實驗部分 - 多取代螺環己烷化合物之有機催化[4+2]連鎖環化反應

3-1 分析儀器及基本實驗操作

核磁共振儀（NMR）：以 Bruker Avance 型（400/500 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

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。

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。

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。

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.）

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）。

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。

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。

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

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。

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。

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

General procedure for the synthesis of dispirocyclohexanes: To a stirred solution of

,-

L-diphenylprolinol trimethylsilyl ether catalyst 32 (0.02 mmol), and DIPEA (0.02 mmol) in ether (0.5 mL) was added Glutaraldehyde 61 (0.25 mmol) slowly at - 0 ^oC. The mixture was stirred for 5 min followed by addition of 2-arylideneindane -1,3-dione 92 a-n (0.1 mmol). Stirring was continued until the starting material was no longer consumed by inspection of TLC. The reaction mixture was determined d.r.

ratio by NMR then 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 SiO₂ flash column chromatography (hexanes/ethyl aeetate = 4:1~3:1) to give the corresponding spirocyclohexanes 96 a-n.

42 NMR (100 MHz, CDCl₃): δ 202.83, 202.71, 202.40, 143.51, 142.77, 136.03, 135.38, 135.14, 128.69, 128.50, 127.63, 122.49, 122.39, 73.91, 63.04, 48.13, 47.84, 29.24, 24.45 ppm; FTIR (ν/cm^-1): 3412, 3061, 2946, 2870, 2137, 1737, 1695, 1596, 1493, 1455, 1348, 1257, 1180, 1097, 1055; HRMS (FAB) m/z calcd. for C₂₁H₁₈O₄ [M]⁺ 334.1205, found 334.1202; HPLC conditions: AS-H column, n-hexane/2-propanol = 90/10, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t_R (minor) = 67.5 min, t_R (major) = 75.6 min.

43 63.03, 48.18, 47.01, 29.14, 24.41, 20.69 ppm; FTIR (ν/cm^-1): 3412, 2946, 2854, 2717, 1760, 1737, 1691, 1641, 1508, 1260, 1215; HRMS (FAB) m/z calcd. for C₂₃H₂₀O₆ [M-H]^- 391.1182, found 391.1175; HPLC conditions: AS-H column,

n-hexane/2-propanol = 92/8, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t

_R (minor) = 208.6 min, t_R (major) = 229.7 min.

44 62.94, 55.02, 48.07, 29.10, 24.38 ppm; FTIR (ν/cm^-1): 3450, 3068, 2938, 2877, 2839, 2725, 1740, 1702, 1600, 1489, 1451, 1337, 1257, 1161, 1047; HRMS (FAB) m/z calcd. for C₂₂H₂₀O₅ [M]⁺364.1311, found 364.1313; HPLC conditions: AS-H column,

n-hexane/2-propanol = 90/10, flow rate = 0.8 mL/min, λ = 220 nm, retention time: t

_R (minor) = 99.9 min, t_R (major) = 144.4 min.

45 29.23, 24.44, 20.79 ppm; FTIR (ν/cm^-1): 3412, 2954, 2847, 1740, 1706, 1592, 1504, 1264; HRMS (FAB) m/z calcd. for C₂₂H₂₀O₄ [M-H]^- 347.1283, found 347.1282;

HPLC conditions: AS-H column, n-hexane/2-propanol = 90/10, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t_R (minor) = 62.1 min, t_R (major) = 77.6 min.

46 130.22, 122.49, 122.37, 121.51, 73.83, 62.77, 48.16, 46.61, 28.97, 24.29 ppm; FTIR (ν/cm^-1): 3473, 2946, 2877, 1733, 1699, 1596, 1489, 1352, 1260; HRMS (FAB) m/z calcd. for C₂₁H₁₇BrO₄ [M-H]^- 411.0232, found 411.0226; Crystal data for compound 4e at 200 (2) K: C₂₁H₁₇BrO₄, M 413.26, Monoclinic, P 21 21 21, a = 10.5579(5) Å , b

= 14.7272(6) Å , c = 23.0504(11) Å , Z = 8, D_x

= 1.532 Mg/m

³, µ = 2.317 mm^-1, 24579 reflections for all data. HPLC conditions: AS-H column, n-hexane/2-propanol = 90/10, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t_R (minor) = 67.1 min, t_R (major) = 73.2 min.

47 351.1028; HPLC conditions: AS-H column, n-hexane/2-propanol = 92/8, flow rate = 0.5 mL/min, λ = 220 nm, retention time: t_R (minor) = 96.7 min, t_R (major) = 103.6 min

48 133.42, 129.97, 128.66, 122.59, 122.46, 73.96, 62.83, 48.26, 46.71, 29.97, 24.29 ppm;

FTIR (ν/cm^-1): 3396, 3053, 2931, 2870, 2740, 1737, 1706, 1596, 1493, 1459, 1413, 1356, 1260; HRMS (FAB) m/z calcd. for C₂₁H₁₇ClO₄ [M-H]^-367.0737, found 367.0728; HPLC conditions: AD-H column, n-hexane/2-propanol = 96/4, flow rate = 0.45 mL/min, λ = 220 nm, retention time: t_R (minor) = 270.4 min, t_R (major) = 289.1 min.

49 74.02, 62.50, 48.36, 46.62, 29.16, 24.32 ppm; FTIR (ν/cm^-1): 3450, 3114, 3076, 2946, 2862, 1732, 1737, 1699, 1600, 1520, 1451, 1348, 1260, 1100, 1055; HRMS (FAB)

m/z calcd. for C

₂₁H₁₇NO₆ [M-H]^- 378.0978, found 378.0986; HPLC conditions: OD-H column, n-hexane/2-propanol = 92/8, flow rate = 0.8 mL/min, λ = 220 nm, retention time: t_R (major) = 96.8 min, t_R (minor) = 158.4 min.

50 123.31, 123.28, 123.15, 122.63, 122.55, 73.94, 62.58, 48.32, 46.52, 29.14, 24.33 ppm;

FTIR (ν/cm^-1): 3427, 2938, 2862, 2732, 2099, 1737, 1695, 1634, 1600, 1527, 1352, 1260, 1074; HRMS (FAB) m/z calcd. for C₂₁H₁₇NO₆ [M-H]^- 378.0978, found 378.0972; HPLC conditions: OD-H column, n-hexane/2-propanol = 95/5, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t_R (maior) = 160.9 min, t_R (minor) = 264.6 min.

51 124.99, 122.61, 122.48, 122.28, 74.00, 62.69, 48.23, 47.04, 29.19, 24.39 ppm; FTIR (ν/cm^-1): 3450, 3076, 2938, 2870, 2725, 1740, 1706, 1622, 1596, 1447, 1420, 1325, 1264, 1169, 1123, 1070; HRMS (FAB) m/z calcd. for C₂₂H₁₇F₃O₄ [M]⁺ 402.1082, found 402.1079; HPLC conditions: OD-H column, n-hexane/2-propanol = 95/5, flow rate = 0.7 mL/min, λ = 220 nm, retention time: t_R (major) = 81.2 min, t_R (minor) = 257.2 min.

53 129.30, 128.72, 122.55, 122.45, 73.95, 62.68, 51.99, 48.18, 47.27, 29.13, 24.37 ppm;

FTIR (ν/cm^-1): 3458, 3106, 2946, 2870, 2717, 2366, 1737, 1702, 1592, 1447, 1344, 1260; HRMS (FAB) m/z calcd. for C₂₃H₂₀O₆ [M]⁺ 392.4092, found 392.1260; HPLC conditions: OD-H column, n-hexane/2-propanol = 92/8, flow rate = 0.5 mL/min, λ = 220 nm, retention time: t_R (major) = 92.1 min, t_R (minor) = 111.8 min.

54 73.73, 63.10, 49.57, 42.74, 28.74, 24.44 ppm; FTIR (ν/cm^-1): 3442, 2938, 2877, 2358, 1737, 1702, 1584, 1340, 1257; HRMS (FAB) m/z calcd. for C₁₉H₁₆O₄S [M-H] -339.0691, found 339.0688; HPLC conditions: AD-H column, n-hexane/2-propanol = 90/10, flow rate = 0.5 mL/min, λ = 220 nm, retention time: t_R (minor) = 191.9 min, t_R (major) = 223.1 min.

55 127.23, 126.07, 123.34, 122.41, 122.35, 73.51, 62.78, 48.73, 42.89, 28.98, 24.28 ppm;

FTIR (ν/cm^-1): 3458, 3106, 2946, 2870, 2717, 2366, 1737, 1702, 1592, 1447, 1344, 1260; HRMS (FAB) m/z calcd. for C₁₉H₁₆O₄S [M]⁺ 340.0769, found 340.0763; HPLC conditions: IA column, n-hexane/2-propanol = 90/10, flow rate = 1 mL/min, λ = 220 nm, retention time: t_R (minor) = 31.0 min, t_R (major) = 34.9 min.

在文檔中多取代螺環己烷化合物之有機催化[4+2]連鎖環化反應 (頁 48-65)