M. G. Banwell et al. / Tetrahedron 63 (2007) 6388–6403
6395
0.9 Hz, 1H), 3.81 (dd, J¼7.2 and 1.2 Hz, 1H), 2.86 (m, 1H),
2.48 (m, 1H), 2.14 (d, J¼10.5 Hz, 1H), 1.87 (dd, J¼12.9
and 8.9 Hz, 1H), 1.56 (s, 3H), 1.34 (m, 1H), 1.30 (s, 3H),
1.27 (s, 3H), 0.97 (s, 3H), 0.92 (s, 3H); 13C NMR (CDCl3,
75 MHz) d 221.3, 135.9, 129.8, 109.0, 83.2, 78.9, 49.6,
47.0, 40.7, 40.4, 33.4, 26.4, 25.5, 25.0, 22.1, 18.7 (one signal
obscured or overlapping); IR nmax 2963, 2933, 2871, 1731,
1455, 1373, 1324, 1269, 1254, 1208, 1166, 1054, 1073,
hexane.) 1H NMR (CDCl3, 300 MHz) d 5.97 (d, J¼8.1 Hz,
1H), 5.81 (dd, J¼8.1 and 6.8 Hz, 1H), 4.36 (dd, J¼7.2
and 3.6 Hz, 1H), 4.02 (br d, J¼6.8 Hz, 1H), 3.82 (s, 3H),
2.85 (m, 1H), 2.70 (m, 2H), 1.80–1.55 (complex m, 2H),
1.40 (s, 3H), 1.32 (s, 3H), 1.28 (s, 3H), 1.10 (d, J¼6.8 Hz,
3H); 13C NMR (CDCl3, 75 MHz) d 153.8, 145.5, 138.0,
130.9, 127.2, 109.5, 80.6, 80.3, 55.2, 42.6, 41.7, 40.1,
39.3, 37.7, 25.5, 25.0, 16.3(5), 16.3(2); IR nmax 2958,
2939, 2881, 1764, 1693, 1456, 1441, 1371, 1272, 1245,
1207, 1182, 1072, 1045, 1010, 950, 896, 871, 818, 783,
ꢃ
891, 875, 820, 732 cmꢀ1; MS m/z (EI, 70 eV) 276 (M+ ,
13%), 261 (38), 218 (90), 176 (78), 134 (80), 105 (100).
ꢃ
729 cmꢀ1; MS m/z (EI, 70 eV) 320 (M+ , 5%), 305 (4),
Concentration of fraction B afforded the title compound 10
(1.58 g, 82% at 92% conversion) as a white crystalline solid,
247 (51), 203 (100), 187 (69), 186 (95), 161 (60), 144
(92), 101 (77).
ꢃ
mp¼67–69 ꢂC, [a]D +172 (c 0.5, CHCl3). (Found: M+ ,
ꢃ
262.1568. C16H22O3 requires: M+ , 262.1569.) (Rf¼0.3 in
Concentration of fraction B afforded a solid that was recrys-
tallized (ethyl acetate) to give the title keto-ester 12 (2.09 g,
88%) as a white needles, mp¼91–94 ꢂC, [a]D +105 (c 1.0,
3:7 v/v ethyl acetate/hexane.) 1H NMR (CDCl3, 300 MHz)
d 6.16 (br t, J¼8.3 Hz, 1H), 5.71 (d, J¼8.3 Hz, 1H), 4.26
(ddd, J¼7.8, 3.5, and 0.7 Hz, 1H), 3.83 (dd, J¼7.2 and
1.2 Hz, 1H), 2.93 (m, 1H), 2.31 (br t, J¼9.4 Hz, 1H), 2.13
(m, 1H), 1.95 (d, J¼9.3 Hz, 2H), 1.63 (m, 1H), 1.40 (s,
3H), 1.30 (s, 3H), 1.27 (s, 3H), 0.93 (d, J¼6.8 Hz, 3H);
13C NMR (CDCl3, 75 MHz) d 219.5, 134.9, 129.7, 108.2,
82.2, 78.6, 52.4, 43.7, 41.8, 40.4, 34.4, 33.2, 25.0, 24.6,
18.4, 13.8; IR nmax 2974, 2932, 2874, 1732, 1455, 1373,
1266, 1207, 1164, 1078, 1055, 886, 732 cmꢀ1; MS m/z
ꢃ
ꢃ
CHCl3). (Found: M+ , 320.1621. C18H24O5 requires: M+ ,
320.1624.) (Rf¼0.2 in 3:7 v/v ethyl acetate/hexane.) 1H
NMR (CDCl3, 500 MHz) d 5.97 (br t, J¼ca. 5.0 Hz, 1H),
5.84 (d, J¼5.0 Hz, 1H), 4.28 (dd, J¼4.2 and 2.1 Hz, 1H),
3.82 (d, J¼4.2 Hz, 1H), 3.66 (s, 3H), 2.88 (m, 1H), 2.57
(m, 2H), 2.26 (d, J¼6.0 Hz, 1H), 1.57 (s, 3H), 1.34 (m,
1H), 1.30 (s, 3H), 1.27 (s, 3H), 1.17 (s, 3H); 13C NMR
(CDCl3, 75 MHz) d 213.2, 173.0, 136.5, 130.0, 109.6,
83.3, 79.1, 58.4, 52.9, 51.8, 41.3, 39.7, 38.2, 34.8, 25.8,
25.3, 18.9, 18.8; IR nmax 2976, 2935, 2878, 1753, 1728,
1456, 1375, 1267, 1208, 1151, 1069, 889, 736 cmꢀ1; MS
ꢃ
(EI, 70 eV) 262 (M+ , 10%), 247 (43), 204 (86), 175 (57),
162 (72), 134 (100), 105 (96), 100 (82), 92 (60), 91 (63),
43 (69).
ꢃ
m/z (EI, 70 eV) 320 (M+ , 18%), 305 (60), 262 (89), 247
Concentration of fraction C afforded the starting ketone 9
(169 mg, 8% recovery) as a white crystalline solid
[Rf¼0.2(5) in 3:7 v/v ethyl acetate/hexane]. This material
was identical, in all respects, with an authentic sample.
(74), 202 (78), 173 (55), 157 (59), 134 (78), 105 (84), 100
(100), 92 (62), 91 (66), 85 (59), 69 (52), 43 (71), 41 (58).
4.2.5. Methyl (3aR,4R,4aR,6R,7aR,8S,8aS)-3a,4a,5,6,7,
7a,8,8a-octahydro-2,2,4,6-tetramethyl-5-oxo-4,8-etheno-
4H-indeno[5,6-d]-1,3-dioxole-6-carboxylate (6-epi-12).
Step i: a magnetically stirred solution of ketone 9 (202 mg,
0.82 mmol) in THF (2.5 mL) was cooled to ꢀ78 ꢂC and
then treated, dropwise over 0.5 h, with LiHMDS (1.22 mL
of 1.0 M solution in THF, 1.22 mmol). The ensuing mixture
was stirred at ꢀ78 ꢂC for 1.5 h and then treated with Mand-
er’s reagent28 (71 mL, 0.90 mmol) before being allowed to
warm to 18 ꢂC over 14 h. The reaction mixture was then
treated with water (5 mL) and dichloromethane (5 mL),
and the separated aqueous phase was extracted with di-
chloromethane (2ꢄ5 mL). The combined organic fractions
were washed with NaHCO3 (1ꢄ2 mL of a saturated aqueous
solution) and brine (1ꢄ2 mL), then dried (Na2SO4), filtered,
and concentrated under reduced pressure to give a pale-yel-
low oil. Subjection of this material to flash chromatography
(silica, 1:9/1:3 v/v ethyl acetate/hexane gradient elution)
and concentration of the relevant fractions gave a light-
yellow oil tentatively identified as a mixture of methyl
(3aR,4R,4aR,6R,7aR,8S,8aS)-3a,4a,5,6,7,7a,8,8a-octahydro-
2,2,4-trimethyl-5-oxo-4,8-etheno-4H-indeno[5,6-d]-1,3-dioxole-
6-carboxylate and its various tautomers (191 mg, 78%)
(Rf¼0.3 in 3:7 v/v ethyl acetate/hexane). This material was
subjected, without full characterization, to step ii of the reac-
tion sequence as detailed immediately below.
4.2.4. Methyl (3aR,4R,6S,7aR,8S,8aS)-4,6,7,7a,8,8a-
hexahydro-2,2,4,6-tetramethyl-4,8-etheno-3aH-indeno-
[5,6-d]-1,3-dioxol-5-yl carbonate (11) and methyl (3aR,
4R,4aR,6S,7aR,8S,8aS)-3a,4a,5,6,7,7a,8,8a-octahydro-
2,2,4,6-tetramethyl-5-oxo-4,8-etheno-4H-indeno[5,6-d]-
1,3-dioxole-6-carboxylate (12). A magnetically stirred
solution of compound 10 (1.94 g, 7.41 mmol) in THF
(75 mL) was cooled to 0 ꢂC and then treated, dropwise,
with LiHMDS (8.9 mL of a 1.0 M solution in THF,
8.90 mmol). The resulting mixture was maintained at 0 ꢂC
for 0.75 h, warmed to 18 ꢂC over 1.25 h, and then re-cooled
to 0 ꢂC and treated dropwise with Mander’s reagent28
(1.18 mL, 14.9 mmol). Stirring was continued at 0 ꢂC for
0.75 h, then the reaction mixture was warmed to 18 ꢂC
over 1.25 h, and quenched with NH4Cl (20 mL of a satu-
rated aqueous solution) and diluted with dichloromethane
(80 mL). The separated aqueous phase was extracted with
dichloromethane (3ꢄ20 mL) and the combined organic
phases were then washed with water (2ꢄ10 mL) before
being dried (Na2SO4), filtered, and concentrated under re-
duced pressure. The ensuing pale-yellow oil was subjected
to flash chromatography (silica, 5:95/15:85 v/v ethyl
acetate/hexane gradient elution) thus affording two fractions,
A and B.
Concentration of fraction A afforded the title enol carbonate
11 (71 mg, 3%) as white needles, mp¼100–104 ꢂC, [a]D
Step ii: a magnetically stirred suspension of NaH (15 mg,
0.63 mmol) in THF (5 mL) was cooled to 0 ꢂC and then
treated with a sample of the material obtained in step i
(94 mg, 0.31 mmol) dissolved in THF (1.5 mL). The
ꢃ
+50 (c 0.9, CHCl3). (Found: M+ , 320.1631. C18H24O5 re-
ꢃ
quires: M+ , 320.1624.) (Rf¼0.5 in 3:7 v/v ethyl acetate/