實驗部分 - 多取代環己烷化合物之有機催化連鎖環化反應

3-1 分析儀器及基本實驗操作

1. 核磁共振儀（NMR）：以 Bruker Avance 型（500 MHz）核磁共振光譜儀作為測定儀器，樣品之溶劑為氘化氯仿（CDCl₃）。化學位移（δ, chemical shift）

以 ppm 為單位，¹H-NMR 光譜化學位移以四甲基矽烷（tetramethylsilane，簡稱 TMS）為內標準，定義其化學位移為 0 ppm。分裂形式（splitting pattern）

之定義如下：s，單重峰（singlet）；d，雙重峰（doublet）；t，三重峰（triplet）；

q，四重峰（quartet）；m，多重峰（multiplet）。偶合常數（coupling constant）

以 J 表示，單位為 Hz。光譜數據之記錄依序是：化學位移（分裂形式，偶合 常數，氫數）。¹³C-NMR 光譜是以同型儀器操作，化學位移以氘化氯仿中間線為內標準，定義其化學位移為 77.0 ppm。

2. 質譜（Mass Spectrometry，簡稱 MS）：使用 Finnigan TSQ-700 型質譜儀為測定儀器。係委託國科會台灣師範大學貴重儀器中心代為測定。高解析質譜

（High Resolution Mass Spectrometry，簡稱 HRMS）：委託中央研究院化學研究所質譜服務中心（EI、ESI 和 FAB）代為測定。

3. X 光單晶繞射：使用 Enraf nonius CAD-4 或 Nonius FR-590 型儀器為測定儀器。係委託國科會台灣師範大學貴重儀器中心代為測定。

4. 分析用之薄層色層分析片（Thin Layer Chromatography，簡稱 TLC）：使用 Silica gel 60 F254 Merck 之玻璃 TLC 薄片，展開後以紫外燈（254 nm）檢視。

5. 管柱色層分析（Column Chromatography）：使用 Merck Silica gel F60，230-400 mesh ATSM 為填充物，用加壓快速層析（flash column chromatography）依 Still 的操作方法來分離。沖堤液（eluent）若是兩種溶劑系統，是以體積比值 而配置，記錄方法為兩種溶液之體積比值。（J. Org. Chem. 1978, 43, 2923.）

6. 所有反應物和溶劑均為試藥級、分析級或高效能液相層析級，純化方式依 Perrin, D. D.; Armarego, W. L. F.及 Perrin, D. R.所著 Purification of Laboratory

Chemicals 的方法處理。乙腈、二氯甲烷、四氫呋喃（THF）、甲苯與乙醚均

經過溶劑純化系統乾燥及純化（active alumina column）。

7. 減壓式迴旋濃縮儀：使用 Büchi Rotavapor R-114 型旋轉濃縮器，連接空氣式或水流式幫浦。

8. 低溫反應控制裝置：使用 NES-LAB Cryobath CB-80 型低溫控制裝置與 UR-8500/5000 超低溫反應器，並以工業級異丙醇（IPA）為冷劑。

9. 旋光儀：使用 Japan JASCO P-1010 型 Digital polarimeter 自動旋光光度計。

10. 高效能液相層析儀（HPLC）：使用 JASCO PU-1580 與 PU-2890 型高壓幫浦以及 JASCO 870-UV 型紫外/可見光檢測器。

11. 紅外線光譜儀（IR Spectroscopy）：使用 Perkin Elmer FTIR 型紅外線光譜儀為測定儀器。

12. 熔點：使用 MEL-TEMP II 型為測定熔點儀器。

3-2 連鎖反應合成多取代環己烷之一般步驟

To a stirred solution of ,-L-diphenylprolinol trimethylsilyl ether catalyst 32 (0.005 mmol) and DABCO (0.02 mmol) in DMF (0.5 mL) was added 2-arylideneindane-1,3-dione 105 (0.1 mmol) at -20 ^oC. The mixture was stirred for 5 mins followed by addition of aldehydes 106 (0.2 mmol) slowly. Stirring was continued until the starting material was no longer consumed by inspection of TLC.

The reaction mixture was worked up with H₂O and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over by MgSO4. After removal of the solvent, a crude residue was purified by flash column chromatography (Hex/EtOAc = 2:1 ~ 3:2) to give the corresponding dispirocyclohexanes 104a-o.

3-3 光譜數據 Compound 104a

96% ee, [α]^25.5D = +2.5 (c = 0.5 in CH₂Cl₂); colorless oil;

R_f = 0.15 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl₃): δ 8.01-7.94 (m, 2H), 7.90-7.81 (m, 1H), 7.76-7.71 (m, 1H), 7.69-7.65 (m, 1H), 7.65-7.59 (m, 2H), 7.58-7.46 (m, 4H), 7.46-7.39 (m, 2H), 7.14-7.06 (m, 1H), 6.97 (d, J = 9.0 Hz, 2H), 4.17 (dd, J = 10.5, 3.6 Hz, 1H), 4.14 (s, 1H), 3.96 (ddq, J = 12.5, 10.5, 6.5 Hz, 1H), 3.35 (d, J = 12.5 Hz, 1H), 1.99 (d, J = 3.6 Hz, 1H), 0.90 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl₃): δ 201.7, 201.4, 199.5, 199.1, 147.1, 147.0, 144.1, 144.1, 142.9, 141.5, 140.7, 140.4, 136.5, 136.3, 135.7, 135.4, 132.1, 129.7, 123.4, 123.2, 123.0, 122.9, 122.7, 122.6, 78.1, 62.9, 62.7, 53.3, 52.8, 33.4, 15.2 ppm; FTIR (ν/cm^-1): 3520, 2952, 2923, 2856, 1738, 1712, 1594, 1521, 1462, 1347, 1248, 1104, 1075, 1053, 1016; HRMS (FAB) m/z calcd. for C₃₅H₂₅N₂O₉ [M+H]⁺ 617.1560, found 617.1563;

HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 29.0 min, t_R (major) = 103.4 min.

Compound 104b

95% ee, [α]^25.5D = +2.2 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.15 (3:2 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.93 (d, J = 7.5 Hz, 1H), 7.78-7.72 (m, 1H), 7.69-7.65 (m, 1H), 7.64-7.60 (m, 2H), 7.60-7.57 (m, 1H), 7.57-7.53 (m, 1H), 7.46-7.40 (m, 1H), 7.40-7.36 (m, 1H), 7.36-7.33 (m, 2H), 7.33-7.27 (m, 2H), 7.04-6.93 (m, 1H), 6.84 (d, J = 8.5 Hz, 2H), 4.16 (d, J

= 10.5 Hz, 1H), 4.06 (s, 1H), 3.95 (ddq, J = 12.5, 10.5, 6.5 Hz, 1H), 3.79 (s, 3H), 3.67 (s, 3H), 3.28 (d, J = 12.5 Hz, 1H), 0.89 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.1, 201.9, 200.0, 199.6, 166.6, 166.1, 144.3, 143.1, 142.1, 141.6, 140.7, 138,6, 135.9, 135.8, 135.0, 134.9, 129.9, 129.4, 129.3, 129.3, 129.2, 129.0, 122.9, 122.7, 122.5, 122.4, 78.2, 63.3, 62.9, 53.6, 53.3, 52.0, 51.9, 33.5, 15.2 ppm; FTIR (ν/cm^-1): 3432, 3048, 2959, 2923, 2849, 1738, 1712, 1609, 1594, 1428, 1262, 1112, 1019; HRMS (ESI) m/z calcd. for C39H30O9Na [M+Na]⁺ 665.1788, found 665.1789;

HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 15.8 min, tR (major) = 26.3 min.

Compound 104c

92% ee, [α]^25.5D = +6.2 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.24 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.93 (d, J = 7.5 Hz, 1H), 7.72-7.67 (m, 1H), 7.66-7.63 (m, 1H), 7.62-7.57 (m, 2H), 7.49-7.45 (m, 1H), 7.45-7.40 (m, 1H), 7.40-7.38 (m, 2H), 7.37-7.29 (m, 1H), 7.26-7.18 (m, 1H), 7.10-6.97 (m, 1H), 6.96-6.85 (m, 4H), 4.16 (d, J = 10.5 Hz, 1H), 4.07 (s, 1H), 3.94 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.28 (d, J = 12.0 Hz, 1H), 1.95 (br s, 1H, OH), 0.90 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.0, 201.8, 200.0, 199.5, 144.2, 143.1, 141.6, 140.8, 140.7, 137.6, 136.7, 136.0, 135.9, 135.2, 135.0, 130.5, 129.8 (q, J = 32.5 Hz), 129.4 (q, J = 32.4 Hz), 125.0, 124.9, 123.5 (q, J = 206.9 Hz), 123.0 (q, J = 209.1 Hz), 122.8, 122.8, 122.5, 122.5, 78.1, 63.3, 63.0, 53.5, 53.0, 33.5, 15.2 ppm; FTIR (ν/cm^-1): 3469, 2959, 2923, 2849, 1742, 1709, 1617, 1594, 1325, 1259, 1167, 1123, 1067, 1016; HRMS (ESI) m/z calcd. for C37H24F6O5Na [M+Na]⁺ 685.1426, found 685.1430; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.0 mL/min, λ = 254 nm, retention time: tR (minor) = 11.9 min, tR (major) = 75.2 min.

Compound 104d

93% ee, [α]^25.5D = +4.0 (c = 0.5 in CH2Cl2); pale yellow oil;

Rf = 0.17 (3:2 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3):

δ 7.94 (d, J = 7.5 Hz, 1H), 7.76-7.70 (m, 1H), 7.68-7.65 (m, 1H), 7.65-7.60 (m, 2H), 7.56-7.51 (m, 1H), 7.49-7.44 (m, 1H), 7.44-7.36 (m, 3H), 7.35-7.27 (m, 1H), 7.09-6.92 (m, 3H), 6.88 (d, J = 8.5 Hz, 2H), 4.14 (d, J = 10.5 Hz, 1H), 4.05 (s, 1H), 3.92 (ddq, J = 12.5, 10.5, 6.5 Hz, 1H), 3.27 (d, J = 12.5 Hz, 1H), 2.00 (br s, 1H, OH), 0.89 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 201.8, 201.5, 199.6, 199.2, 144.1, 142.9, 142.1, 141.5, 140.5, 138.7, 136.3, 136.2, 135.6, 135.3, 131.9, 131.8, 130.6, 129.6, 122.9, 122.8, 122.6, 122.5, 118.2, 117.6, 111.9, 111.4, 78.0, 63.0, 62.7, 53.6, 53.1, 33.2, 15.2 ppm; FTIR (ν/cm^-1): 3432, 2967, 2923, 2856, 2229, 1738, 1709, 1661, 1591, 1259, 1093, 1056, 1019; HRMS (ESI) m/z calcd. for C37H24N2O5Na [M+Na]⁺ 599.1583, found 599.1589; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 20.9 min, tR (major) = 109.8 min.

Compound 104e

91% ee, [α]^25.5D = +4.0 (c = 0.5 in CH2Cl2); pale yellow oil;

Rf = 0.20 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3):

δ 7.92 (d, J = 7.5 Hz, 1H), 7.72-7.67 (m, 1H), 7.67-7.64 (m, 1H), 7.63-7.58 (m, 2H), 7.52-7.48 (m, 1H), 7.45-7.40 (m, 2H), 7.26-7.04 (m, 3H), 6.86-6.71 (m, 3H), 6.62 (d, J

= 8.5 Hz, 2H), 4.10 (dd, J = 10.5, 5.0 Hz, 1H), 3.94 (s, 1H), 3.85 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.15 (d, J = 12.0 Hz, 1H), 1.87 (d, J = 5.0 Hz, 1H), 0.87 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.3, 202.2, 200.3, 199.7, 144.3, 143.2, 141.7, 140.8, 135.9, 135.8, 135.1, 135.0, 132.8, 132.6, 131.4, 131.2, 130.3, 128.2, 122.8, 122.7, 122.5, 122.4, 121.9, 121.2, 78.2, 63.4, 63.0, 53.0, 52.7, 33.6, 15.2 ppm; FTIR (ν/cm^-1): 3432, 2959, 2915, 2849, 1738, 1712, 1594, 1488, 1351, 1263, 1093, 1012; HRMS (ESI) m/z calcd. for C35H24Cl2O5Na [M+Na]⁺ 617.0898, found 617.0897; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR

(minor) = 12.4 min, tR (major) = 60.6 min.

Compound 104f

90% ee, [α]^25.5D = +3.6 (c = 0.5 in CH2Cl2); colorless crystal; Rf = 0.20 (2:1 Hex/EtOAc); mp (^oC) 219-220; ¹H NMR (500 MHz, CDCl3): δ 7.92 (d, J = 7.5 Hz, 1H), 7.72-7.67 (m, 1H), 7.67-7.64 (m, 1H), 7.63-7.60 (m, 2H), 7.53-7.48 (m, 1H), 7.46-7.39 (m, 2H), 7.25-7.04 (m, 3H), 6.85-6.69 (m, 3H), 6.62 (d, J = 8.5 Hz, 2H), 4.10 (dd, J = 10.5, 7.0 Hz, 1H), 3.94 (s, 1H), 3.85 (ddq, J = 12.5, 10.5, 6.5 Hz, 1H), 3.15 (d, J = 12.5 Hz, 1H), 1.86 (d, J = 7.0 Hz, 1H), 0.87 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.3, 202.2, 200.3, 199.7, 144.3, 143.2, 141.7, 140.8, 135.9, 135.8, 135.1, 135.0, 132.6, 131.2, 130.4, 129.0, 128.2, 125.3, 122.8, 122.7, 122.5, 122.4, 121.9, 121.2, 78.2, 63.4, 63.0, 53.0, 52.7, 33.6, 15.2 ppm; FTIR (ν/cm^-1): 3424, 2959, 2923, 2849, 1738, 1712, 1591, 1488, 1259, 1078, 1008; HRMS (ESI) m/z calcd. for C35H24Br2O5Na [M+Na]⁺ 704.9888, found 704.9891; Crystal data for compound 4f at 200 (2) K: C35H26Br2O6, M 702.38, Monoclinic, P 21/c, a = 13.0262 (15) Å , b = 19.874 (2) Å , c = 27.922 (3) Å , V = 7113.9 (14) Å³, Z = 8, Dx = 1.312 Mg/m³, µ = 2.318 mm^-1, 40287 reflections, 398 parameters, R = 0.3283, Rw = 0.3591 for all data. X-ray CCDC 912729. HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR

(minor) = 13.6 min, tR (major) = 73.5 min.

Compound 104g

85% ee, [α]^25.5D = +1.8 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.16 (3:2 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.97 (d, J = 7.5 Hz, 1H), 7.89-7.74 (m, 2H), 7.72-7.67 (m, 1H), 7.66-7.61 (m, 2H), 7.61-7.57 (m, 2H), 7.56-7.52 (m, 1H), 7.50-7.44 (m, 1H), 7.43-7.37 (m, 2H), 7.39-7.28 (m, 1H), 7.26-7.16 (m, 1H), 7.16-7.11 (m, 1H), 6.95-6.85 (m, 1H), 4.19 (d, J = 10.0 Hz, 1H), 4.13 (s, 1H), 4.06-3.96 (m, 1H), 3.37 (d, J = 12.0 Hz, 1H), 2.05 (br s, 1H, OH), 0.93 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 201.6, 201.6, 199.0, 199.0, 148.2, 147.7, 147.4, 144.1, 143.0, 141.5, 140.5, 138.8, 137.0, 136.2, 135.9, 135.7, 135.5, 135.2, 135.0, 129.2, 125.6, 124.6, 123.6, 123.0, 122.8, 122.8, 122.6, 122.4, 77.9, 63.1, 62.8, 53.1, 52.8, 33.5, 15.3 ppm; FTIR (ν/cm^-1): 3513, 3063, 2967, 2915, 2849, 1738, 1712, 1591, 1528, 1351, 1248, 1082, 1049, 1016; HRMS (ESI) m/z calcd. for C35H24N2O9Na [M+Na]⁺ 639.1380, found 639.1381; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (major) = 15.0 min, tR (minor) = 23.4 min.

Compound 104h

83% ee, [α]^25.5D = +3.4 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.10 (3:2 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.91 (d, J = 7.5 Hz, 1H), 7.69-7.63 (m, 2H), 7.62-7.55 (m, 2H), 7.47-7.43 (m, 1H), 7.42-7.36 (m, 2H), 7.32-7.27 (m, 1H), 6.97-6.85 (m, 1H), 6.85-6.78 (m, 1H), 6.75 (d, J = 9.0 Hz, 2H), 6.72-6.64 (m, 1H), 6.45-6.29 (m, 2H), 4.14 (d, J = 10.5 Hz, 1H), 4.00 (s, 1H), 3.88 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.21 (d, J = 12.0 Hz, 1H), 2.16 (s, 3H), 2.02 (s, 3H), 1.89 (br s, 1H, OH), 0.91 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.4, 202.4, 200.6, 199.9, 168.9, 168.4, 149.8, 149.6, 144.4, 143.3, 141.7, 141.0, 135.7, 135.6, 134.8, 134.8, 134.3, 132.1, 131.1, 129.5, 129.0, 122.7, 122.7, 122.4, 122.4, 121.1, 78.2, 63.8, 63.4, 53.2, 52.8, 33.8, 21.0, 20.9, 15.3 ppm; FTIR (ν/cm^-1): 3424, 3055, 2959, 2922, 2849, 1742, 1712, 1594, 1502, 1421, 1366, 1263, 1200, 1170, 1016; HRMS (ESI) m/z calcd. for C39H30O9Na [M+Na]⁺ 665.1788, found 665.1790;

HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 17.5 min, tR (major) = 40.8 min.

Compound 104i

76% ee, [α]^25.5D = +3.2 (c = 0.5 in CH2Cl2); pale yellow oil;

Rf = 0.17 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3):

δ 7.91 (d, J = 8.0 Hz, 1H), 7.66-7.61 (m, 2H), 7.60-7.57 (m, 1H), 7.55-7.50 (m, 1H), 7.43-7.39 (m, 1H), 7.39-7.36 (m, 1H), 7.35-7.31 (m, 1H), 7.21-7.09 (m, 1H), 6.91-6.69 (m, 3H), 6.60 (d, J = 8.5 Hz, 2H), 6.46-6.34 (m, 2H), 4.13 (d, J = 10.5 Hz, 1H), 3.96 (s, 1H), 3.88 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.16 (d, J = 12.0 Hz, 1H), 2.07 (s, 3H), 1.86 (br s, 1H, OH), 1.81 (s, 3H), 0.89 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.8, 202.8, 200.9, 200.2, 144.6, 143.6, 141.8, 141.2, 137.0, 136.4, 135.4, 135.0, 134.4, 134.3, 133.8, 131.2, 130.5, 129.8, 128.6, 128.4, 122.7, 122.5, 122.3, 122.2, 78.4, 64.0, 63.6, 53.4, 53.2, 33.8, 20.8, 20.6, 15.2 ppm; FTIR (ν/cm^-1): 3454, 3048, 2952, 2915, 2856, 1738, 1712, 1594, 1517, 1262; HRMS (ESI) m/z calcd. for C37H30O5Na [M+Na]⁺ 577.1991, found 577.1987; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 0.8 mL/min, λ = 254 nm, retention time: tR (minor) = 16.4 min, tR

(major) = 32.7 min.

Compound 104j

75% ee, [α]^25.5D = +3.2 (c = 0.44 in CH2Cl2); colorless oil; Rf

= 0.20 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.92 (d, J = 8.0 Hz, 1H), 7.67-7.57 (m, 3H), 7.55-7.51 (m, 1H), 7.44-7.27 (m, 4H), 7.11-7.02 (m, 1H), 6.97-6.86 (m, 3H), 6.78-6.72 (m, 2H), 6.67-6.59 (m, 3H), 4.17 (d, J = 10.5 Hz, 1H), 3.99 (s, 1H), 3.93 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.21 (d, J = 12.0 Hz, 1H), 1.84 (br s, 1H, OH), 0.91 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.6, 202.5, 200.7, 200.0, 144.6, 143.5, 141.8, 141.1, 136.9, 135.5, 135.2, 134.5, 134.5, 133.6, 131.3, 130.1, 128.6, 128.0, 127.5, 127.0, 122.7, 122.5, 122.3, 122.2, 78.3, 63.9, 63.5, 53.9, 53.6, 33.7, 15.3 ppm; FTIR (ν/cm^-1): 3446, 3055, 2959, 2923, 2856, 1738, 1712, 1594, 1454, 1262, 1093, 1019;

HRMS (ESI) m/z calcd. for C35H26O5Na [M+Na]⁺ 549.1678, found 549.1678; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 10.8 min, tR (major) = 15.2 min.

Compound 104k

80% ee, [α]^25.5D = +5.9 (c = 0.5 in CH2Cl2); colorless crystal;

Rf = 0.12 (2:1 Hex/EtOAc); mp (^oC) 181-182; ¹H NMR (500 MHz, CDCl3): δ 7.93 (d, J = 8.0 Hz, 1H), 7.72 (dd, J = 7.5, 2.0 Hz, 2H), 7.70-7.67 (m, 1H), 7.62-7.58 (m, 1H), 7.55-7.51 (m, 2H), 7.46-7.42 (m, 1H), 6.86 (d, J = 5.0 Hz, 1H), 6.74 (d, J = 3.5 Hz, 1H), 6.63 (dd, J = 5.0, 3.5 Hz, 1H), 6.52 (d, J = 5.0 Hz, 1H), 6.41 (d, J = 3.0 Hz, 1H), 6.22 (dd, J = 5.0, 3.0 Hz, 1H), 4.31 (s, 1H), 4.07 (dd, J = 10.5, 7.5 Hz, 1H), 3.78 (ddq, J = 12.0, 10.5, 6.5 Hz, 1H), 3.47 (d, J = 12.0 Hz, 1H), 1.87 (d, J = 7.5 Hz, 1H), 0.96 (d, J = 6.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.5, 202.4, 200.2, 199.2, 144.7, 143.9, 141.7, 141.1, 139.1, 135.6, 135.4, 134.8, 134.6, 134.5, 129.2, 127.8, 126.3, 126.1, 125.3, 124.4, 122.9, 122.7, 122.5, 122.5, 78.0, 64.0, 63.4, 47.4, 35.5, 29.7, 15.1 ppm; FTIR (ν/cm^-1): 3469, 3048, 2959, 2923, 2849, 1738, 1712, 1594, 1454, 1418, 1263, 1100, 1019; HRMS (ESI) m/z calcd. for C31H22O5S2Na [M+Na]⁺ 561.0806, found 561.0798; Crystal data for compound 4k at 296(2) K: C31H22O5S2, M 538.61, Monoclinic, P 21, a = 11.5063 (9) Å , b = 12.1155 (11) Å , c = 18.3088 (14) Å , V = 2537.9 (4) Å³, Z = 4, Dx = 1.410 Mg/m³, µ = 0.252 mm^-1, 16985 reflections, 662 parameters, R = 0.1808, Rw = 0.2725 for all data. X-ray CCDC 912734. HPLC conditions: IA column, n-hexane/2-propanol

= 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 11.3 min, tR

(major) = 16.5 min.

Compound 104l

90% ee, [α]^25.5D = +1.9 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.16 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 8.00-7.94 (m, 2H), 7.90-7.80 (m, 1H), 7.76-7.70 (m, 1H), 7.69-7.65 (m, 1H), 7.65-7.59 (m, 2H), 7.58-7.48 (m, 4H), 7.46-7.38 (m, 2H), 7.19-7.07 (m, 1H), 6.96 (d, J = 9.0 Hz, 2H), 4.44 (dd, J = 10.7, 7.4 Hz, 1H), 4.11 (s, 1H), 4.09-4.01 (m, 1H), 3.56 (d, J = 12.5 Hz, 1H), 1.90 (d, J = 7.4 Hz, 1H), 1.77 (dqd, J = 15.0, 7.5, 3.8 Hz, 1H), 1.30 (dqd, J = 15.0, 7.5, 3.8 Hz, 1H), 0.73 (t, J = 7.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 201.9, 201.6, 199.7, 199.3, 147.1, 147.0, 144.0, 143.7, 142.8, 141.5, 140.7, 140.4, 136.5, 136.3, 135.7, 135.4, 131.9, 130.1, 123.3, 123.2, 123.0, 122.9, 122.7, 122.6, 74.2, 63.0, 62.6, 52.6, 49.8, 36.3, 18.7, 6.5 ppm; FTIR (ν/cm^-1): 3424, 2967, 2923, 2849, 1738, 1712, 1631, 1594, 1521, 1347, 1255; HRMS (FAB) m/z calcd. for C36H27N2O9

[M+H]⁺ 631.1717, found 631.1724; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR

(minor) = 29.6 min, tR (major) = 148.3 min.

Compound 104m

82% ee, [α]^25.5D = +1.6 (c = 0.5 in CH2Cl2); colorless oil;

Rf = 0.11 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.94 (d, J = 7.5 Hz, 1H), 7.76-7.71 (m, 1H), 7.68-7.59 (m, 3H), 7.56-7.51 (m, 1H), 7.49-7.37 (m, 4H), 7.34-7.27 (m, 1H), 7.10-7.01 (m, 1H), 7.01-6.92 (m, 2H), 6.88 (d, J = 9.0 Hz, 2H), 4.42 (dd, J = 10.7, 7.5 Hz, 1H), 4.05-3.97 (m, 1H), 4.02 (s, 1H), 3.48 (d, J = 12.0 Hz, 1H), 1.95 (d, J = 7.5 Hz, 1H), 1.76 (dqd, J = 15.0, 7.5, 3.5 Hz, 1H), 1.29 (dqd, J = 15.0, 7.5, 3.5 Hz, 1H), 0.72 (t, J = 7.5 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 202.0, 201.7, 199.8, 199.3, 144.1, 142.8, 141.6, 141.5, 140.4, 138.7, 136.3, 136.2, 135.6, 135.3, 131.8, 131.8, 130.6, 129.9, 122.9, 122.8, 122.6, 122.5, 118.3, 117.7, 111.9, 111.3, 74.1, 63.0, 62.6, 52.9, 50.0, 36.1, 18.7, 6.5 ppm; FTIR (ν/cm^-1): 3461, 3055, 2959, 2915, 2849, 2229, 1738, 1709, 1594, 1502, 1351, 1259, 1056; HRMS (FAB) m/z calcd. for C38H27N2O5 [M+H]⁺ 591.1920, found 591.1927; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 20.8 min, tR (major) = 147.0 min.

Compound 104n

83% ee, [α]^25.5D = +3.7 (c = 0.35 in CH2Cl2); pale yellow oil; Rf = 0.20 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 8.00-7.93 (m, 2H), 7.87-7.81 (m, 1H), 7.76-7.70 (m, 1H), 7.67-7.59 (m, 3H), 7.58-7.47 (m, 4H), 7.46-7.36 (m, 2H), 7.11-7.05 (m, 1H), 6.97-6.92 (m, 2H), 4.55 (dd, J = 10.6, 8.0 Hz, 1H), 4.07 (s, 1H), 3.95-3.86 (m, 1H), 3.52 (d, J = 12.0 Hz, 1H), 1.80 (d, J = 8.0 Hz, 1H), 1.72-1.65 (m, 1H), 1.14 (d, J = 7.0 Hz, 3H), 0.88 (d, J = 7.0 Hz, 3H); ¹³C NMR (125 MHz, CDCl3): δ 201.9, 201.6, 199.8, 199.4, 147.0, 147.0, 144.7, 144.1, 142.8, 141.5, 140.6, 140.3, 136.5, 136.3, 135.7, 135.3, 131.9, 129.7, 123.3, 123.2, 123.0, 122.8, 122.6, 122.6, 75.4, 63.6, 62.7, 52.6, 51.0, 41.5, 27.8, 23.7, 15.1 ppm; FTIR (ν/cm^-1): 3424, 3055, 2915, 2841, 1690, 1639, 1517, 1347, 1262, 1203; HRMS (FAB) m/z calcd. for C37H29N2O9 [M+H]⁺ 645.1873, found 645.1874; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 27.5 min, tR (major) = 165.2 min.

Compound 104o

99% ee, [α]^25.5D = +3.1 (c = 0.5 in CH2Cl2); pale white oil;

Rf = 0.16 (2:1 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 8.03-7.98 (m, 1H), 7.77-7.67 (m, 4H), 7.66-7.62 (m, 2H), 7.62-7.55 (m, 2H), 7.54-7.50 (m, 1H), 7.47-7.43 (m, 2H), 7.39-7.29 (m, 2H), 7.24-7.15 (m, 3H), 7.13-7.03 (m, 4H), 5.19 (dd, J = 12.5, 10.4 Hz, 1H), 4.53 (dd, J = 10.4, 2.6 Hz, 1H), 4.36 (s, 1H), 4.08 (d, J = 12.5 Hz, 1H); ¹³C NMR (125 MHz, CDCl3): δ 201.3, 201.2, 199.1, 198.5, 147.1, 146.6, 143.8, 143.4, 142.9, 141.3, 140.7, 140.3, 136.6, 136.6, 136.3, 135.8, 135.4, 131.3, 131.1, 129.5, 129.1, 127.9, 123.3, 123.0, 122.9, 122.9, 122.8, 122.7, 77.6, 63.0, 62.3, 52.4, 51.1, 45.2 ppm; FTIR (ν/cm^-1): 3432, 2982, 2923, 2849, 1716, 1646, 1517, 1347, 1252, 1089; HRMS (FAB) m/z calcd. for C40H27N2O9 [M+H]⁺ 679.1717, found 679.1710; HPLC conditions: IA column, n-hexane/2-propanol = 50/50, flow rate = 1.2 mL/min, λ = 254 nm, retention time: tR (minor) = 139.9 min, tR (major) = 193.1 min.

3-4 連鎖Michael/ Michael/環化反應之一般步驟及光譜數據

To a stirred solution of quinine catalyst 112 (0.02 mmol) and 2-arylideneindane-1,3-dione 98 (0.1 mmol) in DMF (0.5 mL) at 0 ^oC. The mixture was stirred for 5 mins followed by addition of acrolein 110 (0.11 mmol) slowly.

Stirring was continued until the starting material was no longer consumed by inspection of TLC. After that, the reaction was followed by addition of acetic acid and excess sodium cyanoborohydride slowly at room temperature under reduction of aldehyde. The reaction mixture was worked up with H₂O and extracted with ethyl acetate. The combined organic layers were washed with brine and dried over by MgSO₄. After removal of the solvent, a crude residue was purified by flash column chromatography (Hex/EtOAc = 3:2) to give the dispirocyclohexanes 120.

Compound 120

56% ee, pale white oil; Rf = 0.2 (3:2 Hex/EtOAc); ¹H NMR (500 MHz, CDCl3): δ 7.99-7.94 (m, 1H), 7.94-7.88 (m, 2H), 7.80-7.74 (m, 1H), 7.70-7.63 (m, 3H), 7.55 (d, J = 8.5 Hz, 2H), 7.53-7.49 (m, 1H), 7.45-7.42 (m, 2H), 7.41-7.27 (m, 2H), 7.00 (d, J = 9.0 Hz, 2H), 4.18 (s, 1H), 3.92-3.83 (m, 1H), 3.64 (d, J = 12.0 Hz, 1H), 3.56 (dd, J = 11.0, 2.0 Hz, 1H), 3.37 (dd, J = 11.0, 6.0 Hz, 1H), 2.36-2.23 (m, 2H); ¹³C NMR (125 MHz, CDCl3): δ 201.5, 201.4, 200.8, 200.2, 147.0, 144.3, 142.9, 142.0, 141.8, 140.5, 139.9, 136.5, 136.3, 135.8, 135.7, 131.0, 131.0, 123.5, 123.5, 123.3, 123.3, 123.2, 122.6, 122.6, 63.8, 62.8, 57.4, 52.5, 49.7, 34.7, 33.1 ppm; FTIR (ν/cm^-1): 3458, 3076, 2923, 2855, 1710, 1592, 1520, 1349, 1250, 1109; HRMS (ESI) m/z calcd. for C35H23N2O9 [M-H]^- 615.1404, found 615.1398; HPLC conditions: OD-H column, n-hexane/2-propanol = 30/70, flow rate = 0.7 mL/min, λ = 254 nm, retention time: tR (minor) = 38.0 min, tR (major) = 54.5 min.

在文檔中多取代環己烷化合物之有機催化連鎖環化反應 (頁 53-73)