Synthetic procedures
General procedure A for reduction with NaBH4
Sodium borohydride (2.2 equiv) and boron trifluoride diethyl etherate (0.3 equiv) were added at 0°C to a solution of the ester (1.0 equiv) in dry and degassed tetrahydrofuran (THF, 0.35 m) (Zhang and Li 2018). The reaction mixture was stirred at rt and monitored by TLC. After completion, the reaction was quenched with sat. aq. NaHCO3 solution and diethyl ether was added. The phases were separated, and the aq. layer was extracted with diethyl ether (3 times). The comb. org. layers were dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography.
General procedure B for oxidation using the Corey-Schmidt method
Pyridinium dichromate (PDC) (5.0 equiv) was added to a solution of the alcohol (1.0 equiv) in N,N-dimethylformamide (DMF) (0.2 m) at rt (Peram et al. 2017). After stirring for 24 h at rt, the reaction mixture was filtered through Celite®, and the filter cake was washed with diethyl ether. The filtrate was washed with 1 m HCl, the phases were separated, and the aq. layer was extracted with diethyl ether (3 times). The comb. org. layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography.
General procedure C for coupling with Gilman-cuprate: The iodide (9.5 equiv) was dissolved in a 3:2 mixture of dry hexane and diethyl ether (0.5 m, degassed using the freeze pump thaw method) (Nurdin et al. 2020). Then t-butyllithium (Attention: careful handling required, extremely flammable reagent, 19.0 equiv) was added at − 78°C and the reaction mixture was stirred at this temperature for 1.5 h. The obtained organolithium solution was used in the next step without further purification. To a solution of copper cyanide (4.75 equiv) in dry diethyl ether (0.3 m) was slowly added the organolithium solution at − 78°C (Chiou and Chen 2017). The reaction mixture was allowed to warm to − 10°C over 2 h and then recooled to − 78°C. Then a solution of tosylate (1.0 equiv) in dry diethyl ether (0.14 m) was slowly added and the reaction mixture was allowed to warm to rt over 3 h and stirred for 16 h at rt. The reaction mixture was quenched with aq. ammonia solution, water and diethyl ether were added and the phases were separated. The aq. layer was extracted with diethyl ether (3 times), the comb. org. layers were dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography.
General procedure D for deprotection of silyl ethers
Tetra-n-butylammonium fluoride (TBAF, 1.2 equiv) was added to a solution of the silyl ether (1.0 equiv) in dry THF (0.3 m) at 0°C (Dash et al. 2015). After stirring for 18 h at rt, the reaction mixture was quenched with sat. aq. NaHCO3 solution, diethyl ether was added, and the phases were separated. The aq. layer was extracted with diethyl ether (3 times), the comb. org. layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography.
General procedure E for esterification: The alcohol (1.0 equiv) and the carboxylic acid (1.0 equiv) were dissolved in dry DCM (0.2 m), followed by addition of 4-(dimethylamino)pyridine (DMAP, 10 mol%) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimid-hydrochlorid (EDC-HCl, 1.1 equiv) in portions at 0°C (Chinta et al. 2016). After stirring for one hour at 0°C and 18 h at rt, the reaction mixture was quenched with water and DCM was added. The phases were separated, and the aq. layer was extracted with DCM (3 times). The comb. org. layers were washed with brine, dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 20:1) to afford the ester.
General procedure F for ring-closing metathesis: Hexafluorobenzene (10 equiv), tetrafluoro-p-benzoquinone (10 mol %) and benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium (Grubbs II generation catalyst, 10 mol %) were added to a solution of the ester (1.0 equiv) in dry toluene (0.8 mm, degassed using the freeze pump thaw method) (Peram et al. 2017). After stirring for 6 h at 80°C, further Grubbs catalyst (10 mol%) was added and the reaction mixture was stirred for 16 h at 80°C. The catalyst was removed by filtration over a short column (8 cm silica gel filling height, diethyl ether) and the filtrate was washed with sat. aq. NaHCO3 solution. The phases were separated, and the aq. layer was extracted with diethyl ether (3 times). The comb. org. layers were dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 40:1) to afford a mixture of the E/Z isomers.
Preparation of methyl (S)-2-methyl-3-(tosyloxy)propanoate (7). Triethylamine (2.45 ml, 1.79 g, 17.7 mmol, 1.3 equiv), DMAP (249 mg, 2.04 mmol, 0.15 equiv) and tosyl chloride (3.11 g, 16.3 mmol, 1.2 equiv) were added sequentially to a solution of methyl (S)-3-hydroxy-2-methylpropanoate ((S)-Roche ester, 6, 1.61 g, 13.6 mmol, 1.0 equiv) in dry DCM (20 ml) at 0°C (Han 2018). After stirring for 4.5 h at rt, water (100 ml) was added, the phases were separated, and the aq. layer was extracted with diethyl ether (3×50 ml). The comb. org. layers were washed with brine (100 ml), dried over anhydrous Na2SO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 1:1) to afford methyl (S)-2-methyl-3-(tosyloxy)propanoate (7) as a colorless oil (2.94 g, 10.8 mmol, 79 %). Rf =0.39 (pentane/diethyl ether 1:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +11.9 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 7.81–7.76 (m, 2H, CHAr), 7.38–7.33 (m, 2H, CHAr), 4.19 (dd, J = 9.7, 6.8 Hz, 1H, CHaHb), 4.06 (dd, J = 9.7, 6.1 Hz, 1H, CHaHb), 3.65 (s, 3H, CH3), 2.88–2.75 (m, 1H, CH), 2.46 (s, 3H, CH3), 1.17 (d, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 173.1 (Cq), 144.9 (Cq), 132.7 (Cq), 129.8 (2C, CH), 128.0 (2C, CH), 70.7 (CH2), 52.0 (CH3), 39.2 (CH), 21.6 (CH3), 13.6 (CH3); EIMS m/z (%) 272 (3) [M]+, 187 (5), 172 (6), 155 (58), 139 (3), 117 (42), 107 (7), 101 (4), 91 (100), 85 (21), 77 (5), 65 (32), 59 (15), 51 (4), 41 (10).
Preparation of ( R )-3-hydroxy-2-methylpropyl 4-methylbenzenesulfonate (8). Ester 7 (100 mg, 0.367 mmol, 1.0 equiv) was reduced to alcohol 8 using sodium borohydride (30.5 mg, 0.807 mmol, 2.2 equiv) and boron trifluoride diethyl etherate (0.01 ml, 15.6 mg, 0.110 mmol, 0.3 equiv) in dry and degassed THF (1 ml) by following the general procedure A. The reaction mixture was stirred for 18 h at rt. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 1:1 → 1:5) to afford (R)-3-hydroxy-2-methylpropyl 4-methylbenzenesulfonate (8) as a colorless liquid (80.0 mg, 0.327 mmol, 89%). Rf = 0.46 (pentane/diethyl ether 1:2); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 4.8 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 7.83–7.76 (m, 2H, CHAr), 7.39–7.32 (m, 2H, CHAr), 4.07–3.97 (m, 2H, CH2), 3.59 (dd, J = 11.0, 5.1 Hz, 1H, CHaHb), 3.51 (dd, J = 11.0, 6.5 Hz, 1H, CHaHb), 2.45 (s, 3H, CH3), 2.08–1.93 (m, 1H, CH), 1.76 (br. s, 1H, OH), 0.92 (d, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 144.8 (Cq), 132.9 (Cq), 129.9 (2C, CH), 127.9 (2C, CH), 71.9 (CH2), 63.6 (CH2), 35.5 (CH), 21.6 (CH3), 13.0 (CH3); EIMS m/z (%) 203 (8), 173 (75), 155 (28), 139 (2), 107 (15), 91 (100), 77 (9), 72 (22), 65 (36), 62 (2), 57 (11), 51 (4), 39 (12).
Preparation of (S)-2-methylhex-5-en-1-ol (9). Dilithium tetrachlorocuprate (0.1 m in THF, 2.46 ml, 0.246 mmol, 0.1 equiv) was added to a solution of tosylate 8 (600 mg, 2.46 mmol, 1.0 equiv) in degassed dry THF (25 ml) (Nunomoto et al. 1983). Allylmagnesium bromide (1 m in diethyl ether, 7.38 ml, 7.38 mmol, 3.0 equiv) was added dropwise over 20 minutes at 0°C and the reaction mixture was stirred for 6 h at rt. Further allylmagnesium bromide (1 m in diethyl ether, 1.23 ml, 1.23 mmol, 0.5 equiv) was added dropwise to the reaction mixture at 0°C. After stirring for 17 h at rt, the reaction mixture was quenched with sat. aq. NH4Cl solution (40 ml) and the phases were separated. The aq. layer was extracted with diethyl ether (3×40 ml), the comb. org. layers were washed with sat. aq. NH4Cl solution (100 ml), dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 1:1) to afford (S)-2-methylhex-5-en-1-ol (9) as a colorless liquid (268 mg, 2.35 mmol, 96 %). Rf = 0.44 (pentae/diethyl ether 1:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 12.3 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 5.82 (ddt, J = 16.8, 10.1, 6.6 Hz, 1H, CH), 5.09–4.91 (m, 2H, CH2), 3.52 (dd, J = 10.5, 5.8 Hz, 1H, CHaHb), 3.44 (dd, J = 10.5, 6.4 Hz, 1H, CHaHb), 2.23–1.96 (m, 2H, CH2), 1.79–1.39 (m, 2H, CH2), 1.44 (br. s, 1H, OH), 1.30–1.11 (m, 1H, CH), 0.93 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 138.9 (CH), 114.4 (CH2), 68.2 (CH2), 35.2 (CH), 32.3 (CH2), 31.2 (CH2), 16.4 (CH3); EIMS m/z (%) 114 (< 1) [M]+, 96 (11) [M–H2O]+, 82 (6), 81 (86), 79 (9), 71 (31), 68 (13), 67 (28), 58 (17), 57 (33), 56 (15), 55 (100), 54 (74), 53 (16), 51 (6), 45 (7), 43 (30), 42 (21), 41 (94), 40 (9), 39 (55).
Preparation of ( S )-2-methylhex-5-enoic acid (10). Alcohol (S)-9 (235 mg, 2.06 mmol, 1.0 equiv) was converted to carboxylic acid (S)-10 using PDC (3.87 g, 10.3 mmol, 5.0 equiv) and DMF (10 ml) by following the general procedure B. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 4:1) to afford (S)-2-methylhex-5-enoic acid (10) as a colorless liquid (213 mg, 1.66 mmol, 81%). Rf = 0.62 (pentane/diethyl ether 1:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +24.8 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 10.59 (br. s, 1H, COOH), 5.79 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.09–4.95 (m, 2H, CH2), 2.50 (sext, J = 7.0 Hz, 1H, CH), 2.18–2.04 (m, 2H, CH2), 1.88–1.74 (m, 1H, CHaHb), 1.59–1.45 (m, 1H, CHaHb), 1.19 (d, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 183.1 (Cq), 137.7 (CH), 115.2 (CH2), 38.7 (CH), 32.5 (CH2), 31.2 (CH2), 16.8 (CH3); EIMS (TMS derivative) m/z (%) 200 (2) [M]+, 185 (10) [M–CH3]+, 146 (11), 143 (18), 131 (6), 75 (62), 74 (11), 73 (100), 56 (18), 55 (14), 47 (7), 45 (15), 43 (6), 41 (17), 39 (10).
Preparation of (R)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropyl 4-methylbenzenesulfonate (11). Imidazole (274 mg, 4.02 mmol, 1.4 equiv), tert-butyldimethylsilyl chloride (TBSCl) (562 mg, 3.73 mmol, 1.3 equiv) and DMAP (17.6 mg, 0.144 mmol, 5 mol%) were added to a solution of alcohol 8 (700 mg, 2.87 mmol, 1.0 equiv) in dry THF (12 ml) at rt (Gieseler and Kalesse 2014). After stirring for 18 h at rt, the reaction mixture was diluted with pentane (10 ml) and sat. aq. NH4Cl solution (20 ml) was added. Water (5 ml) was added to improve phase separation. Then the phases were separated, and the aq. layer was extracted with pentane (3×20 ml). The comb. org. layers were washed with sat. aq. NaHCO3 solution (60 ml), dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 10:1) to afford (R)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropyl 4-methylbenzenesulfonate (11) as a colorless oil (1.03 g, 2.87 mmol, quant.). Rf = 0.46 (pentane/diethyl ether 5:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 5.7 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 7.81–7.76 (m, 2H, CHAr), 7.36–7.31 (m, 2H, CHAr), 4.02 (dd, J = 9.3, 5.9 Hz, 1H, CHaHb), 3.92 (dd, J = 9.3, 5.9 Hz, 1H, CHaHb), 3.50 (dd, J = 10.0, 5.0 Hz, 1H, CHaHb), 3.40 (dd, J = 10.0, 6.5 Hz, 1H, CHaHb), 2.46–2.43 (m, 3H, CH3), 2.03–1.86 (m, 1H, CH), 0.88 (d, J = 6.9 Hz, 3H, CH3), 0.82 (s, 9H, 3×CH3), − 0.02 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 144.6 (Cq), 133.1 (Cq), 129.8 (2C, CH), 127.9 (2C, CH), 72.1 (CH2), 63.7 (CH2), 35.6 (CH), 25.8 (3C, CH3), 21.6 (CH3), 18.2 (Cq), 13.2 (CH3), − 5.58 (CH3), − 5.61 (CH3); EIMS m/z (%) 271 (3), 231 (15), 230 (23), 229 (100), 165 (6), 155 (3), 149 (12), 131 (2), 115 (2), 101 (2), 91 (19), 85 (1), 75 (10), 73 (7), 65 (6), 59 (3), 57 (3), 55 (2), 41 (3).
Preparation of 4-iodo-2-methylbut-1-ene (12). Iodine (15.2 g, 59.9 mmol, 1.5 equiv) was added in portions at 0°C to a solution of triphenylphosphine (15.7 g, 59.9 mmol, 1.5 equiv) and imidazole (5.43 g, 79.8 mmol, 2.0 equiv) in dry DCM (100 ml), followed by stirring for 15 minutes at this temperature (Helmboldt et al. 2006). Then 3-methylbut-3-en-1-ol (4.00 ml, 3.44 g, 39.9 mmol, 1.0 equiv) was added dropwise at 0°C and the reaction mixture was stirred for 4.5 h at rt. The reaction mixture was quenched with sat. aq. sodium sulfite solution (80 ml), the phases were separated, and the aq. layer was extracted with DCM (2×80 ml). The comb. org. layers were washed with brine (200 ml), dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was filtered through a short column (Celite®, pentane) and purified by column chromatography (silica gel, pentane) to afford 4-iodo-2-methylbut-1-ene (12) as a colorless liquid (6.86 g, 35.0 mmol, 88 %). Rf = 0.60 (pentan); 1H NMR (300 MHz, CDCl3) δ 4.88–4.84 (m, 1H, CHaHb), 4.77–4.74 (m, 1H, CHaHb), 3.26 (t, J = 7.6 Hz, 2H, CH2), 2.59 (t, J = 7.5 Hz, 2H, CH2), 1.76–1.72 (m, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 143.9 (Cq), 112.3 (CH2), 41.9 (CH2), 21.7 (CH3), 3.50 (CH2).
Preparation of ( S )- tert -butyl((2,6-dimethylhept-6-en-1-yl)oxy)dimethylsilane (13). The organolithium reagent was prepared from isoprenyl iodide (12, 1.28 g, 6.52 mmol, 9.5 equiv) and t-butyllithium (1.7 m in pentane, 7.65 ml, 13.0 mmol, 19.0 equiv, Attention: careful handling required, extremely flammable reagent) in a 3:2 mixture of dry and degassed hexane and diethyl ether (12.5 ml) by following the general procedure C. Then the coupling was performed with copper cyanide (292 mg, 3.26 mmol, 4.75 equiv) in dry diethyl ether (10 ml), organolithium solution and tosylate (R)-11 (246 mg, 0.686 mmol, 1.0 equiv) in dry diethyl ether (5 ml) by following the general procedure C. The crude product was purified by column chromatography (silica gel, pentane) to afford (S)-tert-butyl((2,6-dimethylhept-6-en-1-yl)oxy)dimethylsilane (13) as a colorless liquid (148 mg, 0.577 mmol, 84%). Rf = 0.56 (pentane/diethyl ether 100:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 3.6 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 4.71–4.64 (m, 2H, CH2), 3.45 (dd, J = 9.8, 5.9 Hz, 1H, CHaHb), 3.36 (dd, J = 9.8, 6.6 Hz, 1H, CHaHb), 1.99 (t, J = 7.4 Hz, 2H, CH2), 1.72–1.69 (m, 3H, CH3), 1.67–1.21 (m, 4H), 1.12–0.96 (m, 1H), 0.89 (s, 9H, 3×CH3), 0.87 (d, J = 6.7 Hz, 3H, CH3), 0.04 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 146.2 (Cq), 109.7 (CH2), 68.4 (CH2), 38.1 (CH2), 35.7 (CH), 32.9 (CH2), 26.0 (3C, CH3), 25.0 (CH2), 22.4 (CH3), 18.4 (Cq), 16.7 (CH3), − 5.4 (2C, CH3); IR (neat) ṽ 2931 (m), 2893 (m), 2857 (m), 2323 (w), 1649 (w), 1464 (m), 1384 (w), 1367 (w), 1252 (m), 1091 (s), 1008 (w), 884 (m), 835 (s), 772 (s), 667 (m); EIMS m/z (%) 200 (3), 199 (16) [M–tBu]+, 143 (4), 129 (2), 123 (2), 115 (7), 101 (3), 89 (6), 81 (4), 77 (4), 76 (8), 75 (100), 73 (15), 69 (5), 61 (3), 59 (7), 55 (7), 47 (3), 41 (11).
Preparation of ( S )-2,6-dimethylhept-6-en-1-ol (14). Silyl ether (S)-13 (394 mg, 1.54 mmol, 1.0 equiv) was converted to alcohol (S)-14 using TBAF (1 m in THF/approx. 5% water, 1.85 ml, 1.85 mmol, 1.2 equiv) in dry THF (5 ml) by following the general procedure D. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 2:1) to afford (S)-2,6-dimethylhept-6-en-1-ol (14) as a colorless liquid (216 mg, 1.52 mmol, 99%). Rf = 0.37 (pentane/diethyl ether 2:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 12.0 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 4.72–4.65 (m, 2H, CH2), 3.52 (dd, J = 10.5, 5.8 Hz, 1H, CHaHb), 3.43 (dd, J = 10.4, 6.5 Hz, 1H, CHaHb), 2.01 (t, J = 7.4 Hz, 2H, CH2), 1.73–1.70 (m, 3H, CH3), 1.73–1.30 (m, 4H), 1.33 (br. s, 1H, OH), 1.18–1.03 (m, 1H), 0.93 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 145.6 (Cq), 109.4 (CH2), 67.9 (CH2), 37.6 (CH2), 35.3 (CH), 32.3 (CH2), 24.5 (CH2), 21.9 (CH3), 16.1 (CH3); IR (neat) ṽ 3334 (br), 3076 (w), 2929 (m), 2870 (m), 1648 (m), 1453 (m), 1375 (m), 1243 (w), 1103 (w), 1035 (s), 987 (m), 938 (w), 884 (s), 735 (m), 573 (m); EIMS m/z (%) 142 (4) [M]+, 124 (5) [M–H2O]+, 109 (45), 95 (29), 82 (59), 81 (37), 71 (23), 69 (75), 68 (74), 67 (65), 58 (14), 57 (29), 56 (74), 55 (76), 53 (24), 43 (25), 42 (11), 41 (100), 40 (10), 39 (48).
Preparation of methyl (S)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanoate (16). Imidazole (1.73 g, 25.4 mmol, 2.0 equiv), TBSCl (2.29 g, 15.2 mmol, 1.2 equiv) and DMAP (78.0 mg, 0.635 mmol, 5 mol%) were added at 0°C to a solution of methyl (S)-3-hydroxy-2-methylpropanoate ((S)-Roche ester, 6, 1.50 g, 12.7 mmol, 1.0 equiv) in dry DCM (13 ml) (Gieseler and Kalesse 2014). After stirring for 4 h at rt, the reaction mixture was diluted with DCM (10 ml) and sat. aq. NH4Cl solution (20 ml) was added. Water (5 ml) was added to improve phase separation. Then the phases were separated, and the aq. layer was extracted with DCM (2×20 ml). The comb. org. layers were dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 10:1) to afford methyl (S)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanoate (16) as a colorless liquid (2.31 g, 9.94 mmol, 78 %). Rf = 0.54 (pentane/dithyl ether 10:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +20.9 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 3.81–3.61 (m, 2H, CH2), 3.68 (s, 3H, CH3), 2.71–2.59 (m, 1H, CH), 1.14 (d, J = 7.0 Hz, 3H, CH3), 0.87 (s, 9H, 3×CH3), 0.04 (d, J = 0.9 Hz, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 175.5 (Cq), 65.2 (CH2), 51.5 (CH3), 42.5 (CH), 25.8 (3C, CH3), 18.2 (Cq), 13.4 (CH3), − 5.5 (2C, CH3); EIMS m/z (%) = 217 (3) [M–CH3]+, 201 (6), 176 (10), 175 (68) [M–tBu]+, 147 (7), 119 (46), 105 (5), 91 (7), 90 (11), 89 (100), 75 (27), 73 (27), 59 (30), 58 (7), 57 (7), 45 (8), 41 (11).
Preparation of ( R )-3-(( tert -butyldimethylsilyl)oxy)-2-methylpropan-1-ol (17). Ester 16 (1.17 g, 5.03 mmol, 1.0 equiv) was reduced to alcohol 17 using sodium borohydride (420 mg, 11.1 mmol, 2.2 equiv) and boron trifluoride diethyl etherate (0.19 ml, 214 mg, 1.51 mmol, 0.3 equiv) in dry and degassed THF (14 ml) by following the general procedure A. The reaction was stirred for 24 h at rt. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 2:1) to afford (R)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropan-1-ol (17) as a colorless liquid (715 mg, 3.50 mmol, 70%). Rf = 0.42 (pentane/diethyl ether 2:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +10.0 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 3.77–3.71 (m, 1H, CHaHb), 3.68–3.51 (m, 3H, CHaHb, CH2), 2.76 (br. s, 1H, OH), 2.02–1.86 (m, 1H, CH), 0.90 (s, 9H, 3×CH3), 0.84 (d, J = 7.0 Hz, 3H, CH3), 0.08 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 68.8 (CH2), 68.3 (CH2), 37.0 (CH), 25.8 (3C, CH3), 18.2 (Cq), 13.1 (CH3), − 5.56 (CH3), − 5.62 (CH3); EIMS m/z (%) 147 (24) [M–tBu]+, 129 (6), 105 (58), 89 (6), 77 (12), 76 (16), 75 (100), 73 (26), 61 (6), 59 (12), 58 (6), 57 (6), 55 (13), 47 (9), 45 (12), 43 (6), 41 (10).
Preparation of (S)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropyl 4-methylbenzenesulfonate (11). Triethylamine (0.65 ml, 475 mg, 4.69 mmol, 1.4 equiv), DMAP (61.5 mg, 0.503 mmol, 15 mol%) and tosyl chloride (831 mg, 4.36 mmol, 1.3 equiv) were added sequentially to a solution of alcohol 17 (685 mg, 3.35 mmol, 1.0 equiv) in dry DCM (5 ml) at 0°C (Han 2018). After stirring for 18 h at rt, further triethylamine (0.09 ml, 67.8 mg, 0.670 mmol, 0.2 equiv) and tosyl chloride (128 mg, 0.670 mmol, 0.2 equiv) were added at 0°C. The reaction mixture was stirred for additional 3 h at rt. Then water (10 ml) was added, the phases were separated, and the aq. layer was extracted with diethyl ether (3×10 ml). The comb. org. layers were washed with brine (30 ml), dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 2:1) to afford (S)-3-((tert-butyldimethylsilyl)oxy)-2-methylpropyl 4-methylbenzenesulfonate (11) as a colorless oil (1.04 g, 2.90 mmol, 87 %). Rf =0.46 (pentane/diethyl ether 5:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +6.2 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 7.81–7.76 (m, 2H, CHAr), 7.37–7.31 (m, 2H, CHAr), 4.02 (dd, J = 9.3, 5.9 Hz, 1H, CHaHb), 3.92 (dd, J = 9.2, 5.9 Hz, 1H, CHaHb), 3.50 (dd, J = 10.0, 5.0 Hz, 1H, CHaHb), 3.40 (dd, J = 10.0, 6.5 Hz, 1H, CHaHb), 2.46–2.43 (m, 3H, CH3), 2.02–1.87 (m, 1H, CH), 0.88 (d, J = 6.9 Hz, 3H, CH3), 0.82 (s, 9H, 3×CH3), − 0.02 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 144.6 (Cq), 133.1 (Cq), 129.8 (2C, CH), 127.9 (2C, CH), 72.1 (CH2), 63.7 (CH2), 35.6 (CH), 25.8 (3C, CH3), 21.6 (CH3), 18.2 (Cq), 13.2 (CH3), − 5.58 (CH3), − 5.61 (CH3); EIMS m/z (%) 271 (2), 231 (15), 230 (24), 229 (100), 165 (7), 155 (4), 149 (17), 91 (32), 77 (4), 75 (22), 73 (18), 65 (11), 59 (7), 57 (6), 55 (6), 41 (5).
Preparation of (R)-tert-butyldimethyl((2-methylhex-5-en-1-yl)oxy)silane (18). Dilithium tetrachlorocuprate (0.1 m in THF, 2.22 ml, 0.222 mmol, 0.1 equiv) was added to a solution of tosylate (S)-11 (797 mg, 2.22 mmol, 1.0 equiv) in degassed and dry THF (22 ml) (Nunomoto et al. 1983). Allylmagnesium bromide (1 m in diethyl ether, 7.77 ml, 7.77 mmol, 3.5 equiv) was added dropwise over 15 minutes at 0°C. The reaction mixture was stirred for 22 h at rt. Further allylmagnesium bromide (1 m in diethyl ether, 2.22 ml, 2.22 mmol, 1.0 equiv) was added dropwise to the reaction mixture at 0°C. After stirring for 8 h at rt, the reaction mixture was quenched with sat. aq. NH4Cl solution (40 ml) and the phases were separated. The aq. layer was extracted with diethyl ether (3×40 ml). The comb. org. layers were washed with sat. aq. NH4Cl solution (100 ml), dried over anhydrous MgSO4, filtered and concentrated under reduce pressure. The residue was purified by column chromatography (silica gel, pentane/diethyl ether 100:1) to afford (R)-tert-butyldimethyl((2-methylhex-5-en-1-yl)oxy)silane (18) as a colorless liquid (324 mg, 1.42 mmol, 64 %). Rf = 0.56 (pentae/diethyl ether 100:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +2.2 (c = 0.99, DCM); 1H NMR (300 MHz, CDCl3) δ 5.81 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.04–4.90 (m, 2H, CH2), 3.45 (dd, J = 9.8, 5.8 Hz, 1H, CHaHb), 3.38 (dd, J = 9.8, 6.3 Hz, 1H, CHaHb), 2.19–1.95 (m, 2H, CH2), 1.69–1.43 (m, 1H, CH), 1.37–1.07 (m, 2H, CH2), 0.89 (s, 9H, 3×CH3), 0.88 (d, J = 6.6 Hz, 3H, CH3), 0.04 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 139.3 (CH), 114.1 (CH2), 68.2 (CH2), 35.2 (CH), 32.4 (CH2), 31.3 (CH2), 26.0 (3C, CH3), 18.4 (Cq), 16.6 (CH3), − 5.4 (2C, CH3); IR (neat) ṽ 2929 (m), 2858 (m), 2322 (w), 1640 (w), 1465 (m), 1390 (w), 1253 (m), 1094 (m), 1003 (w), 909 (m), 842 (s), 775 (m), 670 (m), 557 (m); EIMS m/z (%) 172 (3), 171 (18) [M–tBu]+, 141 (3), 115 (10), 99 (3), 89 (5), 77 (4), 76 (7), 75 (100), 73 (19), 61 (3), 59 (8), 58 (4), 57 (4), 55 (7), 47 (4), 45 (4), 41 (9), 39 (4).
Preparation of ( R )-2-methylhex-5-en-1-ol (9). Silyl ether (R)-18 (300 mg, 1.31 mmol, 1.0 equiv) was converted to alcohol (R)-9 using TBAF (1 m in THF/approx. 5% water, 1.57 ml, 1.57 mmol, 1.2 equiv) in dry THF (4 ml) by following the general procedure D. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 5:1) to afford (R)-2-methylhex-5-en-1-ol (9) as a colorless liquid (132 mg, 1.16 mmol, 89%). Rf = 0.44 (pentane/diethyl ether 5:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +11.3 (c = 1.01, DCM); 1H NMR (300 MHz, CDCl3) δ 5.82 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.06–4.92 (m, 2H, CH2), 3.52 (dd, J = 10.5, 5.8 Hz, 1H, CHaHb), 3.44 (dd, J = 10.5, 6.4 Hz, 1H, CHaHb), 2.22–1.97 (m, 2H, CH2), 1.74–1.40 (m, 2H, CH2), 1.45 (br. s, 1H, OH), 1.29–1.14 (m, 1H, CH), 0.93 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 138.9 (CH), 114.4 (CH2), 68.1 (CH2), 35.2 (CH), 32.3 (CH2), 31.2 (CH2), 16.4 (CH3); EIMS m/z (%) 114 (< 1) [M]+, 96 (12) [M–H2O]+, 82 (6), 81 (88), 79 (9), 71 (32), 68 (13), 67 (29), 58 (17), 57 (34), 56 (16), 55 (100), 54 (74), 53 (16), 51 (5), 45 (6), 43 (28), 42 (20), 41 (86), 40 (8), 39 (48).
Preparation of ( R )-2-methylhex-5-enoic acid (10). Alcohol (R)-9 (107 mg, 0.937 mmol, 1.0 equiv) was converted to carboxylic acid (R)-10 using PDC (1.76 g, 4.69 mmol, 5.0 equiv) and DMF (5 ml) by following the general procedure B. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 4:1) to afford (R)-2-methylhex-5-enoic acid (10) as a colorless liquid (97.0 mg, 0.757 mmol, 81%). Rf = 0.62 (pentane/diethyl ether 1:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 24.1 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 11.63 (br. s, 1H, COOH), 5.79 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.09–4.95 (m, 2H, CH2), 2.50 (sext, J = 7.0 Hz, 1H, CH), 2.17–2.06 (m, 2H, CH2), 1.88–1.75 (m, 1H, CHaHb), 1.59–1.46 (m, 1H, CHaHb), 1.20 (d, J = 7.0 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 183.3 (Cq), 137.7 (CH), 115.2 (CH2), 38.7 (CH), 32.5 (CH2), 31.2 (CH2), 16.7 (CH3); EIMS (TMS derivative) m/z (%) 200 (4) [M]+, 185 (13) [M–CH3]+, 146 (15), 143 (23), 131 (8), 130 (14), 75 (66), 74 (11), 73 (100), 56 (18), 55 (14), 47 (7), 45 (15), 41 (16), 39 (9).
Preparation of ( R )- tert -butyl((2,6-dimethylhept-6-en-1-yl)oxy)dimethylsilane (13). The organolithium reagent was prepared from isoprenyl iodide (12, 2.76 g, 14.1 mmol, 7.0 equiv) and t-butyllithium (Attention: careful handling required, extremely flammable reagent, 1.7 m in pentane, 16.5 ml, 28.1 mmol, 14.0 equiv) in a 3:2 mixture of dry and degassed hexane and diethyl ether (28 ml) by following the general procedure C. Then the coupling was performed with copper cyanide (631 mg, 7.04 mmol, 3.5 equiv) in dry diethyl ether (25 ml), organolithium solution and tosylate (S)-11 (720 mg, 2.01 mmol, 1.0 equiv) in dry diethyl ether (14 ml) by following the general procedure C. The crude product was purified by column chromatography (silica gel, pentane) to afford (R)-tert-butyl((2,6-dimethylhept-6-en-1-yl)oxy)dimethylsilane (13) as a colorless liquid (439 mg, 1.71 mmol, 85%). Rf = 0.56 (pentane/diethyl ether 100:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +3.6 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 4.71–4.64 (m, 2H, CH2), 3.45 (dd, J = 9.8, 5.9 Hz, 1H, CHaHb), 3.36 (dd, J = 9.8, 6.6 Hz, 1H, CHaHb), 1.99 (t, J = 7.4 Hz, 2H, CH2), 1.73–1.69 (m, 3H, CH3), 1.67–1.20 (m, 4H), 1.13–0.96 (m, 1H), 0.89 (s, 9H, 3×CH3), 0.87 (d, J = 6.7 Hz, 3H, CH3), 0.03 (s, 6H, 2×CH3); 13C NMR (75 MHz, CDCl3) δ 146.2 (Cq), 109.7 (CH2), 68.4 (CH2), 38.1 (CH2), 35.7 (CH), 32.9 (CH2), 26.0 (3C, CH3), 25.0 (CH2), 22.4 (CH3), 18.4 (Cq), 16.7 (CH3), − 5.4 (2C, CH3); EIMS m/z (%) 200 (6), 199 (35) [M–tBu]+, 143 (7), 129 (4), 123 (4), 115 (12), 101 (4), 89 (9), 81 (6), 77 (6), 76 (10), 75 (100), 73 (20), 69 (7), 61 (4), 59 (8), 55 (9), 41 (13), 39 (4).
Preparation of ( R )-2,6-dimethylhept-6-en-1-ol (14). Silyl ether (R)-13 (398 mg, 1.55 mmol, 1.0 equiv) was converted to alcohol (R)-14 using TBAF (1 m in THF/approx. 5% water, 1.86 ml, 1.86 mmol, 1.2 equiv) in dry THF (5 ml) by following the general procedure D. The crude product was purified by column chromatography (silica gel, pentane/diethyl ether 2:1) to afford (R)-2,6-dimethylhept-6-en-1-ol (14) as a colorless liquid (205 mg, 1.44 mmol, 93%). Rf = 0.37 (pentane/diethyl ether 2:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +12.1 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 4.72–4.65 (m, 2H, CH2), 3.51 (dd, J = 10.5, 5.8 Hz, 1H, CHaHb), 3.42 (dd, J = 10.5, 6.5 Hz, 1H, CHaHb), 2.01 (t, J = 7.4 Hz, 2H, CH2), 1.73–1.69 (m, 3H, CH3), 1.73–1.33 (m, 5H), 1.18–1.03 (m, 1H), 0.93 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 146.0 (Cq), 109.8 (CH2), 68.3 (CH2), 38.0 (CH2), 35.7 (CH), 32.7 (CH2), 24.9 (CH2), 22.3 (CH3), 16.5 (CH3); EIMS m/z (%) 142 (3) [M]+, 124 (3) [M–H2O]+, 109 (30), 95 (23), 82 (51), 81 (32), 71 (23), 69 (72), 68 (73), 67 (59), 58 (15), 57 (30), 56 (81), 55 (77), 53 (21), 43 (28), 42 (11), 41 (100), 40 (9), 39 (41).
Preparation of ( S )-2,6-dimethylhept-6-en-1-yl ( S )-2-methylhex-5-enoate (15). The alcohol (S)-14 (75.0 mg, 0.527 mmol, 1.0 equiv) and carboxylic acid (S)-10 (67.0 mg, 0.527 mmol, 1.0 equiv) were esterified by following the general procedure E using EDC-HCl (111 mg, 0.580 mmol, 1.1 equiv) and DMAP (6.4 mg, 0.0527 mmol, 10 mol%) in dry DCM (2.5 ml) to yield (S)-2,6-dimethylhept-6-en-1-yl (S)-2-methylhex-5-enoate ((S,S)-15) as a colorless liquid (122 mg, 0.483 mmol, 92%). Rf = 0.48 (pentane/diethyl ether 20:1); \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +11.5 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 5.79 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.06–4.93 (m, 2H, 2×CHaHb), 4.72–4.64 (m, 2H, 2×CHaHb), 3.96 (dd, J = 10.7, 5.9 Hz, 1H, CHaHb), 3.87 (dd, J = 10.7, 6.7 Hz, 1H, CHaHb), 2.47 (sext, J = 7.0 Hz, 1H, CH), 2.12–1.94 (m, 4H), 1.88–1.69 (m, 2H), 1.72–1.69 (m, 3H, CH3), 1.58–1.31 (m, 4H), 1.22–1.08 (m, 1H), 1.16 (d, J = 7.0 Hz, 3H, CH3), 0.94 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 176.7 (Cq), 145.8 (Cq), 137.9 (CH), 115.0 (CH2), 109.9 (CH2), 69.1 (CH2), 39.0 (CH), 37.9 (CH2), 32.94 (CH2), 32.86 (CH2), 32.5 (CH), 31.4 (CH2), 24.7 (CH2), 22.3 (CH3), 17.1 (CH3), 16.9 (CH3); IR (neat) ṽ 3076 (w), 2969 (m), 2933 (m), 2323 (w), 1732 (s), 1645 (w), 1457 (m), 1377 (m), 1171 (s), 991 (m), 911 (m), 886 (s), 749 (w), 643 (w), 538 (m); EIMS m/z (%) 252 (< 1) [M]+, 141 (1), 124 (12), 111 (19), 109 (24), 95 (18), 83 (65), 82 (87), 81 (43), 74 (19), 69 (94), 68 (59), 67 (37), 57 (11), 56 (25), 55 (100), 53 (14), 43 (12), 42 (11), 41 (74), 39 (22).
Preparation of ( R )-2,6-dimethylhept-6-en-1-yl ( R )-2-methylhex-5-enoate (15). The alcohol (R)-14 (39.0 mg, 0.273 mmol, 1.0 equiv) and carboxylic acid (R)-10 (35.0 mg, 0.273 mmol, 1.0 equiv) were esterified by following the general procedure E using EDC-HCl (58.0 mg, 0.300 mmol, 1.1 equiv) and DMAP (3.3 mg, 0.0273 mmol, 10 mol%) in dry DCM (1.5 ml) to yield (R)-2,6-dimethylhept-6-en-1-yl (R)-2-methylhex-5-enoate ((R,R)-15) as a colorless liquid (58.0 mg, 0.230 mmol, 84%). \({\text{[α]}}_{\text{D}}^{\text{20}}\) = − 11.7 (c = 1.01, DCM). The other analytical data were identical to that of its enantiomer, (S,S)-15.
Preparation of ( R )-2,6-dimethylhept-6-en-1-yl ( S )-2-methylhex-5-enoate (15). The alcohol (R)-14 (65.0 mg, 0.457 mmol, 1.0 equiv) and carboxylic acid (S)-10 (59.0 mg, 0.457 mmol, 1.0 equiv) were esterified by following the general procedure E using EDC-HCl (96.0 mg, 0.503 mmol, 1.1 equiv) and DMAP (5.6 mg, 0.0457 mmol, 10 mol%) in dry DCM (2.3 ml) to yield (R)-2,6-dimethylhept-6-en-1-yl (S)-2-methylhex-5-enoate ((R,S)-15) as a colorless liquid (98.0 mg, 0.388 mmol, 85%). \({\text{[α]}}_{\text{D}}^{\text{25}}\) = +15.0 (c = 1.00, DCM); 1H NMR (300 MHz, CDCl3) δ 5.79 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H, CH), 5.06–4.93 (m, 2H, 2×CHaHb), 4.72–4.64 (m, 2H, 2×CHaHb), 3.96 (dd, J = 10.7, 5.9 Hz, 1H, CHaHb), 3.87 (dd, J = 10.7, 6.7 Hz, 1H, CHaHb), 2.47 (sext, J = 7.0 Hz, 1H, CH), 2.12–1.95 (m, 4H), 1.87–1.69 (m, 2H), 1.72–1.69 (m, 3H, CH3), 1.58–1.31 (m, 4H), 1.22–1.08 (m, 1H), 1.16 (d, J = 7.0 Hz, 3H, CH3), 0.94 (d, J = 6.7 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 176.7 (Cq), 145.8 (Cq), 137.9 (CH), 115.0 (CH2), 109.9 (CH2), 69.1 (CH2), 39.0 (CH), 37.9 (CH2), 32.94 (CH2), 32.86 (CH2), 32.5 (CH), 31.4 (CH2), 24.7 (CH2), 22.3 (CH3), 17.1 (CH3), 16.9 (CH3); IR (neat) ṽ 3076 (w), 2969 (m), 2934 (m), 2322 (w), 1732 (s), 1645 (m), 1377 (m), 1241 (m), 1171 (s), 1049 (m), 991 (m), 911 (m), 886 (s), 748 (w), 636 (w); EIMS m/z (%) 252 (< 1) [M]+, 141 (1), 124 (10), 111 (17), 109 (22), 95 (17), 83 (62), 82 (86), 81 (42), 74 (18), 69 (95), 68 (60), 67 (35), 57 (11), 56 (24), 55 (100), 53 (13), 43 (13), 42 (11), 41 (76), 39 (21).
Preparation of ( S )-2,6-Dimethylhept-6-en-1-yl ( R )-2-methylhex-5-enoate (15). The alcohol (S)-14 (39.0 mg, 0.273 mmol, 1.0 equiv) and carboxylic acid (R)-10 (35.0 mg, 0.273 mmol, 1.0 equiv) were esterified by following the general procedure E using EDC-HCl (58.0 mg, 0.300 mmol, 1.1 equiv) and DMAP (3.3 mg, 0.0273 mmol, 10 mol%) in dry DCM (1.5 ml) to yield (S)-2,6-dimethylhept-6-en-1-yl (R)-2-methylhex-5-enoate ((S,R)-15) as a colorless liquid (47.0 mg, 0.186 mmol, 68%). \({\text{[α]}}_{\text{D}}^{\text{25}}\) = − 15.5 (c = 1.01, DCM). The other analytical data were identical to that of its enantiomer, (R,S)-15.
Preparation of (2S,5E,10S)-2,6,10-Trimethyl-5-undecen-11-olide (3). The ester (S,S)-15 (40.0 mg, 0.158 mmol, 1.0 equiv) was cyclized by following the general procedure F using Grubbs II generation catalyst (13.4 mg, 0.0158 mmol, 10 mol%), tetrafluoro-p-benzoquinone (2.8 mg, 0.0158 mmol, 10 mol%) and hexafluorobenzene (0.18 ml, 294 mg, 1.58 mmol, 10 equiv) in dry and degassed toluene (200 ml) to yield a mixture of the E/Z isomers (30.0 mg, 0.134 mmol, 85%). After final purification by column chromatography (silica gel-AgNO3, pentane/diethyl ether 50:1), (2S,5E,10S)-2,6,10-trimethyl-5-undecen-11-olide ((2S,10S)-3) was obtained as a colorless liquid (6.0 mg, 0.0267 mmol, 17%). Rf = 0.48 (pentane/diethyl ether 20:1); 1H NMR (500 MHz, CDCl3) δ 5.01–4.95 (m, 1H, CH), 4.45 (dd, J = 10.4, 3.6 Hz, 1H, CHaHb), 3.13 (t, J = 10.9 Hz, 1H, CHaHb), 2.32–2.15 (m, 2H, CH, CHaHb), 2.13–1.86 (m, 5H), 1.64–1.52 (m, 3H), 1.54 (s, 3H, CH3), 1.47–1.38 (m, 1H, CHaHb), 1.14 (d, J = 7.1 Hz, 3H, CH3), 0.92–0.79 (m, 1H), 0.81 (d, J = 6.8 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ 177.7 (Cq), 133.9 (Cq), 126.2 (CH), 69.5 (CH2), 40.1 (CH), 35.9 (CH2), 33.8 (CH2), 28.6 (CH2), 27.4 (CH), 26.9 (CH2), 20.0 (CH2), 18.9 (CH3), 15.2 (CH3), 14.4 (CH3); IR (neat) ṽ 2923 (s), 2855 (m), 2322 (w), 1733 (s), 1455 (m), 1372 (m), 1255 (w), 1179 (s), 1150 (s), 1097 (w), 1027 (w), 992 (w), 849 (w), 805 (m), 757 (w); HRMS (EI+) m/z [C14H24O2]+ calculated: 224.17763, found: 224.17707; EIMS m/z (%) 224 (6) [M]+, 206 (1), 191 (2), 181 (2), 168 (4), 163 (2), 151 (5), 135 (7), 126 (47), 109 (50), 95 (67), 81 (77), 67 (77), 55 (72), 41 (100); gas chromatographic retention index (Hydrodex β-6TBDM) I = 1618, (HP-5 MS) I = 1582.
Preparation of (2R,5E,10R)-2,6,10-trimethyl-5-undecen-11-olide (3). The ester (R,R)-15 (35.0 mg, 0.139 mmol, 1.0 equiv) was cyclized by following the general procedure F using Grubbs II generation catalyst (11.8 mg, 0.0139 mmol, 10 mol%), tetrafluoro-p-benzoquinone (2.5 mg, 0.0139 mmol, 10 mol%) and hexafluorobenzene (0.16 ml, 259 mg, 1.39 mmol, 10 equiv) in dry and degassed toluene (175 ml) to yield a mixture of the E/Z isomers (23.8 mg, 0.106 mmol, 76%). Gas chromatographic retention index (Hydrodex β-6TBDM) I = 1614, (HP-5 MS) I = 1582. The other analytical data were identical to that of its enantiomer, (2S,10S)-3.
Preparation of (2S,5E,10R)-2,6,10-trimethyl-5-undecen-11-olide (3). The ester (R,S)-15 (40.0 mg, 0.158 mmol, 1.0 equiv) was cyclized by following the general procedure F using Grubbs II generation catalyst (13.4 mg, 0.0158 mmol, 10 mol%), tetrafluoro-p-benzoquinone (2.8 mg, 0.0158 mmol, 10 mol%) and hexafluorobenzene (0.18 ml, 294 mg, 1.58 mmol, 10 equiv) in dry and degassed toluene (200 ml) to yield a mixture of the E/Z isomers (30.3 mg, 0.135 mmol, 85%). After final purification by column chromatography (silica gel-AgNO3, pentane/diethyl ether 50:1), (2S,5E,10R)-2,6,10-trimethyl-5-undecen-11-olide ((2S,10R)-3) was obtained as a colorless liquid (4.0 mg, 0.0178 mmol, 11%). 1H NMR (500 MHz, CDCl3) δ 5.18–5.12 (m, 1H, CH), 4.39 (dd, J = 10.4, 3.6 Hz, 1H, CHaHb), 3.28 (t, J = 10.8 Hz, 1H, CHaHb), 2.52–2.43 (m, 1H, CH), 2.43–2.34 (m, 1H), 2.07–1.85 (m, 5H), 1.78–1.69 (m, 1H), 1.61–1.50 (m, 2H), 1.55 (s, 3H, CH3), 1.47–1.37 (m, 1H), 1.13 (d, J = 7.1 Hz, 3H, CH3), 0.92–0.80 (m, 1H), 0.82 (d, J = 6.8 Hz, 3H, CH3); 13C NMR (125 MHz, CDCl3) δ 176.9 (Cq), 134.2 (Cq), 125.7 (CH), 69.3 (CH2), 41.0 (CH), 35.9 (CH2), 34.3 (CH2), 28.5 (CH2), 27.8 (CH), 26.1 (CH2), 20.3 (CH2), 17.4 (CH3), 15.3 (CH3), 14.4 (CH3); IR (neat) ṽ 2930 (s), 2858 (m), 2322 (w), 1726 (s), 1453 (m), 1378 (w), 1343 (w), 1260 (m), 1231 (m), 1182 (m), 1092 (w), 1070 (w), 1037 (m), 804 (w), 676 (w); EIMS m/z (%) 224 (7) [M]+, 206 (1), 191 (3), 181 (2), 168 (5), 163 (3), 151 (6), 135 (9), 126 (58), 109 (61), 95 (80), 81 (85), 67 (80), 55 (74), 41 (100); gas chromatographic retention index (Hydrodex β-6TBDM) I = 1624, (HP-5 MS) I = 1595.
Preparation of (2R,5E,10S)-2,6,10-trimethyl-5-undecen-11-olide (3). The ester (R,S)-15 (30.0 mg, 0.119 mmol, 1.0 equiv) was cyclized by following the general procedure F using Grubbs II generation catalyst (10.1 mg, 0.0119 mmol, 10 mol%), tetrafluoro-p-benzoquinone (2.1 mg, 0.0119 mmol, 10 mol%) and hexafluorobenzene (0.14 ml, 221 mg, 1.19 mmol, 10 equiv) in dry and degassed toluene (150 ml) to yield a mixture of the E/Z isomers (22.0 mg, 0.0981 mmol, 82%). Gas chromatographic retention index (Hydrodex β-6TBDM) I = 1629, (HP-5 MS) I = 1595. The other analytical data were identical to that of its enantiomer, (2S,10R)-3.