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Enone 1.112: A solution of dicyclopentadiene (20.0 g, 151 mmol). Ac2O (15.0 mL, 159 mmol), pyridine (6.20 mL, 76.8 mmol), TPP (100 mg, 0.160 mmol) and DMAP (400 mg, 3.27 mmol) in CH2Cl2 (50 mL) was stirred under an O2-atmosphere at room temperature for 3 d while being irradiated with reptile lamp. The reaction was diluted with Ch2Cl2 and washed with saturated aqueous NaHCO3, aqueous HCl (1 M), saturated aqueous CuSO4 and brine. The organic phase was dried over MgSO4 and concentrated under reduced pressure. Purification by flash column chromatography (pentane:EtOAc 9:1, Rf= 0.2) gave enone 1.112 (14.7 g, 101 mmol, 67%) as a colorless oil.

Data for 1.112: 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.37 (dd, J = 5.7, 2.6 Hz, 1H, 6), 5.97 – 5.89 (m, 2H, 7 & 2), 5.76 (dd, J = 5.7, 3.0 Hz, 1H, 1), 3.46 – 3.36 (m, 1H, 8), 3.20 (s, 2H, 4), 2.95 (s, 2H, 9), 2.79 (t, J = 5.0 Hz, 1H, 5), 1.74 (d, J = 8.4 Hz, 1H, 3), 1.61 (d, J = 8.4 Hz, 1H, 3). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 210.9, 164.8, 137.0, 132.6, 132.5, 52.8, 50.3, 48.4, 45.1, 44.1. IR (ATR): 𝜈max (cm−1) = 3060 (w), 2959 (m), 2930 (w), 2874 (w), 1727 (s), 1460 (w), 1402 (w), 1380 (w), 1340 (w), 1307 (w), 1231 (w), 1191 (m), 1158 (w), 1137 (w), 1089 (w), 1067 (w), 1022 (w), 957 (w)9, 909 (w), 860 (w), 779 (w), 730 (s). HRMS (EI): calc. for C10H10O [M]+: 146.0732, found: 146.0733.

Ketone 1.114:35 CuI (426 mg, 2.24 mmol) was added to EtMgBr (0.9 M in THF, 73.8 mL, 66.4 mmol) at 0 °C and the mixture was stirred for 30 min at that temperature. The reaction was cooled to –78 °C and a solution of enone 1.112 (2.00 g, 13.7 mmol) in THF (60 mL) was added slowly. The reaction was stirred for 3 h at that temperature, quenched with saturated aqueous NH4Cl and extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure.

Purification of the resulting residue by flash column chromatography (pentane:EtOAc 95:5, Rf = 0.2) gave ketone 1.114 (2.22 g, 12.6 mmol, 92%) as a colorless oil.

Data for 1.114: 1H NMR (400 MHz, CDCl3): δ (ppm) = 6.15 (dd, J = 5.8, 2.9 Hz, 1H, 1), 6.11 (dd, J = 5.8, 2.8 Hz, 1H, 2), 3.15 (s, 1H, 4), 3.01 (s, 1H, 9), 2.91 (ddd, J = 9.7, 4.8, 1.8 Hz, 1H, 5), 2.61 (dt, J = 9.4, 4.0 Hz, 1H, 8), 2.19 (dd, J = 18.6, 9.0 Hz, 1H, 6), 1.92 (ddd, J = 18.6, 6.7, 2.0 Hz, 1H, 6), 1.66 – 1.56 (m, 1H, 7), 1.53 (d, J = 8.2 Hz, 1H, 3), 1.50 – 1.42 (m, 1H, 3), 1.41 – 1.32 (m, 2H, 10), 0.90 (t, J = 7.3 Hz, 3H, 11). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 136.2, 135.4, 55.0, 52.4, 48.6, 48.1, 47.3, 46.3, 38.7, 30.7, 12.1. IR (ATR): 𝜈max (cm−1) = 3062 (w), 2977 (w), 2872 (w), 1691 (s), 1580 (m), 1453 (w), 1348 (m), 1336 (m), 1297 (w), 1223 (m), 1195 (m), 1175 (m), 1125 (w), 1084 (w), 1052 (w), 1016 (m), 949 (w), 907 (m), 851 (m), 816 (w), 779 (s), 738 (m), 721 (s), 690 (w).

HRMS (EI): calc. for C12H12O [M]+: 176.1201, found: 176.1204.

Tertiary alcohol 1.111: LaCl3.2LiCl (0.6 M in THF, 21.0 mL, 12.60 mmol) was added to a solution of ketone 1.114 (2.22 g, 12.6 mmol) in THF (30 mL) and the solution was stirred for 1 h at room temperature. The solution was cooled to 0 °C, EtMgBr (0.60 M in THF, 28.0 mL, 25.2 mmol) was added slowly and the reaction was stirred for 1 h at 0 °C.

The reaction was quenched by the addition of saturated aqueous NH4Cl and extracted with Et2O. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to give tertiary alcohol 1.111 (2.33 g, 11.3 mmol, 90%) as a colorless oil.

Data for 1.111: 1H NMR (400 MHz, CDCl3): δ (ppm) = 6.42 (dd, J = 5.8, 3.0 Hz, 1H), 6.13 (dd, J = 5.7, 3.2 Hz, 1H), 2.77 (s, 2H, 4 & 9), 2.51 (dd, J = 10.7, 3.8 Hz, 1H, 5), 2.32 (td, J = 10.5, 9.9, 4.1 Hz, 1H, 8), 1.72 (dd, J = 12.6, 5.7 Hz, 1H, 6), 1.60 (d, J = 7.9 Hz, 1H, 3), 1.55 (q, J = 7.4 Hz, 2H, 12), 1.50 (s, 1H, OH), 1.45 (d, J = 7.9 Hz, 1H, 3), 1.39 – 1.25 (m, 3H, 10 & 6), 1.18 (ddt, J = 12.6, 9.0, 6.2 Hz, 1H, 7), 0.96 (t, J = 7.4 Hz, 3H, 13), 0.88 (t, J = 7.4 Hz, 3H, 11). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 136.8, 135.4, 80.5, 57.9, 55.2, 54.9, 50.7, 45.4, 45.1, 41.9, 35.2, 28.3, 13.2, 9.0. IR (ATR): 𝜈max (cm−1) = 3484 (w, b), 3057 (w), 2958 (s), 2920 (s), 2873 (m), 1459 (m), 1377 (m), 1345 (w), 1335

(w), 1304 (w), 1250 (w), 1229 (w), 1201 (w), 1147 (m), 1062 (w), 985 (m), 961 (m), 947 (m), 917 (w), 869 (w), 836 (w), 819 (w), 793 (w), 777 (w), 744 (s), 724 (w), 696 (w).

HRMS (EI): calc. for C14H22O [M]+: 206.1665, found: 206.1622.

Cyclopentene 1.109: A solution of tertiary alcohol 1.111 (100 mg, 0.485 mmol) in Et2O (2.0 mL) was subjected to flash vacuum pyrolysis. Purification of the resulting residue by flash column chromatography (pentane:Et2O 3:1, Rf= 0.25) gave cyclopentene 1.109 (54 mg, 0.388 mmol, 80%) as a solution in pentane and ether.

Data for 1.109: 1H NMR (400 MHz, CDCl3): δ (ppm) =5.85 (dd, J = 5.6, 2.0 Hz, 1H), 5.68 (dd, J = 5.6, 2.4 Hz, 1H), 2.79 (dddt, J = 14.2, 8.1, 6.2, 2.2 Hz, 1H), 2.06 – 2.00 (m, 1H), 1.68 (qd, J = 7.5, 1.3 Hz, 2H), 1.54 – 1.49 (m, 1H), 1.43 (d, J = 2.7 Hz, 1H), 1.34 – 1.28 (m, 1H), 0.93 (dt, J = 9.7, 7.4 Hz, 6H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 138.8, 135.4, 86.5, 46.0, 43.7, 33.8, 28.7, 12.5, 9.1. IR (ATR): 𝜈max (cm−1) = 3374 (br), 2961 (vs), 2924 (s), 2875 (s), 2856 (m), 1730 (w), 1651 (w), 1461 (m), 1378 (m), 1326 (w), 1147 (w), 1030 (w), 996 (w), 834 (w), 757 (w). MS (EI): calc. for C9H15 [M–OH]+: 123.13, found: 123.12.

Carboxylic acid 1.108:33 DIBAL-H (1 M, in PhMe, 25.0 mL, 25.0 mmol) was added slowly to a solution of 3-hexyne (2.84 mL, 25.0 mmol) in cyclohexane (12.5 mL) and the reaction was stirred at 60 °C for 2.5 h. The mixture was cooled to room temperature, MeLi (1.6 M in Et2O, 15.6 mL, 25.0 mmol) was added and the solution was stirred for 15 min at room temperature. The reaction was cooled to –30 °C, purged with CO2 and stirred for 3 h at that temperature. The mixture was poured into a mixture of aqueous conc. HCl and ice and extracted with Et2O. The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. Purification of the resultant

residue by flash column chromatography (pentane:EtOAc 9:1, Rf= 0.3) gave carboxylic acid 1.108 (1.93 g, 15.0 mmol, 60%) as a colorless oil.

Data for 1.108: 1H NMR (400 MHz, CDCl3): δ (ppm) =11.92 (s, 1H, OH), 6.87 (t, J = 7.5 Hz, 1H, 1), 2.31 (q, J = 7.5 Hz, 2H, 4), 2.23 (p, J = 7.5 Hz, 2H, 2), 1.06 (t, J = 7.6 Hz, 3H, 5), 1.02 (t, J = 7.4 Hz, 3H, 3). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 173.8, 146.6, 132.9, 22.0, 19.8, 14.1, 13.4. IR (ATR): 𝜈max (cm−1) = 2969 (m), 2937 (m), 2877 (m), 2654 (s), 2581 (s), 2539 (s), 1682 (h), 1638 (m), 1463 (s), 1418 (m), 1377 (s), 1304 (m), 1288 (m), 1166 (s), 1107 (s), 1072 (s), 1041 (s), 949 (s), 816 (s), 781 (s), 645 (s), 574 (s), 564 (s).

MS (EI): calc. for C7H12O2 [M]+: 128.0832, found: 128.0849.

Allylic alcohol 1.125: Peracidic acid (40% in AcOH, 9.5 mL, 56.9 mmol) was added to a suspension of freshly distilled cyclopenta-1,3-dien (15.8 g, 238 mmol), Na2CO3 (30.8 g, 290 mmol) and NaOAc (390 mg, 4.76 mmol) in CH2Cl2 (150 mL) and the reaction was stirred for 1 h at room temperature. The CH2Cl2 was removed under reduced pressure and the resulting mixture was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to give crude oxirane S1.1 (3.19 g) as a colorless oil that was used in the next step without further purification.

EtMgBr (3.2 M inEt2O, 15.8 mL, 50.6 mmol) was added slowly to a solution of CuCN (5.22 g, 58.3 mmol) in Et2O (100 mL) at –40 °C and the mixture was stirred for 1 h at that temperature. A solution of crude oxirane S1.1 (3.19 g) in Et2O (10 mL) was added slowly and the reaction was allowed to warm to room temperature overnight. The mixture was extracted with Et2O and the combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography (pentane:Et2O 3:1, Rf = 0.2) gave allylic alcohol 1.25 (2.21 g, 19.7 mmol, 35% over 2 steps) as a colorless oil.

Data for 1.25: 1H NMR (400 MHz, CDCl3): δ (ppm) =5.95 (ddd, J = 5.6, 2.1, 0.8 Hz, 1H), 5.82 (dt, J = 5.6, 2.2 Hz, 1H), 4.85 (dd, J = 7.1, 2.4 Hz, 1H), 2.80 (ddt, J = 5.3, 4.4, 2.2 Hz, 1H), 1.89 (dd, J = 7.5, 2.7 Hz, 1H), 1.79 (dd, J = 7.0, 1.8 Hz, 1H), 1.45 – 1.37 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 140.1, 132.7, 77.4, 45.8, 40.3, 28.6, 12.2. IR (ATR): 𝜈max (cm−1) = 3341 (m), 3055 (w), 2959 (vs), 2931 (s),

2874 (s), 2359 (w), 2341 (w), 2205 (w), 2167 (w), 2102 (w), 2049 (w), 2016 (w), 1981 (w), 1725 (m), 1616 (w), 1460 (s), 1408 (m), 1378 (s), 1325 (m), 1307 (m), 1264 (m), 1159 (m), 1112 (m), 1095 (m), 1069 (s), 1031 (vs), 1001 (vs), 948 (m), 907 (m), 867 (m), 832 (m), 795 (s), 777 (m), 750 (s), 726 (s), 709 (s), 668 (s), 645 (s), 622 (s), 615 (s), 607 (s), 597 (s), 580 (s), 572 (s), 564 (s), 556 (s). MS (EI): calc. for C7H11 [M–OH]+: 95.08, found: 95.12.

Allylic ester 1.128: n-BuLi (2.36 M in hexanes, 1.53 mL, 3.60 mmol) was added dropwise to an ice cooled solution of allylic alcohol 1.125 (337 mg, 3.00 mmol) in THF (17 mL) and the solution was stirred for 30 min at 0 °C. A solution of acid chloride 1.115 (540 mg, 3.68 mmol) in THF (5 mL) was added dropwise and the reaction was stirred for 2 h at 0 °C before the reaction was quenched with aqueous saturated NH4Cl and extracted with Et2O. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography (hexanes:Et2O 99:1, Rf= 0.2) gave allylic ester 1.128 (447 mg, 2.01 mmol, 67%) as a colorless oil.

Data for 1.128: 1H NMR (400 MHz, CDCl3): δ (ppm) = 6.66 (t, J = 7.5 Hz, 1H), 6.05 (ddd, J = 5.6, 2.1, 0.8 Hz, 1H), 5.84 (dt, J = 5.6, 2.3 Hz, 1H), 5.74 (dq, J = 7.4, 2.8 Hz, 1H), 2.88 – 2.77 (m, 1H), 2.28 (q, J = 7.5 Hz, 2H), 2.17 (p, J = 7.5 Hz, 2H), 2.04 (ddd, J = 14.3, 7.7, 2.8 Hz, 1H), 1.85 (ddd, J = 14.4, 7.4, 5.1 Hz, 1H), 1.45 (ddd, J = 13.9, 7.6, 6.5 Hz, 1H), 1.38 – 1.30 (m, 1H), 1.04 (t, J = 7.6 Hz, 3H), 0.98 (t, J = 7.5 Hz, 3H), 0.92 (t, J

= 7.4 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 168.2, 143.4, 142.2, 133.9, 129.1, 80.3, 77.5, 76.8, 46.1, 36.9, 28.6, 21.8, 20.1, 14.2, 13.6, 12.23, 12.21.

Ethyl ester 1.130:37 BF3.OEt2 (3.27 mL, 25.8 mmol) and ethyl diazoacetate (8.36 M in CH2Cl2, 4.02 mL, 33.6 mmol) were sequentially added to a solution of tetrahydro-4H-thiopyran-4one (3.00 g, 25.8 mmol) in Et2O at –30 °C and the solution was stirred for 2 h at that temperature. The reaction was warmed to room temperature, quenched with aqueous K2CO3 (30%) and extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. Purification of the resultant residue by flash column chromatography (pentane:EtOAc 4:1, Rf= 0.3) gave ethyl ester 1.130 (4.14 g, 20.5 mmol, 79%) as a colorless oil.

Data for 1.130: 1H NMR (400 MHz, CDCl3): δ (ppm) =12.84 (s, 1H), 4.18 (q, J = 6.9 Hz, 2H), 4.11 (q, J = 7.1 Hz, 2H), 3.74 (dd, J = 10.5, 3.3 Hz, 1H), 3.02 – 2.89 (m, 2H), 2.89 – 2.75 (m, 3H), 2.75 – 2.66 (m, 1H), 2.59 – 2.56 (m, 3H), 2.35 (m, 1H), 2.14 (m, 1H), 1.30 (t, J = 7.1 Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 206.1, 169.7, 61.5, 60.9, 57.2, 47.1, 39.2, 32.8, 31.0, 29.1, 28.0, 26.9, 25.5, 14.4, 14.2.

IR (ATR): 𝜈max (cm−1) = 2980 (w), 2926 (w), 2363 (w), 1738 (vs), 1705 (vs), 1638 (w), 1465 (w), 1428 (m), 1368 (m), 1353 (m), 1325 (m), 1301 (s), 1268 (s), 1220 (vs), 1180 (vs), 1142 (vs), 1094 (s), 1055 (w), 1030 (s), 1005 (m), 963 (w), 932 (w), 852 (m), 838 (m), 818 (w), 728 (w), 650 (w), 607 (w), 591 (w), 575 (w), 567 (w), 560 (w). HRMS (EI):

calc. for C9H14O3S [M]+: 202.0658, found: 202.0656.

Thiepane 1.131:37 NaBH4 (550 mg, 14.7 mmol) was added to a solution of ethyl ester 1.130 (2.38 g, 11.7 mmol) in EtOH (72 mL) at –78 °C and the mixture was stirred for 10 min at that temperature and for 2 h at room temperature. The reaction was quenched with saturated aqueous NaHCO3 and the ethanol was removed under reduced pressure.

The aqueous phase was extracted with EtOAc, the combined organic phases were washed with aqueous HCl (1 M), saturated aqueous NaHCO3 and brine, dried over MgSO4 and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography (pentane:EtOAC 5:1, Rf= 0.35) gave thiepane 1.131 (800 mg, 3.92 mmol, 33%) as a colorless oil.

Data for 1.131: 1H NMR (400 MHz, CDCl3): δ (ppm) =4.36 (br, 1H, H-9), 4.17 (q, J = 7.1 Hz, 2H, H-2), 2.98 – 2.88 (m, 3H, H-4,6,10), 2.86 – 2.78 (m, 1H, H-7), 2.77 – 2.69 (m,

1H, H-6), 2.58 – 2.51 (m, 1H, H-7), 2.38 – 2.25 (m, 2H, H-5,8), 2.13 – 2.03 (m, 1H, H-5), 1.97 – 1.87 (m, 1H, H-8), 1.27 (t, J = 7.1 Hz, 2H, H-1). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 176.4, 70.0, 61.0, 48.2, 38.1, 31.0, 27.2, 27.2, 14.3. IR (ATR): 𝜈max (cm−1) = 3471 (m), 2923 (m), 1720 (vs), 1425 (m), 1368 (m), 1276 (m), 1207 (s), 1190 (s), 1156 (s), 1076 (m), 1031 (s), 931 (w), 908 (w), 858 (w), 628 (w), 601 (w), 581 (w), 567 (w). HRMS (EI): calc. for C9H16O3S [M]+: 204.0815, found: 204.0816.

Alkene 1.13237: NEt3 (2.08 mL, 15.1 mmol) and MsCl (0.93 mL, 12.0 mmol) were sequentially added to an ice cooled solution of thiepane 1.131 (1.23 g, 6.02 mmol) in CH2Cl2 (40 mL) and the mixture was stirred for 4 h at that temperature before the reaction was quenched with saturated aqueous NaHCO3 and extracted with CH2Cl2. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to give crude mesylate S1.2 (1.74 g) that was used in the next step without further purification.

DBU (1.10 mL, 5.20 mmol) was added to a solution of crude mesylate S1.2 (1.74 g) in THF (35 mL) and the reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4Cl and brine.

The organic phase was dried over MgSO4 and concentrated under reduced pressure.

Purification of the resulting residue by flash column chromatography (pentane:Et2O 97:3, Rf= 0.34) gave alkene 1.132 (873 mg, 4.68 mmol, 76% over 2 steps) as a colorless oil.

Data for 1.132: 1H NMR (400 MHz, CDCl3): δ (ppm) =7.17 (t, J = 6.8 Hz, 1H), 4.18 (q, J = 7.1 Hz), 3.03 – 2.99 (m, 2H), 2.80 – 2.74 (m, 2H), 2.67 – 2.62 (m, 4H), 1.29 (t, J = 7.1 Hz, 3H. 13C-NMR (101 MHz, CDCl3): δ (ppm) = 167.9, 142.5, 135.9, 61.0, 32.6, 31.1, 28.2, 27.1, 14.4. IR (ATR): 𝜈max (cm−1) = 2979 (w), 2907 (w), 2359 (w), 1703 (vs), 1645 (w), 1442 (w), 1377 (w), 1283 (m), 1254 (s), 1205 (s), 1173 (w), 1154 (w), 1094 (w), 1057 (m), 1029 (w), 921 (w), 864 (w), 752 (w), 668 (w), 628 (w), 601 (w), 582 (w), 568 (w).

HRMS (EI): calc. for C9H14O2S [M]+: 186.0709, found: 186.0705.

Acid 1.133: An aqueous solution of LiOH (1 M, 40.3 mL, 40.3 mmol) was added to a solution of alkene 1.132 (150 mg, 0.805 mmol) in THF (53 mL) and the solution was stirred at room temperature for 17 h. The reaction acidified with aqueous HCl (1 M) and extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography (pentane:Et2O 3:2, Rf = 0.3) gave acid 1.133 (127 mg, 0.799 mmol, 99%) as a colorless solid.

Data for 1.133: 1H NMR (400 MHz, CDCl3): δ (ppm) =9.40 (br, 1H), 7.33 (t, J = 6.7 Hz, 1H), 3.04 – 2.99 (m, 2H), 2.86 – 2.77 (m, 2H), 2.71 – 2.64 (m, 4H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 172.8, 145.7, 134.9, 32.8, 30.7, 28.2, 26.9. IR (ATR): 𝜈max (cm−1) = 2359 (m), 1683 (m), 668 (m), 600 (m), 590 (m), 568 (vs). HRMS (EI): calc. for C7H10O2S [M]+: 158.0396, found: 158.0399.

Allylic ester 1.134: DMF (1 drop) was added to an ice cooled solution of acid 1.133 (107 mg, 0.676 mmol) and oxalyl chloride (0.08 mL, 0.946 mmol) in CH2Cl2 (5.5 mL) and the reaction mixture was stirred for 15 min at that temperature and for 1 h at room temperature. Evaporation of the volatiles under reduced pressure gave crude acid chloride S1.3 that was used in the next step without further purification.

n-BuLi (2.36 M in hexanes, 0.30 mL, 0.686 mmol) was added dropwise to an ice cooled solution of allylic alcohol 1.133 (63 mg, 0.563 mmol) in THF (3.5 mL) and the solution was stirred for 30 min at 0 °C. The mixture was added to an ice cooled solution of crude acid chloride S1.3 in THF (5 mL) and the reaction was stirred at that temperature for 2 h.

The reaction was quenched with MeOH (0.5 mL) and aqueous NaOH (1 M) and extracted with Et2O.The combined organic phases were dried over MgSO4 and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography

(pentane:Et2O 95:5, Rf= 0.32) gave allylic ester 1.134 (36 mg, 0.143 mmol, 21% over 2 steps) as a colorless oil.

Data for 1.134: 1H NMR (400 MHz, CDCl3): δ (ppm) =7.13 (t, J = 6.7 Hz, 1H), 6.07 (ddd, J = 5.6, 2.1, 0.8 Hz, 1H), 5.83 (dt, J = 5.7, 2.3 Hz, 1H), 5.71 (dtd, J = 7.3, 3.0, 2.2 Hz, 1H), 3.02 – 2.96 (m, 2H), 2.85 – 2.78 (m, 1H), 2.78 – 2.72 (m, 2H), 2.66 – 2.61 (m, 4H), 2.03 (ddd, J = 14.3, 7.6, 2.7 Hz, 1H), 1.85 (ddd, J = 14.4, 7.4, 5.2 Hz, 1H), 1.50 – 1.40 (m, 1H), 1.32 (dq, J = 13.6, 7.4 Hz, 1H), 0.92 (t, J = 7.4 Hz, 3H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 168.0, 142.6, 136.1, 128.8, 80.9, 46.1, 36.8, 32.7, 31.2, 28.5, 28.3, 27.1, 12.2. IR (ATR): 𝜈max (cm−1) = 3050 (w), 2958 (m), 2925 (m), 2873 (w), 2358 (w), 2333 (w), 2173 (w), 2148 (w), 2102 (w), 2048 (w), 2016 (w), 1968 (w), 1702 (vs), 1644 (w), 1460 (w), 1439 (w), 1420 (w), 1379 (w), 1367 (w), 1337 (w), 1296 (w), 1283 (m), 1252 (vs), 1204 (s), 1154 (m), 1093 (w), 1053 (m), 1021 (w), 968 (w), 943 (w), 911 (w), 887 (w), 831 (w), 800 (w), 752 (m), 667 (w), 646 (w), 632 (w), 623 (w), 614 (w), 607 (w), 597 (w), 580 (w), 570 (w), 556 (w). HRMS (EI): calc. for C14H20O2S [M]+: 252.1179, found:

252.1177.

Dioxanone 1.137: CDI (151 mg, 0.936 mmol) was added to a solution of acid 1.108 (100 mg, 0.780 mmol) in THF (5 mL) and the reaction was stirred at room temperature for 17 h before it was diluted with saturated aqueous NaHCO3 and extracted with Et2O.

The combined organic phases were dried over MgSO4 and concentrated under reduced pressure to give crude amide S1.4 that was used in the next step without further purification.

n-BuLi (2.36 M in hexanes, 0.37 mL, 0.87 mmol) was added dropwise to an ice cooled solution of DIPA (0.12 mL, 0.87 mmol) in THF (5 mL) and the solution was stirred for 30 min at 0 °C. The reaction mixture was cooled to –78 °C, t-BuOAc (0.12 mL, 0.87 mmol) was added dropwise and the resulting solution was stirred at –78 °C for 30 min. A solution of crude amide S1.4 in THF (5 mL) was added and the reaction mixture was allowed to warm to room temperature overnight before the reaction was diluted with saturated aqueous NH4Cl (5 mL) and aqueous HCl (1 M, 5 mL) and extracted with EtOAc.

The combined organic phases were washed with brine, dried over MgSO4 and

concentrated under reduced pressure. Purification of the resulting residue gave crude -keto ester S.1.5 (51 mg) that was used in the next step without further purification.

H2SO4 (conc. 20 µL, 0.448 mmol) was added to an ice cooled solution of crude -keto ester S1.5 (51 mg) and Ac2O (0.7 mL, 7.41 mmol) in acetone (0.7 mL) and the reaction mixture was slowed to warm to room temperature overnight. The reaction was diluted with aqueous K2CO3 and stirred for 30 min at room temperature before it was extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4

and concentrated under reduced pressure. Purification of the resulting residue by flash column chromatography (pentane:Et2O 6:1, Rf= 0.3) gave dioxanone 1.137 (28 mg, 0.133 mmol, 59%) as a colorless oil.

Data for 1.137: 1H NMR (400 MHz, CDCl3): δ (ppm) =6.32 (t, J = 7.5 Hz, 1H), 5.45 (s, 1H), 2.24 (p, J = 7.5 Hz, 4H), 1.71 (s, 6H), 1.08 – 1.01 (m, 6H). 13C-NMR (101 MHz, CDCl3): δ (ppm) = 165.4, 162.8, 139.3, 133.3, 106.1, 91.3, 25.1, 21.8, 19.8, 14.0, 13.7.

IR (ATR): 𝜈max (cm−1) = 2970 (w), 2937 (w), 2876 (w), 2360 (w), 2340 (w), 1726 (vs), 1633 (m), 1593 (m), 1457 (w), 1392 (m), 1376 (m), 1339 (m), 1280 (m), 1254 (m), 1206 (m), 1147 (w), 1065 (w), 1039 (w), 1019 (w), 997 (w), 962 (w), 905 (w), 865 (w), 809 (w), 695 (w), 668 (w), 601 (w), 590 (w), 568 (w), 560 (w).

-Keto ester 1.136: A solution of dioxanone 1.137 (90 mg, 0.427 mmol) and allylic alcohol 1.125 (47 mg, 0.427 mmol) in PhMe (10 mL) was stirred at 100 °C overnight.

Evaporation of the volatiles under reduced pressure and purification of the resulting residue by flash column chromatography (penatane:Et2O 99:1, Rf= 0.2) gave -keto ester 1.136 (42 mg, 0.159 mmol, 37%) as a colorless oil. The product was obtained as mixture of tautomers.

Data for 1.136: 1H NMR (400 MHz, CDCl3): δ (ppm) =12.30 (s, 0H), 6.51 (d, J = 7.2 Hz, 1H), 6.45 (t, J = 7.4 Hz, 0H), 6.10 (dd, J = 5.6, 2.1 Hz, 0H), 5.84 (dt, J = 5.2, 2.3 Hz, 0H), 5.80 (dt, J = 5.2, 2.3 Hz, 1H), 5.73 (dt, J = 7.4, 2.4 Hz, 1H), 5.68 – 5.65 (m, 0H), 3.68 (s, 1H), 3.66 (s, 2H), 2.78 (dddd, J = 8.9, 6.6, 4.8, 2.8 Hz, 1H), 2.29 (qd, J = 7.5, 3.4 Hz, 5H), 2.20 (ddd, J = 15.0, 10.6, 7.2 Hz, 1H), 2.04 (ddd, J = 15.0, 7.6, 2.6 Hz, 1H), 1.81 (ddd, J = 14.5, 7.4, 5.3 Hz, 1H), 1.45 – 1.40 (m, 1H), 1.35 – 1.24 (m, 2H), 1.08 (t, J = 7.6

Hz, 4H), 1.03 – 0.98 (m, 1H), 0.92 (dt, J = 11.5, 7.4 Hz, 9H). 13C-NMR (101 MHz, CDCl3):

δ (ppm) = 193.9, 168.3, 146.2, 143.0, 142.7, 128.3, 81.4, 46.0, 45.4, 36.6, 28.4, 22.3, 18.9, 13.9, 13.5, 12.2. IR (ATR): 𝜈max (cm−1) = 2965 (m), 2934 (m), 2875 (m), 2360 (w), 2340 (w), 1735 (vs), 1671 (s), 1636 (m), 1461 (m), 1413 (m), 1366 (m), 1318 (m), 1298 (m), 1262 (m), 1237 (m), 1191 (m), 1150 (m), 1094 (m), 1068 (m), 1035 (m), 975 (m), 895 (w), 801 (m), 753 (w), 667 (w), 628 (w), 601 (w), 582 (w), 567 (w). HRMS (EI): calc.

for C16H24O3 [M]+: 264.1720, found: 264.1719.

α-Tropolone methyl ester (11)172: Methyl iodide (16.0 mL, 257 mmol) was added to a suspension of -tropolone (6.43 g, 52.7 mmol), potassium carbonate (21.8 g, 158 mmol) and dicyclohexyl-18-crown-6 (2.00 g, 5.37 mmol) in acetonitrile (265 mL). The resulting mixture was stirred at 82 °C overnight, then cooled to room temperature, filtered and concentrated. The resulting residue was redissolved in methylene chloride and washed with saturated aqueous potassium carbonate. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (ethyl acetate) gave α-tropolone methyl ester 11 as a white solid (6.26 g, 46.0 mmol, 87%).

Data for 11: Rf: 0.2 (EtOAc); 1H-NMR (400 MHz, CDCl3): δ (ppm) = 7.26-7.23 (m, 2H), 7.09 (ddt, J = 10.9, 9.9, 1.0 Hz, 1H), 6.90-6.84 (m, 1H), 6.74 (dt, J = 9.9, 0.7 Hz, 1H), 3.96 (s, 3H). 13C-NMR (100 MHz, CDCl3): δ (ppm) = 180.7, 165.6, 137.1, 136.8, 132.8, 128.1, 112.5, 56.5. IR (ATR): 𝜈max (cm−1) = 3476 (br w), 2942 (w), 1624 (m), 1590 (s), 1568 (vs), 1494 (s), 1470 (s), 1400 (m), 1278 (s), 1264 (s), 1231 (m), 1211 (vs), 1164 (s), 1078 (s), 986 (m), 948 (m), 906 (m), 870 (m), 851 (w), 769 (s), 706 (s), 665 (m).

HRMS (EI): calc. for C8H8O2 [M]+: 136.0524, found: 136.0515.

Bicycle 1032: A stirred solution of -tropolone methyl ester 11 (2.00 g, 14.7 mmol) in MeOH (160 mL) was irradiated at room temperature for 13 h using a medium pressure mercury lamp (150 W) in an immersion well photoreactor containing a Pyrex® filter. After evaporation of the solvent, the crude product was purified by flash column chromatography (hexanes:EtOAc 5:1) to afford bicycle 10 (1.05 g, 7.71 mmol, 52%) as a colorless oil.

Data for 10: Rf: 0.4 (hexanes:EtOAc 5:1); 1H-NMR (400 MHz, CDCl3): δ (ppm) = 7.69 (dd, J = 5.8, 2.3 Hz, 1H), 5.98 (d, J = 5.7 Hz, 1H), 5.01 (s, 1H), 3.62 (d, J = 2.9 Hz, 1H), 3.60 (s, 3H), 3.58 (t, J = 2.6 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ (ppm) = 204.9, 165.1, 155.6, 133.2, 100.9, 56.3, 54.5, 40.8. IR (ATR): 𝜈max (cm−1) = 2937 (br w), 1737 (w), 1693 (vs), 1628 (vs), 1573 (w), 1453 (w), 1435 (w), 1342 (w), 1296 (s), 1259 (m), 1208 (m), 1175 (m), 1150 (w), 1118 (w), 1078 (m), 1021 (s), 998 (m), 972 (w), 956 (m), 930 (w), 898 (w), 851 (w), 790 (s), 748 (s), 708 (m). HRMS (EI): calc. for C8H8O2 [M]+: 136.0524, found: 136.0520.

Ketone 13: EtMgBr (3.0 M in Et2O, 15.31 mL, 45.92 mmol) was added dropwise to solution of CuI (4.37 g, 22.96 mmol) in Et2O (190 mL) cooled to –5 °C and stirred for 30 min at that temperature. The solution was cooled to –78 °C and a solution of enone 10 (1.56 g, 11.48 mmol) in Et2O (62 mL) was added dropwise. The reaction was stirred for 2 h at –78 °C before it was quenched with saturated aqueous NH4Cl and extracted

with Et2O. The combined organic phases were washed with brine, dried over MgSO4 and concentrated under reduced pressure to give ketone 13, which was used in the next step without further purification.

Enol ether S1: KOtBu (3.86 g, 34.44 mmol) was added to an ice cooled suspension of ethyl triphenylphosphonium bromide (12.78 g, 34.44 mmol) in THF (67 mL) and stirred for 30 min at that temperature. A solution of crude ketone 13 in THF (38 mL) was added dropwise and the reaction was stirred for 2 h at room temperature before it was quenched with saturated aqueous NH4Cl and extracted with Et2O. The organic phase was dried over MgSO4 and concentrated under reduced pressure to give crude enol S1 ether which was used in the next step without further purification.

Ketone 14: A solution of p-TSA.H2O (360 mg, 1.89 mmol) in water (80 mL) was added to a solution of crude enol ether S1 in acetone (80 mL) and stirred for 2 h at room temperature. The reaction mixture was extracted with Et2O. The combined organic phases were washed with saturated aqueous NaHCO3 and brine and dried over MgSO4. Evaporation of the solvent and purification by flash column chromatography (hexanes:Et2O 94:6) afforded ketone 14 (1.12 g, 6.81 mmol, 59% over 3 steps, Z:E = 10:1 mixture of diastereomers at the double bond) as a colorless oil.

Data for 14: Rf: 0.4 (hexanes:Et2O 94:6); 1H-NMR (400 MHz, CDCl3): δ (ppm) = 5.46 (qt, J = 7.0, 1.7 Hz, 1H), 4.17 – 4.05 (m, 1H), 3.15 (ddd, J = 18.1, 8.7, 4.9 Hz, 1H), 2.73 (ddd, J = 17.8, 5.6, 3.0 Hz, 1H), 2.69 – 2.60 (m, 2H), 2.20 (d, J = 15.7 Hz, 1H), 1.92 – 1.81 (m, 1H), 1.23 (dq, J = 17.1, 6.9 Hz, 2H), 0.89 (t, J = 7.4 Hz, 3H). 13C-NMR (100 MHz, CDCl3): δ (ppm) = 207.6, 138.0, 120.0, 66.5, 51.2, 45.8, 37.7, 35.3, 27.8, 15.3, 12.2. IR (ATR): 𝜈max (cm−1) = 2960 (m), 2918 (m), 1778 (s), 1724 (w), 1460 (w), 1381 (w), 1170 (w), 1079 (m), 816 (w), 777 (w). HRMS (EI): calc. for C11H15O [M-H]+: 163.1117, found: 163.1118.

Vinyl triflate S2: KHMDS (0.5 M in toluene, 10.8 mL, 5.42 mmol) was added to a solution of ketone 14 in THF (36 mL) at –78 °C and stirred for 30 min at 0 °C before a solution of Comins’ reagent (2.13 g, 5.42 mmol) in THF (32 mL) was added slowly at – 78 °C. The solution was stirred for 2 h at 0 °C, quenched with saturated aqueous NaHCO3 and extracted with Et2O. The combined organic phases were washed with brine, dried over MgSO4 and concentrated. Purification by flash column chromatography (hexanes:NEt3 999:1) on silica gave vinyl triflate S2 (1.21 g, 4.07 mmol, 91%, 10:1 mixture of diastereomers at the double bond) as a colorless liquid.

Data for S2: Rf: 0.4 (hexanes); 1H-NMR (400 MHz, CDCl3): δ (ppm) = 5.47 (d, J = 10.3 Hz, 2H), 4.02 – 3.97 (m, 1H), 2.81 (d, J = 3.2 Hz, 1H), 2.64 (ddd, J = 16.7, 5.5, 2.4 Hz, 1H), 2.04 (d, J = 15.1 Hz, 1H), 1.71 – 1.64 (m, 4H), 1.13 (pd, J = 7.2, 2.2 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). 13C-NMR (100 MHz, CDCl3): δ (ppm) = 139.4, 135.1, 121.7, 119.0, 51.2, 45.9, 38.3, 35.3, 26.3, 14.7, 12.0. IR (ATR): 𝜈max (cm−1) = 2962 (w), 2924 (w), 2860 (w), 1623 (m), 1424 (s), 1382 (w), 1277 (w), 1248 (m), 1205 (s), 1180 (m), 1138 (s), 1098 (w), 1076 (w), 1062 (w), 985 (w), 928 (s), 910 (m), 860 (s), 806 (m), 769 (w), 717 (m), 670 (w). HRMS (EI): calc. for C12H15F3O332S [M]+: 296.0694, found:

296.0701.

Methyl ester 9: Pd(OAc)2 (36.6 mg, 0.163 mmol), PPh3 (85.4 mg, 0.326 mmol) and NEt3

(1.13 mL, 8.14 mmol) were sequentially added to a stirred solution of vinyl triflate S2 (1.21 g, 4.07 mmol) in DMF (70 mL) and MeOH (70 mL). The solution was purged with CO gas and stirred for 1 h at 50 °C under 1 atm CO pressure. The reaction mixture was cooled to room temperature and extracted with Et2O. The combined organic phases were washed with brine, dried over MgSO4 and concentrated. Purification by flash column chromatography (hexanes:Et2O:NEt3 969:30:1) gave methyl ester 9 (742 mg, 3.60 mmol, 88%) as a colorless liquid.