Supporting Information

Bio-Inspired Total Synthesis of (±)-Yezo’otogirin C

Shuzhong He,§,† Wei Yang,§Lizhi Zhu, Guangyan Du and Chi-Sing Lee*

*Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School,
Shenzhen University Town, Xili, Shenzhen 518055, China; E-mail: lizc@pkusz.edu.cn
†
Present address: School of Pharmacy, University of Wisconsin at Madison, Madison, Wisconsin 53705, United States

Table of Contents

Generation information…………………………………………………………..………...................................................….…......................S2
Experimental section: Synthesis of compound 3, 5-6, 13, 15 and 17-22…………………………………………………...........................S2–S6
References ………………………………………………………………………………..................................................….............................S6
X-ray structure of compound 13 (Figure S1)……………………………………………………………………………………......................S7
NMR spectra of compound 3, 5-6, 13, 15 and 17-22...................................................................................................................................S8–S30

S1
General Information
All the chemicals were purchased commercially and used without further purification. Anhydrous THF was distilled from sodium-
benzophenone, and dichloromethane was distilled from calcium hydride. Yields refer to isolated yields after silica gel flesh column
chromatography, unless otherwise stated. All air and water sensitive reactions were carried out under a nitrogen atmosphere with dry solvents
under anhydrous conditions, unless otherwise noted. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm
silica gel plates (60F-254) that were analyzed by staining with KMnO4 (200 mL H2O of 1.5 g KMnO4, 10 g K2CO3 and 1.25 mL of 10%
aqueous NaOH). Silica gel (60, particle size 0.040-0.063 mm) was used for flash column chromatography.

NMR spectra were recorded on either a 300 (1H: 300 MHz, 13C: 75 MHz), 400 (1H: 400 MHz, 13C: 100 MHz) or 500 (1H: 500 MHz, 13C: 125
MHz) spectrometer. The NOESY experiments were performed on a 500 or 600 MHz spectrometer. The following abbreviations were used to
explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad. High resolution mass spectra were
obtained from a MALDI-TOF mass Spectrometer. Melting points were uncorrected and determined on a micro-melting point meter.
Crystallographic data were obtained from a single crystal X-ray diffractometer. All the IR spectra were recorded with a FTIR spectrometer.

Experimental Section

Synthesis of compound 17

To a stirred solution of iPr2NH (4.88 mL, 34.69 mmol) in THF (100 mL) at 0 ºC was added nBuLi (13.88 mL, 33.30 mmol) dropwise. The
resulting mixture was stirred at room temperature for 30 minutes and cooled to -78 ºC. Compound 161 (4.94 g, 27.75 mmol) in THF (20 mL)
was added slowly to the mixture at -78 ºC. After stirring for 30 minutes, CH3I (3.46 mL, 55.51 mmol) was added dropwise to the solution at -
78 ºC. Then the mixture was stirred at -78 ºC for 30 minutes and 0 ºC until TLC showed the consumption of 16. The reaction was then
quenched by addition of a saturated NH4Cl aqueous solution and the aqueous layer was extracted with ethyl acetate (100 mL × 3). The
combined organic extracts were washed by brine, dried over MgSO4, filtered and concentrated. Silica gel flash column chromatography
(EtOAc/hexanes = 1:20) of the residue gave a yellow oil (4.80 g, 24.98 mmol, 90%) as the product. 17: 1H NMR (500 MHz, CDCl3) δ 5.79
(s, 1H), 5.15 (t, J = 6.5 Hz, 1H), 2.49-2.42 (m, 1H), 2.31-2.17 (m, 3H), 1.97-1.93 (m, 4H), 1.78-1.72 (m, 4H), 1.63 (s, 3H), 1.10 (d, J = 6.5
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 201.8, 164.4, 133.8, 126.2, 122.3, 40.1, 36.2, 34.9, 29.8, 25.7, 22.8, 17.8, 15.4; IR (neat, cm-1): 3027,
2970, 2927, 2872, 1674, 1628, 1448, 1374, 1213, 878, 854; HRMS (ESI/[M+H]+) calcd. for C13H21O: 193.1592, found 193.1588.

Synthesis of compound 5

To a stirred suspension of mashed magnesium (2.5 g, 104.2 mmol) and iodine (0.1 g) in THF (80 mL) under argon was added a portion (3
mL) of a solution of 5-bromo-2-methyl-2-pentene (10.2 g, 62.5 mmol) in THF (15 mL). The mixture was heated gently until the reaction was
initiated. Then the rest of the solution was added slowly to the suspension. The resulting mixture was heated under reflux for 1.5 hour and
cooled to room temperature. This solution was transferred to a solution of CuBr·Me2S (1.1 g, 5.2 mmol) in THF (10 mL) at -20 ºC slowly
using a gas-tight syringe. After the stirring for 30 minutes, a solution of 17 (4 g, 20.84 mmol) in THF (10 mL) was added dropwise to the
mixture at -20 ºC. After stirring at -20 ºC for 20 minutes, HMPA (12.8 ml, 72.9 mmol) and methyl cyanoformate (5.8 mL, 72.9 mmol) were
added sequentially to the mixture at -20 ºC. The resulting mixture was stirred at -20 ºC for 30 minutes and 0 ºC overnight. The reaction was
then quenched by addition of saturated NH4Cl aqueous solution and the aqueous layer was extracted with ethyl acetate (100 mL × 3). The
combined organic extracts were dried over MgSO4, filtered and concentrated. Silica gel flash column chromatography (EtOAc/hexanes =
1:50) of the residue provide a colorless oil (5.78 g, 17.30 mmol, 83%) as the product. 5 (a mixture a high enolizable β-keto esters): 1H NMR
(500 MHz, CDCl3) δ 5.17-5.04 (m, 2H), 3.70-3.56 (m, 3H), 2.67-2.42 (m, 1H), 2.56-2.22 (m, 1H), 2.16-2.10 (m, 1H), 2.01-1.83 (m, 3H),
1.81-1.73 (m, 5H), 1.68-1.65 (m, 5H), 1.63-1.60 (m, 4H), 1.57-1.49 (m, 2H), 1.32-1.12 (m, 3H), 1.09-1.02 (m, 4H); 13C NMR (125 MHz,
CDCl3) δ 210.6, 207.3, 169.3, 169.0, 133.1, 132.9, 131.8, 131.4, 124.2, 123.6, 123.4, 122.8, 63.0, 60.4, 51.5, 44.5, 44.5, 42.9, 39.9, 39.7,
38.3, 37.2, 34.5, 33.6, 33.2, 27.0, 25.8, 25.8, 25.7, 25.6, 22.7, 21.6, 21.3, 18.2, 17.9, 17.9, 17.6, 17.4, 14.4; IR (neat, cm-1): 3457, 2966, 2927,
2881, 1755, 1713, 1633, 1597, 1436, 1378, 1339, 1213, 1133, 1007, 846; HRMS (ESI/[M+H]+) calcd. for C21H35O3: 335.2586, found
335.2581.

S2
Synthesis of compound 20

To a stirred suspension of mashed magnesium (0.25 g, 10.42 mmol) and iodine (0.01 g) in THF (12 mL) under argon was added a portion
(0.3 mL) of a solution of 5-bromo-2-methyl-2-pentene (1.36 g, 8.3 mmol) in dried THF (2 mL). The mixture was heated gently until the
reaction was initiated. Then the rest of the solution was added slowly to the suspension. The resulting mixture was heated under reflux for
1.5 hour and cooled to room temperature. This solution was transferred to a solution of CuBr·Me2S (54 mg, 0.26 mmol) in THF (5 mL) at -
20 ºC slowly using a gas-tight syringe. After stirring for 30 minutes, a solution of 17 (1 g, 5.2 mmol) in THF (2 mL) was added dropwise to
the mixture at -20 ºC. After stirring at -20 ºC for 20 minutes, a solution of isobutyraldehyde (0.61mL, 6.8 mmol) in THF (2 mL) was added
to the mixture slowly at -78 ºC. The resulting mixture was stirred at -78 ºC until TLC analysis showed the consumption of 17. The reaction
was then quenched by addition of a saturated NH4Cl aqueous solution and the aqueous layer was extracted with ethyl acetate (20 mL × 3).
The combined organic extracts were dried over MgSO4, filtered and concentrated under vacuum. Silica gel flash column chromatography
(EtOAc/hexanes = 1:40) of the residue afforded a colorless oil (1.4 g, 4.1 mmol, 78%) as the product. 20 (a mixture of diastereomer): 1H
NMR (500 MHz, CDCl3) δ 5.08-5.07 (m, 2H), 3.72 (d, J = 11.0 Hz, 1H), 3.35 (dd, J = 11.0, 9.0 Hz, 1H), 2.88 (s, 1H), 2.50-2.45 (m, 1H),
2.17-2.14 (m, 1H), 2.07-1.94 (m, 2H), 1.84-1.78 (m, 2H), 1.76-1.74 (m, 1H), 1.73-1.68 (m, 8H), 1.66-1.63 (m, 1H), 1.62 (s, 3H), 1.60 (s, 3H),
1.58-1.55 (m, 1H), 1.23 (d, J = 7.5 Hz, 3H), 1.01 (d, J = 7.0 Hz, 3H), 0.97 (s, 3H), 0.85 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
221.8, 132.6, 131.6, 123.8, 123.2, 75.7, 51.0, 46.5, 45.6, 37.8, 36.8, 35.0, 34.2, 27.6, 25.8, 25.7, 21.2, 20.2, 19.8, 18.3, 17.9, 17.7; IR (neat,
cm-1): 3520, 2981, 2927, 2869, 1689, 1456, 1385, 1201, 1121, 994, 832; HRMS (ESI/[M+H]+) calcd. for C23H41O2: 349.3107, found
349.3089.

Synthesis of compound 6

To a stirred mixture of 20 (1.4 g, 4.0 mmol) and NaHCO3 (1.35 g, 16.1 mmol) in CH2Cl2 (30 mL) was added Dess-Martin periodinate (2.1 g,
4.8 mmol) at 0 ºC. The resulting mixture was stirred at room temperature until TLC analysis showed the consumption of 20. The reaction
was diluted with diethyl ether (30 mL) and quenched by addition of saturated Na2S2O3 aqueous solution at 0 ºC. After the solution has turned
clear, the aqueous layer was extracted with ethyl acetate (30 mL × 3). The combined organic extracts were dried over MgSO 4, filtered and
concentrated. Silica gel flash column chromatography (EtOAc/hexanes = 1:70) of the residue provided a colorless oil (1.11 g, 3.2 mmol,
80 %) as the product. 6: 1H NMR (500 MHz, CDCl3) δ 5.07-5.06 (m, 1H), 5.00 (t, J = 6.5 Hz, 1H), 4.00 (s, 1H), 2.68-2.61 (m, 1H), 2.55-
2.47 (m, 1H), 2.16-2.12 (m, 1H), 2.07-2.01 (m, 1H), 1.89-1.81 (m, 3H), 1.75-1.70 (m, 5H), 1.70 (s, 3H), 1.62 (s, 3H), 1.59 (s, 3H), 1.46-1.42
(m, 2H), 1.24 (d, J = 7.5 Hz, 3H), 1.08-1.05 (m, 9H); 13C NMR (125 MHz, CDCl3) δ 212.8, 211.2, 132.8, 131.7, 123.6, 123.1, 64.2, 45.3,
43.2, 43.0, 38.0, 37.8, 33.8, 26.8, 25.8, 25.6, 22.0, 18.0, 18.0, 17.9, 17.8, 17.6, 17.5; IR (neat, cm-1): 3466, 2971, 2927, 2869, 1726, 1699,
1458, 1380, 1092, 1048, 836; HRMS (ESI/[M+H]+) calcd. for C23H39O2: 347.2950, found 347.2938.

General procedures for oxidative cascade cyclization reaction under an oxygen-free environment

To a solution of 5 (~50 mg, 0.15 mmol) in EtOH (10 mL) was added the appropriate oxidant (2 equiv), co-oxidant (1 equiv). The mixture
was then frozen and degassed under vacuum (× 3). The mixture was stirred at the selected reaction temperature for 2 days or until TLC
showed the consumption of 5. The reaction was then quenched by addition of a saturated NH4Cl aqueous solution and the aqueous layer was
extracted with ethyl acetate (10 mL × 3). The combined organic extracts were dried over MgSO 4, filtered and concentrated. The product was
obtained by silica gel flash column chromatography (EtOAc/hexanes 1:100 to 1:40) of the residue.

Synthesis of compound 15 from 5

The general procedures were followed with 5 (47 mg, 0.14 mmol) as the substrate in EtOH (10 mL) using Mn(OAc)3·2H2O (151 mg, 0.56
mmol) and Cu(OAc)2·H2O (56 mg, 0.28 mmol). A white solid (10 mg, 0.03 mmol, 22%) was obtained after silica gel flash column

S3
chromatography (EtOAc/hexanes 1:40). 15: m.p. = 65.7-66.8ºC, 1H NMR (400 MHz, CDCl3) δ 5.09 (t, J = 6.8 Hz, 1H), 3.67 (s, 3H), 3.02
(dd, J = 10.8, 7.2 Hz, 1H), 1.98-1.75 (m, 5H), 1.71-1.69 (m, 4H), 1.66 (s, 3H), 1.64-1.49 (m, 5H), 1.44-1.36 (m, 1H), 1.25 (s, 3H), 1.21 (s,
3H), 0.91 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 175.0, 147.7, 132.2, 124.4, 107.0, 67.0, 56.2, 51.9, 48.7, 46.9, 41.1, 31.5, 29.7, 29.3, 25.8,
25.8, 25.2, 19.6, 17.8, 16.0; IR (neat, cm-1): 2971, 2932, 2859, 1721, 1449, 1381, 1237, 1160, 1024, 870, 730; HRMS (ESI/[M+H]+) calcd.
for C21H33O3: 333.2430, found 333.2425.

General procedures for oxidative cascade cyclization reaction under an oxygen atmosphere

To a solution of 5 (~50 mg, 0.15 mmol) in a solvent (10 mL) was added the appropriate oxidant (2 equiv), co-oxidant (0.2 equiv). The
resulting mixture was stirred at the appropriate temperature under an oxygen atmosphere for 2 days or until TLC analysis showed the
consumption of 5. The reaction was then quenched by addition of a saturated NaCl aqueous solution and the aqueous layer was extracted
with ethyl acetate (10 mL × 3). The combined organic extracts were dried over MgSO4, filtered and concentrated. The product was obtained
by silica gel column chromatography ((EtOAc/hexanes = 1:20) of the residue.

Synthesis of compound 13

The general procedures were followed with Mn(OAc)2·4H2O (73 mg, 0.30 mmol) and Mn(OAc)3·2H2O (8 mg, 0.03 mmol) at room
temperature. A white solid (30 mg, 0.08 mmol, 55%) was obtained as the product after silica gel flash column chromatography
(EtOAc/hexanes 1:10). 13: m.p. = 101.5-102.2 ºC, 1H NMR (400 MHz, CDCl3) δ 5.10 (t, J = 6.4 Hz, 1H), 3.83 (s, 1H), 3.69 (s, 3H), 3.17 (d,
J = 7.2 Hz, 1H), 2.99-2.90 (m, 1H), 2.07-1.87 (m, 4H), 1.81-1.70 (m, 5H), 1.60 (s, 3H), 1.55-1.47 (m, 2H), 1.44 (s, 3H), 1.39-1.31 (m, 1H),
1.27 (s, 3H), 1.02 (d, J = 7.2 Hz, 3H), 0.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.5, 132.2, 123.6, 102.1, 80.5, 64.0, 51.3, 50.0, 48.9,
42.1, 41.3, 32.2, 31.9, 30.4, 29.6, 26.7, 25.8, 24.1, 21.9, 17.8, 14.9; IR (neat, cm-1): 3471, 2966, 2939, 2881, 1725, 1638, 1453, 1385, 1237,
1082; HRMS (ESI/[M+H]+) calcd. for C21H35O5: 367.2484, found 367.2534.

Synthesis of compound 15 from 13

To a stirred solution of 13 (44 mg, 0.12 mmol) in MeOH (2 mL) was added thiourea (11 mg, 0.14 mmol). The resulting mixture was heated
under refluxed and stirred for 10 hours. Concentration and silica gel flash column chromatography (EtOAc/hexanes = 1:40) of the residue
gave a white solid (36 mg, 0.105 mmol, 92%) as the product. The characterization data of the white solid is identical to that prepared from 5.

Synthesis of compound 18

To a stirred solution of 15 (106 mg, 0.32 mmol) in THF (2 mL) was added isopropyllithium (0.96 mL, 0.96 mmol) dropwise at 0 ºC under
argon. The resulting mixture was stirred at 0 ºC for 10 minutes, and then treated with saturated NH4Cl aqueous solution. The aqueous layer
was extracted with ethyl acetate (5 mL × 3). The combined organic extracts were dried over MgSO4, filtered and concentrated. Silica gel
column chromatography (EtOAc/hexanes 1:50) of the residue gave a pale yellow oil (70 mg, 0.25 mmol, 80%) as the product. 18: 1H NMR
(500 MHz, CDCl3 5.13 (t, J = 7.3 Hz, 1H), 2.57 (d, J = 6.5 Hz, 1H), 2.28 (m, 1H), 2.05-2.02 (m, 1H), 1.90-1.83 (m, 1H), 1.78-1.67 (m,
7H), 1.60-1.56 (m, 6H), 1.54-1.47 (m, 1H), 1.33 (s, 3H), 1.30-1.24 (m, 4H), 1.22-1.17 (m, 1H), 1.00 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
150.0, 131.7, 124.9, 100.6, 84.2, 54.1, 52.2, 46.5, 44.3, 39.8, 32.2, 30.1, 29.2, 26.1, 25.8, 24.5, 17.8, 15.6, 15.5; IR (neat, cm-1): 2971, 2932,
2884, 2855, 1718, 1645, 1446, 1378, 1269, 1162, 1099, 909, 866, 749; HRMS (ESI/[M+H]+) calcd. for C21H33O3: 275.2375, found 275.2372.

S4
Synthesis of compound 21

To a stirred solution of 15 (55 mg, 0.17 mmol) in CH2Cl2 (4 mL) was added DIBAL (0.83 mL of a 1.2 M solution in toluene, 0.99 mmol)
slowly at -78 ºC under argon. The mixture was stirred for 2 hours at -78 ºC, and the reaction was quenched by addition of methanol (0.5 mL)
and then saturated NaCl aqueous solution (10 mL). After stirring at room temperature for 30 minutes, the aqueous layer was extracted with
ethyl acetate (10 mL × 3). The combined organic extracts were dried over MgSO4, filtered and concentration. Silica gel column
chromatography (EtOAc/hexanes 1:50) of the residue give a white solid (49 mg, 0.16 mmol, 93%) as the product. 21: 1H NMR (500 MHz,
CDCl3 5.11 (t, J = 6.5 Hz, 1H), 3.70-3.62 (m, 2H), 2.21 (t, J = 8.0 Hz, 1H), 2.02-1.99 (m, 1H), 1.88-1.84 (m, 2H), 1.82-1.76 (m, 1H),
1.74-1.70 (m, 4H), 1.65 (s, 3H), 1.60 (s, 3H), 1.58-1.55 (m, 2H), 1.41 (s, 3H), 1.39-1.33 (m, 1H), 1.27-1.23 (m, 1H), 1.19 (s, 3H), 1.07 (s,
3H); 13C NMR (125 MHz, CDCl3) δ = 149.60, 131.95, 124.87, 107.62, 83.96, 65.43, 61.27, 55.09, 46.50, 46.05, 41.68, 31.85, 30.23, 29.76,
25.79, 25.50, 25.36, 18.32, 17.83, 16.00; IR (neat, cm-1): 3461, 2976, 2927, 2859, 1718, 1645, 1451, 1381, 1259, 1164, 1101, 1053, 861;
HRMS (ESI/[M+H]+) calcd. for C20H33O2: 305.2481, found 305.2473.

Synthesis of compound 19

To a stirred solution of 21 (50 mg, 0.16 mmol), NMO (77 mg, 0.008 mmol) and 4 Å M.S. (20 mg) in CH2Cl2 (10 mL) was added TPAP (130
mg, 0.32 mmol) at room temperature. The resulting mixture was stirred at room temperature for 3 hours and then treated with saturated NaCl
aqueous solution (10 mL). The aqueous layer was extracted with ethyl acetate (10 mL × 3). The combined organic extracts were dried over
MgSO4, filtered and concentration. Silica gel column chromatography (EtOAc/hexanes 1:50) of the residue give a colorless oil (41 mg, 0.14
mmol, 83 %) as the product. 19: 1H NMR (500 MHz, CDCl3 9.36 (s, 1H), 5.11 (t, J = 7.0 Hz, 1H), 2.94 (dd, J = 10.0, 7.5 Hz, 1H), 2.00-
1.96 (m, 1H), 1.94-1.91 (m, 1H), 1.87-1.78 (m, 3H), 1.72 (s, 3H), 1.71 (s, 3H), 1.69-1.65 (m, 1H), 1.63-1.54 (m, 4H), 1.40-1.34 (m, 1H),
1.26-1.24 (m, 4H), 1.22 (s, 3H), 0.90 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 200.9, 146.7, 132.5, 124.0, 107.2, 84.9, 72.4, 51.6, 49.0, 45.6,
41.2, 32.3, 29.6, 29.3, 25.8, 25.3, 25.3, 19.9, 17.8, 16.2; IR (neat, cm-1): 2971, 2932, 2859, 2711, 1715, 1446, 1383, 1262, 1169, 1101, 866,
722; HRMS (ESI/[M+H]+) calcd. for C20H31O2: 303.2324, found 303.2315.

Synthesis of compound 22

To a stirred solution of 19 (15 mg, 0.05 mmol) in THF (2.5 mL) was added isopropyllithium (0.25 mL of a 1 M solution in hexanes, 0.25
mmol) dropwise at 0 ºC under argon. The mixture was stirred at 0 ºC for 5 minutes and then treated with saturated NaCl aqueous solution (5
mL). The aqueous layer was extracted with ethyl acetate (10 mL × 3) and the combined extracts were dried over MgSO4, filter and
concentrated. Silica gel column chromatography (EtOAc/hexanes 1:100) of the residue give a pale yellow oil (16 mg, 0.047 mmol, 93%) as
the product. 22 (a mixture of diastereomers): 1H NMR (500 MHz, CDCl3 5.11 (t, J = 7.0 Hz, 1H), 3.49 (dd, J = 10.5, 1.5 Hz, 1H), 2.76 (t,
J = 7.5 Hz, 1H), 2.11-2.07 (m, 1H), 1.97-1.78 (m, 6H), 1.72 (s, 3H), 1.61 (s, 3H), 1.60 (s, 3H), 1.55-1.51 (m, 2H), 1.47 (s, 3H), 1.44-1.39 (m,
1H), 1.13 (s, 3H), 1.01 (s, 3H), 0.99 (d, J = 7.0 Hz, 3H), 0.88 (d, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 149.4, 131.9, 124.8, 109.8,
84.3, 79.7, 63.9, 55.9, 47.0, 44.4, 43.7, 32.9, 31.0, 30.3, 28.2, 25.8, 25.0, 24.7, 23.0, 19.3, 17.8, 16.3, 16.0; IR (neat, cm-1): 3491, 2971, 2923,
2869, 1721, 1643, 1451, 1381, 1242, 1099, 997, 853; HRMS (ESI/[M+H]+) calcd. for C23H39O2: 347.2950, found 347.2941.

Synthesis of (±)-yezo’otogirin C (3)

To a stirred solution of 22 (16 mg, 0.046 mmol) and NaHCO3 (16 mg, 0.185 mmol) in CH2Cl2 (3 mL) was added Dess-Martin periodinate
(23 mg, 0.055 mmol) at 0 ºC. The mixture was stirred at room temperature for 1 hour and then treated with saturated Na2S2O3 aqueous
solution. The aqueous layer was extracted with ethyl acetate (10 mL × 3). The combined organic extracts were dried over MgSO4, filter and

S5
concentrated. Silica gel column chromatography (EtOAc/hexanes 1:100) of the residue afforded a colorless oil (13 mg, 0.039 mmol, 84%) as
the prodcut. (±)-Yezo’otogirin C (3): 1H NMR (400 MHz, CDCl3 5.12 (t, J = 6.8 Hz, 1H), 3.19 (t, J = 9.6 Hz, 1H), 2.96 (m, 1H), 1.99-
1.92 (m, 2H), 1.89-1.87 (m, 1H), 1.85-1.80 (m, 1H), 1.78-1.76 (m, 1H), 1.73 (s, 3H), 1.71 (s, 3H), 1.61 (s, 3H), 1.56-1.52 (m, 2H), 1.40-1.35
(m, 1H), 1.24-1.21 (m, 1H), 1.18 (s, 3H), 1.15 (s, 3H), 1.03 (d, J = 2.4 Hz, 3H), 1.01 (d, J = 2.8 Hz, 3H), 0.75 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 217.4, 149.3, 132.4, 124.2, 107.5, 83.4, 73.6, 54.9, 48.5, 47.0, 41.54 37.9, 32.8, 29.6, 29.5, 25.9, 25.4, 25.4, 21.5, 19.6, 18.3, 17.8,
16.3; IR (neat, cm-1): 3466, 2971, 2932, 2876, 2850, 1715, 1694, 1643, 1468, 1451, 1381, 1259, 1162, 1104, 1026, 802; HRMS
(ESI/[M+H]+) calcd. for C23H37O2: 345.2794, found 345.2788.

References

1. (a) Hara, R.; Furukawa, T.; Kashima, H.; Kusama, H.; Horiguchi, Y.; Kuwajima, I. J. Am. Chem. Soc. 1999, 121, 3072-3082; (b)
Spessard, S. J.; Stoltz, B. M. Org. Lett. 2002, 4, 1943-1946.

S6
X-ray structure of compound 13

Figure S1. X-ray structure of compound 13. The crystals of compound 13 were obtained by recrystallization from nhexane

S7
1
H and 13C NMR of compound 17

S8
1
H and 13C NMR spectra of compound 5 (a mixture of β-keto esters)

S9
1
H and 13C NMR of compound 20 (a mixture a diastereomer)

S10
HSQC and COSY spectra of compound 20 (a mixture of diastereomer)

S11
NOESY spectra and the stereochemistry assignment of compound 20 (a mixture of diastereomer)

S12
1
H and 13C NMR spectra of compound 6

S13
HSQC and COSY spectra of compound 6

S14
NOESY spectrum and the stereochemistry assignment of compound 6

S15
1
H and 13C NMR spectra of compound 13

S16
HSQC and COSY spectra of compound 13

S17
NOESY spectra and the stereochemistry assignment of compound 13

S18
1
H and 13C NMR spectra of compound 15

S19
HSQC and COSY spectra of compound 15

S20
NOESY spectra and the stereochemistry assignment of compound 15

S21
1
H and 13C NMR spectra of compound 18

S22
HSQC and COSY spectra of compound 18

S23
NOESY spectra and the stereochemistry assignment of compound 18

S24
1
H and 13C NMR spectra of compound 21

S25
1
H and 13C NMR spectra of compound 19

S26
1
H and 13C NMR spectra of compound 22 (a mixture of alcohol diastereomers)

S27
1
H and 13C NMR spectra of (±)-yezo’otogirin C (3)

S28
HSQC and COSY spectra of (±)-yezo’otogirin C (3)

S29
NOESY spectra and the stereochemistry assignment of (±)-yezo’otogirin C (3)

S30