128
Vol. 52, No. 1
(17) (Table 1, entry 15) A solution of 2,4-dimethyl-3-pentyl acetate 6
whole was allowed to warm up to rt and diluted with ethyl acetate. The or-
(0.54 ml, 3 mmol) and 18 (1.02 g, 4.2 mmol) in toluene (7 ml) was added to a ganic layers were washed with brine and dried over potassium carbonate.
solution of LDA (3 mmol) in toluene (23 ml) at Ϫ78 °C dropwise over 5 min. Concentration and distillation (180—190 °C/7 mmHg) gave 22 as colorless
1
The mixture was stirred at Ϫ20 °C for 1 h. A solution of 8 (188 mg, 1 mmol) needles (13.9 g, 46%) of mp 36—40 °C. H-NMR: 0.15 (18H, s), 0.89 (6H,
in toluene (6 ml) was then added to the mixture dropwise over 2 min at d, Jϭ6.7 Hz), 0.90 (6H, d, Jϭ6.7 Hz), 1.70 (1H, s), 1.88 (2H, dqq, Jϭ5.8,
Ϫ78 °C, and the whole was stirred for 0.5 h. Concentration and chromatog- 6.7, 6.7 Hz), 4.51 (1H, dd, Jϭ5.8, 5.8 Hz). 13C-NMR: 0.29, 17.9, 19.9, 29.5,
raphy (hexane/EtOAcϭ20 : 1—3 : 1) gave 17 (344 mg, 99%) as a colorless 30.5, 82.5, 174.3. IR (nujol): 1690 cmϪ1. EI-MS m/z: 287 (MϩϪMe), 187
oil of [a]D25 ϩ0.45° (cϭ1.12, CHCl3). 1H-NMR: 0.71 (6H, d, Jϭ6.7 Hz), (MϩϪOCH(iPr)2). Anal. Calcd for C15H34O2Si2: C, 59.54; H, 11.33. Found:
0.83 (3H, d, Jϭ6.7 Hz), 0.84 (3H, d, Jϭ6.7 Hz), 1.01 (9H, s), 1.79 (1H, dqq, C, 59.37; H, 11.28.
Jϭ6.1, 6.7, 6.7 Hz), 1.86 (1H, dqq, Jϭ6.1, 6.7, 6.7 Hz), 2.74 (2H, s), 4.54
2,4-Dimethylpent-3-yl 2-(trimethylsilanyl)-2-(3-oxocyclohexyl)acetate
(1H, s), 4.56 (1H, dd, Jϭ6.1, 6.1 Hz), 6.30 (1H, d, Jϭ15.9 Hz), 6.65 (1H, d, (28: nϭ6) and 2,4-Dimethylpentan-3-yl 2-(cyclohex-2-enylidene)acetate
Jϭ15.9 Hz), 7.17—7.33 (5H, m). 13C-NMR: 17.1, 17.3, 19.3, 19.4, 25.2, (30) (Table 2, entry 8) The same reaction for entry 2, Table 2 gave an in-
29.1, 29.2, 38.1, 39.0, 77.4, 83.5, 126.5, 127.2, 128.4, 130.5, 132.0, 136.9, separable 2.1 : 1 diastereomeric mixture of 28 as a colorless oil in 4% and an
174.1. IR (neat): 1600, 1710, 3450 cmϪ1. EI-MS m/z: 289 (MϩϪtBu), 191. inseparable 1 : 3 E/Z-mixture of 30 as a colorless oil in 60% yield. 28 (nϭ6):
HR-FAB-MS m/z: [MϪH]Ϫ Calcd for C22H33O3, 345.2430; Found, 1H-NMR: 0.17 (9H, s), 0.89 (3H, d, Jϭ6.4 Hz), 0.91 (6H, d, Jϭ6.4 Hz), 0.92
345.2417.
(3H, d, Jϭ6.4 Hz), 1.57—2.13 (8H, m), 2.19 (1H, d, Jϭ4.9 Hz), 2.23—2.36
2,4-Dimethylpent-3-yl 2-(trimethylsilanyl)-2-(3-oxocyclopentyl)acetate (2H, m), 2.96 (1H, m), 4.61 (1H, dd, Jϭ5.8, 5.8 Hz). 13C-NMR: Ϫ0.96,
(26) and 2,4-Dimethylpentan-3-yl 2-(cyclopent-2-enylidene)acetate (29) 17.7, 17.8, 19.7, 19.8, 25.2, 29.4, 29.5, 31.6, 38.7, 40.9, 42.9, 46.3, 82.6,
(Table 2, entry 2) A solution of 1 (0.39 ml, 1.5 mmol) and 18 (508 mg, 174.3, 211.7. IR (nujol): 1710 cmϪ1. EI-MS m/z: 327 (Mϩϩ1), 228, 211
2.1 mmol) in toluene (5 ml) was added to a solution of LDA (1.6 mmol) in
(MϩϪOCH(iPr)2). HR-MS m/z: Calcd for C18H34O3Si, 326.2277; Found,
toluene (7 ml) at Ϫ78 °C dropwise over 5 min. The mixture was stirred at 326.2281. 30: The E/Z stereochemistry was assigned by analogy to 29 in
Ϫ20 °C for 1 h. A solution of cyclopentenone 23 (0.08 ml, 1 mmol) in which the Z-isomer possessed the lower field g-proton. IR (neat): 1600,
toluene (3 ml) was then added to the mixture at Ϫ78 °C dropwise over 2 min, 1630, 1710 cmϪ1. EI-MS m/z: 236 (Mϩ), 138, 121 (MϩϪOCH(iPr)2). Anal.
and the whole was stirred for 0.5 h at the same temperature. Concentration Calcd for C15H24O2: C, 76.23; H, 10.24. Found: C, 75.97; H, 10.43. major Z-
1
and chromatography (hexane/Et2Oϭ9/1) gave an inseparable 10 : 1 diastere- 30: H-NMR: 0.87 (6H, d, Jϭ7.1 Hz), 0.89 (6H, d, Jϭ7.1 Hz), 1.79 (1H, tt,
omeric mixture of 26 (140 mg, 47%) as a colorless oil of [a]D25 ϩ40.1°
(cϭ1.00, CHCl3) and an inseparable 6.5 : 1 E/Z-mixture of 29 (22%). 26:
The NMR peaks of major isomer were presented. H-NMR: 0.18 (9H, s),
Jϭ6.5, 6.5 Hz), 1.91 (2H, dqq, Jϭ6.4, 7.1, 7.1 Hz), 2.19—2.23 (2H, m),
2.40 (2H, dt, Jϭ1.6, 6.5 Hz), 4.63 (1H, dd, Jϭ6.4, 6.4 Hz), 5.52 (1H, s),
1
6.18—6.24 (2H, m), 7.49 (1H, d, Jϭ10.1 Hz). 13C-NMR: 17.3, 19.5, 22.6,
1
0.88 (3H, d, Jϭ6.8 Hz), 0.89 (3H, d, Jϭ6.8 Hz), 0.90 (3H, d, Jϭ6.8 Hz), 26.1, 29.4, 32.5, 81.5, 113.4, 125.4, 137.9, 152.2, 166.7. minor E-30: H-
0.91 (3H, d, Jϭ6.8 Hz), 1.68—2.59 (10H, m), 4.59 (1H, dd, Jϭ5.8, 5.8 Hz). NMR: 0.87 (6H, d, Jϭ7.1 Hz), 0.89 (6H, d, Jϭ7.1 Hz), 1.73 (1H, tt, Jϭ6.5,
13C-NMR: Ϫ1.11, 17.7, 18.0, 19.7, 19.9, 29.4, 29.5, 29.6, 36.5, 38.9, 42.0,
44.5, 82.8, 174.3, 218.7. IR (nujol): 1710, 1750 cmϪ1. EI-MS m/z: 312 (Mϩ),
214, 197 (MϩϪOCH(iPr)2). Anal. Calcd for C17H32O3Si: C, 65.33; H, 10.32.
6.5 Hz), 1.91 (2H, dqq, Jϭ6.4, 7.1, 7.1 Hz), 2.19—2.23 (2H, m), 2.97 (2H,
dt, Jϭ1.6, 6.5 Hz), 4.61 (1H, dd, Jϭ6.4, 6.4 Hz), 5.61 (1H, s), 6.13 (1H, d,
Jϭ10.1 Hz), 6.18—6.24 (2H, m). 13C-NMR: 17.3, 19.5, 21.8, 25.5, 29.4,
Found: C, 65.32; H, 10.04. 29: IR (neat) 1630, 1690 cmϪ1. EI-MS m/z: 222 32.5, 81.5, 115.3, 130.4, 137.6, 153.6, 167.4.
(Mϩ), 124, 107 (MϩϪOCH(iPr)2). HR-MS m/z: Calcd for C14H22O2,
2,4-Dimethylpent-3-yl 2-(cyclohept-2-enylidene)acetate (31) (Table 2,
222.1620; Found, 222.1612. major E-29: Irradiation of the a-vinyl proton entry 10) Obtained as a separable 1 : 3.6 E/Z-mixture of 31 in 64% yield
gave a nOe with the g-proton, allowing assignment as the E-isomer. 1H- as a colorless oil under the same conditions for Table 2, entry 2. The E/Z-
NMR: 0.88 (6H, d, Jϭ6.4 Hz), 0.90 (6H, d, Jϭ6.4 Hz), 1.92 (2H, dqq, stereochemistry was assigned by analogy to 29 in which the Z-isomer pos-
Jϭ6.1, 6.4, 6.4 Hz), 2.61—2.63 (2H, m), 3.01—3.03 (2H, m), 4.65 (1H, dd, sessed the lower field g-proton. More polar major Z-31: 1H-NMR: 0.87 (6H,
Jϭ6.1, 6.1 Hz), 5.80 (1H, s), 6.31 (1H, d, Jϭ5.5 Hz), 6.59—6.61 (1H, m).
d, Jϭ7.0 Hz), 0.89 (6H, d, Jϭ7.0 Hz), 1.70—1.79 (4H, m), 1.90 (2H, dqq,
Jϭ6.1, 7.0, 7.0 Hz), 2.29—2.31 (2H, m), 2.47 (2H, t, Jϭ5.8 Hz), 4.62 (1H,
13C-NMR: 17.3, 19.5, 29.5, 29.8, 33.3, 81.4, 109.2, 134.8, 147.6, 167.2,
168.0. minor Z-29: 1H-NMR: 0.88 (6H, d, Jϭ6.4 Hz), 0.90 (6H, d, dd, Jϭ6.1, 6.1 Hz), 5.63 (1H, s), 6.13 (1H, ddd, Jϭ6.1, 11.6, 11.6 Hz), 7.24
Jϭ6.4 Hz), 1.92 (2H, dqq, Jϭ6.1, 6.4, 6.4 Hz), 2.53—2.54 (2H, m), 2.68— (1H, d, Jϭ11.6 Hz). 13C-NMR: 17.3, 19.5, 26.4, 27.1, 28.5, 29.4, 37.3, 81.6,
2.69 (2H, m), 4.65 (1H, dd, Jϭ6.1, 6.1 Hz), 5.66 (1H, s), 6.63 (1H, m), 7.38 116.3, 119.2, 138.7, 156.9, 166.6. IR (neat): 1590, 1630, 1710 cmϪ1. EI-MS
(1H, d, Jϭ5.5 Hz). 13C-NMR: 17.3, 19.5, 29.5, 31.0, 31.2, 81.4, 107.5, m/z: 250 (Mϩ), 152, 135 (MϩϪOCH(iPr)2). Anal. Calcd for C16H26O2: C,
132.3, 148.4, 165.6, 167.1.
2,4-Dimethylpent-3-yl 2-(3-oxocyclopentyl)acetate (27) Protodesilyla- NMR: 0.87 (6H, d, Jϭ6.8 Hz), 0.89 (6H, d, Jϭ6.8 Hz), 1.70—1.81 (4H, m),
76.75; H, 10.47. Found: C, 76.75; H, 10.35. less polar minor E-31: 1H-
tion of 26 (Table 2, entry 2) with CsF in aq. acetonitrile gave 27 as a color-
1.91 (2H, dqq, Jϭ6.1, 6.8, 6.8 Hz), 2.29—2.31 (2H, m), 3.03 (2H, t,
less oil of [a]D25 ϩ58.1° (cϭ0.73, CHCl3) in 39% yield. 1H-NMR: 0.86 (6H, Jϭ6.4 Hz), 4.63 (1H, dd, Jϭ6.1, 6.1 Hz), 5.71 (1H, s), 6.04 (1H, ddd, Jϭ5.5,
d, Jϭ6.7 Hz), 0.88 (6H, d, Jϭ6.7 Hz), 1.58—2.67 (11H, m), 4.62 (1H, dd, 11.6, 11.6 Hz), 6.14 (1H, d, Jϭ11.6 Hz). 13C-NMR: 17.2, 19.5, 25.5, 26.8,
Jϭ6.1, 6.1 Hz). 13C-NMR: 17.3, 19.6, 29.3, 33.5, 38.3, 40.0, 44.7, 82.9,
172.1, 218.4. IR (neat): 1730, 1740 cmϪ1. EI-MS m/z: 240 (Mϩ), 197
28.5, 29.4, 29.6, 81.6, 118.3, 133.9, 138.8, 158.0, 167.3. IR (neat): 1600,
1630, 1710 cmϪ1. EI-MS m/z: 250 (Mϩ), 152, 135 (MϩϪOCH(iPr)2). HR-
(MϩϪCH(CH3)2), 141 (MϩϪCH(iPr)2), 125 (MϩϪOCH(iPr)2). Anal. Calcd MS m/z: Calcd for C16H26O2, 250.1933; Found, 250.1941.
for C14H24O3: C, 69.96; H, 10.07. Found: C, 70.10; H, 9.77. The ee was de-
termined to be 74% by 13C-NMR of the aminals (major: 30.7, minor:
Acknowledgements This research was partially supported by the 21st
31.1 ppm) obtained by treating 27 (2.9 mg, 0.01 mmol) with (R,R)-1,2- Century COE (Center of excellence) Program “Knowledge Information In-
diphenylethane-1,2-diamine (3 mg, 0.015 mmol) in CDCl3 in the presence of
molecular sieves 4A at rt for 12 h.
frastructure for Genome Science and a Grant-in-Aid for Scientific Research
on Priority Areas (A) “Exploitation of Multi-Element Cyclic Molecules”
Determination of the Absolute Configuration of 27 by Converting to from the Ministry of Education, Culture, Sports, Science and Technology,
R-(ϩ)-2-(3-Oxocyclopentyl)acetic acid (32) A mixture of (ϩ)-27 (23 mg, Japan.
0.09 mmol) and conc. HCl (0.2 ml) in 1 : 1 mixture of dioxane and water
(0.4 ml) was stirred under reflux for 19 h. After the mixture was basified References and Notes
with satd aq. sodium bicarbonate (20 ml), the aqueous layer was separated,
which was then acidified with 10% HCl and extracted with ethyl acetate.
Concentration and chromatography gave R-(ϩ)-3256) (8 mg, 63%) as a color-
less oil of [a]D23 ϩ88.1° (cϭ0.79, CHCl3). 1H-NMR: 1.62 (1H, m), 1.92 (1H,
dd, Jϭ10.1, 18.2 Hz), 2.18—2.37 (3H, m), 2.48—2.66 (4H, m). 13C-NMR:
1) Perlmutter P., “Conjugate Addition Reactions in Organic Synthesis,”
Pergamon Press, Oxford, 1992.
2) Rossiter B. E., Swingle N. M., Chem. Rev., 92, 771—806 (1992).
3) Tomioka K., Nagaoka Y., “Comprehensive Asymmetric Catalysis,”
Vol. III, Chap. 31.1, ed. by Jacobsen E. N., Pfaltz A., Yamamoto H.,
Springer-Verlag, Berlin, 1999.
4) Tomioka K., “Modern Carbonyl Chemistry,” Chap. 12, ed. by Otera J.,
Wiley-VCH, Weinheim, 2000.
5) Sibi M. P., Manyem S., Tetrahedron, 56, 8033—8061 (2000).
6) Krause N., Hoffmann-Röder A., Synthesis, 2001, 171—196.
7) Iguchi M., Yamada K., Tomioka K., “Organolithiums in Enantioselec-
tive Synthesis,” ed. by Hodgson D. M., Springer-Verlag, Berlin, 2003.
29.2, 33.1, 38.3, 39.3, 44.5, 177.6, 218.2. IR (neat): 1720, 1740, 3200 cmϪ1
.
EI-MS m/z: 142 (Mϩ).
2,4-Dimethylpent-3-yl 2,2-bis(trimethylsilanyl)acetate (22) A solu-
tion of 1 (26.2 ml, 0.1 mol) in THF (50 ml) was added to a solution of LDA
(0.15 mol) in THF (350 ml) at Ϫ78 °C dropwise over 10 min. After stirring
for 2 h at Ϫ78 °C a solution of trimethylsilyl chloride (127 ml, 1 mol) in THF
(200 ml) was added to the mixture at Ϫ78 °C dropwise over 10 min. The