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Enantioselective Iodolactonization of Allenoic Acids

Kenichi Murai*, Nozomi Shimizu, and Hiromichi Fujioka*

Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka, 565-0871 (Japan)

Tel: (+81) 6-6879-8225, Fax: (+81) 6-6879-8229 E-mail: [email protected], [email protected]

Electronic Supplementary Information

Table of Contents

1. Page S2 General

2. Page S2-S11 Preparation of allenoic acids 3. Page S11-S12 Preparation of DMP-tris

4. Page S12-S18 Iodolactonization of allenoic acids 5. Page S19-S21 Optimization study

6. Page S22-S23 Determination of stereochemistry of 3a

7. Page S24-36 HPLC Data

8. Page 37-113 1H and 13C NMR Data, NOESY for 3l

S1

Electronic Supplementary Material (ESI) for ChemComm.

This journal is © The Royal Society of Chemistry 2014

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1. General

Melting points were measured by BÜCHI B-545 and all melting points were uncorrected. 1_{H-NMR and} 13_{C-NMR spectra were measured by JEOL JNM-ECS 400, JEOL ECS 300 or JEOL JNM-LA 500} spectrometers with tetramethylsilane as an internal standard. IR spectra were recorded by Shimadzu FTIR 8400 using a diffuse reflectance measurement of samples dispersed in KBr powder. Optical rotation was measured by JASCO P-1020. High resolution mass spectra and elemental analysis were performed by the Elemental Analysis Section of Osaka University. Enantiomeric excesses (ee) were measured by chiral HPLC analysis: DAICEL CHIRALPAK AD-H, IC columns and DAICEL CHIRALCEL OD-H columns using a multiwavelength detector JASCO MD-2010. Column chromatography was performed with SiO2 (Merck Silica Gel 60 (230-400 mesh) or Kanto Chemical Silicagel 60 (spherical, 63-210 m).

Unless otherwise noted, materials were purchased from Aldrich Inc., Kanto Kagaku, Wako Chemicals, and other commercial suppliers and were used without purification.

2. Preparation of allenoic acids

Allenoic acids were synthesized by the hydrolysis of corresponding allenoic esters, which were prepared from propargyl mesylates and zinc reagents according to the procedure reported by Kondo et al. 1

General procedure A (Synthesis of alcohol 4)

To the solution of arylhalide and propargyl alcohol in triethylamine was added Pd(PPh3)4 and CuI under N2 and the resulting reaction mixture was stirred at rt (for ArI) or under reflux (for ArBr). After the reaction completed, the reaction mixture was diluted with AcOEt and filtered through short pad SiO2 (eluent AcOEt). The filtrate was concentrated in vacuo and the residue was purified by SiO2 column chromatography to give alcohol 4.

General procedure B (Synthesis of mesylate 5)

To the solution of alcohol 4 and triethylamine in CH2Cl2 was added MsCl at 0 oC under N2 and the resulting reaction mixture was stirred at the same temperature. After the reaction completed, H2O was added to the reaction mixture and the resulting solution was extracted with AcOEt. The organic layer was washed with H2O, 5% HCl aq., sat. NaHCO3 aq, and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by SiO2 column chromatography to give mesylate 5.

General procedure C (Synthesis of allenoic acid 2)

To the solution of mesylate 2 in DMSO was added 4-ethoxy-4-oxobutylzinc bromide or 3-ethoxy-3-oxopropylzinc bromide (0.5 M solution in THF) at rt under Arand the resulting reaction mixture

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was stirred at the same temperature. After the reaction completed, NH4Cl aq. was added to the reaction mixture at 0 o_{C and the resulting solution was extracted with AcOEt. The organic layer was washed with H}

2O and brine, dried over with Na2SO4 and concentrated in vacuo. The residue was roughly purified by SiO2 column chromatography to give allenoic ester. Although the products included impurities, it was subjected subsequent hydrolysis. To the solution of crude allenoic ester in THF/MeOH/H2O (3/1/1) was added LiOH and the resulting solution was stirred at rt. After the reaction completed, THF was removed by evaporator and the resulting mixture was acidified with 10% HCl aq. at 0 o_{C and the resulting solution was extracted with CH}

2Cl2. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by SiO2 column chromatography to give allenoic acid 2.

5-Phenylhepta-5,6-dienoic acid (2a)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 3-phenylprop-2-yn-1-yl methanesulfonate2_{(209 mg, 0.994 mmol) and 4-ethoxy-4-oxobutylzinc bromide (2.0} ml, 0.5 M solution in THF, 1.0 mmol) in DMSO (2.0 ml); hydrolysis: LiOH (60 mg, 2.5 mmol) in THF/MeOH/H2O (3/1/1, 4 ml)) to give 2a (68.6 mg, 34%, 2 steps). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 12/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

Colorless solid; Mp: 109-110 o_C;1_{H NMR (300 MHz, CDCl}

3): δ= 7.41-7.17 (m, 5H), 5.11 (t, J = 3.3 Hz, 2H), 2.53-2.44 (m, 4H), 1.97-1.87 ppm (m, 2H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 208.4, 179.7, 135.9, 128.4, 126.7, 125.9, 104.0, 78.8, 33.4, 28.6, 22.7 ppm; IR (KBr): 3039, 2954, 1938, 1705, 1452, 1286, 1201 cm-1_; HRMS (MALDI-TOF): calcd for C13H15O2 [M+H]+: 203.1066, found 203.1062.

3-(4-tert-Butylphenyl)prop-2-yn-1-yl methanesulfonate (5b)

The reaction was carried out according to the general procedure B with 3-(4-tert-butylphenyl)prop-2-yn-1-ol3 (558 mg, 2.96 mmol), MsCl (0.3 ml, 0.39 mmol), and triethylamine (0.8 ml, 5.7 mmol) in CH2Cl2 (10 ml) to give 5b (547 mg, 69%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

3): δ= 7.41-7.35 (m, 4H), 5.09 (s, 2H), 3.16 (s, 3H), 1.31 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 152.9, 131.7, 125.5, 118.0, 89.7, 80.1, 58.7, 39.1, 34.8, 31.0 ppm; IR (KBr): 2964, 2225, 1506, 1365, 1176 cm-1_;_{HRMS ((MALDI-TOF)): calcd for C}

14H18O3NaS [M+Na]+_{: 289.0868, found 289.0866.}

2 _{A. Claesson, and C. Sahlberg, Tetrahedron 1982, 38, 363.}

3_{S. Kusaka, R. Sakamoto, Y. Kitagawa, M. Okumura, and H. Nishihara, Chem. Asian J. 2013, 8, 723.}

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5-(4-tert-Butylphenyl)hepta-5,6-dienoic acid (2b)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5b (225 mg, 0.845 mmol) and 4-ethoxy-4-oxobutylzinc bromide (3.5 ml, 0.5 M solution in THF, 1.75 mmol) in DMSO (3.5 ml); hydrolysis: LiOH (80 mg, 3.34 mmol) in THF/MeOH/H2O (3/1/1, 5 ml)) to give 2b (110.6 mg, 51%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 10/1; 2nd step Hexane/AcOEt= 3/1). Colorless solid; Mp: 75-76 o_C;1_{H NMR (300 MHz, CDCl}

3): δ= 7.37-7.31 (m, 4H), 5.09 (t, J = 3.3 Hz, 2H), 2.52-2.44 (m, 4H), 1.96-1.86 (m, 2H) 1.31 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 208.3, 179.7, 149.7, 132.9, 125.6, 125.4, 103.7, 78.6, 34.4, 33.4, 31.3, 28.6, 22.7 ppm; IR (KBr): 3047, 2960, 1940, 1699, 1512, 1408, 1203 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

17H22O2Na [M+Na]+: 281.1512, found 281.1510.

3-(4-((tert-Butyldimethylsilyloxy)methyl)phenyl)prop-2-yn-1-ol (4c)

The reaction was carried out according to the general procedure A with

tert-butyl((4-iodobenzyloxy)dimethylsilane4 (561 mg, 1.61 mmol), propargyl alcohol (0.3 ml, 5.1 mmol),

Pd(PPh3)4 (18.5 mg, 0.016 mmol) and CuI (13.5 mg, 0.07 mmol) in triethylamine (10 ml) to give 4c (436 mg, 98%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

Pale yellow oil;1_{H NMR (300 MHz, CDCl}

3): δ= 7.38 (d, J = 8.3 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 4.71 (s, 2H), 4.88 (d, J = 5.8 Hz, 2H), 0.92 (s, 9H), 0.08 ppm (s, 6H); 13_{C NMR (100.5 MHz, CDCl}

3): δ= 142.0, 131.6, 125.9, 120.9, 86.7, 85.8, 64.6, 51.7, 25.9, 18.4, -5.3 ppm; IR (KBr): 3280, 2954, 2929, 2858, 1257, 839 cm-1_;_HRMS (MALDI-TOF): calcd for C16H24NaO2Si [M+Na]+: 299.1443, found 299.1432.

3-(4-((tert-Butyldimethylsilyloxy)methyl)phenyl)prop-2-yn-1-yl methanesulfonate (5c)

The reaction was carried out according to the general procedure B with 4c (436.3 mg, 1.58 mmol), MsCl (0.2 ml, 2.58 mmol), and triethylamine (0.5 ml, 3.6 mmol) in CH2Cl2 (10 mL) to give 5c (515.5 mg, 92%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

Colorless oil;1_{H NMR (300 MHz, CDCl}

3): δ= 7.42-7.39 (m, 2H), 7.29-7.26 (m, 2H), 5.07 (s, 2H), 4.72 (s, 2H), 3.14 (s, 3H), 0.92 (s, 9H), 0.08 ppm (s, 6H); 13_{C NMR (100.5 MHz, CDCl}

3): δ= 143.2, 131.9, 126.0, 119.5,

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89.6, 80.3, 64.5, 58.5, 39.1, 25.9, 18.4, -5.3 ppm; IR (KBr): 2929, 1365, 1259, 1176 cm-1_; _HRMS (MALDI-TOF): calcd for C17H26O4NaSiS [M+Na]+: 377.1213, found 377.1213.

5-(4-((tert-Butyldimethylsilyloxy)methyl)phenyl)hepta-5,6-dienoic acid (2c)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5c (510 mg, 1.44 mmol) and 4-ethoxy-4-oxobutylzinc bromide (5.8 ml, 0.5 M solution in THF, 2.9 mmol) in DMSO (5.8 ml); hydrolysis: LiOH (133 mg, 5.55 mmol) in THF/MeOH/H2O (3/1/1, 3 ml)) to give 2c (160.4 mg, 32%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 12/1; 2nd step Hexane/AcOEt= 4/1). Colorless solid; Mp: 74-76; 1_{H NMR (300 MHz, CDCl}

3): δ= 7.34 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 5.09-5.07 (m, 2H), 4.70 (s, 2H), 2.49-2.42 (m, 4H), 1.92-1.86 (m, 2H), 0.92 (s, 9H), 0.07 ppm (s, 6H); 13_C NMR (125.8 MHz, CDCl3): δ= 208.4, 178.1, 140.0, 134.5, 126.2, 125.8, 103.9, 78.7, 64.7, 33.1, 28.7, 25.9, 22.7, 18.4, -5.3 ppm; IR (KBr): 2953, 2929, 1707, 1257, 1091, 839 cm-1_;_{HRMS (MALDI-TOF): calcd for} C20H30NaO3Si [M+Na]+: 369.1862, found 369.1867.

3-(4-Trimethylsilylphenyl)prop-2-yn-1-ol (4d)

The reaction was carried out according to the general procedure A with (4-bromophenyl)trimethylsilane (1.35 g, 5.89 mmol), propargyl alcohol (0.7 ml, 11.8 mmol), Pd(PPh3)4 (68 mg, 0.059 mmol) and CuI (22 mg, 0.116 mmol) in triethylamine (10 ml) to give 4d (263.9 mg, 22%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 7/2

Pale yellow oil; 1_{H NMR (300 MHz, CDCl}

3): δ= 7.46-7.43 (m, 2H), 7.40-7.37 (m, 2H), 4.48 (d, J = 5.1 Hz, 2H), 0.24 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 141.4, 133.2, 130.7, 122.7, 87.5, 85.8, 51.7, -1.28 ppm; IR (KBr): 3325, 2954, 1249, 1109 cm-1_; _{HRMS (MALDI-TOF): calcd for C}

12H16OSiNa [M+Na]+: 227.0868, found 227.0878.

3-(4-Trimethylsilylphenyl)prop-2-yn-1-yl methanesulfonate (5d)

The reaction was carried out according to the general procedure B with 4d (258.7 mg, 1.27 mmol), MsCl (0.15 ml, 1.94 mmol), and triethylamine (0.4 ml, 2.87 mmol) in CH2Cl2 (12 mL) to give 5d (286.3 mg, 80%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

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Colorless oil; 1_{H NMR (400 MHz, CDCl}

3): δ= 7.49-7.40 (m, 4H), 5.07 (s, 2H), 3.14 (s, 3H), 0.25 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 142.8, 133.3, 130.9, 121.3, 89.6, 81.0, 58.5, 39.1, -1.34 ppm; IR (KBr): 2956, 1361, 1176 cm-1_;_{HRMS (FAB): calcd for C}

13H18O3SSiNa [M+Na]+: 305.0644, found 305.0644.

5-(4-Trimethylsilylphenyl)hepta-5,6-dienoic acid (2d)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5d (272.9 mg, 0.97 mmol) and 4-ethoxy-4- oxobutylzinc bromide (4 ml, 0.5 M solution in THF, 2 mmol) in DMSO (4 ml); hydrolysis: LiOH (70 mg, 2.92 mmol) in THF/MeOH/H2O (3/1/1, 5 ml)) to give 2d (87.1 mg, 33%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 12/1; 2nd step Hexane/AcOEt= 4/1). Colorless solid; Mp: 104-105 o_C;1_{H NMR (300 MHz, CDCl}

3): δ= 7.47 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 5.12-5.09 (m, 2H), 2.53-2.44 (m, 4H), 1.97-1.87 (m, 2H), 0.26 ppm (s, 9H); 13_{C NMR (125.8 MHz,} CDCl3): δ= 208.6, 178.3, 138,8, 136.4, 133.5, 125.2, 104.0, 78.7, 33.1, 28.6, 22.7, -1.2 ppm; IR (KBr): 2953, 1712 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

16H22O2SiNa [M+Na]+: 297.1287, found 297.1281.

5-(4-tert-Butoxyphenyl)hepta-5,6-dienoic acid (2e)

The reaction was carried out according to the general procedure B with 3-(4-(tert-butoxyphenyl)prop-2-yn-1-ol5_{(450.9 mg, 2.21 mmol), MsCl (0.3 ml, 3.88 mmol), and triethylamine} (1.0 ml, 7.2 mmol) in CH2Cl2 (6 ml) to give crude 3-(4-tert-butoxyphenyl)prop-2-yn-1-yl methanesulfonate. This mesylate was used directly without the purification by SiO2 column chromatography to the next transformation after the extraction and concentration. The following reaction was carried out according to the general procedure C (nucleophilic substitution: obtained crude mesylate and 4-ethoxy-4-oxobutylzinc bromide (8 ml, 0.5 M solution in THF, 4 mmol) in DMSO (8 ml); hydrolysis: LiOH (300 mg, 12.5 mmol) in THF/MeOH/H2O (3/1/1, 5 ml)) to give 2e (228.6 mg, 38%, 3 steps). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 9/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

Colorless solid; Mp: 84-85o_C;1_{H NMR (300 MHz, CDCl}

3): δ= 7.29 (d, J = 8.6 Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 5.10 (t, J = 3.0 Hz, 2H), 2.45-2.43 (m, 4H), 1.96-1.86 (m, 2H), 1.34 ppm (s, 9H); 13_{C NMR (125.8 MHz,} CDCl3): δ= 208.2, 179.3, 154.2, 130.8, 126.3, 124.2, 103.7, 78.8, 78.6, 33.4, 28.8, 28.7, 22.7 ppm; IR (KBr): 3035, 2976, 1938, 1708, 1506, 1238, 1163 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

17H22O3Na [M+Na]+: 297.1461, found 297.1462.

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5-(4-Fluorophenyl)hepta-5,6-dienoic acid (2f)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 3-(4-fluorophenyl)prop-2-yn-1-yl methanesulfonate6_{(540 mg, 2.37 mmol) and 4-ethoxy-4-oxobutylzinc} bromide (9.5 ml, 0.5 M solution in THF, 4.75 mmol) in DMSO (9.5 ml); hydrolysis: LiOH (227 mg, 9.48 mmol) in THF/MeOH/H2O (3/1/1, 3 ml)) to give 2f (127 mg, 24%). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 10/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

3): δ= 7.37-7.32 (m, 2H), 7.03-6.97 (m, 2H), 5.11 (t, J = 3.1 Hz, 2H), 2.49-2.42 (m, 4H), 1.90 ppm (tt, J = 7.4 Hz, 2H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 208.2, 179.4, 161.8 (d, J = 245.9 Hz), 131.8 (d, J = 3.5 Hz), 127.4 (d, J = 7.3 Hz), 115.3 (d, J = 21.6 Hz), 103.3, 79.0, 33.3, 28.8, 22.6 ppm; IR (KBr): 3070, 1710, 1510, 1232 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

13H13O2FNa [M+Na]+_{: 243.0791, found 243.0780.} 5-(4-Trifluoromethylphenyl)hepta-5,6-dienoic acid (2g) O OH F3C

The reaction was carried out according to the general procedure C (nucleophilic substitution: 3-(4-trifluoromethylphenyl)prop-2-yn-1-yl methanesulfonate 7 (949 mg, 3.41 mmol) and 4-ethoxy-4-oxobutylzinc bromide (12 ml, 0.5 M solution in THF, 6 mmol) in DMSO (12 ml); hydrolysis: LiOH (250 mg, 10.4 mmol) in THF/MeOH/H2O (3/1/1, 5 ml)) to give 2g (135 mg, 15%, 2 steps). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 10/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

3): δ= 7.56 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.6 Hz, 2H), 5.18 (t, J = 3.2 Hz, 2H), 2.52-2.47 (m, 4H), 1.92 ppm (tt, J = 7.4 Hz, 2H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 208.8, 179.5, 139.9, 128.6 (q, J = 32.4 Hz), 126.1, 125.3 (q, J = 3.0 Hz), 124.2 (q, J = 272 Hz), 103.5, 79.4, 33.3, 28.4, 22.6 ppm; IR (KBr): 3041, 1938, 1714, 1325, 1126 cm-1_;_{HRMS (MALDI-TOF): calcd for} C14H14O2F3 [M+H]+: 271.0940, found 271.0948.

6_{L. Jeppesen, P. H. et al J. Med. Chem. 1999, 42, 1999.}

7 _{T. J. Martins, K. W. Fowler, J. Odingo, E. A. Kesicki, A. Oliver, L. E. Burgess, J. J. Gaudino, Z. S. Jones, B. J.}

Newhouse, S. T. Schlachter, U.S. Patent 6423710B1, 2002.

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3-(3,5-Dimethylphenyl)prop-2-yn-1-yl methanesulfonate (5h)

The reaction was carried out according to the general procedure B with 3-(3,5-dimethylphenyl)prop-2-yn-1-ol8 (467.1 mg, 2.92 mmol), MsCl (0.3 ml, 4.4 mmol), and triethylamine (1.2 ml, 8.8 mmol) in CH2Cl2 (15 mL) to give 5h (607.3 mg, 87%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

3): δ= 7.09 (s, 2H), 7.02 (s, 1H), 5.08 (s, 2H), 3.16 (s, 3H), 2.30 ppm (s, 6H); 13_{C NMR (100.5 MHz, CDCl}

3): δ= 138.2, 131.4, 129.6, 120.7, 89.9, 80.0, 58.6, 39.2, 21.1 ppm; IR (KBr): 2228, 1599, 1352, 1174 cm-1_; _{HRMS (MALDI-TOF): calcd for C}

12H14O3NaS [M+H]+: 261.0555, found 261.0555.

5-(3,5-Dimethylphenyl)hepta-5,6-dienoic acid (2h)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5h (603.5 mg, 2.53 mmol) and 4-ethoxy-4-oxobutylzinc bromide (10 ml, 0.5 M solution in THF, 5 mmol) in DMSO (10 ml); hydrolysis: LiOH (240 mg, 10.0 mmol) in THF/MeOH/H2O (3/1/1, 8 ml)) to give 2h (267.1 mg, 46%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 12/1; 2nd step Hexane/AcOEt= 4/1). Colorless solid; Mp: 117-118 o_C;1_{H NMR (400 MHz, CDCl}

3): δ= 7.01 (s, 2H), 6.85 (s, 1H), 5.08 (d, J = 3.7 Hz, 1H), 5.08 (d, J = 3.2 Hz, 1H), 2.49-2.43 (m, 4H), 2.30 (s, 6H), 1.94-1.88 ppm (m, 2H); 13_{C NMR (125.8 MHz,} CDCl3): δ= 208.4, 179.5, 137.9, 135.8, 128.5, 123.8, 104.0, 78.4, 33.4, 28.8, 22.8, 21.3 ppm; IR (KBr): 3041, 2960, 1932, 1710, 1597, 1429, 1273 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

15H19O2 [M+H]+: 231.1379, found 231.1379.

3-(3-((tert-Butyldimethylsilyloxy)methyl)phenyl)prop-2-yn-1-ol (4i)

The reaction was carried out according to the general procedure A with

tert-butyl(3-iodobenzyloxy)dimethylsilane9 (1.49 g, 4.27 mmol), propargyl alcohol (0.76 ml, 12.9 mmol),

Pd(PPh3)4 (25 mg, 0.022 mmol) and CuI (12 mg, 0.063 mmol) in triethylamine (10 ml) to give 4i (1.16 g, 99%).

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Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1 Pale yellow oil; 1_{H NMR (500 MHz, CDCl}

3): δ= 7.39 (s, 1H), 7.32-7.26 (m, 3H), 4.71 (s, 2H), 4.50 (d, J = 3.4 Hz, 2H), 0.94 (s, 9H), 0.10 ppm (s, 6H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 141.6, 130.2, 129.2, 128.2, 126.3, 122.3, 86.9, 85.8, 64.5, 51.7, 25.9, 18.4, -5.3 ppm; IR (KBr): 3302, 2929, 1257, 1105, 1082, 1033, 837 cm-1_; HRMS (MALDI-TOF): calcd for C16H24NaO2Si [M+Na]+: 299.1442, found 299.1437.

3-(3-((tert-Butyldimethylsilyloxy)methyl)phenyl)prop-2-yn-1-yl methanesulfonate (5i)

The reaction was carried out according to the general procedure B with 4i (1.16 g, 4.2 mmol), MsCl (0.4 ml, 5.2 mmol), and triethylamine (1.8 ml, 12.9 mmol) in CH2Cl2 (12 ml) to give 5i (781 mg, 52%). Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1

3): δ= 7.42 (s, 1H), 7.35-7.31 (m, 3H), 5.10 (s, 2H), 4.72 (s, 2H), 3.17 (s, 3H), 0.95 (s, 9H), 0.11 ppm (s, 6H);13_{C NMR (125.8 MHz, CDCl}

3): δ= 142.0, 130.4, 129.4, 128.4, 127.1, 121.0, 89.6, 80.5, 64.3, 58.5, 39.1, 25.9, 18.4, -5.3 ppm; IR (KBr): 1355, 1174 cm-1_;_{HRMS (MALDI-TOF):} calcd for C17H27O4SiS [M+H]+: 355.1393, found 355.1392.

5-(3-((tert-Butyldimethylsilyloxy)methyl)phenyl)hepta-5,6-dienoic acid (2i)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5i (780 mg, 2.2 mmol) and 4-ethoxy-4-oxobutylzinc bromide (8.8 ml, 0.5 M solution in THF, 4.4 mmol) in DMSO (8.8 ml); hydrolysis: LiOH (250 mg, 10.4 mmol) in THF/MeOH/H2O (3/1/1, 3 ml)) to give 2i (160.4 mg, 25%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 10/1; 2nd step Hexane/AcOEt= 4/1). Colorless solid; Mp: 69-70 o_C;1_{H NMR (300 MHz, CDCl} 3): δ= 7.38 (s, 1H), 7.29-7.26 (m, 2H), 7.17-7.15 (m, 1H), 5.10 (t, J = 3.0 Hz, 2H), 4.74 (s, 2H), 2.51-2.44 (m, 4H), 1.97-1.89 (m, 2H), 0.94 (s, 9H), 0.10 ppm (s, 6H); 13_{C NMR (125.8 MHz, CDCl} 3): δ= 208.5, 179.5, 141.6, 135.8, 128.3, 124.4, 123.5, 104.1, 78.7, 64.8, 33.4, 28.6, 25.9, 22.7, 18.4, -5.2 ppm; IR (KBr): 3047, 2954, 1940, 1708, 1257 cm-1_;_{HRMS (MALDI-TOF): calcd} for C20H30NaO3Si [M+Na]+: 369.1856, found 369.1856.

5-(o-Tolyl)hepta-5,6-dienoic acid (2j)

O OH

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Title compound was prepared from 1-(3-bromoprop-1-yn-1-yl)-2-methylbenzene10_{instead of mesylate. The} reaction was carried out according to the general procedure C (nucleophilic substitution: 1-(3-bromoprop-1-yn-1-yl)-2-methylbenzene (550.2 mg, 2.5 mmol) and 4-ethoxy-4-oxobutylzinc bromide (10 ml, 0.5 M solution in THF, 5 mmol) in DMSO (10 ml); hydrolysis: LiOH (126.5 mg, 5.28 mmol) in THF/MeOH/H2O (3/1/1, 9 ml)) to give 2j (110.4 mg, 20%, 2 steps). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 20/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

3): δ= 7.19-7.15 (m, 4H), 4.83 (t, J = 3.5 Hz, 2H), 2.43 (t, J = 7.5 Hz, 2H), 2.39-2.33 (m, 5H), 1.85-1.79 ppm (m, 2H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 206.6, 179.7, 136.8, 136.0, 130.5, 127.8, 127.0, 125.9, 102.8, 75.9, 33.4, 32.5, 22.6, 20.2 ppm; IR (KBr): 2951, 1950, 1713, 1454, 1242 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

14H16O2Na [M+Na]+: 239.1042, found 239.1037.

5-Phenethylhepta-5,6-dienoic acid (2k)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 5-phenylpent-2-yn-1-yl methanesulfonate11_{(310 mg, 1.3 mmol) and 4-ethoxy-4-oxobutylzinc bromide (5 ml,} 0.5 M solution in THF, 2.5 mmol) in DMSO (5 ml); hydrolysis: LiOH (125 mg, 5.2 mmol) in THF/MeOH/H2O (3/1/1, 3 ml)) to give 2k (162.1 mg, 54%, 2 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 10/1; 2nd_{step Hexane/AcOEt}_{= 5/1 to 3/1).}

Colorless solid; Mp: <25 o_C;1_{H NMR (300 MHz, CDCl}

3): δ= 7.30-7.15 (m, 5H), 4.73 (tt, J = 3.4, 3.4 Hz, 2H), 2.75-2.69 (m, 2H), 2.38 (t, J = 7.2 Hz, 2H), 2.25-2.18 (m, 2H), 2.05-1.98 (m, 2H), 1.83-1.73 ppm (m, 2H); 13_C NMR (125.8 MHz, CDCl3): δ= 205.6, 180.1, 142.1, 128.4, 128.3, 125.8, 101.9, 76.8, 33.9, 33.8, 33.4, 31.4, 22.3 ppm; IR (KBr): 3026, 2941, 1955, 1699, 1452, 1431, 1411, 1286, 1242 cm-1_;_{HRMS (MALDI-TOF): calcd} for C15H18O2Na [M+Na]+: 253.1199, found 253.1201.

1-(4-tert-Butylphenyl)hex-1-yn-3-ol (4l)

To the solution of 1-tert-butyl-4-ethynylbenzene (0.4 ml, 2.2 mmmol) in THF (11 ml) was added nBuLi (1.6 M solution in hexane, 1.51 ml, 2.42 mmol) under N2 at -78 oC and resulting solution was stirred for 1.5 hr at the same temperature. Butyraldehyde (0.26 ml, 2.86 mmol) was added to the solution, and the reaction mixture was stirred for 1 hr at at -78 o_{C and allowed to warm to 0}o_{C. After the reaction completed, NH}

4Cl aq. was added to the reaction mixture at 0 o_{C and the resulting solution was extracted with AcOEt. The organic layer was washed}

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with H2O and brine, dried over with Na2SO4 and concentrated in vacuo. The residue was purified by SiO2 column chromatography (Hexane/AcOEt= 7/1) to give 4l (342.2 mg, 68%).

Pale yellow oil; 1_{H NMR (300 MHz, CDCl}

3): δ= 7.38-7.31 (m, 4H), 4.60 (t, J = 6.6 Hz, 2H) 1.82-1.74 (m, 2H), 1.58-1.51 (m, 2H), 1.30 (s, 9H), 0.98 ppm (t, J = 7.5 Hz, 3H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 151.6, 131.4, 125.3, 119.6, 89.4, 84.9, 62.8, 40.0, 34.7, 31.1, 18.5, 13.8 ppm; IR (KBr): 3317, 2960, 1504, 1462, 1363, 1267 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

16H22ONa [M+Na]+: 253.1562, found 253.1551.

5-(4-tert-Butylphenyl)deca-5,6-dienoic acid (2l)

The reaction was carried out according to the general procedure B with 4l (342 mg, 1.49 mmol), MsCl (0.15 ml, 1.94 mmol), and triethylamine (0.62 ml, 4.45 mmol) in CH2Cl2 (7.5 ml) to give crude 1-(4-tert-butylphenyl)hex-1-yn-3-yl methanesulfonate. This mesylate was used directly without the purification by SiO2 column chromatography to the next transformation after the extraction and concentration. The following reaction was carried out according to the general procedure C (nucleophilic substitution: obtained crude mesylate and 4-ethoxy-4-oxobutylzinc bromide (6 ml, 0.5 M solution in THF, 3.0 mmol) in DMSO (6 ml); hydrolysis: LiOH (214 mg, 8.94 mmol) in THF/MeOH/H2O (3/1/1, 5 ml)) to give 2x (200.7 mg, 45%, 3 steps). (Eluent of SiO2 column chromatography: 1st step: Hexane/AcOEt= 19/1; 2nd step Hexane/AcOEt= 3/1 to 2/1). Colorless solid; Mp: 58-59 o_C;1_{H NMR (500 MHz, CDCl} 3): δ= 7.33 (s, 4H), 5.53-5.50 (m, 1H), 2.49-2.45 (m, 4H), 2.09 (dt, J = 7.2, 7.2 Hz, 2H), 1.91 (dq, J = 7.4, 7.4 Hz, 2H), 1.50 (tq, J = 7.4, 7.4 Hz, 2H), 1.31 (s, 9H), 0.96 ppm (t, J = 7.2 Hz, 3H); 13_{C NMR (125.8 MHz, CDCl} 3): δ= 203.5, 179.7, 149.4, 134.0, 125.5, 125.3, 104.1, 94.8, 33.4, 33.5, 31.3, 29.1, 22.9, 22.6, 13.9 ppm; IR (KBr): 2959, 1946, 1713, 1512, 1269 cm-1_{; HRMS} (MALDI-TOF): calcd for C20H18O2Na [M+Na]+: 323.1981, found 323.1973.

4-(4-tert-Butylphenyl)hexa-4,5-dienoic acid (2m)

The reaction was carried out according to the general procedure C (nucleophilic substitution: 3-(4-tert-butylphenyl)prop-2-yn-1-yl methanesulfonate (308.3 mg, 1.16 mmol) and 3-ethoxy-3-oxopropylzinc bromide (4.6 ml, 0.5 M solution in THF, 2.3 mmol) in DMSO (4.6 ml); hydrolysis: LiOH (120 mg, 5.0 mmol) in THF/MeOH/H2O (3/1/1, 3 ml)) to give 2m (46.3 mg, 16%, 2 steps). (Eluent of SiO2 column chromatography: 1st_{step: Hexane/AcOEt}_{= 10/1; 2}nd_{step Hexane/AcOEt}_{= 3/1).}

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3): δ= 7.35 (s, 4H), 5.14 (t, J = 3.4 Hz, 2H), 2.74-2.62 (m, 4H), 1.31 ppm (s, 9H); 13_{C NMR (75.6 MHz, CDCl}

3): δ= 207.7, 179.7, 149.9, 132.7, 125.5, 125.4, 103.7, 80.0, 34.4, 32.3, 31.3, 23.8 ppm; IR (KBr): 3030, 2966, 1942, 1708, 1423, 1315, 1288, 1203 cm-1_; HRMS (MALDI-TOF): calcd for C16H20O2Na [M+Na]+: 267.1355, found 267.1353.

3. Preparation of DMP-tris

(1S,2S)-1,2-bis(2,3-dimethylphenyl)ethane-1,2-diamine

Title diamine was prepared according to the literature procedure from HPEN.12

To the solution of 2,3-dimethylbenzaldehyde (680 mg, 5.06 mmol) in DMSO (10 ml) was added (1R, 2R)-1,2-bis(2-hydroxylphenyl)-1,2-diaminoethane (515 mg, 2.11 mmol) and the reaction mixture was stirred 9 hr at room temperature. The reaction was quenched with distilled water and the resulting solution was extracted with diethyl ether. The organic layer was washed with water and brine, dried over Na2SO4, and evaporated in vacuo. The residue was dissolved in THF (20 ml) and cHCl (0.6 ml) was added to the solution. The resulting reaction mixture was stirred for 13 hr to produce a white precipitate.The solid was filtered and washed with Et2O and Hexane. The HCl salt of diamine was treated with 10% NaOH aq. and the solution was extracted with CH2Cl2. Organic layer was dried over Na2SO4, and evaporated in vacuo to give the title diamine (289.5 mg, 51%). Colorless solid; Mp: 98-99 o_{C; []} D26 = +15.3 (c 0.77, CHCl3); 1H NMR (300 MHz, CDCl3) δ: 7.44 (d, J = 7.5 Hz, 2H),7.09 (dd, J = 7.5, 7.5 Hz, 2H), 7.01 (d, J = 7.5 Hz, 2H), 4.40 (s, 2H), 2.20 (s, 6H), 2.03 (s, 6H), 1.79 ppm (brs, 4H); 13_{C NMR (125.8 MHz, CDCl} 3) δ: 141.4, 136.6, 133.8, 128.3, 125.3, 124.4, 55.7, 21.0, 14.8 ppm; IR (KBr): 3292, 2941, 1585, 1460, 1381 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

18H25N2 [M+H]+: 269.2012, found 269.2013.

DMP-tris 1b

1,3,5-Triformylbenzene13_{(21.4 mg, 0.132 mmol) and (1S,2S)-1,2-bis(2,3-dimethylphenyl)ethane- 1,2-diamine}

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(118.4 mg, 0.441 mmol) was dissolved in CH2Cl2 (4 ml) and stired for 2 hr at room temperature under N2. The resulting solution was added NBS (78 mg, 0.438 mmol) at 0 o_{C and stirred for 20 hr at room temperature. After} the reaction was completed (judged by TLC), sat. Na2S2O5 aq. and 5% NaOH aq. was added to the reaction mixture and extracted with CH2Cl2. Organic layer was dried over Na2SO4, and evaporated in vacuo. The residue was purified by SiO2 column chromatography (2 times: Hexane/AcOEt = 3/1 to 1/1; AcOEt/CH2Cl2 = 2/1) to give 1b (70.6 mg, 59 %). Colorless solid; Mp: 277-278 o_{C; []} D27 = -27.8 (c= 0.51 , CHCl3); 1H NMR (300 MHz, CDCl3): δ= 8.59 (s, 3H), 7.39-7.35 (m, 3H), 7.27-7.22 (m, 3H), 7.13-7.02 (m, 12H), 5.77 (brs, 3H), 5.46-5.42 (m, 3H), 5.11-5.07 (m, 3H), 2.24 (s, 18H), 1.94-1.91 ppm (m, 18H); 13_{C NMR (125.8 MHz, CDCl} 3): 161.5, 141.8, 141.0, 136.9, 136.6, 133.7, 133.5, 130.8, 129.1, 128.7, 128.1, 126.1, 125.9, 124.8, 123.8, 76.4, 66.0, 20.8, 14.9, 14.7 ppm; IR (KBr): 3157, 2941, 2916, 1625, 1581, 1469 cm-1_; _{HRMS (MALDI-TOF): calcd for C}

63H67N6 [M +H]+: 907.5421, found 907.5426.

4. Iodolactonization of allenoic acid

General procedure for iodolactonization of allenoic acid

Under the N2 atmosphere, to the solution of allenoic acid 2 and trisimidazoline 1b (10 mol%) in touene (0.1 M) was added DTBP (2.5 equiv) at room temperature and the resulting solution was cooled to 0 o_{C. I}

2 (2.5 equiv) was added in one portion to the solution and the reaction mixture was stirred at 0 o_{C. After the completion of} the reaction (judged by TLC), the reaction was quenched with sat. Na2S2O3 aq. at 0 oC, and the solution was extracted with AcOEt. The organic layer were washed with H2O and brine, dried over Na2SO4 and concentrated

in vacuo. The residue was purified by SiO2 column chromatography to give lactone 3.

Lactone 3a

Reaction was carried out according to the typical procedure with 2a (19.0 mg, 0.0939 mmol), 1b (8.0 mg, 0.0088 mmol), I2 (60.2 mg, 0.273 mmol), and DTBP (54 l, 0.240 mmol) in toluene (0.9 ml) to give 3a (25.6 mg, 83%) as color less oil. Reaction time: 48 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D21 = +49.4 (c= 0.77, CHCl3, 66% ee); 1H NMR (300 MHz, CDCl3): δ= 7.50-7.35 (m, 5H), 6.50 (d, J = 2.4 Hz, 1H), 6.05 (d, J = 2.4 Hz, 1H), 2.72-2.55 (m, 2H), 2.51-2.33 (m, 2H), 1.92-1.82 ppm (m, 2H); 13_{C NMR} (125.8 MHz, CDCl3): δ= 170.1, 139.5, 128.51, 128.45, 127.8, 126.2, 115.2, 88.4, 30.7, 29.1, 16.2 ppm; IR (KBr): 2951, 1732, 1607, 1447, 1240 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

13H13O2NaI [M+Na]+: 350.9852, found 350.9851; HPLC (DAICEL CHIRALCEL OD-H, Hexane/iPrOH = 90/10, flow rate = 1.0 mL/min, 218 nm): tmajor = 16.2 min, tminor = 15.0 min.

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Lactone 3b

Reaction was carried out according to the typical procedure with 2b (11.8 mg, 0.0504 mmol), 1b (4.5 mg, 0.0050 mmol), I2 (35.8 mg, 0.141 mmol), and DTBP (29 l, 0.130 mmol) in toluene (0.5 ml) to give 3b (17.0 mg, 89%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D18 = +53.4 (c= 0.79, CHCl3, 82% ee); 1H NMR (300 MHz, CDCl3): δ= 7.40 (s, 4H), 6.48 (d, J = 2.2 Hz, 1H), 6.03 (d, J = 2.2 Hz, 1H), 2.71-2.54 (m, 2H), 2.50-2.33 (m, 2H), 1.99-1.76 (m, 2H), 1.32 ppm (s, 9H); 13_C NMR (125.8 MHz, CDCl3): δ= 170.2, 151.5, 136.3, 127.8, 126.0, 125.4, 115.5, 88.4, 34.5, 31.2, 30.8, 29.1, 16.2 ppm; IR (KBr): 2961, 1746, 1244 cm-1_{; HRMS (MALDI-TOF): calcd for C}

17H21O2NaI [M+Na]+: 407.0478, found 407.0477; HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 93/7, flow rate = 1.0 mL/min, 223 nm): tmajor = 10.3 min, tminor = 8.0 min.

Lactone 3c

Reaction was carried out according to the typical procedure with 2c (9.4 mg, 0.0271 mmol), 1b (2.9 mg, 0.0032 mmol), I2 (18.2 mg, 0.0717 mmol), and DTBP (15 l, 0.0668 mmol) in toluene (0.3 ml) to give 3c (11.2 mg, 88%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D21 = +39.0 (c= 0.98, CHCl3, 79% ee); 1H NMR (500 MHz, CDCl3): δ= 7.44 (d, J = 8.0 Hz, 2H), 7.34 (d, J

= 8.0 Hz, 2H), 6.48 (d, J = 2.5 Hz, 1H), 6.03 (d, J = 2.5 Hz, 1H), 4.75 (s, 2H), 2.67-2.55 (m, 2H), 2.48-2.35 (m,

2H), 1.95-1.77 (m, 2H), 0.94 (s, 9H), 0.10 ppm (s, 6H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.2, 141.9, 138.0, 127.8, 126.2, 126.0, 115.4, 88.4, 64.4, 30.8, 29.1, 25.9, 18.4, 16.2, -5.3 ppm; IR (KBr): 2953, 1746, 1244 cm-1_; HRMS (MALDI-TOF): calcd for C20H29O3NaSiI [M+Na]+: 495.0822, found 495.0826; HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 96/4, flow rate = 1.0 mL/min, 223 nm): tmajor = 7.3 min, tminor = 9.1 min.

Lactone 3d

Reaction was carried out according to the typical procedure with 2d (9.6 mg, 0.0350 mmol), 1b (3.5 mg, 0.0039 mmol), I2 (22.3 mg, 0.0878 mmol), and DTBP (20 l, 0.0891 mmol) in toluene (0.4 ml) to give 3d (10.9 mg, 78%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1.

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[]D17 = +47.5 (c= 1.00, CHCl3, 80% ee); 1H NMR (300 MHz, CDCl3): δ= 7.53 (d, J = 8.4 Hz, 2H), 7.45 (d, J

= 8.4 Hz, 2H), 6.49 (d, J = 2.4 Hz, 1H), 6.04 (d, J = 2.4 Hz, 1H), 2.71-2.54 (m, 2H), 2.50-2.33 (m, 2H),

1.99-1.75 (m, 2H), 0.27 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.1, 141.1, 139.8, 133.5, 128.0, 125.4, 115.2, 88.4, 30.9, 29.1, 16.2, -1.2 ppm; IR (KBr): 2953, 1746, 1246 cm-1_;_{HRMS (MALDI-TOF): calcd} for C16H21O2NaSiI [M+Na]+: 423.0247, found 423.0247; HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 93/7, flow rate = 1.0 mL/min, 225 nm): tmajor = 7.4 min, tminor = 6.9 min.

Lactone 3e

Reaction was carried out according to the typical procedure with 2e (12.5 mg, 0.0456 mmol), 1b (5.0 mg, 0.0055 mmol), I2 (27.8 mg, 0.109 mmol), and DTBP (25 l, 0.111 mmol) in toluene (0.5 ml) to give 3e (15.7 mg, 85%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. 1_{H NMR (300 MHz, CDCl}

3): δ= 7.39-7.34 (m, 2H), 7.01-6.96 (m, 2H), 6.47 (d, J = 2.4 Hz, 1H), 6.03 (d, J = 2.4 Hz, 1H), 2.71-2.30 (m, 4H), 1.99-1.82 (m, 2H), 1.36 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.2, 155.7, 133.9, 127.7, 127.1, 123.5, 115.5, 88.4, 78.8, 30.6, 29.1, 28.9, 16.2 ppm; IR (KBr): 2974, 1744, 1607, 1506, 1366, 1242, 1163 cm-1_{; HRMS (MALDI-TOF): calcd for C}

17H21O3NaI [M+Na]+: 423.1427, found 423.0425;HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 94/6, flow rate = 1.0 mL/min, 227 nm): tmajor = 16.4 min, tminor = 18.1 min.

Lactone 3f

Reaction was carried out according to the typical procedure with 2f (16.1 mg, 0.0731 mmol), 1b (6.5 mg, 0.0072 mmol), I2 (46.1 mg, 0.0181 mmol), and DTBP (40 l, 0.0178 mmol) in toluene (0.7 ml) to give 3f (19.1 mg, 78%) as color less oil. Reaction time: 42 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D16 = +58.5 (c= 0.88, CHCl3, 68% ee); 1H NMR (300 MHz, CDCl3): δ= 7.51-7.44 (m, 2H), 7.12-7.04 (m, 2H), 6.53 (d, J = 2.4 Hz, 1H), 6.05 (d, J = 2.4 Hz, 1H), 2.75-2.57 (m, 2H), 2.52-2.41 (m, 1H), 2.32 (ddd, J = 14.1, 9.3, 4.2 Hz, 1H), 2.01-1.78 ppm (m, 2H); 13_{C NMR (100.5 MHz, CDCl}

3): δ= 169.9, 162.5 (d, J = 248.5 Hz), 135.5 (d, J = 3.6 Hz), 128.2 (d, J = 8.6 Hz), 127.9, 115.4 (d, J = 21.7 Hz), 114.9, 114.8, 88.0, 30.6, 29.0, 16.1 ppm; IR (KBr): 2951, 1744, 1603, 1508, 1238 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

13H12O2FNaI [M+Na]+_{: 368.9758, found 368.9759; HPLC (DAICEL CHIRALPAK AD-H, Hexane/iPrOH = 95/5, flow rate =} 1.0 mL/min, 217 nm): tmajor = 15.6 min, tminor = 16.4 min.

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Lactone 3g

Reaction was carried out according to the typical procedure with 2g (19.7 mg, 0.0729 mmol), 1b (6.5 mg, 0.0072 mmol), I2 (46.3 mg, 0.182 mmol), and DTBP (40 l, 0.178 mmol) in toluene (0.7 ml) to give 3g (10.4 mg, 53%) as color less oil. Reaction time: 48 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D22 = +39.6 (c= 1.00, CHCl3, 62% ee); 1H NMR (300 MHz, CDCl3): δ= 7.68-7.61 (m, 4H), 6.59 (d, J = 2.6 Hz, 1H), 6.10 (d, J = 2.6 Hz, 1H), 2.75 (ddd, J = 14.1, 7.2, 4.2 Hz, 1H), 2.69-2.43 (m, 2H), 2.35 (ddd, J = 14.1, 9.3, 4.5 Hz, 1H), 2.03-1.77 ppm (m, 2H); 13_{C NMR (100.5 MHz, CDCl}

3): δ= 169.5, 143.7, 130.7 (q, J = 32.4 Hz), 128.4, 126.7, 125.5 (q, J = 3.6 Hz), 123.8 (q, J = 272.4 Hz), 113.8, 87.8, 30.8, 29.1, 16.1 ppm; IR (KBr): 1748, 1327 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

14H12O2F3NaI [M+Na]+: 418.9726, found 418.9731; HPLC (DAICEL CHIRALPAK AD-H, Hexane/iPrOH = 95/5, flow rate = 1.0 mL/min, 218 nm): tmajor = 12.9 min, tminor = 12.1 min.

Lactone 3h

Reaction was carried out according to the typical procedure with 2h (20.4 mg, 0.0886 mmol), 1b (8.0 mg, 0.0088 mmol), I2 (56.2 mg, 0.221 mmol), and DTBP (50 l, 0.223 mmol) in toluene (0.9 ml) to give 3h (27.0 mg, 85%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D22 = +41.9 (c= 1.16, CHCl3, 64% ee); 1H NMR (300 MHz, CDCl3): δ= 7.07 (s, 2H), 6.98 (s, 1H), 6.47 (d, J

= 2.4 Hz, 1H), 6.04 (d, J = 2.4 Hz, 1H), 2.67-2.31 (m, 4H), 2.33 (s, 6H), 1.98-1.74 ppm (m, 2H); 13C NMR

(125.8 MHz, CDCl3): δ= 170.3, 139.4, 138.0, 130.1, 127.8, 124.0, 115.5, 88.5, 30.9, 29.1, 21.5, 16.3 ppm; IR (KBr): 2949, 2916, 1732, 1234 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

Lactone 3i

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0.0055 mmol), I2 (36.1 mg, 0.142 mmol), and DTBP (31 l, 0.138 mmol) in toluene (0.6 ml) to give 3i (22.0 mg, 82%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D18 = +31.8 (c= 1.04, CHCl3, 66% ee); 1H NMR (500 MHz, CDCl3): δ= 7.42 (s, 1H), 7.36-7.32 (m, 3H), 6.49 (d, J = 1.8 Hz, 1H), 6.04 (d, J = 1.8 Hz, 1H), 4.76 (s, 2H), 2.67-2.32 (m, 4H), 1.94-1.79 (m, 2H), 0.94 (s, 9H), 0.09 ppm (s, 6H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.1, 141.8, 139.4, 128.4, 127.8, 126.1, 124.8, 123.8, 115.2, 88.4, 64.7, 30.8, 29.1, 25.9, 18.3, 16.2, -5.2 ppm; IR (KBr): 2953, 1748, 1251, 1231 cm-1_;_HRMS (MALDI-TOF): calcd for C20H29O3NaSiI [M+Na]+: 495.0822, found 495.0821; HPLC (DAICEL CHIRALPAK IC, Hexane/iPrOH = 99/1, flow rate = 1.2 mL/min, 217 nm): tmajor = 33.7 min, tminor = 31.7 min.

Lactone 3j

Reaction was carried out according to the typical procedure with 2j (20.9 mg, 0.0966 mmol), 1b (9.1 mg, 0.0100 mmol), I2 (61.2 mg, 0.241 mmol), and DTBP (54 l, 0.240 mmol) in toluene (1.0 ml) to give 3j (11.5 mg, 35%) as color less oil. Reaction time: 72 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 4/1. []D24 = +49.8 (c= 1.14, CHCl3, 74% ee); 1H NMR (300 MHz, CDCl3): δ= 7.38 (d, J = 7.8 Hz, 1H), 7.28-7.19 (m, 3H), 6.31 (d, J = 2.4 Hz, 1H), 6.10 (d, J = 2.4 Hz, 1H), 2.58-2.50 (m, 3H), 2.46 (s, 3H), 2.39-2.31 (m, 1H) 1.98-1.93 ppm (m, 2H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.3, 137.8, 136.5, 133.3, 128.9, 128.5, 127.4, 125.5, 114.1, 89.5, 31.0, 28.7, 22.2, 16.0 ppm; IR (KBr): 2955, 2926, 1738, 1460, 1238 cm-1_; _HRMS (MALDI-TOF): calcd for C14H15O2NaI [M+Na]+: 365.0008, found 365.0001; HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 93/7, flow rate = 1.0 mL/min, 217 nm): tmajor = 10.7 min, tminor = 9.1 min.

Lactone 3k

Reaction was carried out according to the typical procedure with 2k (17.5 mg, 0.0760 mmol), 1b (7.8 mg, 0.0086 mmol), I2 (48.0 mg, 0.189 mmol), and DTBP (43 l, 0.192 mmol) in toluene (0.8 ml) to give 3k (19.9 mg, 74%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 3/1. []D23 = +8.64 (c= 1.32, CHCl3, 34% ee); 1H NMR (500 MHz, CDCl3): δ= 7.31-7.20 (m, 5H), 6.48 (d, J = 2.3 Hz, 1H), 6.11 (d, J = 2.3 Hz, 1H), 2.85-2.78 (m, 1H), 2.63-2.56 (m, 2H), 2.49-2.40 (m, 2H), 2.32-2.26 (m, 1H), 2.03-1.96 (m, 1H), 1.83-1.77 (m, 2H), 1.71-1.65 ppm (m, 1H);13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.7, 141.3, 129.6, 128.43, 128.39, 126.0, 111.3, 88.0, 41.7, 31.6, 29.2, 28.7, 15.8 ppm; IR (KBr): 2957, 1742, 1236 cm-1_; HRMS (MALDI-TOF): calcd for C15H17O2NaI [M+Na]+: 379.0165, found 379.0164; HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 94/6, flow rate = 1.0 mL/min, 206 nm): tmajor = 10.6 min, tminor = 11.5 min.

(18)

Lactone 3l

Reaction was carried out according to the typical procedure with 2l (24.1 mg, 0.0802 mmol), 1b (7.0 mg, 0.0077 mmol), I2 (49.2 mg, 0.194 mmol), and DTBP (45 l, 0.200 mmol) in toluene (0.8 mL) to give 3l (26.1 mg, 76%) as color less oil. Reaction time: 24 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 4/1. []D23 = +35.2 (c= 0.89, CHCl3, 59% ee); 1H NMR (300 MHz, CDCl3): δ= 7.37 (s, 4H), 5.97 (t, J = 6.6 Hz, 1H), 2.72 (ddd, J = 14.4, 7.2, 4.8 Hz, 1H), 2.62-2.32 (m, 3H), 2.19 (dd, J = 14.1, 4.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.47 (tq, J = 7.4, 7.4 Hz, 2H), 1.32 (s, 9H), 0.93 ppm (t, J = 7.4 Hz, 3H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 170.6, 151.2, 137.5, 137.4, 126.1, 125.2, 113.4, 88.6, 38.8, 34.5, 31.6, 31.2, 29.2, 21.5, 16.2, 13.7 ppm; IR (KBr): 2959, 1732, 1242 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

20H27O2NaI [M+Na]+: 449.0947, found 449.0945;HPLC (DAICEL CHIRALPAK AD-H, Hexane/EtOH = 98/2, flow rate = 1.0 mL/min, 221 nm): tmajor = 11.1 min, tminor = 7.6 min.

Lactone 3m

O _O

I

tBu

Reaction was carried out according to the typical procedure with 2m (19.5 mg, 0.0798 mmol), 1b (7.6 mg, 0.0084 mmol), I2 (51.9 mg, 0.204 mmol), and DTBP (45 l, 0.200 mmol) in toluene (0.8 mL) to give 3m (25.7 mg, 87%) as color less oil. Reaction time: 7 h. Eluent of SiO2 column chromatography: Hexane/AcOEt= 4/1. []D23 = +18.9 (c= 1.11, CHCl3, 21% ee); 1H NMR (500 MHz, CDCl3): δ= 7.41-7.37 (m, 4H), 6.47 (d, J = 2.3 Hz, 1H), 5.97 (d, J = 2.3 Hz, 1H), 2.86-2.79 (m, 1H), 2.77-2.65 (m, 2H), 2.58-2.50 (m, 1H), 1.32 ppm (s, 9H); 13_{C NMR (125.8 MHz, CDCl}

3): δ= 175.2, 151.7, 135.5, 127.1, 126.0, 125.3, 114.1, 90.4, 34.6, 33.3, 31.2, 28.7 ppm; IR (KBr): 2961, 1782 cm-1_;_{HRMS (MALDI-TOF): calcd for C}

(19)

5. Optimization study

(20)

(21)

(22)

6. Determination of stereochemistry of 3a

(i) Vinyl lactone S1 was prepared from 3a using radical reduction conditions with nBu3SnH and AIBN.

(ii) Vinyl lactone S4 was prepared from bromolactone S314_{by DBU mediated elimination of HBr.}

By comparison of HPLC data between S1 and S4, it was revealed that the produced major enantiomer using Ph-tris in iodolactonization of allenoic acid 2a and bromolactonization of ene-carboxylic acid S2 have the same absolute configuration. Consequently, stereochemistry of major enantiomer of 3a was determined to be S as shown in above scheme.

Procedure for S1 (S4) From 3a

To the solution of lactone 3a (20.7 mg, 0.063 mmol, 75 : 25 er) in toluene (1.2 ml) was added nBu3SnH (0.1 ml, 3.7 mmol) and AIBN (4 mg, 0.024 mmol) at rt under N2 and the resulting solution was heated at 80 oC for 30 min. After cooling, the reaction mixture was purified by column chromatography (2 times. 1st column: KF-SiO215, eluent Hexane/AcOEt= 2/1; 2nd column: SiO2, eluent Hexane/AcOEt= 5/2) to give lactone S1 (12.0 mg, 94%, 75.5 : 24.5 er). Colorless oil; 1_{H NMR (500 MHz, CDCl} 3): δ= 7.41-7.28 (m, 5H), 6.05 (dd, J = 16.5, 10.5 Hz, 1H), 5.32 (d, J = 16.5 Hz, 1H), 5.24 (d, J = 10.5 Hz, 1H), 2.58 (ddd, J = 18.0, 6.5, 6.5 Hz, 1H), 2.46 (ddd, J = 18.0, 7.5, 7.5 Hz, 1H), 2.28-2.17 (m, 2H), 1.92-1.87 (m, 1H), 1.77-1.72 ppm (m, 1H); 13_{C NMR (125.8 MHz, CDCl} 3): δ= 171.0, 142.3, 140.9, 128.6, 127.6, 125.1, 114.8, 86.4, 32.5, 29.3, 16.4 ppm; IR (KBr): 2954, 1732, 1492, 1446, 1246 cm-1_;_{HRMS ((MALDI-TOF)): calcd for C}

13H15O2 [M+H]+: 203.1066, found 203.1066; HPLC (DAICEL CHIRALCEL OD-H, Hexane/iPrOH = 90/10, flow rate = 1.0 mL/min, 210 nm): tmajor = 9.8 min, tminor = 10.3 min.

From S3

To the solution of lactone S3 (14.8 mg, 0.052 mmol, 89 : 11 er) in toluene (1.2 ml) was added DBU (0.12 ml, 8.0 mmol) at rt under N2 and the resulting solution was heated at 100 oC for 3 hr. After the reaction completed, H2O was added to the reaction mixture and the resulting solution was extracted with AcOEt. The organic layer

(23)

was was SiO2 colu HPLC d shed with H2O umn chromato data O and brine, d ography (Hex dried over Na xane/AcOEt= 3 a2SO4 and con 3/1) to give S ncentrated in 4 (2.7 mg, 25% vacuo. The re %, 89.5 : 10.5 racemic S4 S1 esidue was pu 5 er ). urified by S23

(24)

7. HPLC Da HPLC char DAICEL CH racemic chiral ata rt for 3a

(25)

HPLC char DAICEL CH

racemic

chiral

rt for 3b

HIRALPAK AAD-H, Hexane/EtOH = 93//7, flow rate = 1.0 mL/minn, 223 nm

(26)

HPLC char DAICEL CH

racemic

chiral

rt for 3c

(27)

HPLC char DAICEL CH

racemic

chiral

rt for 3d

(28)

HPLC char DAICEL CH

racemic

chiral

rt for 3e

(29)

HPLC char DAICEL CH

racemic

chiral

rt for 3f

(30)

HPLC char DAICEL CH

racemic

chiral

rt for 3g

(31)

HPLC char DAICEL CH

racemic

chiral

rt for 3h

(32)

HPLC char DAICEL CH

racemic

chiral

rt for 3i

(33)

HPLC char DAICEL CH

racemic

chiral

rt for 3j

(34)

HPLC char DAICEL CH

racemic

chiral

rt for 3k

(35)

HPLC char DAICEL CH

racemic

chiral

rt for 3l

(36)

HPLC char DAICEL CH

racemic

chiral

rt for 3m

(37)

1 H NMR ch art o f 2a PP M 8 7 6 5 4 3 2 1 0 D F IL E P h-ac id-H (379 6 H -1 ). al s C O M N T 3 7 96H D A T IM 2 7- 02-201 4 16 :1 8: 42 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 1 6 .9 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 3 8 37 96H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \P h-a ci d-H (379 6H -1) .a ls 5.2 1 1.9 0 4.0 0 1.9 7 7.4 11 7.3 87 7.3 47 7.3 40 7.3 23 7.3 17 7.2 97 7.2 55 7.2 28 7.2 04 7.1 80 5.1 23 5.1 13 5.1 01 2.5 27 2.5 17 2.4 99 2.4 93 2.4 75 2.4 68 2.4 49 1.9 68 1.9 41 1.9 17 1.8 93 1.8 68 8 . 1 H and 13 C NMR Data S37

(38)

13 C NMR chart of 2a PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E P h-ac id -C (3 7 9 6C _C ar b on - 1-1) .a ls C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 7- 02-201 4 17 :1 4: 45 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 4 63 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 1 7 .2 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \P h-a ci d-C (3 7 96C _C ar bon -1-1) .a ls 208 .38 3 179 .72 9 135 .90 0 128 .41 2 .72 126 4 125 .87 5 104 .01 3 7 8.75 5 7 7.25 8 7 7.00 0 7 6.74 2 3 3.39 0 2 8.59 2 2 2.67 8

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1 H NMR ch art o f 5b PP M 8 7 6 5 4 3 2 1 0 D F IL E p tB u -M s-H (3 874 _p ro to n - 1-1) .a ls C O M N T si ngl e_ pu ls e D A T IM 2 8- 02-201 4 10 :4 1: 55 OBN U C 1 H E X MO D p ro to n.j xp O B F R Q 5 00 .1 6 M H z O B SE T 2 .9 1 KH z O B F IN 6 .1 7 H z POI N T 1 3 10 7 F R EQU 8 50 3 .4 0 H z SC A N S 1 6 ACQ T M 1 .5 41 4 s ec PD 2 .0 00 0 s ec PW1 5 .8 0 u se c IR N U C 1 H CTEMP 1 7 .5 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 3 0 si n gl e_p u lse C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B u-M s-H (3 874_ p rot on -1-1) .a ls 3.9 4 2.0 0 2.9 3 9.2 4 7.4 12 7.3 96 7.3 74 7.3 57 5.0 86 3.1 58 1.3 11 S39

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13 C NMR chart of 5b PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E p tB u -M s-C (387 4 C _C ar bo n- 1-1 ). al s C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 8- 02-201 4 11 :1 7: 45 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 4 05 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 1 8 .0 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B u-M s-C (3874 C _C ar b on-1-1 ). al s 152 .88 8 131 .68 4 125 .48 4 118 .02 5 8 9.62 9 8 0.11 0 7.25 7 8 7 7.00 0 7 6.74 2 5 8.65 8 3 9.09 4 3 4.83 0 3 1.03 4

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1 H NMR ch art o f 2 b PP M 8 7 6 5 4 3 2 1 0 D F IL E p tB u -ac id -H (3 8 1 2-1) .a ls CO M N T 3 8 12 D A T IM 1 1- 11-201 3 14 :3 9: 35 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 0 .7 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 4 0 38 12 _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B u-ac id -H (381 2-1 ). al s 4.0 4 1.9 4 4.0 0 2.0 0 9.3 4 7.3 40 7.2 59 5.0 98 5.0 88 5.0 76 2.5 07 2.4 93 2.4 83 2.4 69 2.4 57 2.4 44 1.9 41 1.9 17 1.8 93 1.3 09 S41

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13 C NMR chart of 2 b PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 D F IL E p tB u -ac id -C (3 8 12C _C ar bo n - 1-1) .a ls C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 7- 02-201 4 21 :3 5: 12 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 3 70 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 1 7 .8 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B u-ac id -C (3 812C _C ar bo n-1 -1) .a ls 20 8.33 5 17 9.68 2 14 9.73 1 13 2.91 5 12 5.56 0 12 5.37 0 10 3.72 7 7 8.58 3 7 7.25 8 7 7.00 0 7 6.74 2 3 4.43 0 3 3.38 1 3 1.27 3 2 8.63 0 2 2.70 7

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1 H NMR ch art o f 4c PP M 8 7 6 5 4 3 2 1 0 D F IL E p T B SO -O H-H( 3 78 5 H -1) .a ls C O M N T 3 7 85H D A T IM 2 2- 10-201 3 14 :3 9: 48 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 2 .0 c SL V N T C D C L3 E X R E F 7 .2 4 p pm B F 0 .1 2 H z R G AI N 3 8 37 85H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pT B S O -O H-H( 3 78 5 H-1) .a ls 1.9 8 2.2 8 2.0 0 1.9 4 8.9 7 5.9 0 7.3 97 7.3 69 7.2 63 7.2 40 7.2 37 7.2 34 4.7 11 4.4 85 4.4 66 0.9 28 0.9 19 0.9 08 0.0 75 0.0 65 S43

(44)

13 C NMR chart of 4c PP M 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E p T B S O -O H -C(3 7 8 5C-1).al s C O M N T 3 7 85C D A T IM 2 2- 10-201 3 14 :5 8: 32 OBN U C 1 3 C E X M O D si ngl e_ pu ls e_ de c O B F R Q 1 00 .5 3 M H z O B SE T 5 .3 5 KH z O B F IN 5 .8 6 H z POI N T 2 6 21 4 F R EQU 2 51 25 .2 4 H z SC A N S 4 71 ACQ T M 1 .0 43 3 s ec PD 2 .0 00 0 s ec PW1 3 .1 7 u se c IR N U C 1 H CTEMP 2 1 .7 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 37 85C _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \a lle n e fi g\ pT B SO -O H -C (3 785 C -1 ). al s 14 2.01 6 13 1.57 6 12 5.85 5 12 0.88 8 8 6.72 5 8 5.78 1 7 7.31 5 7 7.00 0 7 6.67 6 6 4.57 6 5 1.68 6 2 5.90 4 1 8.38 1 -5.30 2

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1 H NMR ch art o f 5c PP M 8 6 4 2 0 D F IL E p T B S O -M s-H (3 786 H-1) .a ls C O M N T 3 7 86H D A T IM 2 2- 10-201 3 18 :2 8: 01 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 2 .0 c SL V N T C D C L3 E X R E F 7 .2 4 p pm B F 0 .1 2 H z R G AI N 3 6 37 86H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pT B S O -M s-H (37 86H -1) .a ls 2.0 29 1.9 2.0 3 2.0 4 3.0 0 9.0 7 5.9 9 7.4 23 7.4 17 7.4 01 7.3 96 7.2 96 7.2 70 7.2 67 7.2 40 5.0 69 4.7 22 3.1 40 0.9 21 0.0 78 S45

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13 C NMR chart of 5c PP M 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E p T B S O -M s-C (378 6 C -1 ). al s C O M N T 3 7 86C D A T IM 2 2- 10-201 3 19 :0 8: 41 OBN U C 1 3 C E X M O D si ngl e_ pu ls e_ de c O B F R Q 1 00 .5 3 M H z O B SE T 5 .3 5 KH z O B F IN 5 .8 6 H z POI N T 2 6 21 4 F R EQU 2 51 25 .2 4 H z SC A N S 4 11 ACQ T M 1 .0 43 3 s ec PD 2 .0 00 0 s ec PW1 3 .1 7 u se c IR N U C 1 H CTEMP 2 1 .6 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 37 86C _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pT B S O -M s-C (3786 C -1 ). al s 14 3.18 9 13 1.85 2 12 5.95 1 11 9.48 6 8 9.57 6 8 0.34 7 7 7.32 4 7.00 7 0 7 6.68 5 6 4.45 2 5 8.53 2 3 9.11 0 2 5.88 5 1 8.37 2 -5.31 2

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1 H NMR ch art o f 2c PP M 8 6 4 2 0 D F IL E p T B S O -aci d-H (3 7 89 H ). al s CO M N T 3 7 89 D A T IM 2 4- 10-201 3 14 :3 9: 00 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 1 .9 c SL V N T C D C L3 E X R E F 7 .2 4 p pm B F 0 .1 2 H z R G AI N 4 2 37 89 _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pT B S O -ac id -H (378 9H ). als 5.6 5 1.9 4 2.0 0 4.1 5 2.0 2 9.5 1 6.2 5 7.3 52 7.3 25 7.2 66 7.2 40 5.0 88 5.0 77 5.0 66 4.7 00 2.4 90 2.4 71 2.4 47 2.4 31 2.4 21 1.9 18 1.8 94 1.8 70 0.9 16 0.0 72 S47

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13 C NMR chart of 2c PP M 20 0 15 0 10 0 50 0 D F IL E p T B S O -aci d-C (37 89 C _C ar bo n -1 -1) .a ls C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 4- 10-201 3 15 :3 2: 15 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 9 88 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 2 0 .9 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pT B S O -ac id -C (37 89C _C ar bo n-1 -1) .a ls 208 .39 2 178 .09 8 139 .99 2 134 .50 7 126 .16 1 125 .76 1 103 .89 8 7 8.65 0 7 7.24 8 7 7.00 0 7 6.74 2 6 4.71 4 3 3.12 3 2 8.69 7 2 5.94 1 2.72 2 6 1 8.40 5 -5.25 0

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1 H NMR ch art o f 4d PP M 8 7 6 5 4 3 2 1 0 D F IL E T M S-O H-H( 3 7 79 H-1 ). al s C O M N T 3 7 79H D A T IM 1 8- 10-201 3 19 :5 6: 51 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 1 .2 c SL V N T C D C L3 E X R E F 7 .2 4 p pm B F 0 .1 2 H z R G AI N 3 8 37 79H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -O H -H (37 79H -1 ). al s 4.0 7 2.0 0 9.2 4 7.4 62 7.4 41 7.4 35 7.4 00 7.3 93 7.3 73 7.2 40 4.4 93 4.4 76 0.2 40 S49

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13 C NMR chart of 4d PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E T M S-O H -C (3 779 C _C ar b o n-1 -1 ). al s C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 1 9- 10-201 3 09 :4 2: 34 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 1 4 39 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 2 0 .7 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -O H -C (3 779C _C ar bo n-1 -1) .a ls 141 .35 6 133 .17 2 130 .71 1 122 .71 8 8 7.46 4 8 5.84 2 7 7.24 8 7 7.00 0 7 6.74 2 5 1.70 4 -1.28 2

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1 H NMR ch art o f 5d PP M 8 7 6 5 4 3 2 1 0 D F IL E T M S-Ms -H( 37 8 1 H-1) .a ls C O M N T 3 7 81H D A T IM 1 9- 10-201 3 11 :3 1: 08 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 99 .7 8 M H z O B SE T 4 .1 9 KH z O B F IN 7 .2 9 H z POI N T 1 3 10 7 F R EQU 6 00 2 .3 1 H z SC A N S 1 6 ACQ T M 2 .1 83 7 s ec PD 5 .0 00 0 s ec PW1 5 .3 5 u se c IR N U C 1 H CTEMP 2 1 .6 c SL V N T C D C L3 E X R E F 7 .2 4 p pm B F 0 .1 2 H z R G AI N 4 2 37 81H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -M s-H (3781 H -1) .a ls 1.9 96 1.9 2.0 0 3.0 0 9.0 3 7.4 87 7.4 67 7.4 20 7.3 99 7.2 40 5.0 74 3.1 39 1.5 43 0.2 47 S51

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13 C NMR chart of 5d PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 0 D F IL E T M S-M s-C (37 81 C _C ar bon -1 -1 ). al s C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 1 9- 10-201 3 12 :5 2: 07 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 8 95 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 2 0 .9 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -M s-C (37 81C _C ar bon -1-1) .a ls 142 .77 7 133 .31 5 130 .92 1 121 .29 7 8 9.58 1 8 1.03 5 7 7.24 8 7 7.00 0 7 6.74 2 5 8.49 5 3 9.11 3 -1.33 9

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1 H NMR ch art o f 2d PP M 8 6 4 2 0 D F IL E T M S-a ci d-H (3 783 H -1) .a ls C O M N T 3 7 83H D A T IM 2 1- 10-201 3 16 :3 7: 46 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 2 1 .9 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 4 2 37 83H _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -a ci d-H (3 783H -1) .a ls 2.0 5 2.0 8 2.0 0 4.1 0 2.0 1 9.1 5 7.4 92 7.4 65 7.3 92 7.3 65 7.2 60 5.1 15 5.1 04 5.0 93 2.5 17 2.5 04 2.4 93 2.4 80 2.4 68 2.4 57 2.4 44 1.9 43 1.9 18 1.8 94 0.2 55 0.0 00 S53

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13 C NMR chart of 2d PP M 20 0 15 0 10 0 50 0 D F IL E T M S-aci d -C (37 83 C _C arb on- 1-1 ). al s C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 1- 10-201 3 17 :4 4: 38 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 1 0 56 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 2 0 .8 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \T M S -a ci d-C (3783 C _C ar b on-1-1 ). al s 208 .56 4 178 .34 6 138 .80 0 136 .43 4 133 .46 8 125 .21 7 104 .04 2 7 8.67 9 7 7.24 8 7 7.00 0 7 6.74 2 3 3.14 2 2 8.55 4 2 2.74 5 -1.14 9

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1 H NMR ch art o f 2e PP M 8 7 6 5 4 3 2 1 0 D F IL E p tB u O -a ci d-H (38 55 H ). al s CO M N T 3 8 55 D A T IM 1 5- 01-201 4 13 :5 6: 33 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 1 9 .4 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 3 8 38 55 _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B uO -a ci d-H (3855 H ). al s 2.5 5 2.0 4 2.0 0 4.0 7 2.0 3 9.3 5 7.3 06 7.2 77 7.2 61 6.9 62 6.9 34 5.1 09 5.0 99 5.0 88 2.4 97 2.4 88 2.4 73 2.4 65 2.4 49 2.4 39 1.9 39 1.9 14 1.8 90 1.3 38 S55

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13 C NMR chart of 2e PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 D F IL E p tB u O -a ci d-C (38 5 5C _C ar bon -1 -1) .a ls C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 1 5- 01-201 4 15 :0 1: 57 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 3 24 ACQ T M 0 .8 33 6 s ec PD 2 .0 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 2 1 .1 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 si n gl e p u lse d ec ou pl ed g a te d NO E C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \pt B uO -a ci d-C (385 5C _C ar bon -1-1) .a ls 208 .20 2 179 .29 1 154 .23 3 130 .77 8 126 .30 4 124 .16 8 103 .67 9 7 8.76 5 7 8.59 3 7 7.25 8 7 7.00 0 7 6.74 2 3 3.35 2 8.81 2 2 2 8.69 7 2 2.72 6

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1 H NMR ch art o f 2f PP M 8 7 6 5 4 3 2 1 0 D F IL E F -a ci d-H (3 8 48 H ). a ls CO M N T 3 8 48 D A T IM 0 9- 01-201 4 14 :4 3: 23 OBN U C 1 H E X M O D si ngl e_ pu ls e. ex 2 O B F R Q 3 00 .5 3 M H z O B SE T 1 .1 5 KH z O B F IN 8 .5 7 H z POI N T 1 3 10 7 F R EQU 4 50 8 .5 0 H z SC A N S 1 6 ACQ T M 2 .9 07 2 s ec PD 5 .0 00 0 s ec PW1 5 .5 5 u se c IR N U C 1 H CTEMP 1 9 .0 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 4 0 38 48 _C:\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \F -ac id -H (38 48H ). als 2.0 8 2.0 0 2.0 4 4.1 7 2.0 6 7.3 72 7.3 54 7.3 44 7.3 25 7.2 60 7.0 37 7.0 31 7.0 08 6.9 85 6.9 80 5.1 20 5.1 09 5.0 99 2.4 94 2.4 83 2.4 70 2.4 60 2.4 46 2.4 34 2.4 23 1.9 50 1.9 25 1.9 01 1.8 76 1.8 52 S57

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13 C NMR chart of 2f PP M 20 0 17 5 15 0 12 5 10 0 75 50 25 D F IL E 3 8 48C _C ar bo n -1-1 .a ls C O M N T si ngl e pu ls e de c oup le d g at ed N O E D A T IM 2 7- 04-201 4 10 :5 0: 04 OBN U C 1 3 C E X MO D c ar bo n .j x p O B F R Q 1 25 .7 7 M H z O B SE T 7 .8 7 KH z O B F IN 4 .2 1 H z POI N T 2 6 21 4 F R EQU 3 14 46 .5 4 H z SC A N S 2 4 48 ACQ T M 0 .8 33 6 s ec PD 2 .5 00 0 s ec PW1 3 .2 0 u se c IR N U C 1 H CTEMP 1 8 .5 c SL V N T C D C L3 E X R E F 7 7 .0 0 p pm B F 0 .1 2 H z R G AI N 6 0 208 .18 3 179 .34 8 162 .73 2 160 .77 6 131 .84 6 131 .81 8 .42 127 0 127 .36 3 115 .36 4 115 .19 2 103 .25 9 7 8.97 4 7 7.25 8 7 7.00 0 7 6.74 2 3 3.28 5 2 8.78 3 2 2.61 2

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1 H NMR ch art o f 2g PP M 8 7 6 5 4 3 2 1 0 D F IL E C F 3-ac id-H (38 69 _pr o ton -1-1 ). al s C O M N T si ngl e_ pu ls e D A T IM 2 8- 01-201 4 14 :2 0: 28 OBN U C 1 H E X MO D p ro to n.j xp O B F R Q 5 00 .1 6 M H z O B SE T 2 .4 1 KH z O B F IN 6 .0 1 H z POI N T 1 3 10 7 F R EQU 7 50 7 .5 1 H z SC A N S 1 6 ACQ T M 1 .7 45 9 s ec PD 2 .0 00 0 s ec PW1 5 .8 0 u se c IR N U C 1 H CTEMP 1 7 .8 c SL V N T C D C L3 E X R E F 0 .0 0 p pm B F 0 .1 2 H z R G AI N 4 2 si n gl e_p u lse C :\D o cum e nt s an d Se tt ing s\ 前川智弘 \ デスクトップ \ N M R データ保存用 \村井 \ al le ne \C F 3-a ci d-H (3869 _pr o to n-1 -1) .a ls 1.8 7 1.9 2 2.0 0 4.0 2 2.0 1 7.5 71 7.5 54 7.5 01 7.4 84 7.2 59 5.1 87 5.1 81 5.1 74 2.5 21 2.5 14 2.5 06 2.4 99 2.4 91 2.4 85 2.4 77 2.4 70 1.9 49 1.9 34 1.9 19 1.9 04 1.8 90 S59