分析儀器及基本實驗操作
1. 核磁共振光譜儀 (Nuclear Magnetic Resonance Spectroscopy,
NMR)：以 Bruker JEOL JNM-EX400 spectrometer (400 MHz NMR)
核磁共振光譜儀所測定樣品以氘化氯仿 (CDCl3) 為溶劑，化學位
移 (chemical shift)以 ppm 為單位。氫核磁共振光譜 (1H NMR)其化 學位移以四甲基矽烷 (tetramethylsilane, TMS)為內標準定義其化學 位移為 0 ppm，分裂形式 (splitting pattern)定義如下：單峰 (s, singlet)，雙重峰 (d, doublet)，三重峰 (t, triplet)，四重峰 (q,quartet)，
多重峰 (m, multiplet)；耦合常數 (coupling constant)以 J 表示，單 位為 Hz。光譜數據紀錄依序：化學位移 (分裂形式，耦合常數，氫
數)。碳核磁共振光譜 (13C NMR)是以同型儀器操作，其化學位移
以氘化氯仿 (CDCl3)，為內標準，定義其化學位移為 77.0 ppm。
2. 紅外線光譜儀 (Infrared Spectrometer, IR)：使用 Paragon 500 (Perkin Elmer Paragon)型光譜儀為測定儀器。光譜單位為波數(cm -1)。
3. 高解析質譜 (High-Resolution Mass Spectroscopy, HRMS)：使用 JEOL JMS-700 型 質 譜 儀 做 為 測 定 儀 器 ， 以 電 子 撞 擊 游 離 法 (Electron Impact; Electron Ionization,簡稱 EI)進行分析；使用 Xevo G2-S QTof 型質譜儀做為測定儀器，以飛行式正離子電灑游離法
51
(Time-of-Flight-Electrospray Ionization,簡稱 TOF-ESI) 進行分析，係 委託國立臺灣師範大學貴重儀器使用中心技術專員黃岫妮小姐代
6. 管柱色層分析 (Column Chromatography)：使用 KM3 SCIENTIFIC CORPORATION, Silica gel 45‒75 μm 做為填充物。
7. 旋光儀 (Optical Rotation) ： 使用 JASCO P-2000 Polarimeter 做為 測定儀器，測量前先以溶劑進行背景校正。比旋光度記錄為[α]D𝑇 (T：
溫度/ °C，D：鈉 D 線)。
8. 熔點 (Melting Point, M.P.) ：使用 Mel-Temp 熔點測定儀所測定。
9. 高效能液相層析 (High-Performance Liquid Chromatography,
HPLC) ：使用 Hitachi 7000 系列高效能液相層析系統，包括自動 取樣器(Hitachi L-7200 Autosampler)、幫浦(Hitachi L-7100 Pump)、
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介面控 制器 (Hitachi D-7000 Interface) 、偵測 器(Hitachi L-7450H Diode ArrayDetector) 。使 用 CHIRALPAK 管柱(Daicel Chemical Ind.,Ltd., AD-H 4.6 mm×250 mm, AS-H 4.6 mm×250 mm, IA 4.6 mm×250 mm, IB 4.6 mm×250 mm)或 CHIRALCEL 管柱(Daicel Chemical Ind., Ltd., OD-H 4.6 mm×250 mm 或 OJ-H 4.6 mm×250 mm) 。
53
General Procedures for the Synthesis of Compounds 24
General procedure:
A mixture of substituted salicylaldehydes (32a-g) [22] (1.0 mmol), piperidine (0.2 mmol), and various types of substituted malonate (33a-d) (1.2 mmol)in dry EtOH was reflux for 12 h at 130 °C After the reaction is completed, cool to room temperature. Concentrate the excess solvent in vacuum first, and purified by column chromatography on silica gel eluting with 20％ethyl acetate-hexane,the separated organic layer dried (Na2SO4) and concentrated in vacuo to obtain the corresponding coumarins (24a-f), and identified by m.p., and spectra as described below. [23] [24]
54
ethyl 2-oxo-2H-chromene-3-carboxylate (24a)
Isolated as a white solid: 76% yield. Rf value = 0.32 (hexanes/ ethyl acetate = 4 / 1). M.p.98.1–98.3°C
1H NMR (400 MHz, CDCl3): δ 8.54 (s, 1H), 7.68–7.63 (m, 2H), 7.37–7.28 (m, 2H), 4.42 (q, J = 7.12 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H,).
13C NMR (100 MHz, CDCl3): δ 163.0, 156.7, 155.1, 148.6, 134.2, 129.4, 124.8, 118.2, 124.0, 117.8, 116.7, 61.9, 14.2.
FTIR (KBr, neat): ṽ 3065, 2980, 1774, 1609, 1567, 1452, 1375, 1297, 1245, 1209, 1131, 1034, 796, 774, 630 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C12H10O4Na 241.0477; found 241.0480
isopropyl 2-oxo-2H-chromene-3-carboxylate (24b)
Isolated as a white solid: 76% yield. Rf value = 0.29 (hexanes/ ethyl acetate = 4 / 1). M.p.99.1–99.3°C
1H NMR (400 MHz, CDCl3): δ 8.47 (s, 1H), 7.66–7.61 (m, 2H), 7.36–7.32 (m, 2H), 5.30–5.24 (m, 1H), 1.40 (d, J = 6.1 Hz, 6H).
13C NMR (100 MHz, CDCl3): δ 162.3, 156.7, 155.1, 148.0, 134.1, 129.4, 124.7, 118.7, 117.9, 116.7, 70.0, 21.8.
FTIR (KBr, neat): ṽ 3064, 2976, 1716, 1627, 1571, 1458, 1370, 1219, 1112, 794, 755, 627, 466 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C13H12O4Na 255.0633; found 255.0631
benzyl 2-oxo-2H-chromene-3-carboxylate (24c)
Isolated as a white yellow solid: 61% yield. Rf value = 0.28 (hexanes/ ethyl acetate = 4 / 1). M.p.97.3–98.1°C
1H NMR (400 MHz, CDCl3): δ 8.54 (s, 1H), 7.67–7.58 (m, 2H), 7.50–7.48 (m, 2H), 7.42–7.31 (m, 5H), 5.40(s, 2H).
13C NMR (100 MHz, CDCl3): δ 162.7, 156.6, 155.2, 148.9, 135.4, 134.5, 129.6, 128.6, 128.4, 128.3, 124.9, 117.9, 117.8, 116.7, 67.4.
FTIR (KBr, neat): ṽ 3063, 1761, 1610, 1568, 1455, 1380, 1300, 1241, 1210, 1123, 1008, 796, 762, 698, 590, 458 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C17H12O4Na 303.0633; found 303.0630
55 119.7, 118.0, 116.7, 28.1.
FTIR (KBr, neat): ṽ 3055, 2979, 1754, 1608, 1570, 1456, 1370, 1306, 1251, 1159, 1136, 996, 799, 752, 623, 453 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C14H14O4Na 269.0790; found 269.0786
ethyl 4-methyl-2-oxo-2H-chromene-3-carboxylate (24e)
Isolated as a white solid: 70% yield. Rf value = 0.33 (hexanes/ ethyl acetate = 4 / 1). M.p.113.2–114.2°C
1H NMR (400 MHz, CDCl3): δ 7.70–7.57 (m, 2H), 7.37–
7.33 (m, 2H), 4.44 (q, J = 7.1 Hz, 2H), 2.49 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H,).
13C NMR (100 MHz, CDCl3): δ 164.8, 157.8, 153.0, 150.0, 132.7, 125.3, 124.7, 121.4, 119.1, 117.1, 62.1, 16.0, 14.1.
FTIR (KBr, neat): ṽ 3424, 1736, 1718, 1452, 1302, 1244, 1199, 1136, 1036, 750 cm–1
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C13H12O4Na 255.0633; found 255.0633
ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate (24g)
Isolated as a white solid: 70% yield. Rf value = 0.32 (hexanes/ ethyl acetate = 4 / 1). M.p.113.2–114.2°C
1H NMR (400 MHz, CDCl3): δ 8.48 (s, 1H), 7.45 (dd, J
= 8.4, 1.9 Hz, 1H), 7.39 (s, 1H), 7.26 (d, J = 8.5 Hz, 1H), 4.42 (m, 3J = 7.1 Hz, 2H), 2.43 (s, 1H), 1.41 (t, J = 7.1 Hz, 3H)
13C NMR (100 MHz, CDCl3): δ 163.2, 157.0, 153.4, 148.6, 135.5, 134.6, 129.1, 118.2, 117.6, 116.5, 61.9, 20.7, 14.2.
FTIR (KBr, neat): ṽ 3061, 2974, 1746, 1706, 1622, 1576, 1300, 1255, 1031, 839, 796, 588 cm–1
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C13H13O4 233.0814; found 233.0814
56
ethyl 6-methoxy-2-oxo-2H-chromene-3-carboxylate (24h)
Isolated as a yellow solid: 48% yield. Rf value = 0.33 (hexanes/ ethyl acetate = 4 / 1). M.p.150.2–151.2°C
1H NMR (400 MHz, CDCl3): δ 8.49 (s, 1H), 7.30–
7.27 (m, 1H, J = 9.12), 7.23 (dd, 1H, J = 9.1, 2.9 Hz), 7.01 (d, 1H, J = 2.8 Hz), 3.87 (s, 3H) 4.41 (m, 2H, J = 7.12, Hz), 1.41 (t, 3H, J = 7.12 Hz)
13C NMR (100 MHz, CDCl3): δ 163.1, 157.0, 156.2, 149.7, 148.4, 122.6, 118.5, 118.1, 117.9, 110.6, 61.9, 55.9, 14.2.
FTIR (KBr, neat): ṽ 3047, 2993, 1750, 1698, 1577, 1496, 1380, 1299, 1260, 1157, 1140, 1043, 823, 796, 687, 464 cm–1 125.2, 120.6, 118.1, 117.8, 62.5, 14.2.
FTIR (KBr, neat): ṽ 3056, 1780, 1693, 1618, 1528, 1348, 1304, 1257, 1020, 986, 848, 794, 752, 665 cm–1
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C12H9NO6Na286.0328, found 286.0329
ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate (24j)
Isolated as a white solid: 30% yield. Rf value = 0.33 (hexanes/ ethyl acetate = 4 / 1). M.p.101.5–102.1°C
1H NMR (400 MHz, CDCl3): δ 8.51 (s, 1H), 7.51 (d, J = 8.7 Hz, 1H), 6.90 (dd, J = 2.3, 8.7 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H), 4.40 (m, J = 7.1 Hz, 2H), 3.91 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 165.1, 163.4, 157.6, 157.1, 149.0, 130.7, 114.1, 113.7, 111.6, 100.3, 61.7, 56.0, 14.3.
FTIR (KBr, neat): ṽ 3053, 2988, 1751, 1609, 1506, 1381, 1294, 1214, 1132,
57 (hexanes/ ethyl acetate = 4 / 1). M.p.230.3–231.1°C
1H NMR (400 MHz, CDCl3): δ 9.22 (s, 1H), 8.25 (d, J
= 8.3 Hz, 1H), 8.05 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.73 (t, J = 7.5 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.40 (d, J = 9.0 Hz, 1H), 4.48 (m, J = 7.1 Hz, 2H), 1.47 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 163.4, 156.7, 155.8, 144.3, 136.0, 130.0, 129.2, 129.1, 129.0, 126.5, 121.3, 116.5, 116.2, 112.0, 62.0, 14.2.
FTIR (KBr, neat): ṽ 2917, 2850, 1762, 1569, 1263, 1211, 1121, 1034, 738 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C16H12O4Na 291.0633; found 291.0633
ethyl 6,8-di-tert-butyl-2-oxo-2H-chromene-3-carboxylate (24l)
Isolated as a white solid: 44% yield. Rf value = 0.33 (hexanes/ ethyl acetate = 4 / 1). M.p.101.5–102.1°C
1H NMR (400 MHz, CDCl3): δ 8.51 (s, 1H), 7.68 (d, J = 2.3 Hz, 1H), 7.40 (d, J = 2.3 Hz, 1H), 4.41 (m, J = 7.1 Hz, 2H), 1.51 (s, 9H), 1.41 (t, J = 7.1 Hz, 3H), 1.36 (s, 9H).
13C NMR (100 MHz, CDCl3): δ 163.4, 152.1, 150.0, 147.1, 137.5, 129.7, 123.9, 117.8, 117.0, 61.7, 35.1, 34.7, 31.3, 29.8, 14.2.
FTIR (KBr, neat): ṽ 2965, 1771, 1581, 1374, 1238, 1213, 1029, 798cm–1. HRMS (ESI-TOF) m/z: [M+ H]+ Calcd for C20H27O4 331.1909; found 331.1909
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General Procedures for Rhodium-Catalyzed Asymmetric 1,4-Addition Reactions
Under a N2 atmosphere, toluene (0.5 mL) and 1 M KOH (10 μL, 20 mol%) were added to a mixture of [RhCl(C2H4)2]2 (1.2 mg, 3.0 mol % of Rh), chiral ligand L5a (2.0 mg, 3.6 mol %), stir for 10 minutes, then arylboronic acid (0.4 mmol, 2.0 equiv) and coumarin-3-carboxylic Ester (0.2 mmol, 1.0 equiv) and toluene (0.5 mL). The resulting mixture was heated to 60 °C. After TLC indicated complete consumption of α,β-unsaturated β-ketoesters, the product mixture was concentrated in vacuo, and the residue was purified by column chromatography over silica gel (hexanes / ethyl acetate = 4 / 1) to afford the desired product .
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Spectroscopic Data and HPLC Chromatograms
ethyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25aa)
Isolated as a Pale yellow solid: 90% yield after 4.0 h M.p.101.5–102.1°C
HPLC: 99% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times: 128.0, 125.0, 124.0, 117.0, 62.0, 53.9, 44.2, 13.7.
FTIR (KBr, neat): ṽ 2983, 1774, 1740, 1486, 1456, 1223, 1145, 1031, 759, 700 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C18H17O4 297.1127; found 297.1127
60
HPLC chromatogram
61 129.1, 128.7, 127.8, 125.0, 124.3, 116.9, 62.0, 54.0, 439, 21.0, 13.8.
FTIR (KBr, neat): ṽ 2982, 1774, 1740, 1486, 1455, 1223, 1145, 1022, 760 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O4 311.1283; found 311.1286
62
HPLC chromatogram
63
ethyl (3R,4R)-2-oxo-4-(m-tolyl)chromane-3-carboxylate (25ac)
Isolated as a yellow white solid: 33% yield after 9.0 h M.p.82.7–86.5°C
HPLC: 91% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
10.48 min [(S)-enantiomer], 12.80 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟑 −61.9 (c 1.00, CHCl3). Rf value = 0.6 (hexanes/ ethyl acetate = 4 / 129.0, 128.7, 128.6, 125.0, 124.9, 124.1, 116.9, 62.1, 53.9, 44.2, 21.4, 13.8.
FTIR (KBr, neat): ṽ 2981, 1776, 1740, 1486, 1455, 1222, 1143, 1104, 1021, 760, 703 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for [C19H19O4] +311.1283, found 311.1286
64
HPLC chromatogram
65
ethyl (3R,4R)-2-oxo-4-(o-tolyl)chromane-3-carboxylate (25ad)
Isolated as a white solid: 62% yield after 3.0 h M.p.161.8–
163.4°C
HPLC: 7% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 7.89 min [(S)-enantiomer], 9.07 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟑 129.0, 128.4, 127.9, 126.9, 125.1, 124.3, 116.8, 62.0, 52.8, 40.1, 19.4, 13.8.
FTIR (KBr, neat): ṽ 2982, 1775, 1739, 1486, 1455, 1222, 1143, 1031, 757 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O4 311.1283; found 311.1284
66
HPLC chromatogram
67
ethyl (3R,4R)-4-(naphthalen-2-yl)-2-oxochromane-3-carboxylate (25ae)
Isolated as a light brown solid: 77% yield after 4.0 h M.p.114.7–115.4°C
HPLC: 98% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
13.87 min [(S)-enantiomer], 15.57 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟑 −93.1 (c 1.00, CHCl3). Rf value = 0.57 (hexanes/ 129.2, 129.1, 128.7, 127.8, 127.6, 127.4, 126.5, 126.3, 125.2, 125.0, 123.9, 116.9, 62.0, 53.7, 44.3, 13.7.
FTIR (KBr, neat): ṽ 2981, 1774, 1739, 1486, 1454, 1224, 1142, 1102, 1019, 756, 478 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H19O4 347.1283; found 347.1281
68
HPLC chromatogram
69
ethyl (3R,4R)-4-(naphthalen-1-yl)-2-oxochromane-3-carboxylate (25af) Isolated as a white solid: 70% yield after 7.0 h M.p.114.7–
115.4°C
HPLC: 34% ee. The ee was determined on a Chiralpak AD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 18.72 min [(S)-enantiomer], 10.08 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟑 −71.0 (c 1.00, 129.4, 129.2, 128.8, 127.1, 126.1, 125.5, 125.4, 125.3, 123.0, 122.4, 117.0, 64.4, 62.3, 53.3, 40.8, 25.3, 13.8.
FTIR (KBr, neat): ṽ 2984, 1776, 1737, 1488, 1457, 1259, 1223, 1147, 1110, 1028,780, 756 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H19O4 347.1283; found 347.1281
70
HPLC chromatogram
71
ethyl (3R,4R)-4-([1,1'-biphenyl]-4-yl)-2-oxochromane-3-carboxylate (25ag)
Isolated as a white solid: 89% yield after 4.0 h M.p.135.1–
135.2°C
HPLC: 82% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 14.96 min [(S)-enantiomer], 18.69 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟓
FTIR (KBr, neat): ṽ 2984, 1774, 1740, 1487, 1454, 1333, 1256, 1223, 1145, 1104, 1024, 844, 761, 699 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C24H21O4 373.1440; found 373.1441
72
HPLC chromatogram
73
ethyl (3R,4R)-4-(4-(tert-butyl)phenyl)-2-oxochromane-3-carboxylate (25ah)
Isolated as a Brown oil: 47% yield after 7.0 h.
HPLC: 96% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 8.64 min [(S)-enantiomer], 10.75 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟒
−57.5 (c 1.00, CHCl3). Rf value = 0.59 (hexanes/ ethyl 127.5, 126.0, 125.0, 124.1, 116.9, 62.0, 54.0, 43.9, 34.5, 31.2, 13.7.
FTIR (KBr, neat): ṽ 2964, 1777, 1740, 1588, 1486, 1456, 1257, 1223, 1147, 1102, 1019, 759, 606 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H25O4 353.1753; found 353.1751
74
HPLC chromatogram
75
ethyl (3R,4R)-4-(4-methoxyphenyl)-2-oxochromane-3-carboxylate (25ai)
Isolated as a yellow white solid: 93% yield after 4.0 h M.p.93.6–94.0°C
HPLC: 96% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
14.77 min [(S)-enantiomer], 17.15 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟒 −106.0 (c 1.00, CHCl3). Rf value = 0.58 (hexanes 129.0, 128.6, 125.0, 124.5, 116.9, 114.5, 62.0, 55.3, 54.1, 43.5, 13.8.
FTIR (KBr, neat): ṽ 2981, 1774, 1740, 1612, 1514, 1486, 1455, 1336, 1252, 1223, 1180, 1146, 1104, 1032, 910, 828, 760, 574, 527 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O5 327.1232; found 327.1231
76
HPLC chromatogram
77
ethyl (3R,4R)-4-(3-methoxyphenyl)-2-oxochromane-3-carboxylate (25aj)
Isolated as a white oil: 71% yield after 8.0 h.
HPLC: 98% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
14.80 min [(S)-enantiomer], 16.80 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟒 −89.4 (c 1.00, CHCl3). Rf value = 0.59 (hexanes/ ethyl acetate = 4 / 129.1, 128.7, 125.0, 123.8, 120.0, 116.9, 113.9, 113.0, 62.1, 55.2, 53.8, 44.2, 13.8.
FTIR (KBr, neat): ṽ 2981, 1774, 1740, 1600, 1586, 1487, 1456, 1334, 1260, 1223, 1145, 1104, 1104, 1038, 855, 760, 699, 579 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O5 327.1232; found 327.1235
78
HPLC chromatogram
79
ethyl (3R,4R)-4-(2-methoxyphenyl)-2-oxochromane-3-carboxylate (25ak)
Isolated as a pale yellow solid: 9% yield after 24.0 h.
M.p.93.92–94.5°C
HPLC: 82% ee. The ee was determined on a Chiralpak OJ-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
FTIR (KBr, neat): ṽ 1776, 1739, 1588, 1488, 1457, 1247, 1222, 1148, 1026, 755 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O5 327.1232; found 327.1233.
80
HPLC chromatogram
81
ethyl (3R,4R)-4-(4-chlorophenyl)-2-oxochromane-3-carboxylate (25al) Isolated as a white solid: 89% yield after 4.0 h.
M.p.134.5–135.1°C
HPLC: 94% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 9.95 min [(S)-enantiomer], 11.84 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟓 129.3, 128.5, 125.1, 123.5, 117.0, 62.2, 53.7, 43.6, 13.8.
FTIR (KBr, neat): ṽ 1774, 1740, 1489, 1456, 1223, 1146, 1104, 1015, 760 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C18H16ClO4 331.0737; found 331.0738
82
HPLC chromatogram
83
Ethyl (3R,4R)-2-oxo-4-(4-(trifluoromethyl)phenyl)chromane-3- carboxylate (25am)
Isolated as a white solid: 70% yield after 8.0 h.
M.p.113.4–114.4°C
HPLC: 98% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm. Retention times: 11.52 min [(S)-enantiomer], 13.97 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟒 128.4, 126.2, 126.1, 125.3, 123.0, 117.2, 62.3, 53.6, 44.0, 13.7.
FTIR (KBr, neat): ṽ 2984, 1776, 1741, 1487, 1455, 1423, 1372, 1327, 1258, 1225, 1129, 1069, 1019, 912, 848, 759, 614 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H16F3O4 365.1001; found 365.0999.
84
HPLC chromatogram
85 127.6, 127.5, 125.7, 124.6, 117.1, 40.6, 36.9.
FTIR (KBr, neat): ṽ 3030, 1771, 1486, 1456, 1220, 1176, 1135, 925, 758, 699, 490 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C15H13O2 225.0916; found 225.0918
86
HPLC chromatogram
87
isopropyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate(25ba)
Isolated as a pale yellow solid: 90% yield after 8.0 h.
M.p.95.1–95.9°C
HPLC: 95% ee. The ee was determined on a Chiralpak AD-H column with hexanes / 2-propanol = 90 / 10, 128.0, 124.9, 116.9, 69.9, 54.0, 44.4, 21.3, 21.2.
FTIR (KBr, neat): ṽ 2983, 1774, 1734, 1487, 1456, 1262, 1233, 1147, 1103, 992, 908, 759, 700 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H18O4Na 333.1103; found 333.1100
88
HPLC chromatogram
89
benzyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25ca) Isolated as a white solid: 86% yield after 4.0 h.
M.p.101.3–101.8°C
HPLC: 91% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
18.27 min [(S)-enantiomer], 19.39 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟑 −71.2 (c
FTIR (KBr, neat): ṽ 3032, 1773, 1742, 1486, 1456, 1380, 1338, 1257, 1233, 1140, 1104, 1002, 753, 698, 613 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C23H19O4 359.1283; found 359.1281
90
HPLC chromatogram
91
tert-butyl (3S,4R)-2-oxo-4-phenylchromane-3-carboxylate (25da) Isolated as a white solid: 92% yield after 8.0 h.
M.p.125.0–125.8°C
HPLC: 96% ee. The ee was determined on a Chiralpak AD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
13.81 min [(S)-enantiomer], 11.97 min [(R)-enantiomer]. [𝛂]𝐃𝟐𝟒 −62.9 (c 127.9, 124.9, 124.2, 116.8, 83.2, 54.9, 44.7, 27.5.
FTIR (KBr, neat): ṽ 2978, 1774, 1734, 1486, 1456, 1370, 1278, 1223, 1141, 986, 841, 757, 700 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C20H20O4Na 347.1259; found 347.1264
92
HPLC chromatogram
93
ethyl (3R,4R)-6-methyl-2-oxo-4-phenylchromane-3-carboxylate (25ga) Isolated as a orange brown solid. 99% yield after 4.0 h.
M.p.75.4–75.6°C
HPLC: 98% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times: 129.1, 129.0, 127.9, 123.5, 116.7, 62.1, 54.1, 44.3, 20.7, 13.8.
FTIR (KBr, neat): ṽ 2983, 1774, 1740, 1494, 1455, 1371, 1334, 1259, 1208, 1142, 1031,820, 748, 700, 605, 532 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H19O4 311.1283; found 311.1286
94
HPLC chromatogram
95 Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm.
Retention times: 10.77 min [(S)-enantiomer], 12.64 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟐 −50.4 (c 1.00, CHCl3). Rf value = 0.63 (hexanes/ ethyl acetate = 4 / 128.0, 127.9, 124.9, 117.8, 114.2, 113.7, 62.1, 55.6, 53.9, 44.5, 13.8..
FTIR (KBr, neat): ṽ 2981, 1771, 1739, 1593, 1492, 1334, 1255, 1200, 1167, 1143, 1033, 819, 748, 700, 637 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C19H18O5 327.1232; found 327.1228
96
HPLC chromatogram
97
ethyl (3R,4R)-6-nitro-2-oxo-4-phenylchromane-3-carboxylate (25ia) Isolated as a palle yellow oil: 45% yield after 6.0 h.
HPLC: 73% ee. The ee was determined on a
Chiralpak AD-H column with hexanes / 2-propanol = 90 / 10, flow = 1.0 mL/min, wavelength = 220 nm.
Retention times: 11.79 min [(S)-enantiomer], 10.11 min [ (R)-enantiomer]. [𝛂]𝐃𝟐𝟒 −20.8 (c 1.00, 129.6, 129.5, 128.7, 128.4, 127.7, 127.3, 125.5, 125.0, 124.7, 124.3, 118.1, 118.0, 62.6, 60.4, 53.1, 44.2, 40.6, 36.2, 21.0, 14.2, 13.8.
FTIR (KBr, neat): ṽ 2983, 1786, 1740, 1590, 1528, 1481, 1456, 1345, 1237, 1140, 1120, 1089, 1017, 907, 840, 748, 700, 602 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C18H16NO6 342.0978; found 342.0982
98
HPLC chromatogram
99
ethyl (3R,4R)-7-methoxy-2-oxo-4-phenylchromane-3-carboxylate (25ja) Isolated as a white solid: 82% yield after 6.0 h.
M.p.68.2–70.1°C
HPLC: 84% ee. The ee was determined on a Chiralpak OD-H column with hexanes / 2-propanol = 90 / 10, 129.1, 127.9, 127.8, 115.7, 111.2, 102.3, 62.1, 55.5, 54.2, 43.8, 13.8.
FTIR (KBr, neat): ṽ 2979, 1774, 1740, 1625, 1586, 1507, 1456, 1334, 1261, 1194, 1146, 1116, 1032, 844, 748, 700 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ Calcd for C19H18O5Na 349.1052; found 349.1053
100
HPLC chromatogram
101
ethyl (3R,4R)-2-oxo-4-phenyl-3,4-dihydro-2H-benzo[g]chromene-3- carboxylate (25ka)
Isolated as a white solid: 78% yield after 4.5 h.
M.p.116.3–116.8°C
HPLC: 85% ee. The ee was determined on a Chiralpak AD-H column with hexanes / 2-propanol = 90 / 10, flow
= 1.0 mL/min, wavelength = 220 nm. Retention times:
13.71 min [(S)-enantiomer], 14.80 min [(R)-enantiomer].
[𝛂]𝐃𝟐𝟒 −201.1 (c 1.00, CHCl3). Rf value = 0.57 (hexanes/ ethyl acetate = 4 / 130.4, 129.4, 129.2, 128.7, 128.0, 127.7, 127.1, 125.5, 123.0, 117.1, 115.7, 62.5, 54.8, 41.7, 13.8.
FTIR (KBr, neat): ṽ 2978, 1783, 1736, 1516, 1454, 1224, 1156, 1089, 1015, 979, 908, 816, 749, 699 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H19O4 347.1283; found 347.1281
102
HPLC chromatogram
103 Chiralpak AD-H column with hexanes / 2-propanol
= 90 / 10, flow = 0.8 mL/min, wavelength = 220 nm.
FTIR (KBr, neat): ṽ 2963, 1774, 1740, 1458, 1364, 1256, 1220, 1146, 1031, 965, 749, 699 cm–1.
HRMS (ESI-TOF) m/z: [M+Na]+ calcd for C26H32O4Na 431.2198; found 431.2198
104
HPLC chromatogram
105
Preperation of(R)-2-(3-hydroxy-1-phenylpropyl)-4-methylphenol (29)
Step 1：
To a solution of ethyl (3R,4R)-6-methyl-2-oxo-4-phenylchromane- 3-carboxylate 25ga (1.62 g, 5.22 mmol), in Dioxane (50 mL) was added potassium hydroxide (0.58 g, 10.44 mmol) and 5mL H2O. The reaction mixture was stirred for 12 hr and heated to 100 °C，the crude product purification by column chromatography on silica gel (5 g) then get product 28 (white solid, 43.4％ yield )
Step 2：
To a solution of 6-methyl-4-phenylchroman-2-one 28 (0.54 g, 2.26 mmol), in anhydrous toluene (4.5 mL) was slowly added DIBALH (10 mmol) dropwise under N2 at -25 °C , The reaction mixture was stirred for 0.5 hr. cooled to 0 °C and quenched with ethyl acetate and solution of 23％
citric acid (1 mL)was added, then the solution was stirred at room temperature overnight. The aqueous phase was extracted with ethyl acetate, the organic phases were dried over Na2SO4 and filtered, and the solvent was removed under reduced pressure to give the crude product. Further
106
purification by column chromatography on silica gel (5 g) then get product 29 (white solid, 0.45g, 82％) [25] [26] and concentrated in vacuo to provide 30 (64.9 mg) as a brown oil.
107
Step 2：
A reaction mixture of 30 (64.9 mg, 0.163 mmol) and potassium iodide (41 mg, 0.245 mmol, 1.5 equiv.) in acetonitrile (0.7 mL) was heated at reflux for 6 h. The reaction mixture was cooled to room temperature and treated with N,N-diisopropylamine (0.235 mL, 1.63 mmol, 10 equiv.). The resulting mixture was further stirred at reflux for 24 h. After cooling to room temperature, the organic solvent was removed under reduced pressure.
The residue was extracted with ethyl acetate. The combined organic extract was washed with water, dried over Na2SO4 and concentrated in vacuo to afford 31 (55 mg) as yellowish oil. [27]
Step 3：
To a solution of 5 (55.0 mg, 0.136 mmol) in mixture of MeOH and H2O (2:1, 0.6 mL) was added sodium hydroxide (27.2 mg, 0.68 mmol, 5.0 equiv.). The reaction mixture was heated at 85 ºC for 10 h and cooled to room temperature. The volume of reaction mixture was reduced to 1/3 under reduced pressure. The reaction mixture was adjusted to pH 8 with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and concentrated in vacuo to give (R)-tolterodine (14, 22.7 mg, 42% for 3 steps) as oil. [28]
108
(R)-6-methyl-4-phenylchroman-2-one (28)
Isolated as a white solid: 94% yield after 12.0 h.
[𝛂]𝐃𝟐𝟒 −4.4 (c 1.00, CHCl3). Rf value = 0.51 (hexanes / 128.6, 127.6, 127.5, 125.3, 116.8, 40.7, 37.1, 20.7.
FTIR (KBr, neat): ṽ 2983, 1774, 1740, 1494, 1455, 1371, 1334, 1259, 1208, 1142, 1031,820, 748, 700, 605, 532 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C16H15O2 239.1072; found 239.1069
(R)-2-(3-hydroxy-1-phenylpropyl)-4-methylphenol (29)
Isolated as a white solid: 82% yield after 24.0 h.
[𝛂]𝐃𝟐𝟒 +62.5 (c 1.00, CHCl3).Rf value = 0.26 (hexanes/ 128.2, 127.9, 126.3, 116.1, 60.7, 38.7, 36.9, 20.7.
FTIR (KBr, neat): ṽ 3292, 2946, 1600, 1496, 1452, 1257, 1103, 1034, 813, 700 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C16H17O2 241.1229; found 241.1232
109
(R)-2-(3-(diisopropylamino)-1-phenylpropyl)-4-methylphenol (14) Isolated as a colorless oil: 52% yield after 24.0 h.
[𝛂]𝐃𝟐𝟒 +30.0 (c 1.00, CHCl3). Rf value = 0.55 128.2, 127.7, 126.1, 118.1, 48.0, 42.1, 39.3, 33.1, 20.7, 19.9, 19.4.
FTIR (KBr, neat): ṽ 2964, 1727, 1497, 1452, 1243, 699 cm–1.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C22H32NO 326.2484; found 326.2486
110
附錄一
X-ray單晶數據與ORTEP解析圖譜
111
112 Table 1. Crystal data and structure refinement for d22065.
Identification code d22065
Empirical formula C18 H16 O4
Formula weight 296.31
Temperature 200(2) K
Wavelength 0.71073 Å
Crystal system Monoclinic
Space group P 21
Density (calculated) 1.267 Mg/m3
Absorption coefficient 0.089 mm-1
F(000) 312
Crystal size 0.32 x 0.26 x 0.07 mm3
Theta range for data collection 2.57 to 25.19°.
Index ranges -11<=h<=10, -9<=k<=9, -12<=l<=12
Reflections collected 11506
Independent reflections 2752 [R(int) = 0.0588]
Completeness to theta = 25.19° 98.5 %
Absorption correction multi-scan
Max. and min. transmission 0.9938 and 0.9720
Refinement method Full-matrix least-squares on F2
Data / restraints / parameters 2752 / 1 / 200
Goodness-of-fit on F2 1.016
Final R indices [I>2sigma(I)] R1 = 0.0376, wR2 = 0.0979
R indices (all data) R1 = 0.0452, wR2 = 0.1046
Absolute structure parameter -0.2(11)
Largest diff. peak and hole 0.118 and -0.124 e.Å-3
113
Table 2. Atomic coordinates ( x 104) and equivalent isotropic displacement parameters (Å2x 103) for d22065. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
________________________________________________________________________________
114
115
116
Symmetry transformations used to generate equivalent atoms:
117
118
119
附錄二
核磁共振光譜圖
120
1H NMR spectrum of ethyl 2-oxo-2H-chromene-3-carboxylate (24a)
121
13C NMR spectrum of ethyl 2-oxo-2H-chromene-3-carboxylate (24a)
122
1H NMR spectrum of ethyl isopropyl 2-oxo-2H-chromene-3-carboxylate (24b)
123
13C NMR spectrum of ethyl isopropyl 2-oxo-2H-chromene-3-carboxylate (24b)
124
1H NMR spectrum of benzyl 2-oxo-2H-chromene-3-carboxylate (24c)
125
13C NMR spectrum of benzyl 2-oxo-2H-chromene-3-carboxylate (24c)
126
1H NMR spectrum of tert-butyl 2-oxo-2H-chromene-3-carboxylate (24d)
127
13C NMR spectrum of tert-butyl 2-oxo-2H-chromene-3-carboxylate (24d)
128
1H NMR spectrum of ethyl 4-methyl-2-oxo-2H-chromene-3-carboxylate (24e)
129
13C NMR spectrum of ethyl 4-methyl-2-oxo-2H-chromene-3-carboxylate (24e)
130
1H NMR spectrum of ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate (24g)
131
13C NMR spectrum of ethyl 6-methyl-2-oxo-2H-chromene-3-carboxylate (24g)
132
1H NMR spectrum of ethyl 6-methoxy-2-oxo-2H-chromene-3-carboxylate (24h)
133
13C NMR spectrum of ethyl 6-methoxy-2-oxo-2H-chromene-3-carboxylate (24h)
134
1H NMR spectrum of ethyl 6-nitro-2-oxo-2H-chromene-3-carboxylate (24i)
135
13C NMR spectrum of ethyl 6-nitro-2-oxo-2H-chromene-3-carboxylate (24i)
136
1H NMR spectrum of ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate (24j)
137
13C NMR spectrum of ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate (24j)
138
1H NMR spectrum of ethyl 2-oxo-2H-benzo[g]chromene-3-carboxylate (24k)
139
13C NMR spectrum of ethyl 2-oxo-2H-benzo[g]chromene-3-carboxylate (24k)
140
1H NMR spectrum of ethyl 6,8-di-tert-butyl-2-oxo-2H-chromene-3-carboxylate (24l)
141
13C NMR spectrum of ethyl 6,8-di-tert-butyl-2-oxo-2H-chromene-3-carboxylate (24l)
142
1H NMR spectrum of ethyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25aa)
143
13C NMR spectrum of ethyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25aa)
144
1H NMR spectrum of ethyl (3R,4R)-2-oxo-4-(p-tolyl)chromane-3-carboxylate (25ab)
145
13C NMR spectrum of ethyl (3R,4R)-2-oxo-4-(p-tolyl)chromane-3-carboxylate (25ab)
146
1H NMR spectrum of ethyl (3R,4R)-2-oxo-4-(m-tolyl)chromane-3-carboxylate (25ac)
147
13C NMR spectrum of ethyl (3R,4R)-2-oxo-4-(m-tolyl)chromane-3-carboxylate(25ac)
148
1H NMR spectrum of ethyl (3R,4R)-2-oxo-4-(o-tolyl)chromane-3-carboxylate (25ad)
149
13C NMR spectrum of ethyl (3R,4R)-2-oxo-4-(o-tolyl)chromane-3-carboxylate (25ad)
150
1H NMR spectrum of ethyl (3R,4R)-4-(naphthalen-2-yl)-2-oxochromane-3- carboxylate (25ae)
151
13C NMR spectrum of ethyl (3R,4R)-4-(naphthalen-2-yl)-2-oxochromane-3- carboxylate (25ae)
152
1H NMR spectrum of ethyl (3R,4R)-4-(naphthalen-1-yl)-2-oxochromane-3- carboxylate (25af)
153
13C NMR spectrum of ethyl (3R,4R)-4-(naphthalen-1-yl)-2-oxochromane-3- carboxylate (25af)
154
1H NMR spectrum of ethyl (3R,4R)-4-([1,1'-biphenyl]-4-yl)-2-oxochromane-3- carboxylate (25ag)
155
13C NMR spectrum of ethyl (3R,4R)-4-([1,1'-biphenyl]-4-yl)-2-oxochromane-3- carboxylate (25ag)
156
1H NMR spectrum of ethyl (3R,4R)-4-(4-(tert-butyl)phenyl)-2-oxochromane-3- carboxylate (25ah)
157
13C NMR spectrum of ethyl (3R,4R)-4-(4-(tert-butyl)phenyl)-2-oxochromane-3- carboxylate (25ah)
158
1H NMR spectrum of ethyl (3R,4R)-4-(4-methoxyphenyl)-2-oxochromane-3- carboxylate (25ai)
159
13C NMR spectrum of ethyl (3R,4R)-4-(4-methoxyphenyl)-2-oxochromane-3- carboxylate (25ai)
160
1H NMR spectrum of ethyl (3R,4R)-4-(3-methoxyphenyl)-2-oxochromane-3- carboxylate (25aj)
161
13C NMR spectrum of ethyl (3R,4R)-4-(3-methoxyphenyl)-2-oxochromane-3- carboxylate (25aj)
162
1H NMR spectrum of ethyl (3R,4R)-4-(2-methoxyphenyl)-2-oxochromane-3- carboxylate (25ak)
163
13C NMR spectrum of ethyl (3R,4R)-4-(2-methoxyphenyl)-2-oxochromane-3- carboxylate (25ak)
164
1H NMR spectrum of ethyl (3R,4R)-4-(4-chlorophenyl)-2-oxochromane-3- carboxylate (25al)
165
13C NMR spectrum of ethyl (3R,4R)-4-(4-chlorophenyl)-2-oxochromane-3- carboxylate (25al)
166
1H NMR spectrum of Ethyl (3R,4R)-2-oxo-4-(4-(trifluoromethyl)phenyl)chromane- 3-carboxylate (25am)
167
13C NMR spectrum of Ethyl (3R,4R)-2-oxo-4-(4-(trifluoromethyl)phenyl)chromane- 3-carboxylate (25am)
168
1H NMR spectrum of (R)-4-phenylchroman-2-one (26a)
169
13C NMR spectrum of (R)-4-phenylchroman-2-one (26a)
170
1H NMR spectrum of isopropyl (3R,4R)-2-oxo-4-phenylchromane-3- carboxylate(25ba)
171
13C NMR spectrum of isopropyl (3R,4R)-2-oxo-4-phenylchromane-3- carboxylate(25ba)
172
1H NMR spectrum of benzyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25ca)
173
13C NMR spectrum of benzyl (3R,4R)-2-oxo-4-phenylchromane-3-carboxylate (25ca)
174
1H NMR spectrum of tert-butyl (3S,4R)-2-oxo-4-phenylchromane-3- carboxylate (25da)
175
13C NMR spectrum of tert-butyl (3S,4R)-2-oxo-4-phenylchromane-3- carboxylate (25da)
176
1H NMR spectrum of ethyl (3R,4R)-6-methyl-2-oxo-4-phenylchromane-3- carboxylate (25ga)
177
13C NMR spectrum of ethyl (3R,4R)-6-methyl-2-oxo-4-phenylchromane-3- carboxylate (25ga)
178
1H NMR spectrum of ethyl (3R,4R)-6-methoxy-2-oxo-4-phenylchromane-3- carboxylate (25ha)
179
13C NMR spectrum of ethyl (3R,4R)-6-methoxy-2-oxo-4-phenylchromane-3- carboxylate (25ha)
180
1H NMR spectrum of ethyl (3R,4R)-6-nitro-2-oxo-4-phenylchromane- 3-carboxylate (25ia)
181
13C NMR spectrum of ethyl (3R,4R)-6-nitro-2-oxo-4-phenylchromane- 3-carboxylate (25ia)
182
1H NMR spectrum of ethyl (3R,4R)-7-methoxy-2-oxo-4-phenylchromane-3- carboxylate (25ja)
183
13C NMR spectrum of ethyl (3R,4R)-7-methoxy-2-oxo-4-phenylchromane-3- carboxylate (25ja)
184
1H NMR spectrum of ethyl(3R,4R)-2-oxo-4-phenyl-3,4-dihydro-2H-benzo[g]
chromene-3-carboxylate (25ka)
185
13C NMR spectrum of ethyl(3R,4R)-2-oxo-4-phenyl-3,4-dihydro-2H-benzo[g]
chromene-3-carboxylate (25ka)
186
1H NMR spectrum of ethyl (3R,4R)-6,8-di-tert-butyl-2-oxo-4-phenylchromane-3- carboxylate (25la)
187
13C NMR spectrum of ethyl (3R,4R)-6,8-di-tert-butyl-2-oxo-4-phenylchromane-3- carboxylate (25la)
188
1H NMR spectrum of (R)-6-methyl-4-phenylchroman-2-one (28)
189
13C NMR spectrum of (R)-6-methyl-4-phenylchroman-2-one (28)