Intramolecular Diels−Alder Reactions of Optically Active Allenic

Michael E. Jung* andSun-Joon Min. Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569. J. Am. Chem...
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Intramolecular Diels-Alder Reactions of Optically Active Allenic Ketones: Chirality Transfer in the Preparation of Substituted Oxa-bridged Octalones Michael E. Jung* and Sun-Joon Min Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569

Experimental Section

General. 1H and 13C NMR spectra were recorded on Bruker spectrometers at 400 or 500 MHz for proton and at 100 or 125 MHz for carbon as indicated. 1H NMR and 13C NMR data are reported in parts per million (d) downfield from tetramethylsilane. The following abbreviations are used: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad). Second-order spectra in which coupling cannot be obtained by inspection are reported as multiplets. Infrared spectra were recorded on a Thermo Nicolet Avatar 370 infrared spectrophotometer as a liquid film or as a thin crystalline film with the IR data reported in wavenumbers (cm-1). Thin-layer chromatography (TLC) was performed using Merck silica gel 60 F254 0.2 mm aluminabacked plates. Visualization was accomplished using ultraviolet light or one of the following stains: anisaldehyde, phosphomolybdic acid, and potassium permanganate. Flash chromatography was carried out using ICN Biomedicals silica gel 60 (230-400 mesh). All solvents and reagents were purified using literature procedures. All reactions were performed under argon unless otherwise noted.

4-Methyl-2-oxo-3-pentenenitrile (4b) To a solution of 3,3-dimethylacrylic acid 4a (15.0 g, 0.150 mol) in dichloromethane (100 mL) was slowly added oxalyl chloride (19.6 mL, 0.225 mol) at 0 °C. The reaction mixture was stirred for 5 h and then the solvent was removed under reduced pressure without heating. The distillation of crude product (30-35 °C/0.5 mmHg) gave 3-methyl-2-butenoyl chloride (14.9 g, 84%) as a clear oil, which was directly used in the next step. To a solution of acyl chloride (1.85 g, 15.6 mmol) in acetonirile (30 mL) was added anhydrous copper(I) cyanide (2.79 g, 31.1 mmol), and the suspension was stirred at 90 °C for 1.5 h during which time a clear, brown solution was formed. The solution was cooled down to room temperature, and the solvent was removed under reduced pressure without heating. Distillation of the remaining brown solid (70-80 °C/5 mmHg) provided 4-methyl-2-oxo-3-pentenenitrile 4b as colorless oil (980 mg, 59%), which was used directly for the next step. The spectroscopic data of 4b were identical with those reported in the literature.1 1H NMR (CDCl3, 500 MHz) d: 6.24 (dd, J = 1.0, 0.7 Hz, 1H), 2.29 (d, J = 0.7 Hz, 3H), 2.07 (d, J = 1.0 Hz, 3H). 13C NMR (CDCl3, 125 MHz) d: 168.6, 164.3, 122.8, 114.8, 28.4, 22.4.

Methyl 3-methyl-3-[2-(5-methylfuryl)butanoate (5) The acyl cyanide 4b (6.96 g, 63.8 mmol) was dissolved in carbon disulfide (200 mL) under argon atmosphere and cooled in an ice bath. To this solution was added aluminum chloride (2.13 g, 15.9 mmol), resulting in a gummy precipitate. After stirring for 1 h at room temperature, 2-methylfuran (20.0 g, 0.244 mol) was added neat, and the reaction mixture was stirred for 24 h, after which time anhydrous methanol (230 mL) was added to the solution. The reaction mixture was then stirred for an additional 24 h. Evaporation of the carbon disulfide, followed by removal of methanol in vacuo, resulted in a viscous brown material. The crude product was taken up in diethyl ether (300 mL) and water (300 mL) followed by washing with 10% aqueous sodium carbonate (200 mL), then water (200 mL), dried over magnesium sulfate, and the diethyl ether removed in vacuo. Distillation (90 °C/0.1 mmHg) of the crude oil yielded methyl 3-methyl-3-[2-(5-methylfuryl)]-

butanoate 5 as an oil (8.21 g, 66%). The spectroscopic data of 5 were identical with those reported in the literature.1 1H NMR (CDCl3, 500 MHz) d: 5.86 (d, J = 3.0 Hz, 1H), 5.82 (dq, J = 3.0, 0.8 Hz, 1H), 3.60 (s, 3H), 2.58 (s, 2H), 2.25 (d, J = 0.8 Hz, 3H), 1.37 (s, 6H). 13C NMR (CDCl3, 125 MHz) d: 171.9, 159.5, 150.4, 105.6, 103.7, 51.2, 45.8, 34.9, 26.7, 13.5. IR (neat): 3107, 2912, 2878, 1739, 1613, 1562, 1437, 1387, 1367, 1349, 1328, 1221, 1134, 1110, 1023, 953, 937, 782 cm-1.

3-[2-(5-Methylfuryl)]-3-methylbutanol (5a) To a suspension of lithium aluminum hydride (0.594 g, 15.7 mmol) in diethyl ether (70 mL) at 0 °C under argon atmosphere was added dropwise a solution of the ester 5 (2.046 g, 10.4 mmol) in diethyl ether (10 mL). The reaction mixture was warmed to room temperature and stirred for 1.5 h. After cooling to 0 °C, it was quenched with water (0.59 ml), 15% aqueous sodium hydroxide (0.59 mL), and water (1.68 mL). The white precipitate was then filtered through Celite, and the solvent was removed in vacuo to provide 3-[2-(5methylfuryl)]-3-methylbutanol 5a (1.754 g, 100%) as a clear, colorless oil, which was directly used without further purification. The spectroscopic data were identical with those reported in the literature.1,2 1H NMR (CDCl3, 500 MHz) d: 5.85 (d, J = 3.0 Hz, 1H), 5.82 (dq, J = 3.0, 0.7 Hz, 1H), 3.58 (t, J = 7.0 Hz, 2H), 2.25 (s, 3H), 1.87 (t, J = 7.0 Hz, 2H), 1.32 (br s, 1H), 1.27 (s, 6H).

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C NMR (CDCl3, 125 MHz) d: 160.5, 150.4,

105.6, 103.9, 60.1, 44.6, 34.4, 27.3, 13.5. IR (neat): 3356, 3106, 2967, 2946, 2887, 1614, 1562, 1471, 1452, 1385, 1366, 1348, 1221, 1196, 1123, 1023, 939, 853, 780 cm-1.

3-[2-(5-Methylfuryl)]-3-methyl-1-butyl p-toluenesulfonate (5b) To a solution of the alcohol 5a (1.754 g, 10.4 mmol) in dichloromethane (50 mL) were added triethylamine (2.91 mL, 15.6 mmol), p-toluenesulfonyl chloride (2.982 g, 15.6 mmol), and 4-(dimethylamino)pyridine (0.127 g, 0.10 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 17 h. The mixture was poured into aqueous ammonium chloride (50 mL), and extracted with dichloromethane (50 mL x 3). The combined organic layers were washed with water and brine, the dried over magnesium sulfate. The solvent was removed

in vacuo to give a crude oil, which was purified by flash chromatography on silica gel (6:1 hexane/ethyl acetate) to provide 3-[2-(5-methylfuryl)]-3-methyl-1-butyl p-toluenesulfonate 5b (3.323 g, 99%). The spectroscopic data were identical with those reported in the literature.1,2 1H NMR (CDCl3, 500 MHz) d: 7.73 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 5.76 (dq, J = 3.1, 0.5 Hz, 1H), 5.74 (d, J = 3.1 Hz, 1H), 3.953.92 (m, 2H), 2.42 (s, 3H), 2.17 (s, 3H), 1.94-1.91 (m, 2H), 1.20 (s, 6H).

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C NMR (CDCl3, 125 MHz) d:

158.8, 150.3, 144.5, 133.0, 129.6, 127.7, 105.4, 104.3, 68.1, 40.1, 34.3, 26.9, 21.4, 13.3. IR (neat): 3105, 3033, 2969, 2874, 1922, 1655, 1599, 1562, 1495, 1453, 1362, 1307, 1292, 1220, 1177, 1126, 1097, 1022, 1001, 961, 891, 816, 784 cm-1.

4-[2-(5-Methylfuryl)]-4-methylpentanenitrile (5c) To a solution of the tosylate 5b (400 mg, 1.24 mmol) in dimethyl sulfoxide (3 mL) was added sodium cyanide (91 mg, 1.86 mmol) in one portion. The reaction mixture was stirred at 90 °C for 1.5 h. After cooled to room temperature, the mixture was quenched with aqueous ammonium chloride (10 mL), extracted with diethyl ether (15 mL x 3), washed with water (10 mL) and brine (10 mL), and dried over magnesium sulfate. The solvent was removed under pressure to give a crude oil, which was purified by flash chromatography on silica gel (3.5:1 hexane/diethyl ether) to afford 4-[2-(5-methylfuryl)]-4-methylpentanenitrile 5c (211 mg, 96%) as an oil. The spectroscopic data were identical with those reported in the literature.2 1H NMR (CDCl3, 500 MHz) d: 5.87 (d, J = 3.0 Hz, 1H), 5.83 (dq, J = 3.0, 0.8 Hz, 1H), 2.25 (d, J = 0.8 Hz, 1H), 2.14-2.11 (m, 2H), 1.97-1.93 (m, 2H), 1.20 (s, 6H). 13C NMR (CDCl3, 125 MHz) d: 158.0, 150.9, 120.1, 105.6, 105.2, 37.4, 35.3, 26.3, 13.4, 12.9. IR (neat): 2970, 2927, 2872, 2246, 1611, 1562, 1452, 1389, 1220, 1121, 1022, 958, 938, 785 cm-1.

4-Methyl-4-[2-(5-methylfuryl)]pentanal (6) To a solution of the nitrile 5c (1.667 g, 9.41 mmol) in dichloromethane (50 mL) at -78 °C was added dropwise a solution of DIBAL (14.11 mL, 14.1 mmol, 1.0 M in hexane) over a period time of 10 min. After being

stirred for 2 h at -78 °C, the reaction mixture was treated with methanol (10 mL) and saturated aqueous ammonium chloride and the resultant suspension was diluted with diethyl ether (200 mL) and filtered through a pad of Celite. The filtrate was washed with saturated aqueous ammonium chloride and brine. The aqueous layers were extracted with diethyl ether (100 mL x 2), and the combined organic layers were dried over magnesium sulfate. Filtration and concentration followed by column chromatography on silica gel (5:1 pentane/diethyl ether) afforded 4-methyl-4-[2-(5-methylfuryl)]pentanal 6 (1.175 g, 69%) as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 9.63 (t, J = 1.8 Hz, 1H), 5.84 (d, J = 3.0Hz, 1H), 5.82 (dq, J = 3.0, 0.9 Hz, 1H), 2.28 (td, J = 7.9, 1.8 Hz, 2H), 2.24 (d, J = 0.9 Hz, 3H), 1.89 (t, J = 7.9 Hz, 2H), 1.25 (s, 6H).

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C NMR

(CDCl3, 125 MHz) d: 202.5, 159.4, 150.4, 105.4, 104.5, 39.9, 35.0, 33.8, 26.6, 13.4. IR (neat): 2968, 2925, 2821, 2720, 1725, 1562, 1452, 1386, 1367, 1220, 1123, 1022, 938, 783 cm-1. HRMS (EI) m/z found for (MH)+ 179.1071, calcd for C11H15O2 179.1072.

3,7-Dimethyl-7-[2-(5-methylfuryl)]-1,2-octadien-4-ol (6a) To a solution of 1-bromo-2-butyne (0.58 mL, 6.62 mmol) in DMPU (15 mL) at room temperature under argon were simultaneously added tin(II) chloride (1.363 g, 7.18 mmol) and sodium iodide (1.078 g, 7.19 mmol). The resulting yellow slurry was stirred in the absence of light for 4 h. The mixture was cooled to 0 °C, and a solution of the aldehyde 6 (0.997 g, 5.53 mmol) in DMPU (7.5 mL) was added over a 10 min period. After 20 h at 0 °C, the reaction mixture was diluted with ether and quenched with 0.5 N HCl solution, and the resulting mixture was filtered through Celite with aid of ether. The aqueous layer was separated and diluted with brine and water, and then extracted with ether. The combined extracts were washed with 1.0 N HCl solution and then aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated. The crude product was purified by column chromatography on silica gel (4:1 hexane/ethyl acetate) to yield 3,7-dimethyl-7-[2-(5-methylfuryl)]-1,2-octadien-4-ol 6a (1.066 g, 82%) as clear oil. 1H NMR (CDCl3, 500 MHz) d: 5.82 (d, J = 3.1 Hz, 1H), 5.81 (dq, J = 3.1, 0.8 Hz, 1H), 4.77 (q, J = 3.1 Hz, 1H), 4.76 (q, J = 3.1 Hz, 1H), 3.96 (t, J = 6.2 Hz, 1H), 2.24 (d, J = 0.8 Hz, 3H), 1.67 (dd, J = 13.0, 4.7 Hz, 1H), 1.63 (t, J = 3.1 Hz,

3H), 1.56 (dd, J = 12.2, 4.7 Hz, 1H), 1.55 (br s, 1H), 1.51-.1.45 (m, 1H), 1.42-1.34 (m, 1H), 1.23 (s, 6H). 13C NMR (CDCl3, 125 MHz) d: 204.9, 160.7, 149.9, 105.3, 103.8, 101.7, 76.5, 72.7, 37.1, 35.2, 30.0, 26.9, 26.7, 14.0, 13.5. IR (neat): 3346, 2966, 2924, 2869, 1959, 1614, 1562, 1453, 1384, 1367, 1348, 1313, 1221, 1196, 1115, 1021, 846, 780 cm-1. HRMS (EI) m/z found for (M-H)+ 233.1537, calcd for C15H21O2 233.1541.

3,7-Dimethyl-7-[2-(5-methylfuryl)]-1,2-octadien-4-one (7) To a solution of the allenol 6a (1.049 g, 4.46 mmol) in dichloromethane (50 mL) under argon was added Dess-Martin periodinane (2.272 g, 5.36 mmol). The suspension was stirred at room temperature for 1 h, and then an aqueous solution of sodium thiosulfate in saturated sodium bicarbonate (50 mL) was added. The mixture was stirred vigorously until the organic layer became clear. The organic layer was separated. The aqueous layer was extracted with diethyl ether (50 mL x 3). Both organic layers were respectively washed with saturated sodium bicarbonate and brine. The combined organic layers were then dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (6:1 hexane/diethyl ether) to afford 3,7-dimethyl-7-[2-(5-methylfuryl)]-1,2-octadien-4-one 7 (910 mg, 88%) as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 5.82 (d, J = 3.1 Hz, 1H), 5.81 (d, J = 3.1 Hz, 1H), 5.05 (q, J = 3.0 Hz, 2H), 2.53-2.50 (m, 2H), 2.24 (s, 3H), 1.85-1.82 (m, 2H), 1.74 (t, J = 3.0 Hz, 3H), 1.22 (s, 6H). 13C NMR (CDCl3, 125 MHz) d: 216.1, 201.6, 160.1, 150.1, 105.3, 104.0, 103.3, 78.3, 36.9, 35.2, 34.8, 26.6, 13.5, 13.1. IR (neat): 2967, 2926, 2869, 1935, 1678, 1561, 1451, 1412, 1385, 1367, 1348, 1297, 1220, 1117, 1068, 847, 781 cm-1. HRMS (EI) m/z found for (M-H)+ 231.1380, calcd for C15H19O2 231.1385.

2,2,6,8-Tetramethyl-7-methylene-11-oxa-tricyclo[6.2.1.01,6]-9-undecen-5-one (8) To a solution of the allenic ketone 7 (455 mg, 1.96 mmol) in dichloromethane (20 mL) at -78 °C was added a solution of diethylaluminum chloride (2.15 mL, 2.15 mmol, 1.0 M in hexane). After 30 min, the reaction mixture was allowed to warm up to -20 °C and stirred for an additional 3 h. The mixture was quenched with saturated sodium bicarbonate (30 mL), extracted with dichloromethane (25 mL x 3), washed with brine, dried

over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (10:1 hexane/ethyl acetate) to give 2,2,6,8-tetramethyl-7-methylene-11-oxatricyclo[6.2.1.01,6]-9-undecen-5-one 8 (416 mg, 91%) as a solid. 1H NMR (CDCl3, 500 MHz) d: 6.30 (d, J = 5.6 Hz, 1H), 6.19 (d, J = 5.6 Hz, 1H), 5.07 (s, 1H), 4.99 (s, 1H), 2.72 (ddd, J = 15.9, 13.6, 6.1 Hz, 1H), 2.42 (ddd, J = 15.9, 4.7, 3.1 Hz, 1H), 2.08 (ddd, J = 13.6, 13.6, 4.7 Hz, 1H), 1.59 (ddd, J = 13.6, 6.1, 3.1 Hz, 1H), 1.54 (s, 3H), 1.35 (s, 3H), 1.25 (s, 3H), 1.09 (s, 3H).

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C NMR (CDCl3, 125 MHz) d: 210.2, 154.4, 140.0,

133.7, 105.3, 96.8, 86.6, 59.2, 35.1, 34.4, 32.5, 27.1, 25.4, 23.5, 15.6. IR (neat): 3081, 2967, 2931, 2869, 1712, 1476, 1452, 1384, 1370, 1319, 1250, 1201, 1164, 1124, 1083, 1066, 1011, 943, 886, 758 cm-1. HRMS (EI) m/z found for M+ 232.1459 calcd for C15H20O2 212.1463.

2,2,6,8-Tetramethyl-7-methylene-11-oxatricyclo[6.2.1.01,6]-5-undecanone (8a) To a suspension of 8 (0.491 g, 2.11 mmol) and dipotassium diazodicarboxylate6 (1.642 g, 8.45 mmol) in dichloromethane (20 mL) at -78 °C was slowly added a solution of acetic acid (0.97 mL, 16.0 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at -78 °C for 2 h and then slowly warmed to room temperature. Stirring was continued until the suspension became white and then the solvent was removed under reduced pressure. The residue was diluted with ether (30 mL) and the residual potassium acetate was filtered off through a pad of Celite. The solvent was completely removed under reduced pressure to yield the crude product, which was purified by column chromatography on silica gel (10:1 hexane/ethyl acetate) to provide 2,2,6,8-tetramethyl-7-methylene-11-oxatricyclo[6.2.1.01,6]-5-undecanone 8 a (430 mg, 87%) as a white solid. 1H NMR (CDCl3, 500 MHz) d: 4.98 (s, 1H), 4.84 (s, 1H), 2.64 (ddd, J = 15.3, 13.2, 6.0 Hz, 1H), 2.40 (ddd, J = 15.2, 4.9, 3.7 Hz, 1H), 1.81-1.78 (m, 2H), 1.62-1.56 (m, 3H), 1.43 (s, 3H), 1.36 (s, 3H), 1.15 (s, 3H), 1.12 (s, 3H). 13C NMR (CDCl3, 125 MHz) d: 210.5, 158.6, 103.6, 93.5, 84.6, 62.1, 38.2, 35.9, 35.0, 33.7, 25.9, 25.7, 23.7, 22.9, 18.3. IR (neat): 3082, 2973, 2871, 1716, 1665, 1475, 1450, 1420, 1383, 1324, 1248, 1223, 1180, 1102, 1063, 1031, 1014, 922, 888, 828, 780 cm-1. HRMS (EI) m/z found for M+ 234.1629, calcd for C15H22O2 234.1620.

2,2,6,8-Tetramethyl-7-methylene-11-oxatricyclo[6.2.1.01,6]-5-undecanol (9) To a solution of ketone 8a (28 mg, 0.12 mmol) in tetrahydrofuran (0.5 mL) at -78 °C was added L-Selectride (0.36 mL, 0.36 mmol, 1.0 M in tetrahydrofuran). The reaction was warmed to room temperature over 1 h, and then allowed to stand for 3 h. Water (0.1 mL) and ethanol (0.3 ml) were added. After 30 min, 6 N sodium hydroxide (0.2 mL) and 30% hydrogen peroxide (0.3 mL) were added. After 30 min, solid potassium carbonate was added and the mixture was extracted with ether (5 mL x 3). The combined organic extracts were washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by column chromatography on silica gel (5:1 hexane/diethyl ether) to provide the alcohol 9 (22 mg, 78%) as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 4.94 (s, 1H), 4.73 (s, 1H), 3.70 (br s, 1H), 3.45 (br s, 1H), 1.99 (ddd, J = 14.1, 14.1, 3.5 Hz, 1H), 1.89 (dddd, J = 14.4, 14.4, 3.0, 3.0 Hz, 1H), 1.79 (ddd, J = 12.6, 11.0, 5.2 Hz, 1H), 1.71 (ddd, J = 14.3, 6.5, 3.0 Hz, 1H), 1.68 (ddd, J = 12.7, 9.2, 5.4 Hz, 1H), 1.62-1.54 (m, 2H), 1.49 (s, 3H), 1.20 (s, 3H), 1.20-1.18 (m, 1H), 1.06 (s, 3H), 0.99 (s, 3H).

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C NMR (CDCl3, 125 MHz) d: 162.80,

100.2, 93.1, 85.9, 75.6, 51.8, 38.2, 33.5, 30.7, 26.8, 26.3, 25.5, 24.4, 22.2, 17.7. IR (neat): 3503, 3072, 2935, 2866, 1668, 1475, 1410, 1382, 1292, 1201, 1161, 1085, 1057, 1018, 975, 953, 921, 878, 853, 768, 673 cm-1. HRMS (EI) m/z found for M+ 236.1782, calcd for C15H24O2 236.1776.

Structure determination by conversion of 10 to 9 To a solution of known triol 10 (5 mg, 0.020 mmol) in dichloromethane (0.3 mL) was added triethylamine (8

mL, 0.057 mmol), dimethylaminopyridine (0.3 mg, 0.002 mmol), and p-toluenesulfonyl chloride (6 mg, 0.031 mmol). The reaction mixture was stirred for 2 h and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (5:1 hexane/ethyl acetate) to give alcohol 9 (2 mg, 43%). The spectroscopic data were consistent with those of the alcohol 9 which was derived from 8.

3-Pentyn-2-ol (11)

To a 3.0 M solution of ethyl magnesium bromide in diethyl ether (20 mL, 0.06 mol) was passed propyne gas under argon atmosphere. Stirring was continued for 30 min at room temperature until evolution of ethane had ceased. At 0 °C, a solution of acetaldehyde (3.37 mL, 0.06 mol) in ether (5 mL) was added and the solution was stirred 18 h at room temp. The reaction mixture was poured into aqueous ammonium chloride (30 mL) and extracted with ether (25 mL x 3). The organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by distillation (75-80 °C/60 mmHg) to provide 3pentyn-2-ol (2.84 g, 56%) as a clear oil. The spectroscopic data of 11 were identical with those reported in the literature.3 1H NMR (CDCl3, 500 MHz) d: 4.49-4.47 (m, 1H), 1.82 (d, J = 2.1 Hz, 3H), 1.81 (br s, 1H), 1.41 (d, J = 6.6 Hz, 3H). 13C NMR (CDCl3, 125 MHz) d: 81.3, 80.1, 58.5, 24.5, 3.4.

2-(Tri-n-butylstannyl)-2,3-pentadiene (12) To a solution of 3-pentyn-2-ol 11 (100 mg, 1.19 mmol) in dichloromethane (8 mL) at -78 °C was added triethylamine (0.34 mL, 2.44 mmol) with stirring. After 5 min, methansulfonyl chloride (0.18 mL, 2.33 mmol) was added, and the resulting solution was stirred for 1 h. The mixture was quenched with aqueous sodium bicarbonate (10 mL), extracted with ether (10 mL x 3), dried over magnesium sulfate, and concentrated under reduced pressure to yield mesylate which was directly used without further purification. To a solution of diisopropylamine (0.22 mL, 1.57 mmol) in tetrahydrofuran (7 mL) at 0 °C was added a 1.5 M solution of n-butyllithium in hexane (0.99 mL, 1.49 mmol). After 15 min, tributyltin hydride (0.40 mL, 1.49 mmol) was added and after 25 min, the mixture was cooled to -78 °C. To this solution was added CuBr†SMe2 (305 mg, 1.48 mmol) in one portion with stirring. After 35 min, a solution of the mesylate in tetrahydrofuran (1 mL) was added; the mixture was stirred for 15 min and then poured into a rapidly stirring 9:1 mixture of NH4Cl/NH4OH solution (10 mL) and extracted with ether (15 mL x 3). The ether extract was washed with additional portions of aqueous NH4Cl/NH4OH solution until the layer became colorless. The organic extract was then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (50:1 hexane/ethyl acetate) on deactivated silica gel to afford the

desired material along with hexabutylditin. Further purification by treatment with silver acetate (298 mg, 1.79 mmol) in tetrahydrofuran (10 mL) at room temperature gave 2-(tri-n-butylstannyl)-2,3-pentadiene 12 (217 mg, 51%) as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 4.56-4.49 (m, 1H), 1.79 (d, J = 2.8 Hz, 3H), 1.59 (d, J = 6.9 Hz, 3H), 1.55-1.43 (m, 6H), 1.31 (sextet, J = 7.3 Hz, 6H), 0.92 (t, J = 8.2 Hz, 6H), 0.89 (t, J = 7.3 Hz, 9H). 13C NMR (CDCl3, 125 MHz) d: 203.4, 87.0, 75.2, 28.9, 27.2, 19.0, 14.3, 13.6, 9.8. IR (neat): 2956, 2926, 2872, 2855, 1943, 1463, 1377, 1072, 972, 874, 741 cm-1.

4,8-Dimethyl-8-(2-(5-methylfuryl))-2,3-nonadien-5-ol (13) To a solution of the allenylstannane 12 in dichloromethane (2 mL) at -40 °C was added n-butyltin chloride (0.023 mL, 0.14 mmol) with stirring. After 20 min, a solution of aldehyde 6 (25 mg, 0.14 mmol) in dichloromethane (0.2 mL) was added. The reaction mixture was stirred at -40 °C for 5 h, and then aqueous ammonium chloride was added. Upon being warmed to room temperature, the mixture was extracted with diethyl ether (5 mL x 3), and dried over magnesium sulfate. To this suspension was added triethylamine, and after being stirred for 10 min, the slurry was filtered through a pad of Celite, and the filtrate was concentrated to give a yellow oil. Purification by flash column chromatography on silica gel (10:1 hexane/ethyl acetate, 1% triethylamine) provided two diastereomeric mixture of 4,8-dimethyl-8-(2-(5-methylfuryl))-2,3-nonadien-5-ol 13 (16 mg, 46%) along with the remaining aldehyde 6 (13mg, 52 %). Major isomer: 1H NMR (CDCl3, 500 MHz) d: 5.82-5.80 (m, 2H), 5.21-5.17 (m, 1H), 3.91 (br s, 1H), 2.24 (d, J = 0.7 Hz, 3H), 1.67 (d, J = 6.9 Hz, 3H), 1.63-1.47 (m, 3H), 1.60 (d, J = 2.9 Hz, 3H), 1.37-1.32 (m, 1H), 1.23 (s, 6H).

13

C NMR (CDCl3, 125

MHz) d: 200.5, 160.8, 149.9, 105.3, 103.7, 102.0, 88.1, 72.8, 36.9, 35.2, 26.8, 26.8, 26.8, 14.8, 14.7, 13.5. IR (neat): 3373, 2967, 2867, 1966, 1561, 1450, 1367, 1221, 1116, 1021, 962, 938, 780 cm-1. HRMS (EI) m/z found for M+ 248.1772, calcd for C16H24O2 248.1776.

4,8-Dimethyl-8-(2-(5-methylfuryl))-2,3-nonadien-5-one (14) To a solution of the allenol 13 (24 mg, 0.097 mmol) in dichloromethane (1 mL) under argon was added Dess-

Martin periodinane (53 mg, 0.13 mmol). The suspension was stirred at room temperature for 30 min, and then an aqueous solution of sodium thiosulfate in saturated sodium bicarbonate (5 mL) was added. The mixture was stirred vigorously until the organic layer became clear. The organic layer was separated. The aqueous layer was extracted with ether (5 mL x 3). Both organic layers were respectively washed with saturated sodium bicarbonate and brine. The combined organic layer were then dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on neutral alumina (10:1 hexane/ethyl acetate) to afford 4,8-dimethyl-8-(2-(5-methylfuryl))-2,3-nonadien-5-one 14 (22 mg, 92%) as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 5.82-5.80 (m, 2H), 5.39 (qq, J = 7.2, 2.7 Hz, 1H), 2.51-2.41(m, 2H), 2.24 (d, J = 0.4 Hz, 3H), 1.85-1.79 (m, 2H), 1.73 (d, J = 7.2 Hz, 3H), 1.71 (d, J = 2.7 Hz, 3H), 1.21 (s, 6H). 13C NMR (CDCl3, 125 MHz) d: 212.5, 202.5, 160.1, 150.0, 105.3, 104.0, 103.2, 88.8, 37.3, 35.2, 34.8, 26.6, 26.5, 13.5, 13.4, 13.2. IR (neat): 2967, 2926, 2866, 1949, 1677, 1561, 1450, 1367, 1298, 1220, 1117, 1067, 1023, 960, 938, 781 cm-1. HRMS (EI) m/z found for M+ 248.1620, calcd forC16H22O2 248.1620.

7-Ethylidene-2,2,6,8-tetramethyl-11-oxa-tricyclo[6.2.1.01,6]-9-undecen-5-one (15) To a solution of the allenic ketone 14 (15 mg, 0.061 mmol) in dichloromethane (1 mL) at -78 °C was added a solution of dimethylaluminum chloride (71 m L, 0.071 mmol, 1.0 M in hexane). After 30 min, the reaction mixture was allowed to warm up to -20 °C and stirred for an additional 3 h. The mixture was quenched with saturated sodium bicarbonate (3 mL), extracted with dichloromethane (7 mL x 3), washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (10:1 hexane/ethyl acetate) to give 7-ethylidene-2,2,6,8-tetramethyl-11-oxatricyclo[6.2.1.01,6]-9-undecen-5-one 15 (12 mg, 80%) as a solid. 1H NMR (CDCl3, 500 MHz) d: 6.27 (d, J = 5.6 Hz, 1H), 6.17 (d, J = 5.6 Hz, 1H), 5.42 (q, J = 7.1 Hz, 1H), 2.74 (ddd, J = 14.6, 13.0, 6.0 Hz, 1H), 2.42 (ddd, J = 14.6, 5.0, 3.7 Hz, 1H), 2.05 (ddd, J = 13.4, 13.0, 5.0 Hz, 1H), 1.77 (d, J = 7.1 Hz, 3H), 1.60 (ddd, J = 13.4, 6.0, 3.7 Hz, 1H), 1.50 (s, 3H), 1.36 (s, 3H), 1.35 (s, 3H), 1.06 (s, 3H). 13C NMR (CDCl3, 125 MHz) d:

210.7, 145.3, 140.4, 132.6, 116.4, 97.6, 87.5, 59.9, 35.5, 35.4, 32.8, 27.4, 24.3, 22.2, 16.2, 14.6. IR (neat): 2933, 2868, 1713, 1451, 1386, 1250, 1164, 1086, 1028, 937, 730 cm-1. HRMS (EI) m/z found for M+ 246.1620, calcd for C16H22O2 246.1620.

(R)-1-Trimethylsilyl-1-decyn-3-ol (17) In 25 mL flask, 2 mL of toluene solution of trimethylsilylacetylene (0.28 mL, 1.98 mmol) and diethyl zinc (2.0 mL, 2.00 mmol, 1.0 M in hexane) was refluxed for 1 h under Ar. A large amount of grey precipitate was formed. After the solution was cooled to room temp, (S)-BINOL (56 mg, 0.20 mmol), diethyl ether (8 mL), and titanium (IV) isopropoxide (0.15 mL, 0.51 mmol) were added sequentially. The solution was stirred for another hour, and octyl aldehyde (64 mg, 0.50 mmol) was added. After 18 h, the reaction was quenched with 1.0 M tartaric acid, and the mixture was stirred for 30 min. The organic layer was separated and the aqueous layer was extracted with diethyl ether (20mL x 3). The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by column chromatography on silica gel (6:1 hexane/diethyl ether) to afford (R)-1-trimethylsilyl-1-decyn-3-ol 17 (43 mg, 38%) as an oil. 1H NMR (CDCl3, 500 MHz) d: 4.34 (t, J =6.6 Hz, 1H), 1.83 (br s, 1H), 1.70-1.66 (m, 2H), 1.50-1.38 (m, 2H), 1.31-1.27 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H), 0.16 (s, 9H). 13C NMR (CDCl3, 125 MHz) d: 106.8, 89.1, 62.8, 37.6, 31.6, 29.0, 25.0, 22.5, 14.0, -0.2. IR (neat): 3332, 2958, 2927, 2858, 2172, 1467, 1408, 1379, 1333, 1250, 1127, 1047, 1018, 843, 760 cm-1. HRMS (CI) m/z found for (M+H)+ 227.1804, calcd for C13H27O1Si1 227.1831.

(R)-3-(tert-Butyldimethylsilyloxy)-1-trimethylsilyl-1-decyne (17a) To a solution of the propargylic alcohol 17 (43 mg, 0.19 mmol) in dichloromethane (0.5 mL) at 0 °C were added imidazole (39 mg, 0.57 mmol) and tert-butyldimethylsilyl chloride (43 mg, 0.29 mmol). The mixture was stirred at room temperature for 20 h and diluted with diethyl ether (5 mL) and aqueous ammonium chloride (5 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (5mL

x 3). The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by column chromatography on silica gel (20:1 hexane/ethyl acetate) to afford (R)-3-(tert-butyldimethylsilyloxy)-1-trimethylsilyl-1-decyne 17a (63 mg, 97%) as an oil. 1H NMR (CDCl3, 500 MHz) d: 4.31 (t, J =6.4 Hz, 1H), 1.72-1.58 (m, 2H), 1.47-1.23 (m, 10H), 0.90 (s, 9H), 0.88 (t, J = 8.2 Hz, 3H), 0.16 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H).

13

C NMR (CDCl3, 125 MHz) d: 107.9, 88.1, 63.3, 38.3, 31.7,

29.1, 29.0, 25.6, 25.1, 22.5, 18.2, 14.0, -0.3, -4.6, -5.1. IR (neat): 2957, 2929, 2857, 2172, 1471, 1464, 1361, 1337, 1251, 1120, 1094, 1005, 841, 778, 760 cm-1. HRMS (CI) m/z found for (M-CH3)+ 325.2422, calcd for C18H37O1Si2 325.2382.

(R)-tert-Butyl(1-ethynyloctyloxy)dimethylsilane (17b) To a solution of the silyl ether 17a (63 mg, 0.18 mmol) in methanol (1 mL) was added potassium carbonate (28 mg, 0.20 mmol) at once. The resulting mixture was stirred at room temperature for 2 h, diluted with aqueous ammonium chloride (5 mL), and concentrated under reduced pressure to remove methanol. Diethyl ether (5 mL) was added, and the layers were separated. The aqueous layer was extracted with diethyl ether (5 mL x 3), and the combined organic extracts were washed with brine, dried over magnesium sulfate, and concentrated to give (R)-tert-butyl(1-ethynyloctyloxy)dimethylsilane 17b (48 mg, 97%), which was directly used for the next step without further purification. The spectroscopic data of 17b were identical with those reported in the literature.4 1H NMR (CDCl3, 500 MHz) d: 4.33 (td, J =6.5, 2.0 Hz, 1H), 2.37 (d, J = 2.1 Hz, 1H), 1.70-1.63 (m, 2H), 1.48-1.37 (m, 2H), 1.32-1.21 (m, 8H), 0.90 (s, 9H), 0.88 (t, J = 7.0 Hz, 3H), 0.13 (s, 3H), 0.11 (s, 3H). 13C NMR (CDCl3, 125 MHz) d: 85.7, 71.7, 62.6, 38.4, 31.7, 29.1, 25.6, 25.0, 22.5, 18.1, 14.0, -4.7, -5.2. IR (neat): 3313, 2956, 2929, 2858, 1471, 1464, 1361, 1252, 1121, 1094, 1005, 938, 838, 778 cm-1.

(R) -4-(tert-Butyldimethylsilyloxy)-2-undecyne (17c) To a solution of the silyloxy alkyne 17b (48 mg, 0.18 mmol) in THF/HMPA (1.5 mL/0.3 mL) was added n-

butyl lithium (0.19 mL, 0.27 mmol, 1.4 M in hexane) at -45 °C. The reaction mixture was stirred for 1.5 h at -45 °C and methyl iodide (17 m L, 0.27 mmol) was added. The mixture was allowed to warm to -5 °C and stirred for another 1.5 h. The reaction was quenched with aqueous ammonium chloride (5 mL), extracted with diethyl ether (10 mL x 3), washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (20:1 hexane/ethyl acetate) to yield (R)-4-(tertbutyldimethylsilyloxy)-2-undecyne 17c (47 mg, 93%) as an oil. 1H NMR (CDCl3, 500 MHz) d: 4.28 (m, 1H), 1.82 (d, J = 2.1 Hz, 3H), 1.67-1.54 (m, 2H), 1.48-1.36 (m, 2H), 1.35-1.19 (m, 8H), 0.90 (s, 9H), 0.88 (t, J = 7.2 Hz, 3H), 0.12 (s, 3H), 0.10 (s, 3H).

13

C NMR (CDCl3, 125 MHz) d: 81.1, 79.6, 63.1, 38.9, 31.7, 29.1,

25.7, 25.2, 22.5, 18.2, 14.0, 3.4, -4.6, -5.1. IR (neat): 2956, 2928, 2856, 1463, 1361, 1341, 1255, 1087, 837, 777 cm-1. HRMS (EI) m/z found for (M-H)+ 281.2299, calcd for C17H33O1Si1 281.2301

(R)-(-)-2-Undecyn-4-ol (18) To a solution of the silyloxy alkyne 17c (47 mg, 0.17 mmol) in tetrahydrofuran (1 mL) was slowly added tetrabutylammonium fluoride (0.25 mL, 1.0 M in tetrahydrofuran). The reaction mixture was stirred for 45 min and quenched with aqueous sodium bicarbonate (5 mL). The organic layer was separated and the aqueous layer was extracted with diethyl ether (5 mL x 3), washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by column chromatography on silica gel (5:1 hexane/diethyl ether) to afford (R)-(-)-2-undecyn-4-ol 18 (26 mg, 93%) as an oil. The spectroscopic data of 18 were identical with those reported in the literature.5 1H NMR (CDCl3, 500 MHz) d: 4.31 (m, 1H), 1.84 (d, J = 2.1 Hz, 3H), 1.73 (br s, 1H), 1.70-1.58 (m, 2H), 1.48-1.36 (m, 2H), 1.35-1.22 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H). 13C NMR (CDCl3, 125 MHz) d: 80.8, 80.4, 62.7, 38.0, 31.7, 29.1, 25.1, 22.5, 14.0, 3.4. IR (neat): 3354, 2924, 2857, 2235, 1466, 1378, 1340, 1149, 1110, 1018, 890 cm-1. [a]21D -1.67 (c 1.08, CDCl3). The (S)-O-acetyl mandelate derivative was prepared as follows. In a 10 mL round bottom flask were placed (S)-(+)-mandelic acid (59 mg, 0.39 mmol) and acetyl chloride (0.6 mL). As soon as a clear solution resulted, the excess acetyl chloride was removed under reduced pressure. To the crude O-acetyl mandelic acid was

added oxalyl chloride (0.7 mL). The mixture was stirred for 1 h, and the residual oxalyl chloride was thoroughly evaporated in vacuo. The resulting acid chloride was diluted with benzene (1 mL), and a solution of alcohol 18 (10 mg, 0.059 mmol) and pyridine (0.1 mL) in benzene (0.5 mL) was added. After 30 min, the reaction was quenched with water. The aqueous solution was extracted with diethyl ether, and the combined extract was washed with aqueous copper(II) sulfate, water, and brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude oil was purified by column chromatography on silica gel (5:1 hexane/diethyl ether) to give a clear oil, which was analyzed by NMR to show two a-proton signals (5.96 ppm and 5.91 ppm) of carbonyl group with 95:5 ratio, indicating an ee of 90%.

(S)-2-(Tri-n-butylstannyl)-2,3-undecadiene (19) To a solution of (R)-(-)-2-undecyn-4-ol 18 (69 mg, 0.41 mmol) in dichloromethane (2 mL) at -78 °C was added triethylamine (0.11 mL, 0.79 mmol) with stirring. After 5 min, methansulfonyl chloride (60 mL, 0.78 mmol) was added, and the resulting solution was stirred for 1 h. The mixture was quenched with aqueous sodium bicarbonate (5 mL), extracted with ether (5 mL x 3), dried over magnesium sulfate, and concentrated under reduced pressure to yield mesylate which was directly used without further purification. To a solution of diisopropylamine (74 mL, 0.53 mmol) in tetrahydrofuran (2.5 mL) at 0 °C was added a 1.3 M solution of n-butyllithium in hexane (0.39 mL, 0.51 mmol). After 15 min, tributyltin hydride (0.14 mL, 0.52 mmol) was added and after 25 min, the mixture was cooled to -78 °C. To this solution was added CuBr†SMe2 (105 mg, 0.51 mmol) in one portion with stirring. After 35 min, a solution of the mesylate in tetrahydrofuran (0.5 mL) was added; the mixture was stirred for 15 min and then poured into a rapidly stirring 9:1 mixture of NH4Cl/NH4OH solution (5 mL) and extracted with ether (5 mL x 3). The ether extract was washed with additional portions of aqueous NH4Cl/NH4OH solution until the layer became colorless. The organic extract was then dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (50:1 hexane/ethyl acetate, 1% triethylamine) on deactivated silica gel to afford the desired material along with hexabutylditin. Further purification by treatment with silver

acetate (137 mg, 0.82 mmol) in tetrahydrofuran (3 mL) at room temperature for 1 hr gave (S)-2-(tri-nbutylstannyl)-2,3-undecadiene 19 (127 mg, 68%) as a clear oil. The spectroscopic data of 19 were identical with those reported in the literature.5 1H NMR (CDCl3, 500 MHz) d: 4.59-4.55 (m, 1H), 2.01-1.84 (m, 2H), 1.80 (d, J = 3.0 Hz, 3H), 1.60-1.40 (m, 8H), 1.40-1.20 (m, 20H), 0.94 (t, J = 8.2 Hz, 3H), 0.89 (t, J = 7.3 Hz, 9H).

(5S, 7R)-2,6-Dimethyl-2-[2-(5-methylfuryl)]-6,7-petadecadiene-5-ol (19a) To a solution of the allenylstannane 19 (127 mg, 0.28 mmol) in dichloromethane (4 mL) at -40 °C was added n-butyltin trichloride (48 mL, 0.28 mmol) with stirring. After 20 min, a solution of aldehyde 6 (51 mg, 0.28 mmol) in dichloromethane (0.5 mL) was added. The reaction mixture was stirred at -40 °C for 5 h, and then aqueous ammonium chloride (5 mL) was added. Upon being warmed to room temperature, the mixture was extracted with ether (5 mL x 3), and dried over magnesium sulfate. To this suspension was added triethylamine, and after being stirred for 10 min, the slurry was filtered through a pad of Celite, and the filtrate was concentrated to give a yellow oil. Purification by flash column chromatography on silica gel (10:1 hexane/ethyl acetate, 1% triethylamine) provided two diastereomers of 2,6-dimethyl-2-[2-(5-methylfuryl)]6,7-petadecadiene-5-ol 19a (51 mg, 54%) along with the remaining aldehyde 6 (15 mg, 29%). The spectroscopic data of the major isomer were as following. Major isomer: 1H NMR (CDCl3, 500 MHz) d: 5.82 (d, J = 3.1 Hz, 1H), 5.80 (dq, J = 3.1, 0.9 Hz, 1H), 5.24 (tq, J = 6.8, 2.9 Hz, 1H), 3.91 (td, J = 5.8, 2.1 Hz, 1H), 2.24 (s, 3H), 1.99 (q, J =6.8 Hz, 2H), 1.67 (td, J = 12.6, 2.9 Hz, 1H), 1.60 (d, J = 2.9 Hz, 3H), 1.58-1.46 (m, 3H), 1.41-1.35 (m, 2H), 1.34-1.24 (m, 9H), 1.26 (s, 6H), 0.88 (t, J = 6.7 Hz, 3H). 13C NMR (CDCl3, 125 MHz) d: 199.5, 160.8, 149.9, 105.3, 103.7, 102.8, 93.8, 72.6, 36.9, 35.2, 31.8, 30.0, 29.1, 29.1, 29.0, 26.9, 26.7, 22.6, 14.9, 14.0, 13.5. IR (neat): 3358, 2959, 2925, 2855, 1964, 1614, 1562, 1454, 1383, 1366, 1221, 1116, 1021, 938, 779 cm-1. [a]20D -4.17 (c 0.96, CDCl3). HRMS (EI) m/z found for M+ 332.2725, calcd for C22H36O2 332.2715.

(7R)-2,6-Dimethyl-2-[2-(5-methylfuryl)]-6,7-petadecadiene-5-one (20) To a solution of the allenyl alcohol 19a (51 mg, 0.15 mmol) in dichloromethane (1.5 mL) under argon was added Dess-Martin periodinane (98 mg, 0.23 mmol). The suspension was stirred at room temperature for 1.5 h, and then an aqueous solution of sodium thiosulfate in saturated sodium bicarbonate (2 mL) was added. The mixture was stirred vigorously until the organic layer became clear. The organic layer was separated. The aqueous layer was extracted with ether (5 mL x 3). Both organic layers were respectively washed with saturated sodium bicarbonate and brine. The combined organic layer were then dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on neutral alumina (20:1 hexane/diethyl ether) to afford 2,6-dimethyl-2-[2-(5-methylfuryl)]-6,7-petadecadiene-5one (40 mg, 79%) 20 as a clear oil. 1H NMR (CDCl3, 500 MHz) d: 5.81 (d, J = 3.1 Hz, 1H), 5.79 (dq, J = 3.1, 0.7 Hz, 1H), 5.42 (tq, J = 7.0, 2.7 Hz, 1H), 2.54-2.42 (m, 2H), 2.23 (d, J = 0.7 Hz, 3H), 2.08 (q, J = 0.7 Hz, 2H), 1.86-1.79 (m, 2H), 1.73 (d, J = 2.7 Hz, 3H), 1.44-1.34 (m, 2H), 1.33-1.24 (m, 8H), 1.21 (s, 6H), 0.89 (t, J = 6.8 Hz, 3H).

13

C NMR (CDCl3, 125 MHz) d: 211.6, 202.3, 160.2, 150.0, 105.3, 103.9, 103.9, 94.2, 36.9,

35.2, 34.6, 31.7, 29.0, 28.9, 28.8, 28.0, 26.7, 26.5, 22.5, 14.0, 13.5, 13.5. IR (neat): 2960, 2926, 2856, 1948, 1678, 1562, 1455, 1384, 1367, 1298, 1220, 1117, 1068, 1023, 959, 938, 779 cm-1. [a]18D -58.2 (c 0.56, CDCl3). HRMS (EI) m/z found for M+ 330.2561, calcd for C22H34O2 330.2559.

2,2,6,8-Tetramethyl-7-octylidene-11-oxatricyclo[6.2.1.01,6]-9-undecen-5-one (21) To a solution of the allenic ketone 20 (13.0 mg, 0.039 mmol) in dichloromethane (0.5 mL) at -78 °C was added a solution of dimethylaluminum chloride (0.39 mL, 0.039 mmol, 1.0 M in hexane). After 30 min, the reaction mixture was allowed to warm up to -20 °C and stirred for an additional 3 h. The mixture was quenched with 5 drops of saturated sodium bicarbonate, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (10:1 hexane/diethyl ether) to give 2,2,6,8-tetramethyl-7-octylidene-11-oxa-tricyclo[6.2.1.01,6]-9-undecen-5-one 21 (11.5 mg, 88%). 1H NMR (CDCl3, 500 MHz) d: 6.26 (d, J = 5.6 Hz, 1H), 6.17 (d, J = 5.6 Hz, 1H), 5.28 (t, J =

7.5 Hz, 1H), 2.72 (ddd, J = 14.6, 12.6, 6.1 Hz, 1H), 2.43 (ddd, J = 14.6, 5.0, 3.7 Hz, 1H), 2.25-2.08 (m, 2H), 2.04 (ddd, J = 13.4, 12.6, 5.2 Hz, 1H), 1.60 (ddd, J = 13.4, 6.1, 3.7 Hz, 1H), 1.50 (s, 3H), 1.46-1.37 (m, 1H), 1.34 (s, 3H), 1.33 (s, 3H), 1.31-1.18 (m, 9H), 1.06 (s, 3H), 0.87 (t, J = 6.7 Hz, 3H).

13

C NMR (CDCl3, 125

MHz) d: 210.6, 143.9, 140.4, 132.7, 122.7, 97.5, 87.4, 59.9, 35.5, 35.4, 32.8, 31.8, 30.0, 29.4, 29.2, 29.0, 27.4, 24.3, 22.7, 22.6, 16.3, 14.0. IR (neat): 2956, 2925, 2855, 1714, 1455, 1384, 1373, 1318, 1250, 1198, 1161, 1118, 1087, 1010, 940, 868, 728 cm-1. [a ] 19D -179.13 (c 0.81, CDCl3). HRMS (EI) m/z found for M+ 330.2563, calcd for C22H34O2 330.2559.

References (1) Rogers, C.; Keay, B. A. Can. J. Chem. 1992, 70, 2929. (2) Harmata, M.; Kahraman, M.; Adenu, G.; Barnes, C. L. Heterocycles 2004, 62, 583. (3) (a) Fleming, I.; Takaki, K.; Thomas, A. P. J. Chem. Soc., Perkin Trans. 1 1987, 2269. (b) Smith, L. R.; Swenson, J. S. J. Am. Chem. Soc. 1957, 79, 2962. (c) Adam, W.; Klug, P. Synthesis 1994, 567. (4) Iguchi, K.; Kitade, M.; Kashiwagi, T.; Yamada, Y. J. Org. Chem. 1993, 58, 5690. (5) Marshall, J. A.; Yu, R. H.; Perkins, J. F. J. Org. Chem. 1995, 60, 5550. (6) Groves, J. T.; Ma, K. W. J. Am. Chem. Soc. 1977, 99, 4076.