First direct evidence of radical intermediates in samarium diiodide induced cyclization by ESR spectra

Article abstract of DOI:10.1021/ol202403q

The mechanism of samarium diiodide (SmI₂)-induced cyclization of α,β-unsaturated esters and ketones to bicyclic compounds was examined using ESR spectroscopy. This is the first report of direct evidence of the radical intermediates in the SmI

Full text of DOI:10.1021/ol202403q

Supporting Information for
First Direct Evidence of Radical Intermediates in
Samarium Diiodide-induced Cyclization by ESR
Spectra
Masakazu Sono,*,† Shin-ichi Hanamura,† Midori Furumaki,† Hisao Murai,*,‡ and Motoo
Tori*,†
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho,
Tokushima 770-8514, Japan and Department of Chemistry, Faculty of Science, Shizuoka
University, Shizuoka 422-8529, Japan
† Tokushima Bunri University
‡ Shizuoka University
Contents
Experimental General
S1
Synthesis and compound data
S2-S20
S21-S26
S27-S48
ESR spectra of 1, 2, 15, and simulations
Spectra for compounds 1-9, S3, S9, and S10
Experimental
General
IR spectra, on a JASCO FT/IR-5300 spectrophotometer; 1H and 13C NMR spectra, on a
Varian Unity 600 (600 MHz and 150 MHz, respectively) and a Varian Unity 200 (200
MHz and 50 MHz, respectively) spectrometer. Mass spectra, including high-resolution
ones, were recorded on a JEOL JMS-700 MStation. ESR was measured on a
JES-FR30EX. The simulation was carried out using WINEPR SimFonia. Chemcopak
Nucleosil 50-5 (4.6×250 mm) with a solvent system of hexane-ethyl acetate was used
for HPLC (JASCO pump system). Silica gel 60 (300 mesh, Fuji Sylisia) was used for
column chromatography. Silica gel 60 F254 plates (Merck) were used for TLC.
S1

COOMe
CHO
COOMe
O
O
O
O
O
1
S2
S1
O
COOMe
COOMe
O
O
2
S3
CHO
O
O
O
O
O
S4
S6
S5
COOMe
COOMe
O
5
O
O
S7
COOMe
COOMe
O
O
6
O
S8
COOMe
COOMe
OH
O
O
4
S9
OH
CO2Me
O
CO2Me
S10
O
9
Synthesis of S2
To a mixture of NaH (82.0 mg, 2.2 mmol) and (MeO)2POCH2CO2Me (458.0 mg, 2.2
S2

mmol) in THF was added a solution of S1 (365.7 mg, 1.7 mmol) in THF and the
mixture was stirred overnight. Wet Et2O was added and extracted. The organic layer
was washed with brine, dried (MgSO4), and was evaporated to afford a residue. The
residue was purified by silica-gel column chromatography (hexane-EtOAc, 1-40%) to
give S3 (5.2 mg, 4.0%) and S2 (52.5 mg, 41.5%).
COOMe
O
O
S2
1
S2: oil: FT-IR: 1720, 1660 cm-1; H NMR (200MHz, CDCl3) δ 0.93 (3H, s), 1.37-1.62
(10H, m), 2.05-2.21 (2H, m), 3.73 (3H, s), 3.90-4.00 (4H, m), 5.83 (1H, dt, J = 15.7, 1.0
Hz), 7.01 (1H, dt, J = 15.7, 6.2 Hz); 13C NMR (50MHz, CDCl3) δ 19.3, 20.8, 23.5, 26.7,
30.4, 33.0, 34.3, 41.1, 51.3, 64.7, 64.9, 112.7 (C), 120.4 (CH), 150.8 (CH), 167.3 (CO);
MS m/z 268 [M]+, 169 (base), 113, 99; EI-HRMS Found m/z 268.1686 [M]+ C15H24O4
requires 268.1674.
Synthesis of S3
To a stirred mixture of 18-crown-6-ether (983.8 mg, 3.7 mmol), K2CO3 (516.2 mg, 3.7
mmol) in toluene at -20°C was added a THF solution of aldehyde S1 (329.1 mg, 1.5
mmol), (CF3CH2O)2POCH2CO2CH3 (591.7 mg, 1.2 mmol). The mixture was stirred for
3 h. Sat. NH4Cl solution was added 0˚C and the mixture was extracted with EtOAc. The
organic layer was washed with brine, dried (MgSO4), and was evaporated to afford a
residue. The residue was purified by silica-gel column chromatography (hexane-EtOAc,
0-10%) to give cis S3 (80.0 mg, 19.2%) and trans S2 (19.5 mg, 4.7%).
O
COOMe
O
S3
1
S3: oil: FT-IR: 1720, 1640 cm-1; H NMR (200MHz, CDCl3) δ 0.98 (3H, s), 1.39-1.65
(10H, m), 2.60 (2H, m), 3.68 (3H, s), 3.90-4.00 (4H, m), 5.77 (1H, dt, J = 11.0, 1.4 Hz),
6.24 (1H, dt, J = 11.0, 7.1 Hz); 13C NMR (50MHz, CDCl3) δ 19.3, 20.8, 23.6 (X2), 30.5,
33.7, 34.1, 41.3, 51.0, 64.8, 65.0, 112.9 (C), 118.8 (CH), 151.9 (CH), 166.9 (CO); MS
m/z 268 [M]+, 169 (base), 113, 99; EI-HRMS Found m/z 268.1676 [M]+ C15H24O4
requires 268.1675.
Synthesis of 1 and 2
S3

A solution of S3 (68.5 mg, 0.3 mmol) in THF was treated with 1M HCl (1 ml) at rt
overnight. The solvent was evaporated and aq. NaHCO3 soln. was added. The mixture
was extracted with ether. The organic solution was washed with brine, dried (MgSO4),
and evaporated to afford a residue. The residue was purified by silica-gel column
chromatography (hexane-EtOAc, 1-40%) to give 2 (38.5 mg, 67.2%).
Similarly S2 (52.5 mg, 0.2 mmol) was hydrolyzed to give 1 (33.8 mg, 77.0%).
COOMe
O
1
1; oil: FT-IR: 1720, 1700, 1650 cm-1; H NMR (200MHz, CDCl3) δ 1.08 (3H, s),
1.48-1.62 (3H, m), 1.65-1.85 (5H, m), 1.90-2.30 (2H, m), 2.38 (2H, t, J = 6.8 Hz), 3.75
(3H, s), 5.92 (1H, dt, J = 16.7, 1.0 Hz), 6.97 (1H, dt, J = 16.7, 7.2 Hz); 13C NMR
(50MHz, CDCl3) δ 20.9, 22.5, 26.7, 27.3, 35.8, 38.7, 39.1, 48.2, 51.4 (CH3), 121.0 (CH),
149.1 (CH), 167.1 (CO), 215.4 (CO); MS m/z 224 [M]+, 112 (base), 97; EI-HRMS
Found m/z 224.1406 [M]+ C13H20O3 requires 224.1412.
COOMe
O
1
2; oil: FT-IR: 1720, 1700, 1640 cm-1; H NMR (200MHz, CDCl3) δ 1.10 (3H, s),
1.50-1.90 (8H, m), 2.38-2.66 (4H, m), 3.70 (3H, s), 5.78 (1H, dt, J = 10.0, 1.0 Hz), 6.10
13
(1H, dt, J = 10.0, 8.0 Hz); C NMR (50MHz, CDCl3) δ 21.0, 22.5, 23.7, 27.4, 36.4,
38.7, 38.9, 48.4, 51.1 (CH3), 119.5 (CH), 150.1 (CH), 166.7 (CO), 215.5 (CO); MS m/z
224 [M]+, 112 (base), 97; EI-HRMS Found m/z 224.1442 [M]+ C13H20O3 requires
224.1412.
General procedure for SmI2-induced cyclization of 1 and 2 (Table 1)
A THF solution of 1 or 2 (15 mg-30 mg, 0.07 mmol-0.14 mmol) was treated with SmI2
in THF (3.0 mL, 0.3 mmol-15 mL, 1.5 mmol) with or without the additive at rt for a
certain period specified in Table 1. The reaction was worked up as before and the
mixture was separated by silica-gel column chromatography (hexane-EtOAc, 0-30%).
The results for Table 1.
Entry 1: Compound 1 (22.7 mg) was treated with SmI2 to afford compound 4 (17.2 mg,
75.1%).
Entry 2: Compound 1 (24.6 mg) was treated with SmI2 to afford compound 4 (19.1 mg,
77.0%).
S4

Entry 3: Compound 1 (22.1 mg) was treated with SmI2 to afford compound 4 (20.3 mg,
91.0%).
Entry 4: Compound 1 (18.2 mg) was treated with SmI2 to afford compound 3 (3.2 mg,
20.3%) and compound 4 (13.5 mg, 73.5%).
Entry 5: Compound 2 (19.4 mg) was treated with SmI2 to afford compound 3 (14.8 mg,
88.1%) and compound 4 (1.8 mg, 9.2%).
Entry 6: Compound 2 (19.0 mg) was treated with SmI2 to afford compound 3 (14.0 mg,
85.1%) and compound 4 (2.3 mg, 12.0%).
Entry 7: Compound 2 (19.0 mg) was treated with SmI2 to afford compound 3 (11.0 mg,
66.8%) and compound 4 (2.8 mg, 14.6%).
Entry 8: Compound 2 (20.0 mg) was treated with SmI2 to afford compound 3 (1.2 mg,
6.9%) and compound 4 (18.6 mg, 92.2%).
O
O
3; oil: FT-IR: 1770 cm-1; 1H NMR (600 MHz, C6D6) δ 0.75-0.83 (1H, m), 0.84-0.93 (2H,
m), 0.97 (1H, m), 1.01 (3H, s), 1.03 (1H, dd, J = 14.4, 5.4 Hz), 1.07-1.14 (2H, m), 1.22
(1H, dt, J = 13.8, 2.4 Hz), 1.30 (1H, m), 1.44 (1H, td, J = 13.8, 4.8 Hz), 1.59 (1H, td, J
= 6.6, 4.2 Hz), 1.62-1.69 (1H, m), 1.91 (1H, d, J = 18.0 Hz), 2.02 (1H, td, J = 8.4, 3.6
13
Hz), 2.26 (1H, ddd, J = 18.0, 8.4, 0.6 Hz); C NMR (150 MHz, C6D6) δ 19.3 (CH3),
21.1 (CH2), 23.7 (CH2), 29.1 (CH2), 29.4 (CH2), 34.8 (CH2), 37.2 (CH2), 38.6 (CH2),
39.4 (CH2), 45.1 (C), 97.2 (C), 175.4 (CO); MS m/z 194 [M]+,179, 1665, 151, 135, 112
(base); EI-HRMS Found m/z 194.1307 [M]+ C12H18O2 requires194.1307.
COOMe
OH
1
4; oil: FT-IR: 3500, 1720 cm-1; H NMR (600 MHz, C6D6) δ 0.85-0.94 (2H, m), 0.97
(3H, s), 1.01 (1H, ddd, J = 13.8, 10.2, 3.6 Hz), 1.20 (1H, qt, J = 13.8, 4.2 Hz), 1.26 (1H,
m), 1.28 (1H, m), 1.39 (1H, m), 1.42 (1H, m), 1.47 (1H, td, J = 18.0, 4.2 Hz), 1.55-1.65
(2H, m), 1.82 (1H, dtd, J = 13.8, 10.2, 6.6 Hz), 2.03 (1H, dd, J = 16.2, 7.8 Hz), 2.29 (1H,
dd, J = 16.2, 7.8 Hz), 2.49 (1H, tt, J = 10.2, 7.8 Hz), 3.29 (3H, s); 13C NMR (150 MHz,
C6D6) δ 21.5 (CH2), 22.0 (CH2), 25.2 (CH3), 25.4 (CH 2), 30.4 (CH2), 30.8 (CH2), 33.4
S5

(CH2), 34.5 (CH), 43.3 (CH), 43.8 (C), 51.1 (CH3), 78.1 (C), 174.5 (CO); MS m/z 226
[M]+, 169, 151, 135, 112 (base); EI-HRMS Found m/z 226.1560 [M]+ C13H22O3 requires
226.1569.
Preparation of S9
i
To a CH2Cl2 solution of 4 (20.8 mg, 0.09 mmol) was added Pr2NEt (0.05 mL, 0.28
mmol) and MOMCl (0.02 mg, 0.22 mmol) at 0°C and the mixture was stirred at rt
overnight. Sat. NaHCO3 soln. was added and the mixture was extracted with CH2Cl2.
The organic layer was washed with brine, dried (MgSO4), and was evaporated to afford
a residue. The residue was purified by silica-gel column chromatography
(hexane-EtOAc, 0-20%) to give S9 (0.8 mg). The stereochemistry was established by
the NOESY spectrum (in the figure).
H
O
COOMe
NOE
O
S9
1
S9: oil: FT-IR: 1740 cm-1; H NMR (600 MHz, CDCl3) δ 0.99 (3H, s), 1.11-1.21 (3H,
m), 1.33-1.41 (4H, m), 1.44-1.50 (2H, m), 1.72 (1H, br d, J = 12.6 Hz), 1.81 (1H, td, J =
12.0, 7.2 Hz), 2.05 (1H, dd, J = 15.0, 10.8 Hz), 2.13 (1H, tdd, J = 13.8, 10.2, 7.8 Hz),
2.69 (1H, tdd, J = 10.8, 8.4, 3.0 Hz), 2.84 (1H, dd, J = 15.0, 3.0 Hz), 3.38 (3H, s), 3.66
(3H, s), 4.67 (1H, d, J = 7.4 Hz), 4.76 (1H, d, J = 7.4 Hz); 13C NMR (150 MHz, CDCl3)
δ 21.1 (CH2), 21.5 (CH2), 24.8 (CH3), 25.5 (CH2), 26.4 (CH2), 30.7 (CH2), 33.0 (CH2),
35.7 (CH2), 40.7 (CH), 45.3(C), 51.4 (CH3), 55.2 (CH3), 83.8 (C), 90.8 (CH2), 174.3
(CO); MS: m/z 270 [M]+, 238, 225, 209, 193, 183, 165, 156, 135, 112 (base); EI-HRMS
Found m/z 270.1826 C15H26O4 requires 270.1831
Preparation of S6
A solution of 2-methylcyclohexanone (112.2 mg, 1 mmol) in THF (10 mL), was treated
t
with BuOK (158.5 mg, 1.2 mmol) at rt for 30 min. 5-bromopent-1-ene (178.8 mg, 1.2
mmol) was added and the mixture was further stirred for 5 h at rt. Sat. NH4Cl soln. was
added at 0°C and the mixture was extracted with ether. The organic layer was washed
with brine, dried (MgSO4), and was evaporated to afford a residue. The residue was
purified by silica-gel column chromatography to give S4.
A solution of S4 (1.80 g, 10.0 mmol) in benzene was treated with ethylene glycol (744
S6

mg, 12 mmol) and TsOH (150 mg) under reflux for 7 h with the aid of the Dean-Stark
water separator. Sat. NaHCO3 soln was added and the mixture was extracted with ether.
The organic layer was washed with brine, dried (MgSO4), and was evaporated to afford
S5 (1.86 g).
Preparation of S6
Ozone was bubbled through a solution of S5 (1.03 g, 4.6 mmol) in CH2Cl2at -78°C for 1
h. Zn (3.0 g, 46 mmol) and acetic acid (2.8 g, 46 mmol) was added at -78-0°C and the
mixture was stirred for 5 h. The mixture was filtered and NaHCO3 soln. was added. The
mixture was extracted with CH2Cl2 and the organic layer was washed with brine, dried
(MgSO4), and was evaporated to afford S6 (1.40 g).
O
O
O
S6: oil ; FT-IR: 1720 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.94 (3H, s), 1.35-1.65 (12H,
m), 2.41 (2H, td, J = 7.5, 1.5 Hz), 3.85-3.95 (4H,m), 9.77 (1H, t, J = 2.3 Hz); 13C NMR
(50 MHz, CDCl3) δ 16.3, 19.3, 20.8, 23.5, 30.4, 34.2, 64.7 (CH2), 64.9 (CH2), 112.9 (C),
203.1 (CO); MS (CI) m/z 227 [M+H]+, 198, 165, 129, 89 (base); CI-HRMS Found m/z
227.1630[M+H]+ C13H23O3 requires 227.1647.
Preparation of S7 and S8
To a mixture of 18-crown-6-ether (158.3 mg, 0.6 mmol) and K2CO3 (80.9 mg, 0.6
mmol) was added
a
solution of S6 (55.5 mg, 0.2 mmol) and
(CF3CH2O)2POCH2CO2CH3 (92.3 mg, 0.3 mmol) in THF at -20°C and the mixture
was stirred at rt overnight. Sat. NH4Cl soln. was added at 0°C and the mixture was
extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4), and
was evaporated to afford S7 and S8 1:4.5.
To a suspension of NaH (47.3 mg, 1.3 mmol) in THF was added (MeO)2POCH2CO2Me
(209.4 mg, 1.2 mmol) at rt for 1 h. Then a solution of S6 (217.5 mg, 1.0 mmol) in THF
was added and the mixture was stirred overnight. Wet Et2O was added and extracted.
The organic layer was washed with brine, dried (MgSO4), and was evaporated to afford
S7 and S8 in the ratio of 5: 1.
COOMe
O
O
S7

S7: oil; FT-IR: 1660 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.90 (3H, s), 1.35-1.65 (12H,
m), 2.18 (2H, dt, J = 7.0, 5.6 Hz), 3.73 (3H, s), 3.85-4.00 (4H, m), 6.83 (1H, d, J = 15.7
Hz), 6.99 (1H, dt, J = 15.7, 6.7 Hz); 13C NMR (50 MHz, CDCl3) δ 19.4, 20.8, 22.2, 23.6,
30.4, 33.3, 34.1, 34.2, 41.2, 51.4 (CH3), 64.7 (CH2), 64.9 (CH2), 112.9 (C), 120.8 (CH),
149.8 (CH), 167.2 (CO); MS m/z 282 [M]+, 183, 113, 99 (base), 86; EI-HRMS Found
m/z 282.1827 [M]+ C16H26O4 requires282.1831.
Preparation of 5 and 6
A solution of S7 and S8 (201.4 mg, 0.7 mmol) in THF was treated with 1M HCl (2 mL)
at rt overnight. The solvent was evaporated and NaHCO3 soln. was added. The mixture
was extracted with ether and the organic layer was washed with brine, dried (MgSO4),
and was evaporated to afford a residue. The residue was purified by silica-gel column
chromatography (hexane-EtOAc, 0-30%) to give 5 (22.1 mg) and 6 (122.4 mg),
respectively.
COOMe
O
1
5: oil; FT-IR: 1720, 1700 cm-1; H NMR (200 MHz, CDCl3) δ 1.05 (3H, s), 1.20-1.90
(10H, m), 2.20 (2H, m), 2.34 (2H, t, J = 8.5 Hz), 3.71 (3H, s), 5.82 (1H, d, J = 13.0 Hz),
13
6.92 (1H, dt, J = 13.0, 6.2 Hz); C NMR (50 MHz, CDCl3) δ 21.1, 22.4, 22.7, 27.4,
32.7, 37.1, 38.8, 39.2, 48.5 (C), 51.4 (CH3), 121.3 (CH), 149.0 (CH), 167.1 (CO), 215.7
(CO); MS m/z 238 [M]+, 206, 189, 112 (base); EI-HRMS Found m/z 238.1561 [M]+
C13H22O3 requires 238.1569.
COOMe
O
1
6: oil; FT-IR: 1720, 1700, 1640 cm-1; H NMR (200 MHz, CDCl3) δ 1.04 (3H, s),
1.35-2.00 (10H, m), 2.34 (2H, m), 2.64 (2H, m), 3.70 (3H, s), 5.79 (1H, d, J = 11.2 Hz),
13
6.20 (1H, dt, J = 11.2, 7.0 Hz); C NMR (50 MHz, CDCl3) δ 21.0, 22.5, 23.3, 27.4,
29.3, 37.1, 38.7, 39.3, 48.5, 51.0 (CH3), 119.6 (CH), 150.2 (CH), 166.5 (CO), 215.9
(CO); MS m/z 238 [M]+, 206, 189, 112 (base); EI-HRMS Found 238.1560 [M]+
C14H22O3 requires 238.1569.
General procedure for SmI2-induced cyclization of compounds 5 and 6 (Table 2)
S8

To a stirred solution of SmI2 in THF (3.6 mL, 0.36 mmol) was added a solution of 5 or 6
in THF at the temperature for a certain period specified in the Table 2. The reaction was
worked up as before and the mixture was separated by silica-gel column
chromatography (hexane-EtOAc, 0-30%).
The results for Table 2.
Entry 1: Compound 5 (29.8 mg) was treated with SmI2 to afford compound 8 (18.8 mg,
72.2%).
Entry 2: Compound 5 (29.5 mg) was treated with SmI2 to afford compound 8 (25.2 mg,
97.7%).
Entry 3: Compound 5 (18.8 mg) was treated with SmI2 to afford compound 8 (11.5 mg,
70.0%) and compound 9 (2.5 mg, 13.2%).
Entry 4: Compound 5 (21.8 mg) was treated with SmI2 to afford compound 8 (15.7 mg,
82.4%).
Entry 5: Compound 6 (29.2 mg) was treated with SmI2 to afford compound 7 (23.0 mg,
90.1%).
Entry 6: Compound 6 (23.8 mg) was treated with SmI2 to afford compound 7 (15.4 mg,
74.0%).
Entry 7: Compound 6 (19.6 mg) was treated with SmI2 to afford compound 7 (14.8 mg,
86.4%).
Entry 8: Compound 6 (22.4 mg) was treated with SmI2 to afford compound 7 (14.7 mg,
75.1%) and compound 8 (3.4 mg, 17.4%).
O
O
1
7: crystal; mp. 48.8-50.2°C (CHCl3); FT-IR: 1760 cm-1; H NMR (600 MHz, CDCl3) δ
1.10 (3H, s), 1.16-1.27 (3H, m), 1.30-1.38 (1H, m), 1.41-1.46 (1H, m), 1.50-1.58 (4H,
m), 1.65-1.76 (3H, m), 1.78-1.84 (2H, m), 2.06 (1H, dd, J = 17.0, 1.2 Hz), 2.43 (1H, dtd,
13
J = 11.2, 6.6, 1.2 Hz), 2.81 (1H, dd, J = 17.0, 6.6 Hz); C NMR (150 MHz, CDCl3) δ
18.4 (CH2), 20.8 (CH2), 23.2 (CH3), 24.0 (CH2), 29.6 (CH2), 30.9 (CH2), 34.5 (CH2),
34.7 (CH2), 35.5 (CH2), 35.7 (C), 38.4 (CH2), 89.7 (C), 177.2 (CO); MS m/z 208 [M]+,
193, 179, 165, 152, 151 (base), 123, 112; EI-HRMS Found m/z 208.1459 [M]+
C13H20O2 requires 208.1463.
S9

Crystal data
C13H20O2
C13H20O2
Mr = 208.301
Monoclinic
P21/c
a = 11.8390 (9)Å
b = 6.6930 (4)Å
c = 15.221 (2)Å
α = 90.00°
β = 99.424 (3)°
γ = 90.00°
V = 1189.8 (2)Å3
Z = 4
Dx = 1.163 Mg m-3
Density measured by: not measured
fine-focus sealed tube
S10

Mo Kα radiation
λ = 0.71073
ꢀ = 0.076 mm-1
T = 298 K
Needle
Colorless
Crystal source: Local laboratory
Data collection
DIP Image plate
IP
Absorption correction: cylinder
Tmin = 0.975 , Tmax = 0.975
2393 measured reflections
2195 independent reflections
1655 observed reflections
Criterion: >2sigma(I)
θmax = 25.74 °
h = 0 →14
k = 0 →7
l = -18 →18
Refinement
Refinement on F2
full matrix least squares refinement
R(all) = 0.0745
R(gt) = 0.0566
wR(ref) = 0.1700
wR(gt)= 0.1493
S(ref) = 1.060
2195 reflections
137 parameters
0 restraints
Only coordinates of H atoms refined
Calculated weights calc
ꢁ/σmax = 0.000
S11

ꢁρmax = 0.201eÅ3
ꢁρmin = -0.213eÅ3
Extinction correction: SHELXL
Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Extinction coefficient = 0.037 (6)
O
O
1
8: crystal; mp. 92.8-94.2°C (C6H6-EtOAc); FT-IR: 1770cm-1; H NMR (600 MHz,
CDCl3) δ 1.03 (3H, s), 1.12 (1H, dd, J = 9.9, 4.8 Hz), 1.27 (1H, dt, J = 11.5, 3.0 Hz),
1.44 (1H, m), 1.47 (1H, qd, J = 12.6, 4.7 Hz), 1.50-1.56 (2H, m), 1.58-1.67 (3H, m),
1.68-1.71 (2H, m), 1.73 (1H, m), 1.86 (1H, ddd, J = 14.0, 6.0, 5.2 Hz), 2.00 (1H, td, J =
14.4, 6.0 Hz), 2.34 (1H, dd, J = 16.5, 8,5 Hz), 2.38 (1H, dd, J = 16.5, 12.6 Hz), 2.58 (1H,
tdd, J = 12.6, 8.5, 3.3 Hz); 13C NMR (150 MHz, CDCl3) δ 21.1 (CH2), 21.2 (CH3), 21.2
(CH2), 21.8 (CH2), 24.7 (CH2), 25.8 (CH2), 32.3 (CH2), 33.3 (CH2), 36.5 (CH2), 36.7
(C), 39.8 (CH), 89.4 (CO), 176.7 (CO); MS: m/z 208 [M]+, 193, 179, 165, 152 (base),
151, 125; HR-MS: Found m/z 208.1454 [M]+ C13H20O2 requires 208.1463.
S12

Crystal data
C13H20O2
C13H20O2
Mr = 208.301
Monoclinic
C2/c
a = 12.6700 (11)Å
b = 8.5820 (6)Å
c = 21.582 (2)Å
α = 90.00°
β = 100.405 (4)°
γ = 90.00°
V = 2308.1 (4)Å3
Z = 8
Dx = 1.199 Mg m-3
Density measured by: not measured
fine-focus sealed tube
S13

Mo Ka radiation
λ = 0.71073
ꢀ = 0.079 mm-1
T = 298 K
Plate
Colorless
Crystal source: Local laboratory
Data collection
DIP Image plate
IP
Absorption correction: cylinder
Tmin = 0.974 , Tmax = 0.974
2079 measured reflections
1950 independent reflections
1656 observed reflections
Criterion: >2sigma(I)
θmax = 25.85 °
h = 0 →15
k = 0 →9
l = -26 →25
Refinement
Refinement on F2
full matrix least squares refinement
R(all) = 0.0618
R(gt) = 0.0555
wR(ref) = 0.1633
wR(gt)= 0.1558
S(ref) = 1.060
1950 reflections
137 parameters
0 restraints
Only coordinates of H atoms refined
Calculated weights calc
ꢁ/σmax = 0.000
S14

ꢁρmax = 0.217eÅ3
ꢁρmin = -0.215eÅ3
Extinction correction: SHELXL
Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Extinction coefficient = 0.0115 (19)
OH
CO2Me
9: oil; FT-IR: 3500, 1730cm-1; 1H NMR (600 MHz, CDCl3) δ 0.99 (3H, s), 1.07 (1H, m),
1.12 (1H, m), 1.20 (1H, dd, J = 13.0, 4.7 Hz), 1.25-1.85 (11H, m), 1.91 (1H, td, J = 13.7,
4.4 Hz), 1.96 (1H, dd, J = 15.1, 9.3 Hz), 227 (1H, m), 2.68 (1H, dd, J = 15.1, 4.4 Hz),
3.67 (3H, s); 13C NMR (50 MHz, CDCl3) δ 20.8, 21.2, 21.3, 22.2, 26.3, 30.2, 33.8, 34.9,
36.8, 38.2, 40.4, 51.6 (CH3), 74.8 (C), 175.1(CO); MS (GC): m/z 240 [M]+, 208, 184,
152, 151, 112 (base); HR-MS: Found m/z 240.0720 [M]+ C14H24O3 requires 240.1726.
Preparation of S10
To a stirred solution of 8 (12.6 mg, 0.05 mmol) in CH2Cl2 was added iPr2NEt ( 0.09 mL,
0.48 mmol) and MOMCl (0.03 mL, 0.39 mmol) at 0°C. The reaction mixture was
stirred overnight at rt. Sat. NaHCO3 was added and the organic layer was washed with
brine, dried (MgSO4), and was evaporated to afford a residue (36.1 mg). The residue
was purified by a silica-gel column chromatography (hexane-EtOAc, 0-30 %) to give
S10 (10.6 mg). The stereochemistry was established by the NOESY spectrum (in the
figure).
NOE
H
O
CO2Me
O
S10
S10: oil; FT-IR: 1735 cm-1; 1H NMR (600 MHz, CDCl3) δ 1.02 (3H, s), 1.15 (1H, qd, J
= 13.5, 4.4 Hz), 1.22-1.44 (5H, m), 1.45-1.52 (4H, m), 1.67-1.73 (2H, m), 1.78-1.85
(1H, m), 1.90 (1H, dd, J = 15.4, 11.0 Hz), 1.92 (1H, td, J = 14.0, 4.1 Hz), 2.47 (1H, tdd,
J = 11.0, 4.4, 2.2 Hz), 2.81 (1H, dd, J = 15.4, 2.2 Hz), 3.37 (3H, s), 3.66 (3H, s), 4.71
(1H, d, J = 6.9 Hz), 4.82 (1H, d, J = 6.9 Hz); 13C NMR (50 MHz, CDCl3) δ 20.6, 21.0,
21.2, 23.2, 24.5, 30.9, 34.8, 35.3, 36.8, 37.0, 39.3, 51.4 (CH3), 55.0 (CH3), 82.0 (C),
S15

90.9 (CH2), 174.7 (CO); MS m/z 284 [M]+, 252, 239, 223, 173, 156, 147, 112 (base);
EI-HRMS Found m/z 284.1990 [M]+ C16H28O4 requires 284.1988.
Trapping with D2O
A solution of 1 (20.0 mg, 0.090 mmol) and D2O (9.0 mg, 0.45 mmol) in THF was
treated with SmI2 (0.1 M in THF, 1.8 ml, 0.18 mmol) at rt for 1 h. Ether and Rochell’s
salt were added and the organic layer was washed with brine, dried (MgSO4), and was
evaporated to afford a residue. The residue was purified by a silica-gel column
chromatography (hexane-EtOAc, 0–25%) to give 3a (1.7 mg, 9.8%) and 4a (1.6 mg,
7.9%). Compounds 3a (1.7 mg, 9.7%) and 4a (1.6 mg, 7.8%) were obtained from
compound 2.
O
H
D
O
3a: oil; MS m/z 195 [M]+, 180, 166, 152, 136, 112 (base).
S16

(a)
(b)
MS spectra for compound 3 (a) and compound 3a (b) .
O
X
O
3 X=H
3a X=D
S17

COOMe
OH
D
H
4a: oil: MS m/z 227 [M]+, 209, 194, 180, 170, 152, 135, 112 (base).
(a)
(b)
MS spectra for compound 4 (a) and compound 4a (b) .
3
CO2Me
OH
X
4 X=H
4a X=D
S18

1
Assignment of Ha, Hb, Hc, and Hd in compound 3. H NMR spectra of compound 3a
derived from 1 and 2 by quenching with D2O. Ha and Hb significantly diminished.
S19

1
Assignment of He, Hf, and Hg in compound 4. H NMR spectra of compound 4a
derived from 1 and 2 by quenching with D2O. He and Hf significantly diminished.
S20

General procedures of trapping experiment of the substrates and
DMPO
To a solution of the substrate and DMPO in a test tube, SmI2 in THF was added with
stirring, and in 1 min (the blue color faded), the ESR was measured (when the substrate
was not added, no signal was detected). Isolation of the adduct 11, 12, or 13 was not
attempted.
The ESR spectra of the reactions and simulations
(1) The ESR for the reaction of compound 1 with SmI2 in the presence of DMPO.
S21

(2) The ESR for the reaction of compound 2 with SmI2 in the presence of DMPO.
(3) The species 12: a(N)/mT = 1.40, a(H)/mT = 2.19, ꢁB/mT = 0.14
-60
-40
-20
0
20
40
60
S22

(4) The species 13: a(N)/mT = ca. 1.47, a(H)/mT = ca. 2.49, ꢁB/mT = ca. 0.10
-60
-40
-20
0
20
40
60
(5) The unknown species: a(N)/mT = ca. 0.33, a(H)/mT = ca. 1.25
-60
-40
-20
0
20
40
60
S23

(6) The spectrum of 12 and 13 (1:1)
-60
-40
-20
0
20
40
60
(7) The spectrum of 12 and 13 (100:12)
-60
-40
-20
0
20
40
60
S24

(8) The spectrum of 12 and 13 (1:1) and the unknown species.
-60
-40
-20
0
20
40
60
In this system the simulation with a(N)/mT = 0.79, a(H)/mT = 0.33 can also resulted in
a similar spectrum. Therefore, it was not possible to identify the radical species.
However, the signal intensities are very weak and presumably due to a by-product or an
impurity.
S25

(9) The ESR for the reaction of compound 10 with SmI2 in the presence of DMPO.
S26

COOMe
O
1
1H NMR of Compound 1
S27

COOMe
O
1
13C NMR of Compound 1
S28

COOMe
O
2
1H NMR of Compound 2
S29

COOMe
O
2
13C NMR of Compound 2
S30