to give ketal ester 15 (21 mg, 56% yield) as an
oil: [R]20D +25.5 (c ) 1.0, CH2Cl2); TLC Rf ) 0.44 (8:2 petroleum
ether/MTBE); 1H NMR δ 6.84 (s, 1H), 3.72 (s, 3H), 3.52 (s, 2H),
3.45 (d, J ) 4.4 Hz, 2H), 2.95 (m 1H), 2.34 (m, 1H), 2.12 (m,
3H), 1.84 (m, 2H), 1.47 (m, 4H), 0.98 (m, 9H); 13C NMR δ u 185.1,
133.3, 109.5, 72.9, 71.2, 31.2, 30.1, 28.2, 27.7, 25.9; d: 143.2, 51.8,
42.8, 38.1, 36.0, 22.5, 11.3; IR 2958, 1714, 1440, 1249 cm-1; MS
m/z 309 (M + H, 8), 279 (7), 237 (12), 222 (94), 209 (37), 165
give the alkenyl cyclopropane 3 (1.84 g, 78% yield) as an oil: [R]20
D
+20.8 (c ) 1.0, CH2Cl2); TLC Rf ) 0.74 (8:2 petroleum ether/
1
MTBE); H NMR δ 5.70 (d, J ) 8.0 Hz, 1H), 5.48 (m, 1H), 3.56
(d, J ) 11.6 Hz, 1H), 3.43 (d, J ) 11.6 Hz, 1H), 3.40 (s, 2H),
2.18-2.29 (m, 3H), 1.93 (m, 1H), 1.72 (dd, J ) 8.0, 12.0 Hz, 1H),
1.41 (m, 1H), 1.17 (m, 4H), 0.95 (t, J ) 7.2 Hz, 3H), 0.85 (m,
1H), 0.71 (s, 3H), 0.65 (dd, J ) 4.2, 7.2 Hz, 1H); 13C NMR δ u
110.0, 73.1, 71.4, 33.2, 30.1, 24.7, 24.6, 21.8, 14.7; d 136.6, 125.5,
22.7, 22.5, 22.1, 14.3; IR 2950, 2859, 1211, 1153, 1117 cm-1; MS
m/z 237 (M + H, 18), 201 (100), 183 (54), 141 (71); HRMS calcd
for C15H24O2 236.1776, obsd 236.1767.
(3a′R,7a′R)-6′-Ethyl-5,5-dimethyl-2′,3′,3a′,7a′-tetrahydrospiro[1,3-
dioxane-2,1′-inden]-5′(4′H)-one 4. To the alkenyl cyclopropane 3
(236 mg, 1.0 mmol) and potassium carbonate (280 mg, 2.0 mmol)
in 10 mL of 2-propanol and 5 mL of tetrahydrofuran (0.075 M)
was added Fe(CO)5 (392 mg, 2.0 mmol). The Pyrex reaction vessel
was purged with CO, a CO balloon was attached, and the mixture
was irradiated for 4 h at room temperature as a thin film in a
2436 J. Org. Chem. Vol. 74, No. 6, 2009