Supporting Information

Neighboring Effect of Intramolecular Chlorine Atoms on

Epoxide Opening Reaction by Chloride Anions

Taiki Umezawa,* Masayuki Shibata, Ryutaro Tamagawa, Fuyuhiko Matsuda

Division of Environmental Materials Science, Graduate School of Environmental Science,

Hokkaido University, Sapporo 060-0810, Japan

umezawa@ees.hokudai.ac.jp

1
Table of Contents

1. Abbreviation 3

2. General Method 3

3. Experimental Procedures 3

4. Characterization of New Compounds in the Text 5

5. Synthesis of Starting Materials 13

6. NMR Spectra 31

2
Abbreviation
18-C-6 18-Crown-6-ether
DIBAL Diisobutylaluminium hydride
DET Tartaric acid diethyl ester
DCE 1,2-Dichloroethane
DMP Dess-Martin Periodinane
Hex n-C6H13
KHDMS Potassium hexamethyldisilazide
MS4A Molecular sieve 4 A
NaHMDS Sodium bis(trimethylsilyl)amide
NCS N-Chlorosuccinimide
TBHP tert-Butyl hydroperoxide
TBS tert-Butyldimethylsilyl
TDA-1 Tris[2-(2-methoxyethoxy)ethyl]amine
TEMPO 2,2,6,6-Tetramethylpiperidine 1-oxyl

General Methods

Tetrahydrofuran, diethylether, acetone, acetonitrile, and dichloroethane (dehydrated grade) were purchased

from Kanto Chemical Co. Inc. Dichloromethane (CH2Cl2) and triethylamine (Et3N) were distilled from CaH.

All commercially obtained reagents were used as received.

Analytical and preparative TLC were carried out using pre-coated silica gel plates (Macherey-Nagel DC-

Fertigplatten SIL G-25 UV254). Merck Kieselgel 60 Art 7734 silica gel was used for column chromatography.

IR spectra were recorded on a JASCO FTIR-4100 Type A spectrometer using a NaCl cell or a KBr board. 1H-

and 13C-NMR spectra were recorded using a JNM-EX 400 (400 MHz and 100 MHz) spectrometer. Chemical

shifts are reported in ppm relative to CHCl3 ( = 7.26) in CDCl3 and CHD2OD ( = 3.30) in CD3OD for 1H-

NMR, and CDCl3 ( = 77.0) and CD3OD ( = 49.0) for 13C-NMR. Splitting patterns are designated as s, d, t, q,

and m, indicating singlet, doublet, triplet, quartet, and multiplet, respectively.

Experimental Procedures

General procedure for the epoxide opening with BF3.OEt2

To a solution of vinyl epoxide 13c (345 mg, 1.07 mmol) in CH2Cl2 (1.0 mL) were added Et4NCl (8.89 g, 53.5

mmol, purchased from Tokyo Chemical Industry Co., Ltd.) and BF3.OEt2 (661 mL, 5.35 mmol, purchased from
3
sigma-aldrich) at room temperature under Ar atmosphere. The mixture was stirred for 50 min, poured into water,

extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was

purified by silica gel column chromatography (AcOEt:hexane = 2:98 then 6:94) to give anti-23c (292 mg, 1.01

mmol, 73%) as a pale oil.

General procedure for the epoxide opening with Ph3PCl2

To a solution of vinyl epoxide 13c (358 mg, 1.11 mmol) in CH2Cl2 (1.0 mL) was added Ph3PCl2 (1.11 g, 3.33 mmol,

purchased from sigma-aldrich) at 0 oC under Ar atmosphere. The mixture was stirred for 50 min, quenched with sat.

NaHCO3, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The

residue was purified by silica gel column chromatography (AcOEt:hexane = 2:98 then 6:94) to give anti-23c (399

mg, 1.01 mmol, 91%) as a pale oil.

General procedure for the epoxide opening with TiCl(OiPr)3

To a solution of vinyl epoxide 13c (308 mg, 1.04 mmol) in CH2Cl2 (1.0 mL) was added TiCl(OiPr)3 (1.56 mL. 1 M

solution in hexane, purchased from sigma-aldrich) at room temperature under Ar atmosphere. The mixture was

stirred for 3 h, quenched with saturated Na-K tartrate, extracted with AcOEt, washed with brine, dried over Na2SO4,

filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (AcOEt:hexane

= 4:96, 8:92, 12:88 then 16:84) to give 20c (147 mg, 0.478 mmol, 46%) as a mixture of diastereomers.

General procedure for the epoxide opening with ZrCl4

To a solution of vinyl epoxide 10c (346 mg, 1.18 mmol) in CH2Cl2 (1.1 mL) was added ZrCl4 (549 mg, 2.35 mmol)

at 0 oC under Ar atmosphere. The mixture was stirred for 3 h, quenched with saturated aqueous NaHCO3, extracted

with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified

by silica gel column chromatography (AcOEt:hexane = 4:96, 8:92, 12:88 then 16:84) to give 20c (179 mg, 0.581

mmol, 49%) as a mixture of diastereomers.

4
Characterization of New Compounds in the Text

16a

IR (neat) 3398, 3026, 2955, 2926, 2856, 1458, 1378, 1306, 1240, 1034, 875 cm–1; 1H NMR (400 MHz, CDCl3)

0.87 (3H, t, J = 6.8 Hz), 1.27-1.34 (12H, m), 1.49-1.61 (2H, m), 2.82 (1H, td, J = 5.6, 2.0 Hz), 3.36 (1H, dd, J =

8.3, 2.0 Hz), 4.28 (1H, dd, J = 13.2, 6.3 Hz), 4.38 (1H, dd, J = 13.2, 6.8 Hz), 5.21 (1H, dd, J = 10.5, 9.3 Hz), 5.84

(1H, ddd, J = 9.4, 8.5, 5.6 Hz); 13C NMR (CDCl3, 100 MHz)  14.0, 22.6, 25.8, 29.1, 29.3, 31.7, 31.9, 54.1, 58.7,

60.3, 129.5, 134.1; HRMS (ESI) m/z: [M + Na]+; Calcd for C12H22O2Na 221.1517; Found 221.1516.

anti-17

IR (neat) 3334, 2925, 2856, 1457, 1317, 1130, 1023, 795, 722 cm–1; 1H NMR (400 MHz, CDCl3) 0.86 (3H, t, J =

6.8 Hz), 1.23 (8H, s), 1.44-1.57 (2H, m), 1.95 (2H, s), 3.73-3.78 (1H, m), 4.22-4.32 (1H, m), 4.73 (1H, dd, J = 10.2,

4.9 Hz), 5.72 (1H, ddd, J = 11.2, 9.0, 1.5 Hz), 5.84 (1H, dt, J = 8.7, 5.6 Hz); 13C NMR (CDCl3, 100 MHz)  14.1,

22.6, 25.6, 29.2, 29.4, 31.8, 33.1, 58.6, 60.7, 74.4, 128.2, 133.1; HRMS (ESI) m/z: [M + Na]+; Calcd for

C12H23ClO2Na 257.1284; Found 257.1282.

syn-17

IR (neat) 3347, 2954, 2925, 2856, 1464, 1213, 1129, 1081, 1030, 942, 790, 723 cm–1; 1H NMR (400 MHz, CDCl3)

0.88 (3H, t, J = 6.3 Hz), 1.27 – 1.58 (13H, m), 1.92 (1H, br), 3.62 – 3.67 (1H, m), 4.22 – 4.33 (2H, m), 4.73 (1H,

dd, J = 10.2, 5.8 Hz), 5.70 (1H, dd, J = 10.2 Hz), 5.82 (1H, dt, J = 10.7, 6.3 Hz); 13C NMR (CDCl3, 100 MHz) 

14.0, 22.6, 25.7, 29.1, 29.4, 31.8, 33.2, 58.6, 62.2, 74.5, 129.0, 132.6; HRMS (ESI) m/z: [M + Na]+; Calcd for

C12H23ClO2Na 257.1284; Found 257.1281.

To a solution of syn-17 (4.5 mg, 0.0192 mmol) in DMF (0.20 mL) was added NaHMDS (1.15 M in

THF, 25.0 L, 0.0288 mmol) at 0 oC under Ar atmosphere. The mixture was stirred for 30 min,

poured into water, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The residue was purified by silica gel column chromatography (AcOEt:hexane = 8:92, then 12:88) to give 16b (1.8

5
mg, 0.00909 mmol, 47%) as a colorless oil: IR (neat) 3409, 2955, 2925, 2855, 1735, 1464, 1406, 1378, 1258, 1032,

945, 828, 723 cm–1; 1H NMR (400 MHz, CDCl3) 0.88 (3H, t, J = 6.3 Hz), 1.27-1.62 (13H, m), 3.09 (1H, q, J =

4.4 Hz), 3.64 (1H, dd, J = 8.8, 4.4 Hz), 4.29 (1H, ddd, J = 13.6, 6.1, 1.0 Hz), 4.39 (1H, ddd, J = 13.6, 6.8, 1.4 Hz),

5.21 (1H, dt, J = 11.2, 5.8 Hz), 5.94 (1H, m); 13C NMR (CDCl3, 100 MHz)  14.0, 22.6, 26.3, 28.1, 29.1, 29.4, 31.7,

52.8, 58.5, 59.0, 126.3, 135.0; HRMS (ESI) m/z: [M + Na]+; Calcd for C12H22O2Na 221.1517; Found 221.1516.

18

IR (neat) 2957, 2928, 2857, 1719, 1646, 1465, 1193, 1031, 876, 825, cm–1; 1H NMR (400 MHz, CDCl3) 0.85 (3H,

t, J = 6.8 Hz), 1.26-1.32 (11H, m), 1.41-1.50 (2H, m), 1.60-1.66 (2H, m), 2.86 (1H, td, J = 5.4, 2.0 Hz), 4.17 (2H, q,

J = 7.2 Hz), 4.30 (1H, dd, J = 8.3, 1.5 Hz), 5.74 (1H, dd, J = 11.7, 8.3 Hz), 5.93 (1H, d, J = 11.7 Hz); 13C NMR

(CDCl3, 100 MHz)  14.1, 14.2, 22.6, 25.8, 29.2, 29.3, 31.7, 31.9, 54.2, 60.1, 60.4, 123.3, 147.0, 165.9; HRMS

(ESI) m/z: [M + Na]+; Calcd for C14H24O3Na 263.1623; Found 263.1617.

anti-19

IR (neat) 3462, 2927, 2856, 1720, 1651, 1466, 1415, 1388, 1188, 1028, 838 cm–1; 1H NMR (400 MHz, CDCl3)

0.83 (3H, t, J = 6.6 Hz), 1.28-1.32 (12H, m), 1.43 (1H, t, J = 8.5 Hz), 1.48 (1H, t, J = 8.8 Hz), 2.28 (1H, d, J =

3.0 Hz), 3.85 (1H, d, J = 4.4 Hz), 4.17 (2H, q, J = 7.2 Hz), 5.76 (1H, dd, J = 5.1, 3.4 Hz), 5.91 (1H, d, J = 11.7 Hz),

6.31 (1H, t, J = 11.0 Hz); 13C NMR (CDCl3, 100 MHz)  14.1, 14.1, 22.6, 25.6, 29.1, 29.4, 31.8, 33.2, 59.7, 60.6,

74.4, 122.2, 142.7, 165.6; HRMS (ESI) m/z: [M + Na]+; Calcd for C14H25ClO3Na 299.1390; Found 299.1387.

[]D19 +11.4 (c 0.44, CHCl3); IR (neat) 3421, 2925, 2855, 1717, 1540, 1456, 1375, 1039, 725

cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.25-1.41 (8H, m), 1.47-1.57 (2H, m), 1.64-

1.75 (2H, m), 1.84-1.91 (1H, m), 2.02-2.06 (1H, m), 3.76 (1H, dt, J = 10.7, 2.9 Hz), 3.86-3.92

(1H, m), 4.28 (2H, dd, J = 6.3, 0.9 Hz), 4.78 (1H, dd, J = 10.2, 4.8 Hz), 5.75 (1H, t, J = 11.2 Hz), 5.89 (1H, dt, J =

11.2, 6.3 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.3, 28.7, 30.4, 31.6, 34.9, 38.7, 58.6, 60.5, 64.3, 74.3, 127.8, 133.3;

HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C14H26Cl2O2Na 319.1207 ; Found 319.1205.

6
 []D19 +54.2 (c 0.20, CHCl3); IR (neat) 3336, 2925, 2855, 1653, 1507, 1456, 1022 cm–1; 1H

NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.25-1.87 (15H, m), 2.45 (1H, br), 4.02-4.07 (1H, m),

4.17-4.23 (1H, m), 4.25-4.34 (2H, m), 4.74 (1H, dd, J = 10.2, 6.3 Hz), 5.69 (1H, t, J = 10.2 Hz),

5.85 (1H, dt, J = 11.7, 6.3 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.3, 28.7, 31.6, 31.6, 39.0, 42.1, 58.6, 60.4, 62.1,

71.8, 128.6, 133.1; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C14H26Cl2O2Na 319.1207 ; Found 319.1210.

[]D16 +94.6 (c 0.28, CHCl3); IR (neat) 3336, 2925, 2855, 1716, 1456, 1377, 1025, 940, 792,

723 cm–1; 1H NMR (CDCl3) δ 0.89 (3H, t, J = 6.8 Hz), 1.25-1.76 (14H, m) 1.86-1.94 (1H, m),

2.00-2.07 (1H, m), 3.65 (1H, ddd, J = 9.6, 6.6, 2.9 Hz), 3.76-3.80 (1H, m), 3.90-3.96(1H, m),

4.24-4.34 (2H, m), 4.78 (1H, dd, J = 10.0, 4.4 Hz), 5.75 (1H, t, J = 11.2 Hz), 5.88 (1H, dt, J = 11.2, 6.3 Hz); 13C

NMR (CDCl3) δ 14.0, 22.5, 26.5, 28.8, 29.6, 31.6, 34.1, 38.5, 58.6, 60.2, 63.4, 73.5, 128.1, 133.3; HRMS (ESI-

orbitrap) m/z: [M+Na]+; Calcd for C14H26Cl2O2Na 319.1207 ; Found 319.1205.

[]D17 –42.8 (c 0.21, CHCl3); IR (neat) 3335, 2926, 2856, 1699, 1652, 1558, 1540, 1456, 1062,

969, 669 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.25-1.75 (13H, m) 1.80-2.05 (3H,

m), 3.74 (1H, dd, J = 11.7, 7.3 Hz, 3.80 (1H, dd, J = 11.7, 4.9 Hz), 3.89-3.95 (1H, m), 4.19 (1H,

13
q, J = 5.8 Hz), 4.49-4.54 (1H, m), 5.79 (1H, dd, J = 11.7, 7.8 Hz), 5.89 (1H, dt, J = 11.7, 5.8 Hz); C NMR

(CDCl3) δ 14.0, 22.6, 26.4, 28.8, 30.6, 31.7, 34.9, 38.6, 58.7, 62.4, 64.3, 74.6, 128.7, 133.0; HRMS (ESI-orbitrap)

m/z: [M+Na]+; Calcd for C14H26Cl2O2Na 319.1207 ; Found 319.1204.

Cl
IR (neat) 3355, 2954, 2924, 2854, 1716, 1652, 1507, 1456, 1267, 1018, 797, 687 cm–1; 1H
Cl Cl
Hex
OH NMR (CDCl3) δ 0.89 (3H, t, J = 6.8 Hz), 1.25-1.36 (6H, m), 1.53-1.67 (2H, m), 1.80-1.90 (1H,
CH2OH
anti-20c m), 1.97-2.05 (1H, m), 2.17-2.24 (3H, m), 2.49 (1H, ddd, J = 14.1, 11.7, 4.8 Hz), 3.77-3.82 (1H,

13
m), 4.30 (2H, br), 4.81 (1H, dd, J = 9.7, 4.8 Hz), 5.76 (1H, t, J = 10.7 Hz), 5.91 (1H, dt, J = 10.7, 6.3 Hz); C

NMR (CDCl3) δ 14.0, 22.5, 25.1, 28.6, 29.0, 31.5, 44.0, 48.3, 58.6, 60.4, 73.8, 95.2, 127.9, 133.5; HRMS (APCI-

7
orbitrap) m/z: [M]+; Calcd for C14H26Cl3O2 331.0992 ; Found 331.0996.

IR (neat) 3336, 2925, 2854, 1732, 1716, 1698, 1652, 1507, 1456, 1020, 798, 687 cm–1; 1H

NMR (CDCl3) δ 0.89 (3H, t, J = 7.3 Hz), 1.25-1.31 (6H, m), 1.56-1.67 (2H, m), 1.79-1.84 (1H,

m), 1.98-2.04 (1H, m), 2.17-2.25 (3H, m), 2.47 (1H, ddd, J = 14.1, 11.7, 4.3 Hz), 3.70 (1H, m),

4.31 (2H, br), 4.78 (1H, dd, J = 10.2, 6.3 Hz), 5.71 (1H, t, J = 10.7 Hz), 5.87 (1H, dt, J = 11.2, 6.3 Hz); 13C NMR

(CDCl3) δ 14.0, 22.5, 25.1, 28.6, 29.2, 31.5, 43.9, 48.4, 58.7, 62.2, 74.0, 95.2, 128.4, 133.2; HRMS (APCI-orbitrap)

m/z: [M]+; Calcd for C14H26Cl3O2 331.0992; Found 331.0995.

OH Cl []D18 +18.8 (c 0.20, CHCl3); IR (neat) 3361, 2955, 2925, 2855, 1716, 1540, 1507, 1456, 1376,
Hex
Cl 1058, 970 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.24-1.55 (8H, m), 1.71-2.31 (4H,
CH2OH
anti-21a
m), 4.11-4.20 (2H, m), 4.25-4.31 (2H, m), 4.77 (1H, dd, J = 10.7, 4.8 Hz), 5.74 (1H, t, J = 11.7

Hz), 5.88 (1H, dt, J = 11.7, 5.8 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.3, 28.7, 31.6, 39.0, 41.8, 58.6, 60.4, 60.4,

71.5, 128.0, 133.3; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C13H24Cl2O2Na 305.1051; Found 305.1053.

OH Cl []D18 –20.8 (c 0.28, CHCl3); IR (neat) 3420, 2924, 2854, 1733, 1717, 1558, 1540, 1507,
Hex
Cl
1457, 1249, 1027, 669 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.29-1.57 (8H, m),
CH2OH
syn-21a
1.71-1.88 (4H, m), 4.05 (1H, ddd, J = 9.2, 6.3, 2.4 Hz), 4.19-4.23 (1H, m), 4.29 (2H, t, J =

13
6.3 Hz), 4.74 (1H, dd, J = 10.2, 6.8 Hz), 5.70 (1H, t, J = 10.2 Hz), 5.86 (1H, dt, J = 10.7, 6.3 Hz); C NMR

(CDCl3) δ 13.9, 22.4, 26.4, 28.6, 31.6, 38.9, 42.0, 58.6, 60.4, 62.0, 71.7, 128.6, 133.0; HRMS (ESI-orbitrap) m/z:

[M+Na]+; Calcd for C13H24Cl2O2Na 305.1051 ; Found 305.1053.

23
[]D –26.0 (c 0.05, CHCl3); IR (neat) 3328, 2928, 2857, 1457, 1006, 796 cm–1; 1H NMR

(CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.25-1.42 (8H, m), 1.65-1.84 (2H, m), 1.95-2.17 (2H, m),

3.97 (1H, m), 4.21 (1H, m), 4.06-4.12 (2H, m), 4.23-4.30 (2H, m), 4.82 (1H, dd, J = 10.2, 4.8

Hz), 5.75 (1H, t, J = 10.7 Hz), 5.90 (1H, dt, J = 10.2, 6.3 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.3, 28.7, 31.6, 39.0,

8
41.8, 28.6, 60.4, 71.5, 77.2, 128.0, 133.3; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C13H24Cl2O2Na

305.1051 ; Found 305.1057.

27
[]D +97.5 (c 0.61, CHCl3); IR (neat) 3356, 2955, 2928, 2857, 1458, 1377, 1270, 1072,

1027, 941, 843, 787, 670 cm–1; 1H NMR (CDCl3) δ 0.89 (3H, t, J = 6.8 Hz), 1.25-1.42 (10H,

m), 1.66-1.84 (2H, m), 1.90-2.12 (2H, m), 3.90-3.94 (1H, m), 4.08-4.14 (1H, m), 4.29 (2H, d,

J = 6.4 Hz), 4.86 (1H, dd, J = 10.0, 4.9 Hz), 5.71 (1H, t, J = 10.2 Hz), 5.83-5.89 (1H, m); 13C NMR (CDCl3) δ 14.0,

22.5, 26.1, 28.7, 31.6, 37.8, 41.6, 28.6, 58.6, 60.7, 60.9, 72.4, 128.5, 133.3; HRMS (ESI-orbitrap) m/z: [M+Na]+;

Calcd for C13H24Cl2O2Na 305.1051 ; Found 305.1057.

[]D 26 –56.1 (c 0.57, CHCl3); IR (neat) 3352, 2921, 2851, 1731, 1457, 1041 cm–1; 1H NMR (CDCl3)

δ 0.88 (3H, t, J = 6.8 Hz), 1.25-1.74 (10H, m), 2.02-2.05 (1H, m), 3.81-3.91 (2H, m), 4.29 (2H, ddd,

J = 11.7, 6.8, 1.4 Hz), 5.19 (1H, dd, J = 10.7, 3.9 Hz), 5.73 (1H, t, J = 10.7 Hz), 5.93 (1H, dt, J =

10.7, 6.8 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 25.7, 28.7, 31.6, 33.0, 57.7, 58.6, 63.1, 77.2, 126.4, 134.0; HRMS

(ESI-orbitrap) m/z: [M+Cl]–; Calcd for C12H22Cl3O2 303.0697 ; Found 303.0690.

Cl Cl []D 25
+136.9 (c 0.80, CHCl3); IR (neat) 3346, 2955, 2923, 2853, 1732, 1716, 1458, 1377, 1031,
Hex
OH 721 cm–1; 1H NMR (CDCl3) δ 0.89 (3H, t, J = 6.8 Hz), 1.24-1.73 (10H, m), 2.00-2.26 (1H, m), 2.25
OH
syn-22a (1H, br), 3.64 (1H, br), 3.93 (1H, td, J = 8.8, 2.9 Hz), 4.28-4.39 (2H, m), 5.43 (1H, dd, J = 9.2, 2.9

Hz), 5.78-5.89 (2H, m); 13C NMR (CDCl3) δ 14.0, 22.5, 25.8, 28.8, 31.6, 33.2, 58.6, 59.3, 62.7, 77.0, 128.5, 132.8;

HRMS (ESI-orbitrap) m/z: [M+Cl]–; Calcd for C12H22Cl3O2 303.0697 ; Found 303.0690.

25
[]D +148.7 (c 0.77, CHCl3); IR (neat) 3363, 2920, 2850, 1716, 1456, 1017, 801 cm–1; 1H NMR

(CDCl3) δ 0.89 (3H, t, J = 6.8 Hz), 1.25-1.40 (10H, m), 1.76-1.99 (2H, m), 3.63 (1H, d, J = 8.7 Hz),

4.29 (2H, dd, J = 7.3, 6.3 Hz), 4.52 (1H, ddd, J = 8.7, 5.3, 1.4 Hz), 4.89 (1H, t, J = 9.2 Hz), 5.71 (1H,

t, J = 10.7 Hz), 5.93 (1H, dt, J = 10.7, 7.3 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.6, 28.6, 31.5, 35.3, 55.8, 58.4,

9
64.1, 75.6, 130.3, 132.8; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C12H22Cl2O2Na 291.0889 ; Found

291.0891.

Cl Cl

Hex
OH
[]D 25 +407.1 (c 0.07, CHCl3); IR (neat) 3361, 2955, 2923, 2853, 1698, 1456, 1375, 1026, 794, 720

OH
cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.24-1.35 (10H, m), 1.78-1.94 (2H, m), 3.68-
syn-22b

3.72 (1H, m), 3.94-3.97 (1H, m), 4.30-4.35 (2H, m), 4.95 (1H, dd, J = 10.7, 8.3 Hz), 5.56 (1H, t, J =

10.7 Hz), 5.89 (1H, dt, J = 10.7, 6.8 Hz); 13C NMR (CDCl3) δ 14.0, 22.5, 26.5, 28.6, 31.5, 35.4, 58.6, 60.6, 63.8,

76.2, 126.9, 134.2; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C12H22Cl2O2Na 291.0889 ; Found 291.0892.

[]D19 +14.0 (c 1.46, CHCl3); IR (neat) 2927, 2856, 1717, 1456, 1387, 1188, 1026, 836 cm–1;

1
H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.27-1.42 (9H, m), 1.48-1.56 (2H, m), 1.66-1.76

(4H, m), 1.87-1.91 (1H, m), 2.00-2.03 (1H, m), 2.31 (1H, d, J = 4.8 Hz), 3.86-3.92 (2H, m), 4.20 (2H, q, J = 6.8

Hz), 5.78 (1H, dd, J = 10.2, 3.9 Hz), 5.94 (1H, d, J = 12.2 Hz), 6.32 (1H, t, J = 10.2 Hz); 13C NMR (CDCl3) δ 14.0,

14.1, 22.5, 26.3, 28.7, 30.4, 31.6, 34.9, 38.6, 59.6, 60.7, 64.2, 74.3, 122.5, 142.4, 165.5; HRMS (APCI-orbitrap)

m/z: [M+Na]+; Calcd for C16H28Cl2O3Na 361.1307 ; Found 361.1307.

[]D20 –2.0 (c 1.26, CHCl3); IR (neat) 2928, 2856, 1733, 1716, 1232, 1025, 815 cm–1; 1H NMR

(CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.24-1.56 (9H, m), 1.66-1.73 (4H, m), 1.85-1.92 (2H, m),

2.29 (1H, d, J = 5.3 Hz), 3.86-3.92 (2H, m), 4.20 (2H, q, J = 7.3 Hz), 5.77 (1H, dd, J = 10.2, 3.9 Hz), 5.95 (1H, d, J

= 12.2 Hz), 6.32 (1H, dd, J = 11.7, 10.2 Hz); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 26.4, 28.7, 29.8, 31.6, 34.3, 38.5,

59.6, 60.7, 63.4, 73.6, 122.5, 142.6, 165.6; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C14H26Cl3O2

C16H28Cl2O3Na 361.1307 ; Found 361.1307.

Cl Cl Cl
Hex
OH IR (neat) 3480, 2955, 2931, 2857, 1742, 1718, 1446, 1414, 1387, 1189, 1094, 1026, 922, 864,
CO2Et
anti-23c 836, 816, 727, 687 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.23-1.37 (9H, m), 1.58-

1.64 (2H, m), 1.79-1.84 (1H, m), 1.93-1.99 (1H, m), 2.14-2.24 (3H, m), 2.46 (1H, ddd, J = 14.6, 11.7, 4.8 Hz),

10
3.86-3.92 (1H, m), 4.19 (2H, q, J = 6.8 Hz), 5.76 (1H, dd, J = 10.2, 3.4 Hz), 5.95 (1H, d, J = 11.7 Hz), 6.31 (1H, dd,

J = 11.7, 10.2 Hz); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 25.1, 28.6, 29.2, 31.5, 44.0, 48.3, 59.4, 60.8, 73.8, 95.1,

122.7, 142.4, 165.6;; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C16H27Cl3O3Na 395.0918 ; Found 395.0920.

[]D20 +25.0 (c 0.55, CHCl3); IR (neat) 3446, 2956, 2929, 2858, 1717, 1652, 1540, 1507,

1456, 1415, 1188, 1067, 1026, 836 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz), 1.11-

1.57 (11H, m), 1.69-1.91 (4H, m), 2.39 (1H, d, J = 4.8 Hz), 4.18-4.23 (4H, m), 5.75 (1H, dd, J = 9.7, 3.9 Hz), 5.94

(1H, d, J = 11.7 Hz), 6.30 (1H, t, J = 11.2 Hz); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 26.3, 28.7, 31.6, 39.0, 41.8,

59.5, 60.2, 60.7, 71.6, 122.4, 142.5, 165.5; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C15H26Cl2O3Na

347.1148 ; Found 347.1151.

OH Cl

Hex []D21 –16.4 (c 1.43, CHCl3); IR (neat) 3446, 2956, 2929, 2858, 1717, 1652, 1540, 1507, 1457,
Cl
CO2Et
anti-24b 1415, 1387, 1193, 1065, 1027, 836, 726 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 6.8 Hz),

1.11-1.57 (11H, m), 1.69-1.91 (4H, m), 2.39 (1H, d, J = 4.8 Hz), 4.18-4.23 (4H, m), 5.75 (1H, dd, J = 9.7, 3.9 Hz),

5.94 (1H, d, J = 11.7 Hz), 6.30 (1H, t, J = 11.2 Hz); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 26.3, 28.7, 31.6, 39.0,

41.8, 59.5, 60.2, 60.7, 71.6, 122.4, 142.5, 165.5; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C15H26Cl2O3Na

347.1148; Found 347.1151.

25
[]D –11.4 (c 0.21, CHCl3); IR (neat) 3480, 2955, 2927, 2857, 1743, 1464, 1414, 1380, 1222,

1186, 1095, 1028, 836, 728 cm–1; 1H NMR (CDCl3) δ 0.88 (3H, t, J = 7.3 Hz), 1.25-1.38 (9H, m),

1.56-1.68 (2H, m), 1.70-1.77 (1H, m), 1.92-2.00 (1H, m), 2.65 (1H, d, J = 3.9 Hz), 3.91-3.98 (2H, m), 4.22 (2H, q,

J = 7.3 Hz), 5.97 (1H, d, J = 11.2 Hz), 6.05 (1H, dd, J = 10.2, 4.8 Hz), 6.32 (1H, dd, J = 11.2, 10.2 Hz); 13C NMR

(CDCl3) δ 14.0, 14.1, 22.5, 25.9, 28.6, 31.6, 32.6, 55.9, 60.8, 62.9, 76.6, 123.1, 141.1, 165.4; HRMS (ESI-orbitrap)

m/z: [M+Na]+; Calcd for C14H24Cl2O3Na 333.0998 ; Found 333.0994.

11
 Cl Cl

Hex
25
OH []D +54.3 (c 0.61, CHCl3); IR (neat) 3438, 2955, 2927, 2858, 1716, 1652, 1465, 1412, 1386,
CO2Et
anti-25b
1261, 1224, 1196, 1122, 1074, 1024, 959, 907, 841, 812, 710, 667 cm–1; 1H NMR (CDCl3) δ 0.88

(3H, t, J = 7.3 Hz), 1.22-1.55 (11H, m), 1.77-1.98 (2H, m), 2.89 (1H, d, J = 10.7 Hz), 3.64 (1H, ddd, J = 11.2, 9.7,

1.4 Hz), 4.22 (2H, q, J = 7.3 Hz), 4.49 (1H, ddd, J = 9.2, 5.3, 1.4 Hz), 5.71 (1H, dd, J = 9.7, 9.2, Hz), 6.00 (1H, d, J

= 11.2 Hz), 6.25 (1H, dd, J = 11.2, 9.7 Hz); 13C NMR (CDCl3) δ 14.0, 14.1, 22.5, 26.6, 28.0, 31.6, 35.2, 55.7, 61.0,

64.0, 76.0, 123.0, 144.2, 166.4; HRMS (ESI-orbitrap) m/z: [M+Na]+; Calcd for C14H24Cl2O3Na 333.0998 ; Found

333.0994.

12
Synthesis of Starting Materials

,-Unsaturated Ester S2

To a solution of S1 (3.90 mL, 25.0 mmol) in (ClH2C)2 (63 mL) were added pyrrolidine (2.50 mL, 1.85 mmol) and

NCS (10.0 g, 75.0 mmol) at room temperature under an Ar atmosphere. The mixture was heated at 60 °C. After the

mixture was stirred for over, MeO2C(H)C=PPh3 (10.9 g, 32.0 mmol) was added, and the mixture was stirred for 3 h

and then concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt =

99:1, then 98:2) to give S2 (4.02 g, 15.9 mmol, 64%) as a yellow oil: IR (neat) 2954, 2930, 1732, 1435, 1310, 1280,

1196, 1172, 1040, 1012, 970, 779, 727, 647 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.27 -

1.38 (6H, m), 1.53 - 1.61 (2H, m), 2.27 - 2.32 (2H, m), 3.79 (3H, s), 6.30 (1H, d, J = 11.2 Hz), 7.02 (1H, d, J = 14.6

Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.2, 28.6, 31.5, 48.0, 52.0, 88.0, 121.8, 147.2, 165.9; HRMS (ESI)

m/z: [M+Na]+; Calcd for C11H18O2Cl2Na 275.0586; Found 275.0576.

Alcohol S3

To a solution of S2 (89.1 mg, 0.352 mmol) in THF (1.8 mL) was added LiBH4 (15.3 mg, 0.704 mmol) at 0 °C

under Ar atmosphere. After the mixture was stirred for 1 h, and MeOH (14.0 μL, 0.352 mmol) was added and the

mixture was stirred for 1 h at room temperature, quenched with saturated aqueous NaHCO3, extracted with AcOEt,

washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel

13
column chromatography (hexane:AcOEt = 95:5, then 92:8) to give S3 (75.0 mg, 0.330 mmol, 64%) as a colorless

oil: IR (neat) 3333, 2955, 2955, 2931, 1446, 1377, 1198, 1056, 915, 764, 727, 687 cm–1; 1H NMR (CDCl3, 400

MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.27 - 1.38 (6H, m), 1.61 - 1.67 (2H, m), 1.91 - 1.99 (2H, m), 2.18 - 2.31 (2H, m),

13
2.34 - 2.47 (2H, m), 3.68 - 3.76 (2H, m); C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.2, 28.6 (×2), 31.5, 44.3,

48.2, 62.0, 95.4; HRMS (ESI) m/z: [M+Na]+; Calcd for C10H18O2Cl2Na 263.0582; Found 275.0579.

,-Unsaturated Ester S4

To a solution of S3 (1.53 g, 6.73 mmol) in CH2Cl2 (34 mL) were added TEMPO (210 mg, 1.35 mmol) and

PhI(OAc)2 (3.25 g, 10.1 mmol) at room temperature under Ar atmosphere. The mixture was stirred for 24 h. Then

MeO2C(H)C=PPh3 (4.50 g, 13.5 mmol) was added, and the mixture was stirred for 12 h and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane:AcOEt = 99:1) to give unsaturated ester S4

(1.35 g, 4.80 mmol, 88%) as a colorless oil: IR (neat) 2953, 2931, 2857, 1727, 1660, 1435, 1326, 1273, 1211, 1173,

1040, 978, 803, 724, 688 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.27 - 1.38 (6H, m), 1.61 -

1.67 (2H, m), 2.18 - 2.22 (2H, m), 2.28 - 2.32 (2H, m), 2.59 - 2.65 (2H, m), 3.77 (3H, s), 5.89 (1H, dt, J = 16.1, 1.5

Hz), 6.99 (1H, dt, J = 15.6, 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.2, 28.1, 28.6, 31.5, 45.7, 48.3,

51.5, 94.3, 121.9, 146.9, 166.7; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H22O2Cl2Na 303.0899; Found 303.0889.

Epoxide S5

To a solution of S4 (1.35 g, 4.80 mmol) in CH2Cl2 (24 mL) was added DIBAL (1.01 M in PhMe, 11.9 mL, 12.0

mmol) at 0 °C under an Ar atmosphere. The mixture was stirred 30 min, quenched with saturated Na-K tartrate,

stirred for 1 h, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The alcohol was employed directly in the next step.

To a solution of crude allyl alcohol in CH2Cl2 (24 mL) were added mCPBA (1.24 g, 7.20 mmol) and NaHCO3

(806 mg, 9.60 mmol) at rt under an Ar atmosphere. The mixture was stirred overnight, quenched with saturated

Na2S2O3, stirred for 1 h, extracted with AcOEt and NaOH, washed with brine, dried over Na2SO4, filtered, and

concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 90:10) to

14
give epoxide S5 (657 mg, 2.32 mmol, 47%) as a colorless oil: IR (neat) 3419, 2954, 2930, 2858, 1456, 1378, 1208,

1125, 1086, 937, 803, 726, 687 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.90 (3H, t, J = 7.3 Hz), 1.32 - 1.37 (6H, m),

1.63 - 1.67 (2H, m), 1.85 - 1.94 (1H, m), 2.06 - 2.19 (1H, m), 2.19 - 2.22 (2H, m), 2.25 - 2.40 (3H, m), 2.99 - 3.00

(1H, m), 3.05 (1H, ddd, J = 9.0, 4.4, 2.0 Hz), 3.67 (1H, dd, J = 12.7, 4.4 Hz), 3.99 (1H, dd, J = 12.7, 2.4 Hz); 13C

NMR (CDCl3, 100 MHz) δ 14.0, 22.4, 25.1, 27.6, 28.6, 31.5, 43.8, 48.3, 54.8, 58.5, 61.4, 94.6; HRMS (ESI) m/z:

[M+Na]+; Calcd for C12H22O2Cl2Na 291.0898; Found 291.0889.

Olefin 13c

To a solution of S5 (279 mg, 1.04 mmol) in CH2Cl2 (21 mL) was added DMP (573 mg, 1.35 mmol) at room

temperature under Ar atmosphere. The mixture was stirred for 1 h, quench with saturated NH4Cl, extracted with

AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The aldehyde was employed

directly in the next step.

To a solution of Ando regent (417 mg, 1.25 mmol) in THF (2.6 mL) were added TDA-1 (1.00 mL, 3.12 mmol)

and NaHMDS (1.09 mL, 1.25 mmol, 1.14M in THF) at －78 °C under an Ar atmosphere. After the mixture was

stirred for 30 min, a solution of crude aldehyde in THF (2.6 mL) was added. After more 1h, quench with saturated

NH4Cl, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The

residue was purified by silica gel column chromatography (hexane:AcOEt = 99:1) to give olefin 13c (180 mg, 53.5

mmol, 52%) as a colorless oil; IR (neat) 2956, 2932, 2857, 1719, 1645, 1445, 1404, 1269, 1192, 1029, 878, 818,

727, 687, 640 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.24 - 1.35 (6H, m), 1.62 - 1.67 (2H, m),

1.95 - 2.05 (1H, m), 2.11 - 2.16 (1H, m), 2.18 - 2.22 (2H, m), 2.31 - 2.38 (2H, m), 2.97 (1H, ddd, J = 6.5, 4.4, 2.0

Hz), 4.23 (2H, q, J = 7.2 Hz), 4.36 (1H, dd, J = 9.3, 1.0 Hz), 5.78 (1H, dd, J = 11.7, 8.3 Hz), 5.98 (1H, dd, J = 11.7,

1.0 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0 (×2), 22.4, 25.1, 28.0, 28.6, 31.5, 43.7, 48.4, 54.2, 58.2, 60.5, 94.5,

124.0, 146.1, 165.8; HRMS (ESI) m/z: [M+Na]+; Calcd for C16H26O3Cl2Na 359.1155; Found 359.1151.

Allyl alcohol 10c

To a solution of 13c (97.8 mg, 0.290 mmol) in Et2O (1.5 mL) was added DIBAL (1.00 M in THF, 1.90 mL, 1.90

15
mmol) at －78 °C under an Ar atmosphere. The mixture was stirred 30 min, quenched with saturated Na-K tartrate,

stirred for 1 h, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane:AcOEt = 90:10) to give allyl alcohol 10c

(42.7 mg, 0.130 mmol, 44%) as a colorless oil; IR (neat) 3417, 2954, 2930, 2857, 1717, 1445, 1209, 1034, 876, 727,

687, 639 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.90 (3H, t, J = 6.8 Hz), 1.25 - 1.37 (9H, m), 1.62 - 1.67 (2H, m),

1.86 - 1.92 (1H, m), 2.10 - 2.14 (1H, m), 2.16 - 2.22 (2H, m), 2.29 - 2.38 (2H, m), 2.91 (1H, ddd, J = 6.7, 4.4, 2.0

Hz), 3.47 (1H, dd, J = 9.0, 2.0 Hz), 4.33 (1H, dd, J = 13.2, 6.3 Hz), 4.42 (1H, dd, J = 12.7, 6.3 Hz), 5.20 - 5.26 (1H,

13
m), 5.90 (1H, dt, J = 11.2, 6.8 Hz); C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.2, 28.1, 28.7, 31.6, 43.8, 48.4,

54.2, 58.9, 59.1, 94.7, 129.1, 134.5; HRMS (ESI) m/z: [M+Na]+; Calcd for C14H24O2Cl2Na 317.1055; Found

317.1046.

,-Unsaturated Ester S6

To a solution of nitrosobenzene (418 mg, 3.90 mmol) and L-proline (89.8 mg, 0.780 mmol) in CHCl3 (20 mL) was

added S1 (500 mg, 3.90 mmol) at 0 °C under an Ar atmosphere. The reaction mixture was stirred at the same

16
temperature for 24 h, followed by the addition of MeO2C(H)C=PPh3 (1.70 g, 5.07 mmol). The mixture was stirred

24 h, concentrated in vacuo. The ester was employed directly in the next step.

To a solution of crude ester in MeOH (3.9 mL) were added copper sulfate (292 mg, 30 mol %) at rt under an Ar

atmosphere. The mixture was stirred 12 h, concentrated in vacuo. The residue was purified by silica gel column

chromatography (hexane:AcOEt = 99:1 then 95:5) to give unsaturated ester S6 (358 mg, 1.79 mmol, 46%) as a pale

oil. Spectral data of S6 were matched with known compound. (Evans, P.; Leffray, M. Tetrahedron 2003, 59, 7973–

7981)

Diol S7

To a solution of S6 (358 mg, 1.79 mmol) in THF (9.0 mL) was added LiBH4 (78.0 mg, 3.58 mmol) at 0 °C under

Ar atmosphere. After the mixture was stirred for 1 h, and MeOH (72.4 μL, 1.79 mmol) was added and the mixture

was stirred for 1 h at room temperature, quenched with saturated aqueous NaHCO3, extracted with AcOEt, washed

with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column

chromatography (hexane:AcOEt = 95:5 then 92:8) to give diol S7 (261 mg, 1.50 mmol, 84%) as a yellow oil:

[]D21 –3.1 (c 3.24 CHCl3); IR (neat) 3334, 2928, 2857, 1698, 1683, 1456, 1376, 1339, 1184, 1129, 1056, 1012,

835, 724, 699 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.3 Hz), 1.18 - 1.38 (8H, m), 1.43 - 1.49 (3H, m),

1.60 - 1.70 (3H, m), 2.80 (2H, brs), 3.61 - 3.70 (3H, m); 13C NMR (CDCl3, 100 MHz) δ 14.3, 22.9, 26.0, 29.4, 29.6,

32.1, 34.7, 37.8, 63.2, 72.2; HRMS (ESI) m/z: [M+Na]+; Calcd for C10H22O2Na 197.1514; Found 197.1512.

Chloride S8

To a solution of S7 (261 mg, 1.50 mmol) in CH2Cl2 (7.5 mL) were added imidazole (153 mg, 2.25 mmol) and

TBSCl (271 mg, 1.80 mmol) at room temperature under an Ar atmosphere. The mixture was stirred for 16 h,

quenched with EtOH and then saturated NH4Cl, extracted with AcOEt, washed with brine, dried over Na2SO4,

filtered, and concentrated in vacuo. The diol was employed directly in the next step.

To a solution of crude TBS diol in CH2Cl2 (7.5 mL) were added imidazole (204 mg, 3.00 mmol) and Ph3P (433

mg, 1.65 mmol) and NCS (401 mg, 3.00 mmol) at rt under an Ar atmosphere. The mixture was stirred 1h,

17
concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 100:0 then

99:1) to give chloride S8 (254 mg, 0.830 mmol, 55%) as a colorless oil: []D21 +1.3 (c 3.40 CHCl3); IR (neat) 2954,

2929, 2858, 1470, 1387, 1255, 1104, 965, 836, 775, 724, 662, 610 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.00 (6H, s),

0.80 - 0.86 (12H, m), 1.20 - 1.28 (10H, m), 1.30 - 1.38 (1H, m), 1.40 - 1.50 (1H, m), 1.56 - 1.62 (1H, m), 1.63 -

1.72 (2H, m), 1.76 - 1.83 (1H, m), 3.58 (2H, td, J = 5.9, 2.4 Hz), 3.84 - 3.92 (1H, m); 13C NMR (CDCl3, 100 MHz)

δ －5.33, 14.0, 18.3, 22.6, 25.9, 26.5, 28.8, 29.7, 31.7, 34.9, 38.6, 62.5, 64.1; HRMS (ESI) m/z: [M+H]+; Calcd for

C16H36OClSi 307.2221; Found 307.2219.

Alcohol S9

To a solution of S8 in MeOH/CH2Cl2 (8.3 mL) were added CSA (193 mg, 0.831 mmol) at rt under an Ar

atmosphere. The mixture was stirred 1h, concentrated in vacuo. The residue was purified by silica gel column

chromatography (hexane:AcOEt = 95:5) to give alcohol S9 (126 mg, 0.600 mmol, 72%) as a colorless oil: []D21 –

2.4 (c 2.29 CHCl3); IR (neat) 3335, 2932, 2859, 1699, 1683, 1558, 1457, 1376, 1058, 725 cm–1; 1H NMR (CDCl3,

400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.25 - 1.33 (8H, m), 1.35 - 1.44 (1H, m), 1.45 - 1.59 (1H, m), 1.67 - 1.77 (2H,

m), 1.79 - 1.91 (2H, m), 3.61 - 3.70 (2H, m), 3.90 - 3.97 (1H, m); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.4,

28.8, 29.6, 31.7, 34.7, 38.6, 62.4, 64.0; HRMS (ESI) m/z: [M+H]+; Calcd for C10H19OClNa 229.0971; Found

229.0965.

,-Unsaturated Ester S10

To a solution of S9 (124 mg, 0.600 mmol) in CH2Cl2 (3.0 mL) were added TEMPO (18.8 mg, 0.120 mmol) and

PhI(OAc)2 (290 mg, 0.900 mmol) at room temperature under Ar atmosphere. The mixture was stirred for 24 h.

Then MeO2C(H)C=PPh3 (401 mg, 1.20 mmol) was added, and the mixture was stirred for 12 h and concentrated in

vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 99:1) to give unsaturated

ester S10 (87.7 mg, 0.360 mmol, 88%) as a colorless oil: []D19 +16.7 (c 2.24 CHCl3); IR (neat) 2951, 2931, 2856,

1726, 1659, 1435, 1317, 1270, 1200, 1156, 1041, 984, 852, 721, 668 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H,

t, J = 6.8 Hz), 1.28 - 1.39 (7H, m), 1.48 - 1.50 (1H, m), 1.73 (2H, q, J = 7.3 Hz), 1.80 - 1.91 (2H, m), 2.33 - 2.42

18
(1H, m), 2.44 - 2.49 (1H, m), 3.73 (3H, s), 3.76 - 3.90 (1H, m), 5.87 (1H, dt, J = 15.6, 1.5 Hz), 6.94 (1H, dt, J =

15.6, 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.7, 23.2, 27.1, 29.5, 29.8, 32.4, 37.3, 39.2, 52.2, 63.6, 122.5, 148.5,

167.6; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H23O2ClNa 269.1279; Found 269.1279.

Allyl alcohol S11

To a solution of S10 (1.08 g, 4.37 mmol) in CH2Cl2 (22 mL) was added DIBAL (1.01 M in PhMe, 10.8 mL, 10.9

mmol) at 0 °C under an Ar atmosphere. The mixture was stirred 30 min, quenched with saturated Na-K tartrate,

stirred for 1 h, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane:AcOEt = 95:5) to give allyl alcohol S11

(826 mg, 3.79 mmol, 77%) as a colorless oil: []D21 +8.2 (c 1.53 CHCl3); IR (neat) 3335, 2930, 2857, 1698, 1456,

1376, 1088, 1001, 970, 725, 668, 610 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.25 - 1.40 (7H,

m), 1.48 - 1.52 (1H, m), 1.68 - 1.76 (2H, m), 1.79 - 1.82 (2H, m), 2.18 - 2.24 (1H, m), 2.25 - 2.32 (1H, m), 3.89 (1H,

13
quin, J = 6.3 Hz), 4.09 (2H, d, J = 4.4 Hz), 5.67 - 5.72 (2H, m); C NMR (CDCl3, 100 MHz) δ 14.0, 22.6, 26.4,

28.8, 29.1, 31.7, 37.7, 38.5, 63.4, 63.6, 130.0, 131.5; HRMS (ESI) m/z: [M+Na]+; Calcd for C12H23OClNa

241.1330; Found 241.1330.

Epoxide S12

The suspension of activated MS4A (484 mg) was added D-DET (160 mg, 0.774 mmol) in CH2Cl2 (5.0 mL) at –

20 °C under Ar atmosphere. The mixture was stirred for 30 min and added Ti(iPrO)4 (172 µL, 0.580 mmol) and

stirres for 30 min at –20 °C. After the mixture was added TBHP (5.50 M, 0.527 mL, 2.90 mmol) and stirred for 30

min, was added S11 (422 mg, 1.93 mmol) in CH2Cl2 (5.0 mL). The mixture was stirred for 2 h, quenched with iron

sulfate(II) aqueous solution of L-tartaric acid, diluted with AcOEt, washed with brine, dried over Na2SO4, filtered

and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 95:5

then 92:8) to give epoxide S12 (362 mg, 1.54 mmol, 80%) as a yellow oil. []D27 +19.0 (c 0.21 CHCl3); IR (neat)

3420, 2926, 2856, 1456, 1377, 1249, 1133, 1092, 1022, 885, 723 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J

13
= 6.8 Hz), 1.25 - 1.90 (15H, m), 2.96 – 3.02 (2H, m), 3.65 (1H, dd, J = 12.6, 3.9 Hz), 3.90 – 3.97 (2H, m); C

19
NMR (CDCl3, 100 MHz) δ 14.0, 22.6, 26.4, 28.2, 28.8, 31.7, 34.3, 38.5, 54.9, 58.3, 61.4, 63.2; HRMS (ESI) m/z:

[M+Na]+; Calcd for C12H23O2ClNa 257.1281; Found 257.1279.

Olefin 13b

13b (43.1 mg, 45% yield for 2 steps) was prepared according to the procedures for synthesis of 13c; []D21 +62.1

(c 4.46 CHCl3); IR (neat) 2953, 2931, 2858, 1724, 1646, 1446, 1398, 1202, 1181, 999, 874, 823, 761, 725, 662, 609

cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.28 - 1.32 (6H, m), 1.37 - 1.42 (1H, m), 1.64 - 1.75

(3H, m), 1.78 - 1.89 (1H, m), 1.91 - 2.04 (2H, m), 2.91 (1H, ddd, J = 6.6, 4.4, 2.0 Hz), 3.75 (3H, s), 3.88 - 3.94 (1H,

m), 4.31 (1H, dd, J = 8.3, 2.0 Hz), 5.79 (1H, dd, J = 11.7, 8.3 Hz), 5.97 (1H, d, J = 11.7 Hz); 13C NMR (CDCl3, 100

MHz) δ 14.0 , 22.6, 26.4, 28.8, 29.1, 31.7, 34.7, 38.6, 51.2, 54.2, 59.5, 63.5, 123.2, 146.8, 166.3; HRMS (ESI) m/z:

[M+Na]+; Calcd for C15H25O3ClNa 311.1385; Found 311.1384.

Allyl alcohol 10b

10b (5.2 mg, 55% yield) was prepared according to the procedures for synthesis of 10c; IR (neat) 3419, 2953,

2929, 2857, 1732, 1456, 1377, 1307, 1241, 1027, 940, 875, 725, 669, 607 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89

(3H, t, J = 7.3 Hz), 1.22 - 1.29 (6H, m), 1.31 - 1.35 (1H, m), 1.40 - 1.54 (1H, m), 1.56 - 1.64 (1H, m), 1.70 - 1.83

(3H, m), 1.93 - 2.01 (2H, m), 2.87 (1H, ddd, J = 6.8, 3.9, 2.0 Hz), 3.42 (1H, dd, J = 8.8, 2.4 Hz), 3.89 - 3.93 (1H,

m), 4.32 (1H, dd, J = 13.2, 5.9 Hz), 4.40 (1H, dd, J = 13.2, 6.8 Hz), 5.22 (1H, dd, J = 11.2, 8.9 Hz), 5.89 (1H, dt, J

= 11.2, 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.4, 28.8, 29.3, 31.6, 34.9, 38.6, 54.0, 58.8, 59.8, 63.7,

129.2, 134.3; HRMS (ESI) m/z: [M+Na]+; Calcd for C14H25O2ClNa 283.1441; Found 283.1435.

Epoxide S13

The suspension of activated MS4A (425 mg) was added L-DET (140 mg, 0.680 mmol) in CH2Cl2 (4.2 mL) at –

20 °C under Ar atmosphere. The mixture was stirred for 30 min and added Ti(iPrO)4 (151 µL, 0.510 mmol) and

stirres for 30 min at –20 °C. After the mixture was added TBHP (5.50 M, 0.463 mL, 2.55 mmol) and stirred for 30

min, was added S11 (372 mg, 1.70 mmol) in CH2Cl2 (4.2 mL). The mixture was stirred for 2 h, quenched with iron

20
sulfate (II) aqueous solution of L-tartaric acid, diluted with AcOEt, washed with brine, dried over Na2SO4, filtered

and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 95:5

then 92:8) to give epoxide 13 (353 mg, 1.51 mmol, 89%) as a yellow oil. []D27 +30.9 (c 0.68 CHCl3); IR (neat)

3419, 2953, 2928, 2857, 1456, 1377, 1243, 1088, 1029, 885, 724, 608 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89

(3H, t, J = 6.8 Hz), 1.25 - 1.90 (15H, m), 2.96 – 3.02 (2H, m), 3.65 (1H, d, J = 12.2 Hz), 3.90 – 3.98 (2H, m); 13C

NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.4, 28.2, 28.8, 31.7, 34.3, 38.5, 54.9, 58.3, 61.4, 63.1; HRMS (ESI) m/z:

[M+Na]+; Calcd for C12H23O2ClNa 257.1280; Found 257.1279.

Olefin 13a

13a (78.8 mg, 42% yield for 2 steps) was prepared according to the procedures for synthesis of 13c; []D21 –59.2

(c 2.66 CHCl3); IR (neat) 2953, 2930, 2858, 1724, 1647, 1446, 1399, 1202, 1181, 999, 876, 823, 725, 664, 608 cm–

1 1
; H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.28 - 1.32 (6H, m), 1.36 - 1.40 (1H, m), 1.48 - 1.52 (1H,

m), 1.71 (2H, q, J = 7.8 Hz), 1.82 - 1.94 (4H, m), 2.90 - 2.95 (1H, m), 3.75 (3H, s), 3.90 - 3.97 (1H, m), 4.33 (1H,

dd, J = 7.8, 1.0 Hz), 5.77 (1H, dd, J = 11.7, 8.3 Hz), 5.97 (1H, d, J = 11.7 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0,

22.5, 26.4, 28.6, 28.7, 31.7, 38.5, 51.5, 54.2, 59.1, 63.2, 123.2, 146.7, 166.3; HRMS (ESI) m/z: [M+Na]+; Calcd for

C15H25O3ClNa 311.1385; Found 311.1384.

Allyl alcohol 10a

10a (14.8 mg, 59% yield) was prepared according to the procedures for synthesis of 10c; []D24 +190.3 (c 1.48

CHCl3); IR (neat) 3419, 2954, 2929, 2858, 1732, 1456, 1377, 1308, 1246, 1030, 941, 876, 725, 665, 608 cm–1; 1H

NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 7.3 Hz), 1.22 - 1.29 (6H, m), 1.30 - 1.40 (1H, m), 1.51 - 1.64 (1H, m),

1.69 - 1.75 (2H, m), 1.77 - 1.89 (4H, m), 2.87 - 2.89 (1H, m), 3.45 (1H, dd, J = 8.9, 2.4 Hz), 3.87 - 4.03 (1H, m),

4.41 (1H, dd, J = 12.2, 6.8 Hz), 4.41 (1H, dd, J = 12.2, 6.8 Hz), 5.21 (1H, t, J = 10.3 Hz), 5.89 (1H, dt, J = 11.2, 6.3

13
Hz); C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.4, 28.6, 28.8, 31.7, 34.3, 38.5, 54.1, 58.8, 59.2, 63.2, 129.3,

134.3; HRMS (ESI) m/z: [M+Na]+; Calcd for C14H25O2ClNa 283.1440; Found 283.1435.

21
Epoxide S15

The suspension of activated MS4A (1.75 g) was added L-DET (0.480 mL, 2.82 mmol) in CH2Cl2 (17 mL) at －

20 °C under Ar atmosphere. The mixture was stirred for 30 min and added Ti(OiPr)4 (620 µL, 2.12 mmol) and

stirres for 30 min at －20 °C. After the mixture was added TBHP (5.50 M, 1.92 mL, 1.50 mmol) and stirred for 30

min, was added S14 (1.00 g, 7.04 mmol) (Fernández-Mateos et al. Eur. J. Org. Chem. 2010, 856-861) in CH2Cl2

(17 mL). The mixture was stirred for 2 h, quenched with iron sulfate (II) aqueous solution of L-tartaric acid, diluted

with AcOEt, washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by

silica gel column chromatography (hexane:AcOEt = 95:5 then 92:8) to give epoxide S15 (953 mg, 6.02 mmol,

86%) as a yellow oil; []D29 –41.5 (c 2.67, CHCl3 ); IR (neat) 3421, 2956, 2928, 2858, 1465, 1378, 1222, 1079,

1031, 943, 895, 867, 725, 639, 584 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.26 - 1.32 (6H,

m), 1.33 - 1.47 (2H, m), 1.53 - 1.64 (2H, m), 2.91 - 2.98 (2H, m), 3.64 (1H, ddd, J = 12.4, 7.3, 4.4 Hz), 3.92 (1H,

13
ddd, J = 12.2, 5.4, 2.4 Hz); C NMR (CDCl3, 100 MHz) δ 14.8, 23.5, 26.7, 28.8, 32.2, 57.0 (×2), 59.8, 63.0;

HRMS (ESI) m/z: [M+Na]+; Calcd for C9H18O2Na 181.1201; Found 181.1199.

22
Diol S16

To solution of epoxide (953 mg, 6.08 mmol) in THF was added Red-Al (4.17 mL, 15.1 mmol) at 0 °C under an

Ar atmosphere. The mixture was stirred 8 h, quenched with saturated 1M HCl, stirred for 1 h, extracted with AcOEt,

washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel

column chromatography (hexane:AcOEt = 80:20 then 60:40 then 50:50) to give diol S16 (812 mg, 5.07 mmol,

84%) as a colorless oil; []D22 +48.1 (c 1.32, CHCl3 ); IR (neat) 3357, 2928, 2857, 1697, 1457, 1338, 1129, 1056,

772, 724 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 7.3 Hz), 1.22 - 1.37 (8H, m), 1.40 - 1.53 (2H, m),

1.62 - 1.76 (2H, m), 2.34 (1H, brs), 2.40 (1H, brs), 3.80 - 3.88 (3H, m); 13C NMR (CDCl3, 100 MHz) δ 14.3, 22.9,

25.9, 29.5, 32.1, 38.1, 38.5, 61.9, 72.6; HRMS (ESI) m/z: [M+Na]+; Calcd for C9H20O2Na 183.1358; Found

183.1356.

Chloride S17

To a solution of S16 (812 mg, 5.07 mmol) in CH2Cl2 (25 mL) were added imidazole (518 mg, 7.61 mmol) and

TBSCl (917 mg, 6.08 mmol) at room temperature under an Ar atmosphere. The mixture was stirred for 1 h,

quenched with EtOH and then saturated NH4Cl, extracted with AcOEt, washed with brine, dried over Na2SO4,

filtered, and concentrated in vacuo. The diol was employed directly in the next step.

To a solution of crude TBS diol in CH2Cl2 (25 mL) were added imidazole (600 mg, 8.80 mmol) and Ph3P (1.27 g,

4.84 mmol) and NCS (1.18 g, 8.80 mmol) at rt under an Ar atmosphere. The mixture was stirred 1h, concentrated in

vacuo. The residue was purified by silica gel column chromatography (hexane:AcOEt = 100:0 then 99:1) to give

chloride S17 (864 mg, 2.95 mmol, 67%) as an pale oil; []D22 +46.9 (c 1.02, CHCl3 ); IR (neat) 2955, 2929, 2858,

1471, 1387, 1255, 1104, 1006, 937, 835, 776, 724, 667 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.68 (6H, s), 0.85 -

0.90 (12H, m), 1.25 - 1.33 (6H, m), 1.35 - 1.45 (1H, m), 1.48 - 1.55 (1H, m), 1.70 - 1.77 (2H, m), 1.79 - 1.85 (1H,

m), 1.94 - 1.97 (1H, m), 3.75 - 3.80 (2H, m), 4.09 - 4.10 (1H, m); 13C NMR (CDCl3, 100 MHz) δ –5.71, 13.7, 18.0,

22.3, 25.6, 26.0, 28.5, 31.4, 38.4, 41.0, 59.6, 60.3; HRMS (ESI) m/z: [M+H]+; Calcd for C15H34OClSi 293.2064;

Found 293.2062.

23
Alcohol S18

To a solution of S17 (161mg, 0.552 mmol) in MeOH/CH2Cl2 (6.0 mL) were added CSA (12.8 mg, 0.0552 mmol)

at rt under an Ar atmosphere. The mixture was stirred 1h, concentrated in vacuo. The residue was purified by silica

gel column chromatography (hexane:AcOEt = 85:15) to give alcohol S18 (91.8 mg, 0.515 mmol, 93%) as an pale

oil; []D21 +38.6 (c 1.02, CHCl3 ); IR (neat) 3347, 2955, 2929, 2858, 1467, 1053, 887, 834, 725, 667, 613 cm–1; 1H

NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 7.3 Hz), 1.28 - 1.37 (4H, m), 1.39 - 1.44 (2H, m), 1.50 - 1.58 (2H, m),

1.72 - 1.78 (2H, m), 1.84 - 1.92 (2H, m), 1.99 - 2.07 (1H, m), 3.81 - 3.88 (2H, m), 4.08 - 4.14 (1H, m); 13C NMR

(CDCl3, 100 MHz) δ 14.7, 23.3, 27.1, 29.5, 32.4, 39.5, 41.6, 60.7, 61.5; HRMS (ESI) m/z: [M+H]+; Calcd for

C9H18OCl 193.0995; Found 193.0991.

,-Unsaturated Ester S19

To a solution of S18 (1.35 g, 7.58 mmol) in CH2Cl2 (152 mL) was added DMP (418 g, 9.85 mmol) at room

temperature under Ar atmosphere. The mixture was stirred for 1 h, quench with saturated NH4Cl, extracted with

AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The aldehyde was employed

directly in the next step.

To solution of triethylphosphonoacetate (1.81 mL, 9.10 mmol) in THF (38 mL) was added NaH (364 mg, 9.10

mmol) at 0 °C under an Ar atmosphere. The mixture was stirred 30 min and added crude aldehyde. The mixture

was stirred 30 min at －40 °C, quenched with saturated NaHCO3, stirred for 30 min, extracted with AcOEt, washed

with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column

chromatography (hexane:AcOEt = 99:1) to give unsaturated ester S19 (1.45 g, 5.55 mmol, 73%) as a colorless oil;

[]D21 +5.88 (c 2.05, CHCl3 ); IR (neat) 2931, 2914, 1722, 1657, 1465, 1368, 1269, 1202, 1161, 1042, 981, 725

cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 7.3 Hz), 1.24 - 1.33 (8H, m), 1.40 - 1.43 (1H, m), 1.51 - 1.57

(1H, m), 1.67 - 1.76 (2H, m), 2.56 - 2.69 (2H, m), 3.97 (1H, quin, J = 5.4 Hz), 4.20 (3H, q, J = 6.8 Hz), 5.90 (1H, d,

J = 15.6 Hz), 6.96 (1H, dt, J = 15.6, 7.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 15.0, 15.3, 23.6, 27.4, 29.7, 32.7, 39.1,

41.2, 61.4, 62.1, 125.2, 144.9, 167.1; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H23O2ClNa 269.1281; Found

269.1279.

24
Allyl alcohol S20

To a solution of S19 (744 mg, 3.02 mmol) in CH2Cl2 (15 mL) was added DIBAL (1.01 M in PhMe, 7.50 mL, 7.55

mmol) at 0 °C under an Ar atmosphere. The mixture was stirred 30 min, quenched with saturated Na-K tartrate,

stirred for 1 h, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane:AcOEt = 95:5) to give allyl alcohol S20

(602 mg, 2.65 mmol, 89%) as a colorless oil; []D21 +4.15 (c 2.13, CHCl3 ); IR (neat) 3336, 2929, 2914, 1458, 1377,

1272, 1092, 1006, 971, 771, 726, 669, 615 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.28 - 1.42

(7H, m), 1.47 - 1.58 (1H, m), 1.63 - 1.79 (2H, m), 2.43 - 2.55 (2H, m), 3.88 - 3.94 (1H, m), 4.09 - 4.17 (2H, m),

5.70 - 5.78 (2H, m); 13C NMR (CDCl3, 100 MHz) δ 15.1, 23.6, 27.4, 29.8, 32.7, 38.9, 42.1, 63.9, 64.5, 129.1, 133.3;

HRMS (ESI) m/z: [M+Na]+; Calcd for C11H21OClNa 227.1178; Found 227.1173.

Epoxide S21

S21 (585 mg, 90% yield) was prepared according to the procedures for synthesis of S13; []D16 －21.8 (c 1.01

CHCl3 ); IR (neat) 3445, 2954, 2929, 1716, 1458, 1377, 1085, 1038, 909, 760, 726, 669, 611 cm-1; 1H NMR (CDCl3,

400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.28 - 1.41 (6H, m), 1.42 - 1.45 (1H, m), 1.49 - 1.52 (1H, m), 1.74 (2H, q, J =

7.8 Hz), 1.85 - 2.05 (2H, m), 2.99 (1H, td, J = 4.4, 2.0 Hz), 3.19 (1H, ddd, J = 7.1, 4.9, 2.4 Hz), 3.66 (1H, d, J =

12.7 Hz), 3.93 (1H, d, J = 12.7 Hz), 4.04 - 4.11 (1H, m); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.2, 28.7, 31.6,

38.8, 40.9, 53.5, 59.0, 60.5, 61.4; HRMS (ESI) m/z: [M+Na]+; Calcd for C11H21O2ClNa 243.1129; Found 243.1122.

Olefin 14b

14b (99.8 mg, 61% yield for 2 steps) was prepared according to the procedures for synthesis of 13c; []D21 +80.4

(c 3.06 CHCl3 ); IR (neat) 2953, 2930, 2858, 1724, 1652, 1456, 1446, 1399, 1202, 1181, 1000, 930, 879, 824, 725,

668 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.7 Hz), 1.28 - 1.32 (6H, m), 1.40 - 1.43 (1H, m), 1.48 -

1.52 (1H, m), 1.75 (2H, q, J = 7.8 Hz), 1.84 (1H, ddd, J = 14.6, 7.3, 3.4 Hz), 2.15 (1H, ddd, J = 14.6, 9.8, 3.4 Hz),

3.16 (1H, ddd, J = 14.6, 7.3, 2.0 Hz), 3.75 (3H, s), 4.07 - 4.14 (1H, m), 4.39 (1H, dd, J = 8.8, 2.0 Hz), 5.79 (1H, dd,

J = 11.7, 8.3 Hz), 6.00 (1H, d, J = 11.7 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.2, 28.7, 31.7, 41.1, 51.5,

25
54.5, 57.4, 60.4, 123.5, 146.3, 166.2; HRMS (ESI) m/z: [M+Na]+; Calcd for C14H23O3ClNa 297.1229; Found

297.1228.

Allyl alcohol 11b

11b (12.7 mg, 76% yield) was prepared according to the procedures for synthesis of 13c; []D18 +3.0 (c 1.53

CHCl3 ); IR (neat) 3408, 2955, 2929, 2858, 1718, 1654, 1458, 1434, 1379, 1243, 1123, 1026, 938, 880, 796, 726,

671 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 7.3 Hz), 1.22 - 1.29 (6H, m), 1.31 - 1.40 (1H, m), 1.42 -

1.53 (1H, m), 1.72 - 1.78 (2H, m), 1.89 - 1.99 (2H, m), 3.07 (1H, ddd, J = 6.8, 4.9, 2.0 Hz), 3.48 (1H, dd, J = 8.3,

1.5 Hz), 4.07 - 4.10 (1H, m), 4.30 (1H, dd, J = 13.7, 5.4 Hz), 4.42 (1H, dd, J = 14.2, 6.3 Hz), 5.23 (1H, t, J = 8.3

Hz), 5.90 (1H, dt, J = 11.2, 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0 , 22.5, 26.2, 28.7, 31.6, 38.8, 41.2, 54.8,

57.7, 58.8, 60.5, 128.9, 134.6; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H23O2ClNa 269.1284; Found 269.1279.

Epoxide S22

S22 (387 mg, 88% yield) was prepared according to the procedures for synthesis of S12; []D16 +30.9 (c 1.63

CHCl3 ); IR (neat) 3419, 2955, 2929, 2858, 1465, 1377, 1311, 1274, 1084, 1020, 905, 857, 759, 726, 669, 615 cm-1;

1
H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 7.3 Hz), 1.28 - 1.32 (6H, m), 1.34 - 1.42 (1H, m), 1.53 - 1.57 (1H,

m), 1.73 - 1.83 (2H, m), 2.02 - 2.06 (2H, m), 2.99 (1H, dt, J = 3.9, 2.9 Hz), 3.19 (1H, td, J = 5.9, 2.4 Hz), 3.67 (1H,

ddd, J = 12.7, 7.3, 4.4 Hz), 3.93 (1H, ddd, J = 12.4, 5.9, 2.9 Hz), 4.04 (1H, quin, J = 5.9 Hz); 13C NMR (CDCl3,

100 MHz) δ 14.0, 22.6, 26.5, 28.7, 31.7, 38.8, 40.1, 52.9, 57.9, 60.3, 61.5; HRMS (ESI) m/z: [M+Na]+; Calcd for

C11H21O2ClNa 243.1130; Found 243.1122.

Olefin 14a

14a (60.2 mg, 49% yield for 2 steps) was prepared according to the procedures for synthesis of 13c []D22 －98.0

(c 3.20 CHCl3 ); IR (neat) 2953, 2930, 2857, 1724, 1652, 1446, 1398, 1203, 1181, 999, 931, 881, 824, 726, 668,

614 cm–1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.7 Hz), 1.28 - 1.32 (6H, m), 1.40 - 1.43 (1H, m), 1.48 -

1.52 (1H, m), 1.75 - 1.82 (2H, m), 2.00 - 2.14 (2H, m), 3.14 (1H, td, J = 5.9, 2.0 Hz), 3.75 (3H, s), 4.06 - 4.12 (1H,

26
m), 4.34 (1H, dd, J = 6.8, 2.0 Hz), 5.80 (1H, dd, J = 11.7, 7.8 Hz), 5.99 (1H, d, J = 11.7 Hz); 13C NMR (CDCl3, 100

MHz) δ 14.0 , 22.5, 26.4, 28.7, 31.6, 38.2, 40.6, 51.5, 53.7, 57.2, 60.4, 123.4, 146.4, 166.2; HRMS (ESI) m/z:

[M+Na]+; Calcd for C14H23O3ClNa 297.1229; Found 297.1228.

Allyl alcohol 11a

11a (25.8 mg, 64% yield) was prepared according to the procedures for synthesis of 10c; []D26 +5.0 (c 1.30

CHCl3 ); IR (neat) 3389, 2955, 2929, 2858, 1458, 1379, 1307, 1274, 1248, 1027, 940, 881, 793, 725, 670, 612 cm–

1 1
; H NMR (CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.3 Hz), 1.22 - 1.81 (11H, m), 2.00 – 2.11 (2H, m), 3.07 - 3.10 (1H,

m), 3.48 (1H, dd, J = 9.2, 1.0 Hz), 4.02 - 4.08 (1H, m), 4.31 (1H, dd, J = 13.2, 6.3 Hz), 4.41 (1H, dd, J = 13.4, 6.8

Hz), 5.23 (1H, dd, J = 9.7, 8.8 Hz), 5.91 (1H, dt, J = 11.2, 6.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.4,

28.7, 31.6, 38.0, 40.4, 53.6, 57.0, 58.8, 60.2, 129.0, 134.6; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H23O2ClNa

269.1284; Found 269.1279.

,-Unsaturated Ester S23

To solution of MacMillan catalyst A (287 mg, 1.33 mmol) in CHCl3 (60 mL) was added bromoacetic acid (185

mg, 1.33 mmol) and S1 (2.07 mL, 13.3 mmol) and 2,3,4,5,6,6-Hexachloro-2,4-Cyclohexadien-1-One (4.00 g, 13.3

27
mmol) at –30 °C under an Ar atmosphere. After the mixture was stirred for over, MeO2C(H)C=PPh3 (8.90 g, 22.6

mmol) was added, and the mixture was stirred for 3 h and then concentrated in vacuo. The residue was purified by

silica gel column chromatography (hexane:AcOEt = 99:1, then 98:2) to give unsaturated ester S23 (2.41 g, 12.0

mmol, 90%) as a pale oil. []D20 –4.4 (c 1.80, CHCl3 ); IR (neat) 2953, 2930, 2859, 1730, 1661, 1458, 1312, 1276,

1229, 1168, 1039, 976, 859, 762, 726, 631 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.29 - 1.69

(7H, m), 1.81 – 1.87 (2H, m), 3.76 (3H, s), 4.43 (2H, q, J = 6.8 Hz), 6.02 (1H, d, J = 15.1 Hz), 6.89 (1H, dd, J =

13
15.1, 7.8 Hz); C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.1, 28.6, 31.5, 37.6, 51.8, 59.9, 121.9, 146.6, 166.3;

HRMS (ESI) m/z: [M+Na]+; Calcd for C11H19O2ClNa 241.0971; Found 241.0970.

Allyl alcohol S24

To a solution of S23 (337 mg, 1.54 mmol) in CH2Cl2 (7.7 mL) was added DIBAL (1.01 M in PhMe, 3.81 mL, 3.85

mmol) at －78 °C under an Ar atmosphere. The mixture was stirred 30 min, quenched with saturated Na-K tartrate,

stirred for 1 h, extracted with AcOEt, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo.

The residue was purified by silica gel column chromatography (hexane:AcOEt = 95:5) to give allyl alcohol S24

(158 mg, 0.829 mmol, 54%) as an inseparable mixture due to instability of S24, which was used next reaction

immediately.

Epoxide S25

S25 (81.2 mg, 48% yield) was prepared according to the procedures for synthesis of S13; []D20 +9.8 (c 0.51,

CHCl3 ); IR (neat) 3419, 2955, 2929, 2857, 1748, 1456, 1377, 1243, 1078, 1021, 907, 765, 726, 673 cm-1; 1H NMR

(CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.29 - 1.69 (7H, m), 1.75 – 1.86 (2H, m), 3.16 - 3.21 (2H, m), 3.66 –

13
3.73 (2H, m), 3.94 (1H, ddd, J = 13.0, 4.6, 2.4 Hz); C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.2, 28.7, 31.6,

34.9, 58.3, 58.5, 60.7, 62.3; HRMS (ESI) m/z: [M+Na]+; Calcd for C10H17O3ClNa 243.0764; Found 243.0762.

Olefin 15b

15b (31.8 mg, 53% yield for 2 steps) was prepared according to the procedures for synthesis of 13c; []D20 +135.5

28
(c 1.65 CHCl3 ); IR (neat) 2953, 2930, 2859, 1723, 1652, 1541, 1446, 1317, 1202, 1056, 997, 889, 727, 668 cm–1;

1
H NMR (CDCl3, 400 MHz) δ 0.88 (3H, t, J = 6.8 Hz), 1.25 - 1.78 (9H, m), 1.76 - 1.94 (2H, m), 3.08 (1H, dd, J =

7.3, 2.0 Hz), 3.66 (1H, td, J = 7.8, 5.7 Hz), 4.21 (2H, d, J = 7.3 Hz), 4.56 (1H, dd, J = 8.3, 1.0 Hz), 5.79 (1H, dd, J

= 11.7, 8.3 Hz), 6.01 (1H, d, J = 11.7 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0 , 14.2, 22.5, 26.0, 28.7, 31.5, 34.8,

54.8, 60.6, 62.5, 62.9, 124.4, 144.8, 165.6; HRMS (ESI) m/z: [M+Na]+; Calcd for C13H21O3ClNa 283.1073; Found

283.1071.

Allyl alcohol 12b

12b (7.3 mg, 51% yield) was prepared according to the procedures for synthesis of 10c; []D27 +35.4 (c 0.48

CHCl3 ); IR (neat) 3397, 2954, 2928, 2857, 1457, 1377, 1241, 1025, 940, 898, 800, 726, 670 cm-1; 1H NMR (CDCl3,

400 MHz) δ 0.89 (3H, t, J = 7.3 Hz), 1.25 - 1.85 (9H, m), 3.08 (1H, dd, J = 7.3, 1.9 Hz), 3.65 – 3.70 (2H, m), 4.31

(1H, dd, J = 13.7, 5.4 Hz), 4.40 (1H, dd, J = 14.2, 6.3 Hz), 5.24 (1H, t, J = 10.2 Hz), 5.92 (1H, dt, J = 10.2, 6.8 Hz);

13
C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 26.2, 28.7, 31.6, 34.9, 54.3, 58.9, 62.5, 62.6, 127.9, 135.0; HRMS (ESI)

m/z: [M+Na]+; Calcd for C12H19O3ClNa 269.0920; Found 269.0918.

Epoxide S26

S26 (29.8 mg, 42% yield) was prepared according to the procedures for synthesis of S12; []D20 +22.5 (c 3.67

CHCl3 ); IR (neat) 3417, 2929, 2858, 1378, 1215, 1080, 1036, 903, 759, 682 cm-1; 1H NMR (CDCl3, 400 MHz) δ

0.89 (3H, t, J = 6.8 Hz), 1.29 - 1.44 (6H, m), 1.45 - 1.49 (1H, m), 1.50 - 1.60 (1H, m), 1.75 - 1.87 (1H, m), 1.90 -

2.00 (1H, m), 3.11 - 3.16 (2H, m), 3.55 (1H, td, J = 8.3, 4.4 Hz), 3.70 (1H, ddd, J = 12.9, 7.8, 3.9 Hz), 3.97 (1H,

ddd, J = 10.2, 5.4, 2.4 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.8, 28.7, 31.6, 35.8, 57.8, 58.4, 60.9, 61.3;

HRMS (ESI) m/z: [M+Na]+; Calcd for C10H17O3ClNa 243.0764; Found 243.0762.

Olefin 15a

15a (43.4 mg, 65% yield for 2 steps) was prepared according to the procedures for synthesis of 13c; []D20 －101.9

(c 1.59 CHCl3 ) ; IR (neat) 2953, 2933, 2860, 1699, 1558, 1457, 1397, 1202, 1181, 997, 885, 828 cm–1; 1H NMR

29
(CDCl3, 400 MHz) δ 0.89 (3H, t, J = 6.8 Hz), 1.25 - 1.37 (6H, m), 1.40 - 1.49 (1H, m), 1.54 - 1.63 (1H, m), 1.76 -

1.85 (1H, m), 1.90 - 1.99 (1H, m), 3.07 (1H, dd, J = 7.3, 2.0 Hz), 3.63 (1H, ddd, J = 8.9, 7.3, 4.4 Hz), 3.76 (3H, s),

4.56 (1H, d, J = 8.3 Hz), 5.77 (1H, dd, J = 11.2, 8.3 Hz), 6.03 (1H, d, J = 11.2 Hz); 13C NMR (CDCl3, 100 MHz) δ

14.0 , 22.5, 25.8, 28.7, 31.6, 35.5, 51.6, 54.2, 61.0, 62.0, 124.3, 144.8, 166.0; HRMS (ESI) m/z: [M+Na]+; Calcd

for C13H21O3ClNa 283.1073; Found 283.1071.

Allyl alcohol 12a

12a (19.8 mg, 66% yield) was prepared according to the procedures for synthesis of 10c []D27 +3.0 (c 0.25

CHCl3 ); IR (neat) 3366, 2928, 2857, 1458, 1213, 1027, 891, 801, 727 cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.89

(3H, t, J = 7.3 Hz), 1.25 - 1.61 (7H, m), 1.75 - 1.84 (1H, m), 1.84 - 1.99 (1H, m), 3.01 (1H, dd, J = 7.8, 1.9 Hz),

3.53 (1H, td, J = 7.8, 4.4 Hz), 3.61 (1H, d, J = 8.3 Hz), 4.32 – 4.44 (2H, m), 5.25 (1H, t, J = 11.2 Hz), 5.92 (1H, dt,

J = 11.2, 6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 14.0, 22.5, 25.8, 28.7, 31.6, 35.8, 54.3, 59.0, 61.7, 62.1, 127.7,

135.2; HRMS (ESI) m/z: [M+Na]+; Calcd for C12H19O3ClNa 269.0920; Found 269.0918.

30
NMR Spectra

31
32
33
 OH
Hex

EtO2C Cl
anti-19

34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
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53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
 Cl

MeO2C Hex
S10

68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
 OH Cl
O
Hex
S22

85
86
87
88
89
90
91
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93
94