3-Hydroxychromenones via α,β-Unsaturated Acylazoliums NHC

Supporting Information

NHC-Catalyzed Enantioselective C2-Functionalization of 3-Hydroxychromenones via α,β-Unsaturated Acylazoliums

Krzysztof Dzieszkowski, Michał Słotwiński, Katarzyna Rafińska, Tadeusz Muzioł, Zbigniew Rafiński*

Faculty of Chemistry, Nicolaus Copernicus University in ToruńToruń, Poland

e-mail: [email protected]

Electronic Supplementary Material (ESI) for ChemComm.This journal is © The Royal Society of Chemistry 2021

S2

Table of Content

1. General Methods.............................................................................................................................3

2. Synthetic Procedures.......................................................................................................................4

3. X-Ray Crystallography Data ...........................................................................................................19

4. NMR Spectra..................................................................................................................................21

5. HPLC Chromatograms....................................................................................................................88

6. Literature.....................................................................................................................................122

S3

1. General Methods

General information. Presented reactions were carried out in dry glassware under an inert atmosphere of argon. Selected reactions were monitored using thin-layer chromatography (TLC), which was visualized under a UV lamp (254 nm). Anhydrous solvents were prepared using INERT PureSolv Solvent Purification System. Purification of selected products was performed by column chromatography using CombiFlash Rf+ Lumen system with UV-VIS and ELSD detectors. RediSepRf GOLD 4 gram columns were used. NMR spectra were recorded on Bruker AMX 400 [400 MHz (1H)] spectrometer, Bruker AMX 700 [700 MHz (1H)] spectrometer, and Bruker 300 MHz spectrometer using CDCl3 as solvent. Chemical shifts are reported in ppm using the residual solvent peak as reference: δ 7.24 for 1H NMR and relative to the central CDCl3 (δ 77.23) resonance for 13C NMR. Coupling constants (J) were provided in Hz. Infrared spectra were measured on Alpha FT-IR spectrometer from Bruker with an ATR module. Mass spectra were recorded on Agilent 6530 Q-TOF LC/MS system coupled with 1290 Infinity II liquid chromatograph. Melting points of obtained products were measured on Stuart SMP50 Melting Point Apparatus and were not corrected. HPLC chromatograms were recorded using Agilent Technologies 1200 Series HPLC with Phenomenex Amylose-1 3 μm column. The diffraction data of the studied compound were collected at room temperature for the single crystal using Oxford Sapphire CCD diffractometer, MoKα radiation λ = 0.71073 Å.

S4

2. Synthetic Procedures

OH

O

RO

O

RO

O

ROH

R'

H

R'

CHO

O

O

ROH

R' O

Nu

NaHHCOOEt

1. H2O22. HCl

1. NHC2. NuH

nBuLiDMF

0b - 0i 1a - 1i

2a - 2o

3aaa - 3iaa3aaa - 3aoa3aaa - 3aak

GP1 GP2

GP3

GP4

General Procedure 1 (GP1). Sodium hydride (60% dispersion in oil; 4 eq) was washed three times with pentane and dispersed in dry THF. 2-Hydroxyacetophenone derivative (1 eq) was added slowly at room temperature to obtain a 0.5 mol/L solution. Then ethyl formate (3 eq) was added dropwise to the vigorously stirring solution. After the highly exothermic reaction the mixture was stirred for an additional 5 minutes and poured onto the water with ice. The obtained solution was acidified with concentrated hydrochloric acid and extracted with dichloromethane. Combined organic fractions were vigorously stirred with a hydrochloric acid solution (6 mol/L) for an additional hour. The organic fraction was separated, dried over anhydrous magnesium sulfate, and evaporated to obtain pure product.

General Procedure 2 (GP2). A 50% hydrogen peroxide solution (2 eq) was added slowly to the 0.75 mol/L DCM solution of chromene derivative (1 eq) at the temperature of 0 °C. Then solid sodium hydroxide (1.5 eq) was added portion-wise, and the mixture was stirred at 0 °C for 3 hours. The reaction was quenched with water, and the product was extracted with dichloromethane. Collected organic fractions were dried over anhydrous magnesium sulfate and evaporated. The obtained crude diol was added to the large excess of concentrated hydrochloric acid and stirred at 70 °C for an hour. The reaction mixture was cooled down to ambient temperature, diluted with water, and extracted with dichloromethane. Collected organic fractions were dried over anhydrous magnesium sulfate and evaporated. Pentane was added to the crude product, and remained solid was filtered off to obtain pure product.

General Procedure 3 (GP3). An acetylene derivative (1 eq) was dissolved in dry THF to obtain a 0.4 mol/L solution. Then the solution of n-butyllithium (2.5 mol/L in hexanes; 1 eq) was added dropwise at the temperature of -40 °C. Dimethylformamide (2 eq) was added quickly, the obtained mixture was warm up to ambient temperature and stirred for additional 30 minutes. The obtained solution was added to the vigorously stirred mixture containing 1 mol/L aqueous solution of KH2PO4 (2 eq) and the same volume of methyl-tert-butyl ether (MTBE) at 0 °C. The organic fraction was separated, and the aqueous layer was extracted with MTBE. Combined organic fractions were washed with water, dried over anhydrous magnesium sulfate, and evaporated. The obtained crude product was purified using flash column chromatography.

General procedure 4 (GP4). Precatalyst (0.025 mmol) and 1,8-bis(dimethylamino)naphthalene (0.025 mmol) were dissolved in dry dichloromethane (2.5 mL) and stirred at ambient temperature for 15 minutes. Then ynal (0.38 mmol) and 3-hydroxy-4H-chromen-4-one derivative (0.25 mmol) were added. The reaction mixture was stirred for 5 hours and the nucleophilic agent (alcohol or amine; 2.5 mL) was added. The obtained solution was stirred for an additional time defined as an opening time. Then the solution was evaporated and purified by flash column chromatography.

S5

6-Bromo-4H-chromen-4-one (0b). GP1. A scale of 25.0 mmol, solid, 5.123 g (22.8 mmol), isolated yield of 91%; 1H NMR (700 MHz, CDCl3) δ 8.33 (dd, J = 0.4, 2.6 Hz, 1H), 7.85 (d, J = 6.0 Hz, 1H), 7.75 (dd, J = 2.5, 8.9 Hz, 1H), 7.36 (dd, J = 0.4, 8.8 Hz, 1H), 6.35 (d, J = 6.0 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.2, 155.5, 155.2, 136.7, 128.4, 126.1, 120.2, 118.7, 113.0; IR νmax: 3070, 1635, 1605, 1558, 1461, 1437, 1187, 1136, 817 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

79BrO2 224.9551; found: 224.9554; mp 134.8−138.2 °C. The above analysis results correspond to the literature data.1

6-Fluoro-4H-chromen-4-one (0c). GP1. A scale of 25.0 mmol, solid, 3.796 g (23.1 mmol), isolated yield of 92%; 1H NMR (700 MHz, CDCl3) δ 7.89 (d, J = 5.9 Hz, 1H), 7.87 (ddd, J = 0.4, 3.1, 8.1 Hz, 1H), 7.50 (ddd, J = 0.4, 4.2, 9.2 Hz, 1H), 7.42 (ddd, J = 3.2, 7.5, 9.1 Hz,

1H), 6.36 (dd, J = 0.4, 5.9 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.8 (d, J=2.1 Hz), 159.5 (d, J=247.1 Hz), 155.5, 152.7 (d, J=2.1 Hz), 126.0 (d, J=6.9 Hz), 122.0 (d, J=25.6 Hz), 120.3 (d, J=8.3 Hz), 112.2, 110.6 (d, J=23.5 Hz); IR νmax: 3083, 1642, 1615, 1573, 1478, 1456, 1133, 1064, 1025, 826 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO2 165.0352; found: 165.0353; mp 157.8−163.2 °C. The above analysis results correspond to the literature data.1

6-Chloro-4H-chromen-4-one (0d). GP1. A scale of 25.0 mmol, solid, 4.180 g (23.1 mmol), isolated yield of 93%; 1H NMR (700 MHz, CDCl3) δ 8.18-8.17 (m, 1H), 7.85 (d, J = 6.0 Hz, 1H), 7.61 (dd, J = 2.7, 8.9 Hz, 1H), 7.42 (dd, J = 0.4, 8.8 Hz, 1H), 6.35 (d, J = 6.0 Hz, 1H);

13C{1H} NMR (75 MHz, CDCl3) δ 176.3, 155.5, 154.8, 134.0, 131.2, 125.7, 125.2, 119.9, 112.9; IR νmax: 3068, 1634, 1610, 1562, 1464, 1439, 1137, 841, 817 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO2 181.0056; found: 181.0054; mp 135.2−139.8 °C. The above analysis results correspond to the literature data.2

7-Methoxy-4H-chromen-4-one (0e). GP1. A scale of 25.0 mmol, solid, 0.967 g (5.5 mmol), isolated yield of 22%; 1H NMR (700 MHz, CDCl3) δ 8.12-8.10 (m, 1H), 7.77 (d, J = 6.0 Hz, 1H), 6.97 (dd, J = 2.5, 8.9 Hz, 1H), 6.83 (d, J = 2.4 Hz, 1H), 6.27

(d, J = 6.0 Hz, 1H), 3.90 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 177.0, 164.1, 158.2, 154.8, 127.2, 118.7, 114.5, 112.9, 100.3, 55.8; IR νmax: 3064, 3021, 1619, 1589, 1498, 1435, 1268, 1223, 823 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O3 177.0552; found: 177.0552; mp 106.1−107.9 °C. The above analysis results correspond to the literature data.3

5-Methoxy-4H-chromen-4-one (0f). GP1. A scale of 25.0 mmol, solid, 3.347 g (19.0 mmol), isolated yield of 76%; 1H NMR (700 MHz, CDCl3) δ 7.67 (dd, J = 0.5, 5.9 Hz, 1H), 7.53 (dt, J = 1.0, 8.3 Hz, 1H), 7.02-6.97 (m, 1H), 6.80 (d, J = 8.4 Hz, 1H), 6.23 (dd, J = 1.1, 6.0 Hz, 1H),

3.96 (d, J = 1.1 Hz, 3 H); 13C{1H} NMR (75 MHz, CDCl3) δ 177.4, 159.8, 158.5, 153.1, 133.7, 115.6, 114.6, 110.2, 106.4, 56.4; IR νmax: 3083, 1638, 1600, 1569, 1471, 1451, 1263, 1084, 1065, 835 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O3 177.0552; found: 177.0551; mp 78.2−81.1 °C. The above analysis results correspond to the literature data.4

7-Fluoro-4H-chromen-4-one (0g). GP1. A scale of 25.0 mmol, solid, 3.833 g (23.4 mmol), isolated yield of 93%; 1H NMR (700 MHz, CDCl3) δ 8.22 (dd, J = 6.1, 9.6 Hz, 1H), 7.83 (d, J = 6.0 Hz, 1H), 7.15-7.12 (m, 2H), 6.33 (d, J = 6.0 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3)

δ 176.6, 165.6 (d, J=255.3 Hz), 157.4 (d, J=13.1 Hz), 155.4, 128.4 (d, J=10.4 Hz), 121.7 (d, J=2.8 Hz), 114.1 (d, J=22.8 Hz), 113.1, 104.8 (d, J=24.9 Hz); IR νmax: 3092, 1648, 1613, 1496, 1437, 1212, 1126, 1021, 844, 814 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO2 165.0352; found: 165.0349; mp 110.1−112.1 °C. The above analysis results correspond to the literature data.5

O

OBr

O

OF

O

OCl

O

O

MeO

O

OOMe

O

O

F

S6

7-Chloro-4H-chromen-4-one (0h). GP1. A scale of 12.5 mmol, solid, 2.038 g (11.3 mmol), isolated yield of 90%; 1H NMR (700 MHz, CDCl3) δ 8.15-8.13 (m, 1H), 7.82 (d, J = 6.0 Hz, 1H), 7.48 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 1.9, 8.6 Hz, 1H), 6.33 (d, J = 6.0 Hz, 1H);

13C{1H} NMR (75 MHz, CDCl3) δ 176.7, 156.5, 155.3, 139.8, 127.2, 126.1, 123.4, 118.2, 113.3; IR νmax: 3080, 1645, 1598, 1557, 1424, 1177, 1019, 809 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for

C9H635ClO2 181.0056; found: 181.0055; mp 93.1−97.4 °C. The above analysis results

correspond to the literature data.6

6,8-Difluoro-4H-chromen-4-one (0i). GP1. A scale of 12.5 mmol, solid, 2.275 g (12.5 mmol), isolated yield of 99%; 1H NMR (700 MHz, CDCl3) δ 7.89 (d, J = 6.0 Hz, 1H),

7.64 (ddd, J = 1.8, 3.0, 8.1 Hz, 1H), 7.24 (ddd, J = 3.0, 8.0, 10.1 Hz, 1H), 6.37 (d, J = 6.0 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 175.5 (dd, J=2.8, 2.1 Hz), 158.3 (dd, J=249.8, 9.7 Hz), 155.0, 151.5 (dd, J=258.1, 11.1 Hz), 142.1 (dd, J=11.1, 2.8 Hz), 127.0 (d, J=8.3 Hz), 112.7, 109.2 (dd, J=28.4, 20.1 Hz), 106.0 (dd, J=23.5, 4.2 Hz); IR νmax: 3093, 3034, 1646, 1633, 1613, 1575, 1479, 1452, 1112, 1004 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H5F2O2 183.0258; found: 183.0262; mp 149.8−153.6 °C.

3-Hydroxy-4H-chromen-4-one (1a). GP2. A scale of 15.0 mmol, solid, 0.780 g (4.8 mmol), isolated yield of 32%; 1H NMR (700 MHz, CDCl3) δ 8.29 (ddd, J = 0.4, 1.8, 8.1 Hz, 1H), 8.04 (s, 1H), 7.75-7.68 (m, 1H), 7.52 (d, J = 8.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H),

6.29 (s, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 173.4, 156.3, 141.8, 138.5, 133.5, 125.5, 124.6, 121.9, 118.5; IR νmax: 3269, 3096, 1636, 1599, 1562, 1489, 1466, 1421, 1272, 756 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H7O3 163.0395; found: 163.0398; mp 175.1−179.5 °C. The above analysis results correspond to the literature data.7

6-Bromo-3-hydroxy-4H-chromen-4-one (1b). GP2. A scale of 21.4 mmol, solid, 0.405 g (1.7 mmol), isolated yield of 8%; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 2.4 Hz, 1H), 8.02 (s, 1H), 7.78 (dd, J = 2.4, 8.8 Hz, 1H), 7.42 (d, J = 9.0 Hz, 1H),

6.07 (s, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.1, 155.0, 141.9, 138.6, 136.6, 128.0, 123.1, 120.4, 118.0; IR νmax: 3101, 1620, 1599, 1556, 1469, 1405, 1269, 814 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

79BrO3 240.9500; found: 240.9504; mp 199.9−204.3 °C.

6-Fluoro-3-hydroxy-4H-chromen-4-one (1c). GP2. A scale of 21.3 mmol, solid, 1.223 g (6.8 mmol), isolated yield of 32%; 1H NMR (700 MHz, CDCl3) δ 8.05 (s, 1H), 7.90 (ddd, J = 0.4, 3.1, 8.1 Hz, 1H), 7.56-7.51 (m, J = 0.4, 4.2 Hz, 1H), 7.44 (ddd,

J = 3.1, 7.5, 9.2 Hz, 1H), 6.10 (s, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.7, 159.1 (d, J=246.9 Hz), 152.7, 141.4, 138.6, 122.9 (d, J=8.2 Hz), 122.2 (d, J=26.2 Hz), 120.7 (d, J=8.2 Hz), 110.0 (d, J=22.9 Hz); IR νmax: 3331, 1638, 1609, 1575, 1479, 1467, 1405, 1261, 790, 784 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO3 181.0301; found: 181.0303; mp 219.5−225.2 °C.

6-Chloro-3-hydroxy-4H-chromen-4-one (1d). GP2. A scale of 21.0 mmol, solid, 0.606 g (3.2 mmol), isolated yield of 15%; 1H NMR (700 MHz, CDCl3) δ 8.22 (dd, J = 0.4, 2.6 Hz, 1H), 8.00 (s, 1H), 7.62 (dd, J = 2.6, 9.0 Hz, 1H), 7.46 (d, J = 9.0 Hz, 1H),

6.04 (s, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.3, 154.6, 141.8, 138.6, 133.9, 130.7, 124.8, 122.7, 120.2; IR νmax: 3290, 3085, 1629, 1605, 1564, 1470, 1455, 1395, 1248, 824, 769 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO3 197.0005; found: 197.0002; mp 162.3−168.4 °C. The above analysis results correspond to the literature data.7

O

OF

F

O

O

Cl

O

OHO

O

OHO

Br

O

OHO

F

O

OHO

Cl

S7

3-Hydroxy-7-methoxy-4H-chromen-4-one (1e). GP2. A scale of 4.9 mmol, solid, 0.286 g (1.5 mmol), isolated yield of 30%; 1H NMR (700 MHz, CDCl3) δ 8.14 (d, J = 8.8 Hz, 1H), 7.91 (s, 1H), 6.98 (dd, J = 2.4, 9.0 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H),

6.25 (s, 1 H), 3.90 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 164.1, 158.2, 141.5, 137.8, 126.8, 115.8, 114.9, 100.0, 55.8; IR νmax: 3284, 3086, 1600, 1566, 1508, 1454, 1433, 1411, 1248, 818, 779 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O4 193.0501; found: 193.0502; mp 171.1−174.5 °C. The above analysis results correspond to the literature data.8

3-Hydroxy-5-methoxy-4H-chromen-4-one (1f). GP2. A scale of 16.5 mmol, solid, 1.321 g (6.9 mmol), isolated yield of 42%; 1H NMR (700 MHz, CDCl3) δ 7.87 (s, 1H), 7.55

(t, J = 8.4 Hz, 1H), 7.04 (dd, J = 1.0, 8.5 Hz, 1H), 6.78 (dd, J = 0.4, 8.2 Hz, 1H), 6.41 (s, 1 H), 4.01 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 159.8, 158.3, 142.0, 135.7, 133.8, 112.6, 110.5, 105.0, 56.4; IR νmax: 3279, 3089, 1624, 1604, 1571, 1475, 1443, 1417, 1267, 803, 700 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O4 193.0501; found: 193.0503; mp 148.2−153.0 °C.

7-Fluoro-3-hydroxy-4H-chromen-4-one (1g). GP2. A scale of 23.2 mmol, solid, 1.547 g (8.6 mmol), isolated yield of 37%; 1H NMR (700 MHz, CDCl3) δ 8.27 (ddd, J = 0.4, 6.2, 8.8 Hz, 1H), 7.98 (s, 1H), 7.19-7.13 (m, 2H), 6.13 (s, 1H); 13C{1H} NMR

(75 MHz, CDCl3) δ 172.6, 165.6 (d, J=255.3 Hz), 157.3 (d, J=13.8 Hz), 141.7, 138.4 (d, J=1.4 Hz), 128.1 (d, J=11.1 Hz), 118.7 (d, J=2.1 Hz), 114.0 (d, J=23.5 Hz), 104.9 (d, J=25.6 Hz); IR νmax: 3286, 3098, 1635, 1602, 1493, 1454, 1406, 1268, 852, 812, 774 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO3 181.0301; found: 181.0302; mp 213.3−219.9 °C.

7-Chloro-3-hydroxy-4H-chromen-4-one (1h). GP2. A scale of 11.1 mmol, solid, 0.306 g (1.6 mmol), isolated yield of 14%; 1H NMR (700 MHz, CDCl3) δ 8.18 (dd, J = 0.4, 8.6 Hz, 1H), 7.97 (s, 1H), 7.52 (d, J = 1.9 Hz, 1H), 7.37 (dd, J = 1.9, 8.6 Hz, 1H),

6.21 (s, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.7, 156.3, 141.9, 139.9, 138.4, 126.9, 125.7, 120.4, 118.4; IR νmax: 3307, 3110, 1624, 1608, 1561, 1481, 1449, 1400, 1270, 891, 863, 778 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO3 197.0005; found: 197.0006; mp 177.8−185.3 °C.

6,8-Difluoro-3-hydroxy-4H-chromen-4-one (1i). GP2. A scale of 9.7 mmol, solid, 0.860 g (4.4 mmol), isolated yield of 45%; 1H NMR (700 MHz, CDCl3) δ 8.09 (s, 1H), 7.71 (ddd, J = 2.0, 3.0, 8.0 Hz, 1H), 7.31-7.27 (m, 1H), 6.12 (s, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 171.9 (t, J=3.3 Hz), 158.0 (dd, J=248.5, 9.8 Hz), 151.8 (dd, J=258.3,

11.4 Hz), 142.2 (d, J=9.8 Hz), 141.8, 138.5, 123.9 (d, J=8.2 Hz), 109.0 (dd, J=29.4, 19.6 Hz), 105.4 (dd, J=22.9, 4.9 Hz); IR νmax: 3321, 3099, 1641, 1619, 1583, 1499, 1451, 1433, 1297, 864, 768 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H5F2O3 199.0207; found: 199.0203; mp 197.4−204.8 °C.

3-Phenylpropiolaldehyde (2a). GP3. A scale of 25.0 mmol, liquid, 2.459 g (19.0 mmol), isolated yield of 76%; 1H NMR (700 MHz, CDCl3) δ 9.43 (s, 1H), 7.63-7.58 (m, 2H), 7.50 (tdd, J = 1.2, 7.0, 8.0 Hz, 1H), 7.43-7.39 (m, 2H); 13C{1H} NMR (176 MHz, CDCl3) δ 176.4,

132.9, 130.9, 128.4, 119.0, 94.7, 88.1; IR νmax: 2854, 2184, 1653, 1595, 1489 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H7O 131.0497; found: 131.0499. The above analysis results correspond to the literature data.9

O

OHO

MeO

O

OHOOMe

O

OHO

F

O

OHO

F

F

O

OHO

Cl

CHO

S8

3-(4-Fluorophenyl)propiolaldehyde (2b). GP3. A scale of 15.0 mmol, solid, 0.632 g (4.2 mmol), isolated yield of 28%; 1H NMR (700 MHz, CDCl3) δ 9.43 (s, 1H), 7.67-7.61 (m, 2H), 7.16-7.10 (m, 2H); 13C{1H} NMR (176 MHz, CDCl3) δ 176.4, 164.3

(d, J=255.0 Hz), 135.6 (d, J=9.8 Hz), 116.3 (d, J=21.3 Hz), 115.6 (d, J=3.3 Hz), 93.8, 88.4; IR νmax: 2889, 2187, 1649, 1595, 1503 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO 149.0403; found:

149.0405; mp 44.6−48.2 °C. The above analysis results correspond to the literature data.10

3-(4-Chlorophenyl)propiolaldehyde (2c). GP3. A scale of 15.0 mmol, solid, 1.469 g (9.0 mmol), isolated yield of 60%; 1H NMR (700 MHz, CDCl3) δ 9.41 (s, 1H), 7.55-7.52 (m, 2H), 7.41-7.37 (m, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.4, 137.8, 134.4, 129.2, 117.9, 93.5, 89.0; IR νmax: 2187, 1649, 1587, 1476 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO 165.0107; found: 165.0108; mp 92.3−95.9 °C. The above analysis results correspond to the literature data.9

3-(4-Bromophenyl)propiolaldehyde (2d). GP3. A scale of 15.0 mmol, solid, 1.050 g (5.0 mmol), isolated yield of 33%; 1H NMR (400 MHz, CDCl3) δ 9.43 (s, 1H), 7.59-7.54 (m, 2H), 7.50-7.44 (m, 2H); 13C{1H} NMR (101 MHz, CDCl3) δ 176.4, 134.5,

132.2, 126.2, 118.4, 93.5, 89.1; IR νmax: 2972, 2890, 2188, 1649, 1581, 1474 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

79BrO 208.9602; found: 208.9607; mp 95.5−98.0 °C. The above analysis results correspond to the literature data.10

3-(4-(tert-Butyl)phenyl)propiolaldehyde (2e). GP3. A scale of 15.0 mmol, solid, 1.110 g (6.0 mmol), isolated yield of 40%; 1H NMR (700 MHz, CDCl3) δ 9.44 (s, 1H), 7.58-7.56 (m, 2H), 7.46-7.44 (m, 2H), 1.35 (s, 9H); 13C{1H} NMR (176 MHz, CDCl3)

δ 176.8, 155.2, 133.3, 125.9, 116.4, 95.9, 88.5, 35.2, 31.0; IR νmax: 3042, 2955, 2906, 2868, 2185, 1651, 1598, 1502, 1477 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C13H15O 187.1123; found: 187.1122;

mp 40.5−43.1 °C. The above analysis results correspond to the literature data.10

3-(4-Methoxyphenyl)propiolaldehyde (2f). GP3. A scale of 15.0 mmol, solid, 2.214 g (13.8 mmol), isolated yield of 92%; 1H NMR (700 MHz, CDCl3) δ 9.39

(s, 1H), 7.57-7.55 (m, 2H), 6.93-6.90 (m, 2H), 3.85 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.7, 162.1, 135.4, 114.5, 111.1, 96.5, 88.7, 55.4; IR νmax: 2176, 1642, 1597, 1566, 1507 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O2 161.0603; found: 161.0602; mp 45.5−48.0 °C. The above analysis results correspond to the literature data.10

3-(p-Tolyl)propiolaldehyde (2g). GP3. A scale of 15.0 mmol, liquid, 1.311 g (9.2 mmol), isolated yield of 61%; 1H NMR (700 MHz, CDCl3) δ 9.43 (s, 1H), 7.53-7.51 (m, 2H), 7.25-7.22 (m, 2H), 2.42 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3)

δ 176.9, 142.2, 133.4, 129.6, 116.3, 96.0, 88.5, 21.8; IR νmax: 2921, 2854, 2737, 2180, 1651, 1604, 1507 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O 145.0653; found: 145.0655. The above analysis results correspond to the literature data.10

3-(4-(Trifluoromethyl)phenyl)propiolaldehyde (2h). GP3. A scale of 15.0 mmol, solid, 0.629 g (3.2 mmol), isolated yield of 21%; 1H NMR (700 MHz, CDCl3) δ 9.47 (s, 1H), 7.74 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H); 13C{1H} NMR (176 MHz,

CDCl3) δ 176.2, 133.3, 132.7 (q, J=32.7 Hz), 125.7 (q, J=3.3 Hz), 123.3, 123.5 (q, J=273.0 Hz), 92.1, 89.2; IR νmax: 2891, 2191, 1653, 1613, 1258 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H6F3O 199.0371; found: 199.0371; mp 36.3−38.7 °C. The above analysis results correspond to the literature data.10

CHO

F

CHO

Cl

CHO

Br

CHO

tBu

CHO

MeO

CHO

Me

CHO

F3C

S9

3-(2-Chlorophenyl)propiolaldehyde (2i). GP3. A scale of 15.0 mmol, liquid, 1.700 g (10.3 mmol), isolated yield of 69%; 1H NMR (400 MHz, CDCl3) δ 9.50 (s, 1H), 7.63 (ddd, J = 0.5, 1.7, 7.6 Hz, 1H), 7.51-7.40 (m, 2H), 7.35-7.29 (m, 1H); 13C{1H} NMR (101 MHz,

CDCl3) δ 176.4, 137.6, 135.0, 132.2, 129.8, 126.8, 119.8, 92.1, 90.9; IR νmax: 2859, 2189, 1654, 1587, 1471 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO 165.0107; found: 165.0105. The above analysis results correspond to the literature data.11

3-(o-Tolyl)propiolaldehyde (2j). GP3. A scale of 7.5 mmol, liquid, 0.695 g (4.8 mmol), isolated yield of 64%; 1H NMR (700 MHz, CDCl3) δ 9.46 (s, 1H), 7.56 (ddd, J = 0.4, 0.9, 7.7 Hz, 1H), 7.39-7.36 (m, 1H), 7.27 (tdd, J = 0.6, 1.3, 7.7 Hz, 1H), 7.23-7.20 (m, 1H),

2.50 (s, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.8, 142.6, 133.8, 131.3, 129.9, 126.0, 119.2, 94.4, 92.2, 20.5; IR νmax: 2863, 2181, 1653, 1598, 1483 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O 145.0653; found: 145.0656. The above analysis results correspond to the literature data.9

3-(2-Methoxyphenyl)propiolaldehyde (2k). GP3. A scale of 15.0 mmol, liquid, 1.540 g (9.6 mmol), isolated yield of 64%; 1H NMR (700 MHz, CDCl3) δ 9.47 (s, 1H), 7.55 (ddd, J = 0.4, 1.8, 7.7 Hz, 1H), 7.47 (ddd, J = 1.8, 7.5, 8.4 Hz, 1H), 6.98 (dt, J = 1.0, 7.5 Hz, 1H),

6.94 (d, J = 8.6 Hz, 1H), 3.93 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 176.8, 161.7, 135.1, 133.3, 120.7, 111.0, 108.4, 92.7, 92.5, 55.8; IR νmax: 2946, 2840, 2739, 2177, 1648, 1594, 1573, 1489 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O2 161.0603; found: 161.0601. The above analysis results correspond to the literature data.10

3-(2-Fluorophenyl)propiolaldehyde (2l). GP3. A scale of 15.0 mmol, liquid, 0.920 g (6.2 mmol), isolated yield of 41%; 1H NMR (700 MHz, CDCl3) δ 9.47 (s, 1H), 7.60 (ddd, J = 1.8, 6.6, 7.9 Hz, 1H), 7.53-7.49 (m, 1H), 7.21 (dt, J = 0.9, 7.6 Hz, 1H), 7.19-7.15

(m, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 176.3, 163.7 (d, J=256.7 Hz), 134.8, 133.3 (d, J=8.2 Hz), 124.4 (d, J=3.3 Hz), 116.0 (d, J=19.6 Hz), 108.4 (d, J=14.7 Hz), 92.5 (d, J=3.3 Hz), 88.1; IR νmax: 2862, 2742, 2191, 1656, 1609, 1574, 1489 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6FO 149.0403; found: 149.0401. The above analysis results correspond to the literature data.12

3-(3-Chlorophenyl)propiolaldehyde (2m). GP3. A scale of 15.0 mmol, liquid, 1.441 g (8.7 mmol), isolated yield of 58%; 1H NMR (700 MHz, CDCl3) δ 9.41 (s, 1H), 7.60-7.56 (m, 1H), 7.50-7.43 (m, 2H), 7.37-7.31 (m, 1H); 13C{1H} NMR (75 MHz,

CDCl3) δ 176.4, 134.7, 132.8, 131.5, 131.2, 130.0, 121.1, 92.7, 88.6; IR νmax: 2190, 1657, 1589, 1560, 1473 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C9H6

35ClO 165.0107; found: 165.0110. The above analysis results correspond to the literature data.11

3-(m-Tolyl)propiolaldehyde (2n). GP3. A scale of 15.0 mmol, liquid, 1.010 g (7.0 mmol), isolated yield of 47%; 1H NMR (700 MHz, CDCl3) δ 9.44 (s, 1H), 7.46-7.42 (m, 2H), 7.34-7.30 (m, 2H), 2.39 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3)

δ 176.8, 138.6, 133.7, 132.3, 130.4, 128.7, 119.2, 95.6, 88.3, 21.1; IR νmax: 2922, 2855, 2737, 2183, 1655, 1578, 1481 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C10H9O 145.0653; found: 145.0654. The above analysis results correspond to the literature data.9

5-Phenylpent-2-ynal (2o). GP3. A scale of 15.0 mmol, liquid, 1.038 g (6.6 mmol), isolated yield of 44%; 1H NMR (700 MHz, CDCl3) δ 9.18 (t, J = 0.9 Hz, 1H), 7.37-7.33 (m, 2H), 7.29-7.23 (m, 3H), 2.94 (t, J = 7.5 Hz, 2H), 2.74 (dt, J = 0.7, 7.5 Hz, 2H);

13C{1H} NMR (176 MHz, CDCl3) δ 176.9, 139.5, 128.6, 128.4, 126.8, 97.9, 82.2, 33.8, 21.2; IR νmax: 3029, 2929, 2860, 2742, 2197, 1659, 1602, 1495 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C11H11O 159.0810; found: 159.0806. The above analysis results correspond to the literature data.13

CHOCl

CHOMe

CHOOMe

CHOF

CHOCl

CHOMe

CHO

S10

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanoate (3aaa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 61.95 mg (0.19 mmol), isolated yield of 77%, 95% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.67 (ddd, J = 1.5, 7.0, 8.6 Hz, 1H), 7.53-7.50 (m, 1H), 7.49-7.45 (m, 2H), 7.39 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.37-7.33 (m, 2H),

7.30-7.27 (m, 1H), 6.36 (s, 1H), 5.01 (dd, J = 7.0, 9.0 Hz, 1H), 3.66 (s, 3H), 3.39 (dd, J = 9.0, 16.5 Hz, 1H), 3.16 (dd, J = 6.9, 16.4 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 171.4, 155.5, 150.5, 139.2, 137.8, 133.2, 128.8, 127.8, 127.6, 125.5, 124.5, 121.3, 118.2, 51.9, 41.0, 36.6; IR νmax: 3255, 1733, 1609, 1569, 1484, 1468, 1434, 1284, 1258, 754, 700, cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H17O5 325.1076; found: 325.1079; mp 108.4−117.4 °C.

Methyl (R)-3-(6-bromo-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3baa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 95.54 mg (0.24 mmol), isolated yield of 95%, 83% ee; 1H NMR (700 MHz, CDCl3) δ 8.30 (d, J = 2.4 Hz, 1H), 7.70 (dd, J = 2.6, 9.0 Hz, 1H), 7.43-7.40 (m, 2H), 7.38 (d, J = 9.0 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.27-7.24

(m, 1H), 6.32 (s, 1H), 4.95 (dd, J = 7.0, 8.9 Hz, 1H), 3.62 (s, 3H), 3.35 (dd, J = 9.1, 16.5 Hz, 1H), 3.10 (dd, J = 6.8, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 171.6, 171.3, 154.2, 151.0, 139.0, 138.0, 136.2, 128.9, 128.0, 127.7, 127.7, 122.7, 120.1, 117.9, 51.9, 41.1, 36.5; IR νmax: 1736, 1621, 1601, 1584, 1566, 1530, 1495, 1467, 1455, 1436, 1266, 1201, 699 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

79BrO5 403.0181; found: 403.0184; mp 132.7−143.2 °C.

Methyl (R)-3-(6-fluoro-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3caa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 59.05 mg (0.17 mmol), isolated yield of 69%, 88% ee; 1H NMR (700 MHz, CDCl3) δ 7.80 (dd, J = 3.0, 8.0 Hz, 1H), 7.49 (dd, J = 4.1, 9.2 Hz, 1H), 7.42 (dd, J = 1.0, 8.1 Hz, 2H), 7.37 (ddd, J = 3.0, 7.5, 9.3 Hz, 1H), 7.34-7.30 (m,

2H), 7.28-7.24 (m, 1H), 6.31 (s, 1H), 4.97 (dd, J = 6.9, 9.0 Hz, 1H), 3.63 (s, 3H), 3.36 (dd, J = 9.1, 16.5 Hz, 1H), 3.11 (dd, J = 6.9, 16.6 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.1 (d, J=3.3 Hz), 171.3, 158.4 (d, J=246.9 Hz), 151.8, 151.0, 139.1, 137.5, 128.9, 127.7, 127.7, 122.3 (d, J=8.2 Hz), 121.7 (d, J=26.2 Hz), 120.3 (d, J=8.2 Hz), 110.0 (d, J=22.9 Hz), 51.9, 41.2, 36.6; IR νmax: 1737, 1731, 1609, 1575, 1483, 1408, 1259, 1218, 762, 707 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16FO5 343.0982; found: 343.0981; mp 140.8−147.9 °C.

Methyl (R)-3-(6-chloro-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3daa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 76.25 mg (0.21 mmol), isolated yield of 85%, 91% ee; 1H NMR (700 MHz, CDCl3) δ 8.14 (d, J = 2.6 Hz, 1H), 7.57 (dd, J = 2.6, 9.0 Hz, 1H), 7.44 (dd, J = 0.4, 9.0 Hz, 1H), 7.43-7.40 (m, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.28-7.25

(m, 1H), 6.23 (s, 1H), 4.95 (dd, J = 6.7, 9.2 Hz, 1H), 3.63 (s, 3H), 3.35 (dd, J = 9.1, 16.5 Hz, 1H), 3.11 (dd, J = 6.8, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 171.7, 171.3, 153.8, 151.0, 139.0, 137.9, 133.5, 130.6, 128.9, 127.7, 127.7, 124.7, 122.2, 119.9, 51.9, 41.1, 36.5; IR νmax: 3286, 1733, 1621, 1604, 1566, 1469, 1453, 1263, 1227, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

35ClO5 359.0686; found: 359.0688; mp 125.8−135.2 °C.

Methyl (R)-3-(3-hydroxy-7-methoxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3eaa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 58.13 mg (0.16 mmol), isolated yield of 66%, 98% ee; 1H NMR

O

OHO

OMe

O

O

OHO

OMe

O

Br

O

OHO

OMe

O

F

O

OHO

OMe

O

Cl

O

OHO

OMe

OMeO

S11

(700 MHz, CDCl3) δ 8.06 (d, J = 8.8 Hz, 1H), 7.44-7.41 (m, 2H), 7.32 (t, J = 7.7 Hz, 2H), 7.25-7.23 (m, 1H), 6.94 (dd, J = 2.4, 8.8 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.26 (s, 1H), 4.92 (dd, J = 7.1, 9.0 Hz, 1H), 3.90 (s, 3H), 3.62 (s, 3H), 3.34 (dd, J = 9.0, 16.3 Hz, 1H), 3.11 (dd, J = 6.9, 16.3 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.3, 171.4, 164.0, 157.4, 149.5, 139.5, 137.5, 128.8, 127.7, 127.5, 126.8, 115.2, 114.7, 100.0, 55.8, 51.8, 41.1, 36.7; IR νmax: 3275, 1723, 1632, 1601, 1505, 1447, 1436, 1423, 1270, 1218, 706, 697 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O6 355.1182; found: 355.1184; mp 136.9−145.0 °C.

Methyl (R)-3-(3-hydroxy-5-methoxy-4-oxo-4H-c.hromen-2-yl)-3-phenyl-propanoate (3faa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 86.27 mg (0.24 mmol), isolated yield of 97%, 99% ee; 1H NMR (700 MHz, CDCl3) δ 7.51 (t, J = 8.4 Hz, 1H), 7.43-7.40 (m, 2H), 7.33-7.29 (m, 2H), 7.25-7.23 (m, 1H), 7.03 (dd, J = 1.0, 8.6 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 6.58 (s, 1H), 4.88

(dd, J = 7.2, 8.8 Hz, 1H), 3.97 (s, 3H), 3.61 (s, 3H), 3.31 (dd, J = 8.8, 16.3 Hz, 1H), 3.10 (dd, J = 7.2, 16.3 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.4, 171.4, 159.7, 157.5, 147.6, 139.3, 138.0, 133.5, 128.8, 127.7, 127.5, 111.9, 110.3, 105.1, 56.4, 51.9, 41.0, 36.6; IR νmax: 1733, 1606, 1480, 1438, 1258, 1228, 699 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O6 355.1182; found: 355.1181; mp 74.4−87.7 °C.

Methyl (R)-3-(7-fluoro-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3gaa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 84.35 mg (0.25 mmol), isolated yield of 99%, 93% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (dd, J = 6.2, 9.0 Hz, 1H), 7.46-7.43 (m, 2H), 7.35 (t, J = 7.7 Hz, 2H), 7.31-7.29 (m, 1H), 7.20 (dd, J = 2.3, 9.1 Hz, 1H), 7.14 (ddd,

J = 2.4, 8.1, 8.8 Hz, 1H), 6.28 (s, 1H), 4.97 (dd, J = 6.7, 9.1 Hz, 1H), 3.66 (s, 3H), 3.37 (dd, J = 9.1, 16.4 Hz, 1H), 3.13 (dd, J = 6.8, 16.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.1, 171.4, 165.4 (d, J=255.3 Hz), 156.4 (d, J=13.1 Hz), 150.7 (d, J=2.1 Hz), 139.0, 137.7, 128.9, 128.0 (d, J=10.4 Hz), 127.7, 127.6, 118.1 (d, J=2.1 Hz), 113.8 (d, J=23.5 Hz), 104.7 (d, J=25.6 Hz), 51.9, 41.0, 36.4; IR νmax: 3287, 1732, 1639, 1607, 1496, 1452, 1423, 1253, 1237, 704 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16FO5 343.0982; found: 343.0984; mp 141.6−149.5 °C.

Methyl (R)-3-(7-chloro-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3haa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 75.06 mg (0.21 mmol), isolated yield of 84%, 93% ee; 1H NMR (700 MHz, CDCl3) δ 8.11 (d, J = 8.6 Hz, 1H), 7.52 (d, J = 1.9 Hz, 1H), 7.43-7.40 (m, 2H), 7.35-7.31 (m, 3H), 7.28-7.26 (m, 1H), 6.22 (s, 1H), 4.94 (dd, J = 6.8,

9.1 Hz, 1H), 3.63 (s, 3H), 3.34 (dd, J = 9.3, 16.3 Hz, 1H), 3.10 (dd, J = 6.8, 16.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.1, 171.3, 155.5, 150.7, 139.5, 138.9, 137.9, 128.9, 127.7, 127.7, 126.8, 125.5, 119.8, 118.2, 51.9, 41.0, 36.4; IR νmax: 3286, 1722, 1629, 1602, 1560, 1442, 1264, 1221, 705, 697 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

35ClO5 359.0686; found: 359.0689; mp 143.4−150.2 °C.

Methyl (R)-3-(6,8-difluoro-3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenyl-propanoate (3iaa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 66.74 mg (0.19 mmol), isolated yield of 74%, 56% ee; 1H NMR (700 MHz, CDCl3) δ 7.64 (ddd, J = 2.0, 2.9, 7.9 Hz, 1H), 7.50-7.46 (m, 2H), 7.38-7.35 (m, 2H), 7.32-7.29 (m, 1H), 7.24 (ddd, J = 3.0, 7.7, 10.2 Hz, 1H), 6.30

(s, 1H), 5.00 (dd, J = 6.7, 9.4 Hz, 1H), 3.67 (s, 3H), 3.41 (dd, J = 9.2, 16.7 Hz, 1H), 3.15 (dd, J = 6.8, 16.5 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 171.4, 157.8 (dd, J=249.1, 9.7 Hz), 151.4, 151.5 (dd, J=258.1,

O

OHO

OMe

O

OMe

O

OHO

OMe

OF

O

OHO

OMe

OCl

O

OHO

OMe

O

F

F

S12

11.8 Hz), 141.2 (dd, J=12.5, 2.1 Hz), 138.7, 137.8, 129.0, 127.9, 127.8, 123.4 (d, J=9.0 Hz), 108.7 (dd, J=29.1, 20.1 Hz), 105.4 (dd, J=23.5, 4.8 Hz), 52.0, 40.9, 36.4; IR νmax: 3285, 1731, 1619, 1587, 1494, 1422, 1247, 1225, 701 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H15F2O5 361.0888; found: 361.0887; mp 116.1−124.2 °C.

Methyl (R)-3-(4-fluorophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3aba). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 69.92 mg (0.20 mmol), isolated yield of 82%, 80% ee; 1H NMR (700 MHz,

CDCl3) δ 8.22 (dd, J = 0.4, 7.9 Hz, 1H), 7.68 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.51 (dd, J = 0.4, 8.6 Hz, 1H), 7.46-7.42 (m, 2H), 7.40 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.08-6.99 (m, 2H), 6.40 (s, 1H), 4.99 (t, J = 7.9 Hz, 1H), 3.66 (s, 3H), 3.34 (dd, J = 8.5, 16.4 Hz, 1H), 3.14 (dd, J = 7.4, 16.4 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.2, 162.2 (d, J=245.2 Hz), 155.5, 150.2, 137.7, 135.0 (d, J=3.3 Hz), 133.3, 129.4 (d, J=8.2 Hz), 125.6, 124.6, 121.3,

118.1, 115.7 (d, J=21.3 Hz), 51.9, 40.4, 36.7; IR νmax: 3256, 1738, 1622, 1608, 1569, 1509, 1469, 1437, 1288, 1217, 755 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16FO5 343.0982; found: 343.0980; mp 120.5−122.8 °C.

Methyl (R)-3-(4-chlorophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3aca). GP4. A scale of 0.25 mmol, opening time was equal to 24 h,

solid, 59.20 mg (0.17 mmol), isolated yield of 66%, 93% ee; 1H NMR (700 MHz, CDCl3) δ 8.23-8.20 (m, 1H), 7.68 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.52-7.49 (m, 1H),

7.43-7.39 (m, 3H), 7.34-7.30 (m, 2H), 4.97 (t, J = 7.9 Hz, 1H), 3.66 (s, 3H), 3.34 (dd, J = 8.5, 16.4 Hz, 1H), 3.14 (dd, J = 7.5, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.1, 155.5, 149.8, 137.7, 133.5, 133.3, 129.1, 129.0, 125.6, 124.6, 121.3, 118.1, 51.9, 40.5, 36.5; IR νmax: 3266, 2955, 1731, 1612, 1574, 1493, 1481, 1470, 1440, 1426, 1291, 1256, 1223, 758, 703 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

35ClO5 359.0686; found: 359.0687; mp 153.5−155.2 °C.

Methyl (R)-3-(4-bromophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3ada). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 87.57 mg (0.22 mmol), isolated yield of 87%, 83% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.68 (ddd, J = 1.8, 6.8, 8.6 Hz, 1H), 7.52-7.49 (m, 1H), 7.47 (d, J = 8.6 Hz, 2H), 7.42-7.39 (m, 1H), 7.35 (s, 2H), 6.41 (s, 1H), 4.97 (t, J = 7.9 Hz, 1H), 3.66 (s, 3H), 3.34 (dd, J = 8.5, 16.4 Hz, 1H), 3.15 (dd, J = 7.6, 16.4 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 172.9, 171.1, 155.5, 149.8, 138.3, 137.8, 133.4, 132.0, 129.5, 127.8, 125.6, 124.6, 121.6, 118.1, 52.0, 40.5, 36.4; IR νmax: 3270, 2950, 1732, 1610, 1570, 1484, 1469, 1434, 757, 702 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

79BrO5 403.0181; found: 403.0185; mp 123.6−128.9 °C.

Methyl (R)-3-(4-(tert-butyl)phenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3aea). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 48.90 mg (0.13 mmol), isolated yield of 51%, 92% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.5, 7.9 Hz, 1H), 7.67 (ddd, J = 1.8, 7.3, 8.4 Hz, 1H), 7.52 (dd, J = 0.4, 8.6 Hz, 1H), 7.41-7.38 (m, 3H), 7.37-7.34 (m, 2H), 6.28 (s, 1H), 4.97 (dd, J = 6.6, 9.2 Hz, 1H), 3.65 (s, 3H), 3.40 (dd, J = 9.2, 16.5 Hz, 1H), 3.12 (dd, J = 6.6,

16.5 Hz, 1H), 1.30 (s, 9H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.5, 155.6, 150.7, 150.5, 137.8, 136.2, 133.1, 127.4, 125.8, 125.5, 124.4, 121.4, 118.2, 51.8, 40.6, 36.7, 34.4, 31.3; IR νmax: 3282, 2956, 1732, 1624, 1612, 1573, 1516, 1469, 1429, 1290, 1226, 763, 753 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C23H25O5 381.1702; found: 381.1705; mp 153.3−162.5 °C.

O

OHO

OMe

O

F

O

OHO

OMe

O

Cl

O

OHO

OMe

O

Br

O

OHO

OMe

O

tBu

S13

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(4-methoxyphenyl)-propanoate (3afa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 59.36 mg (0.17 mmol), isolated yield of 67%, 94% ee; 1H NMR (700 MHz,

CDCl3) δ 8.21 (dd, J = 1.2, 8.0 Hz, 1H), 7.66 (ddd, J = 1.5, 7.1, 8.5 Hz, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.42-7.37 (m, 3H), 6.90-6.86 (m, 2H), 6.39 (s, 1H), 4.96 (t, J = 7.9 Hz, 1H), 3.79 (s, 3H), 3.65 (s, 3H), 3.35 (dd, J = 8.8, 16.3 Hz, 1H), 3.13 (dd, J = 7.3, 16.3 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.4, 159.1, 155.5, 150.8, 137.6, 133.1, 131.3, 128.8, 125.5,

124.5, 121.3, 118.1, 114.3, 55.2, 51.8, 40.4, 36.8; IR νmax: 3277, 2998, 1733, 1611, 1574, 1513, 1466, 1436, 1418, 1289, 1263, 1223, 758, 702 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O6 355.1182; found: 355.1180; mp 150.3−152.6 °C.

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(p-tolyl)propanoate (3aga). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 80.33 mg

(0.24 mmol), isolated yield of 95%, 93% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.3, 8.1 Hz, 1H), 7.66 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.51 (dd, J = 0.6, 8.5 Hz, 1H), 7.39 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.37-7.34 (m, 2H), 7.16 (d, J = 7.9 Hz, 2H), 6.39 (s, 1H), 4.97 (dd, J = 7.0, 9.0 Hz, 1H), 3.65 (s, 3H), 3.37 (dd, J = 8.9, 16.4 Hz, 1H), 3.14 (dd, J = 6.9, 16.4 Hz, 1H), 2.33 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 171.5, 155.5, 151.0, 137.8, 137.3, 136.3, 133.1, 129.5, 127.7, 125.5, 124.5, 121.4, 118.1, 51.8, 40.7, 36.7, 21.0; IR νmax: 3297, 1730, 1621, 1613, 1574, 1471, 1432, 1418, 1287, 1256, 1218, 757, 703 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O5 339.1232; found: 339.1233; mp 129.3−135.8 °C.

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(4-(trifluoromethyl)-phenyl)propanoate (3aha). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 64.60 mg (0.16 mmol), isolated yield of 66%, 63% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (dd, J = 1.3, 7.9 Hz, 1H), 7.69 (ddd, J = 1.7, 7.1, 8.6 Hz, 1H), 7.63-7.58 (m, 4H), 7.52 (d, J = 8.6 Hz, 1H), 7.41 (ddd, J = 1.0, 7.1, 8.0 Hz, 1H), 6.50 (s, 1H), 5.08 (t, J = 7.8 Hz, 1H), 3.67 (s, 3H), 3.38 (dd, J = 8.4, 16.5 Hz, 1H),

3.20 (dd, J = 7.5, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.0, 155.6, 149.4, 143.2, 137.9, 133.4, 130.0 (q, J=32.7 Hz), 128.2, 125.8 (q, J=3.3 Hz), 125.6, 124.7, 122.4 (q, J=271.4 Hz), 121.3, 118.1, 52.0, 40.9, 36.3; IR νmax: 3292, 2955, 1737, 1611, 1572, 1469, 1420, 1291, 1231, 757, 705 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H16F3O5 393.0950; found: 393.0952; mp 121.5−124.2 °C.

Methyl (R)-3-(2-chlorophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3aia). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 86.74 mg (0.24 mmol), isolated yield of 97%, 92% ee; 1H NMR (700 MHz, CDCl3) δ 8.20 (dd, J = 1.4, 8.0 Hz, 1H), 7.65 (ddd, J = 1.7, 7.0, 8.6 Hz, 1H), 7.47 (dd, J = 0.6, 8.6 Hz, 1H), 7.42-7.37 (m, 3H), 7.24-7.19 (m, 2H), 6.26 (s, 1H), 5.42 (dd, J = 6.2, 9.5 Hz, 1H), 3.64 (s, 3H), 3.33 (dd, J = 9.6, 16.5 Hz, 1H), 3.08 (dd, J = 6.2, 16.6 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.1, 155.6, 149.2, 138.5, 136.9, 133.9, 133.3, 130.0, 128.8, 128.7, 127.2, 125.6, 124.6, 121.3, 118.2, 51.9, 38.6, 36.3; IR νmax: 3062, 1732, 1620, 1610, 1567, 1471, 1434, 1292, 1225, 755, 695 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

35ClO5 359.0686; found: 359.0689; mp 133.8−136.4 °C.

O

OHO

OMe

O

Me

O

OHO

OMe

O

OMe

O

OHO

OMe

O

CF3

O

OHO

OMe

OCl

S14

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(o-tolyl)propanoate (3aja). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, oil, 56.65 mg (0.17 mmol), isolated yield of 67%, 89% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.4, 8.0 Hz, 1H), 7.67 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.51 (d, J = 8.6 Hz, 1H), 7.49-7.45 (m, 1H), 7.40 (ddd, J = 1.0, 7.1, 8.0 Hz, 1H), 7.23-7.15 (m, 3H), 6.33 (s, 1H), 5.24 (dd, J = 6.9, 8.7 Hz, 1H), 3.65 (s, 3H), 3.34 (dd, J = 8.8, 16.3 Hz, 1H), 3.11 (dd, J = 6.9, 16.4 Hz, 1H), 2.56 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.5, 155.6, 150.5, 137.8, 137.6, 136.5, 133.2, 130.8, 127.4, 127.1, 126.4, 125.5, 124.5, 121.3, 118.1, 51.8, 37.0, 36.9, 19.7; IR νmax: 3272, 3066, 1734, 1610, 1567, 1483, 1468, 1435, 1422, 1290, 1231, 756 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O5 339.1232; found: 339.1232.

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(2-methoxyphenyl)-propanoate (3aka). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 24.54 mg (0.07 mmol), isolated yield of 28%, 91% ee; 1H NMR (700 MHz, CDCl3) δ 8.25-8.22 (m, 1H), 7.66 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.50 (dd, J = 0.4, 8.6 Hz, 1H), 7.40 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.30 (dd, J = 1.7, 7.6 Hz, 1H), 7.27

(ddd, J = 1.5, 7.5, 8.1 Hz, 1H), 6.92 (dq, J = 1.0, 7.7 Hz, 2H), 6.31 (s, 1H), 5.36 (dd, J = 5.7, 10.1 Hz, 1H), 3.87 (s, 3H), 3.65 (s, 3H), 3.35 (dd, J = 10.1, 16.5 Hz, 1H), 3.07 (dd, J = 5.7, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.8, 156.9, 155.6, 150.8, 138.4, 133.0, 128.6, 128.3, 127.7, 125.5, 124.4, 121.4, 120.8, 118.2, 111.1, 55.7, 51.7, 36.0, 35.5; IR νmax: 3164, 2995, 1735, 1621, 1611, 1586, 1567, 1491, 1470, 1433, 1291, 1228, 754 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O6 355.1182; found: 355.1183; mp 114.2−122.5 °C.

Methyl (R)-3-(2-fluorophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3ala). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 72.94 mg (0.21 mmol), isolated yield of 85%, 87% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (dd, J = 1.4, 8.0 Hz, 1H), 7.67 (ddd, J = 1.5, 7.0, 8.6 Hz, 1H), 7.51 (dd, J = 0.4, 8.6 Hz, 1H), 7.45 (dt, J = 1.7, 7.6 Hz, 1H), 7.40 (ddd, J = 1.0, 7.1, 8.0 Hz,

1H), 7.28-7.25 (m, 1H), 7.13 (dt, J = 1.1, 7.6 Hz, 1H), 7.08 (ddd, J = 1.1, 8.4, 10.3 Hz, 1H), 6.46 (s, 1H), 5.28 (dd, J = 6.7, 9.1 Hz, 1 H), 3.66 (s, 3H), 3.41 (dd, J = 9.1, 16.6 Hz, 1H), 3.14 (dd, J = 6.8, 16.5 Hz, 1H);

13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 171.2, 160.6 (d, J=248.5 Hz), 155.6, 149.4, 138.2, 133.3, 129.4 (d, J=3.3 Hz), 129.2 (d, J=8.2 Hz), 126.1 (d, J=14.7 Hz), 125.5, 124.5 (d, J=24.5 Hz), 121.3, 118.2, 115.9 (d, J=22.9 Hz), 51.9, 35.9, 35.2; IR νmax: 3135, 2949, 1733, 1622, 1611, 1566, 1490, 1471, 1434, 1291, 1219, 757 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16FO5 343.0982; found: 343.0983; mp 117.8−126.2 °C.

Methyl (R)-3-(3-chlorophenyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-propanoate (3ama). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 77.73 mg (0.22 mmol), isolated yield of 87%, 82% ee; 1H NMR (700 MHz,

CDCl3) δ 8.22 (dd, J = 1.8, 7.9 Hz, 1H), 7.69 (ddd, J = 1.5, 7.0, 8.6 Hz, 1H), 7.52 (dd, J = 0.4, 8.6 Hz, 1H), 7.45 (t, J = 1.9 Hz, 1H), 7.41 (ddd, J = 1.1, 7.2, 8.0 Hz, 1H), 7.36 (td, J = 1.6, 7.2 Hz, 1H), 7.28-7.25 (m, 2H), 6.38 (s, 1H), 4.97 (dd, J = 7.2, 8.7 Hz, 1H), 3.67 (s, 3H), 3.36 (dd, J = 8.6, 16.5 Hz, 1H), 3.14 (dd, J = 7.3, 16.5 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 171.1, 155.5, 149.8, 141.2, 137.9, 134.7, 133.4, 130.1, 128.0, 127.8, 126.1, 125.6, 124.6, 121.4, 118.2, 52.0, 40.7, 36.4; IR νmax:

O

OHO

OMe

OMe

O

OHO

OMe

OMeO

O

OHO

OMe

OF

O

OHO

OMe

O

Cl

S15

3264, 2951, 1734, 1609, 1570, 1469, 1422, 1290, 756, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C19H16

35ClO5 359.0686; found: 359.0687; mp 109.5−113.1 °C.

Methyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-(m-tolyl)propanoate (3ana). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 82.08 mg (0.24 mmol), isolated yield of 97%, 89% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.3, 8.1 Hz, 1H), 7.67 (ddd, J = 1.5, 7.0, 8.6 Hz, 1H), 7.52 (dd, J = 0.4, 8.6 Hz, 1H), 7.40 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.28-7.21 (m, 3H), 7.09 (d, J = 7.0 Hz, 1H), 6.31 (s, 1H), 4.96 (dd, J = 6.8, 9.0 Hz, 1H), 3.66 (s, 3H), 3.38 (dd, J = 9.1, 16.4 Hz, 1H), 3.13 (dd, J = 6.8, 16.5 Hz, 1H), 2.35 (s, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 171.5, 155.6, 150.5, 139.2, 138.5, 137.8, 133.2, 128.7, 128.6, 128.3, 125.5, 124.7, 124.5, 121.3, 118.2, 51.8, 41.1, 36.6, 21.4; IR νmax: 3277, 2948, 1732, 1624, 1612, 1575, 1469, 1439, 1426, 1290, 1250, 1229, 717 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O5 339.1232; found: 339.1233; mp 97.6−104.8 °C.

Methyl (S)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-5-phenylpentanoate (3aoa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, oil, 80.76 mg (0.23 mmol), isolated yield of 92%, 95% ee; 1H NMR (700 MHz, CDCl3) δ 8.24 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.69 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.49 (ddd, J = 0.4, 1.1, 8.6 Hz, 1H), 7.42 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.24-7.21 (m, 2H), 7.17-7.11 (m, 3H), 6.29 (s, 1H), 3.79-3.74 (m, 1H), 3.65 (s, 3H), 2.91 (dd, J = 8.1, 15.8 Hz, 1H), 2.76 (dd, J = 6.7, 16.0 Hz, 1H), 2.69 (ddd, J = 6.4, 9.6, 13.9 Hz, 1H),

2.62 (ddd, J = 5.7, 9.7, 14.1 Hz, 1H), 2.23 (dtd, J = 5.9, 9.8, 13.6 Hz, 1H), 2.06 (dddd, J = 5.1, 6.6, 9.9, 13.6 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.6, 171.8, 155.6, 151.7, 141.1, 138.6, 133.2, 128.3, 128.3, 126.0, 125.5, 124.5, 121.4, 118.1, 51.8, 36.9, 35.9, 33.8, 33.6; IR νmax: 3267, 2949, 1736, 1610, 1571, 1469, 1433, 1286, 1214, 751, 702 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C21H21O5 353.1389; found: 353.1388.

Methyl (S)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)octanoate (3apa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, oil, 18.60 mg (0.06 mmol), isolated yield of 23%, 96% ee; 1H NMR (700 MHz, CDCl3) δ 8.24 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.68 (ddd, J = 1.7, 7.0, 8.5 Hz, 1H), 7.50 (dd, J = 0.4, 8.6 Hz, 1H), 7.41 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 6.21 (s, 1H), 3.71 (dddd, J = 5.5, 6.4, 8.5, 9.5 Hz, 1H), 3.66 (s, 3H), 2.88 (dd, J = 8.5, 16.0 Hz, 1H), 2.73 (dd, J = 6.4, 15.8 Hz, 1H),

1.88-1.81 (m, 1H), 1.74-1.68 (m, 1H), 1.36-1.26 (m, 6H), 0.86 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.6, 172.0, 155.6, 152.1, 138.5, 133.1, 125.5, 124.4, 121.3, 118.1, 51.7, 36.8, 35.9, 32.3, 31.5, 26.7, 22.4, 13.9; IR νmax: 3297, 2949, 1737, 1624, 1612, 1574, 1469, 1427, 1296, 1226, 751, 703 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C18H23O5 319.1545; found: 319.1545.

Methyl 3-(3-hydroxy-4-oxo-4H-chromen-2-yl)propanoate (3aqa). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 37.24 mg (0.15 mmol), isolated yield of 60%; 1H NMR (700 MHz, CDCl3) δ 8.24 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.68 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.48 (ddd, J = 0.4, 1.1, 8.6 Hz, 1H), 7.41

(ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 6.26 (s, 1H), 3.74 (s, 3H), 3.22 (t, J = 7.5 Hz, 2H), 2.84 (t, J = 7.7 Hz, 2H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.5, 172.4, 155.6, 149.7, 138.4, 133.1, 125.5, 124.4, 121.5, 118.1, 51.8, 30.6, 24.5; IR νmax: 3278, 2951, 1731, 1603, 1563, 1484, 1467, 1422, 1287, 753, 695 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C13H13O5 249.0763; found: 249.0760; mp 98.6−106.7 °C.

Ethyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanoate (3aab). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 74.24 mg

O

OHO

OMe

O

Me

O

OHO

OMe

O

O

OHO

OMe

O

O

OHO

OMe

O

O

OHO

OEt

O

S16

(0.22 mmol), isolated yield of 88%, 83% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (ddd, J = 0.4, 1.8, 8.1 Hz, 1H), 7.67 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.52 (ddd, J = 0.4, 1.1, 8.6 Hz, 1H), 7.49-7.46 (m, 2H), 7.41-7.38 (m, 1H), 7.37-7.33 (m, 2H), 7.28-7.26 (m, 1H), 6.33 (s, 1H), 5.00 (dd, J = 7.0, 9.0 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H), 3.37 (dd, J = 9.1, 16.2 Hz, 1H), 3.14 (dd, J = 6.9, 16.2 Hz, 1H), 1.16 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.8, 170.9, 155.5, 150.6, 139.3, 137.8, 133.2, 128.8, 127.8, 127.5, 125.5, 124.5, 121.3, 118.1, 60.7, 41.1, 36.9, 14.0; IR νmax: 3278, 2981, 1731, 1610, 1569, 1468, 1422, 1290, 1230, 755, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C20H19O5 339.1232; found: 339.1234.

Propyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanoate (3aac). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 59.95 mg (0.17 mmol), isolated yield of 68%, 82% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.3, 7.9 Hz, 1H), 7.67 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.48 (dd, J = 1.1, 8.1 Hz, 2H), 7.40 (ddd, J = 1.0, 7.0, 8.0 Hz,

1H), 7.37-7.33 (m, 2H), 7.28-7.26 (m, 1H), 6.33 (s, 1H), 5.00 (dd, J = 6.9, 9.1 Hz, 1H), 4.00 (t, J = 6.6 Hz, 2H), 3.39 (dd, J = 9.2, 16.3 Hz, 1H), 3.16 (dd, J = 6.9, 16.2 Hz, 1H), 1.56 (sxt, J = 7.1 Hz, 2H), 0.85 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.9, 171.1, 155.4, 150.8, 139.3, 137.8, 133.2, 128.8, 127.8, 127.5, 125.5, 124.5, 121.3, 118.1, 66.4, 41.0, 36.9, 21.8, 10.2; IR νmax: 3289, 2966, 1731, 1610, 1569, 1468, 1422, 1289, 1229, 756, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for

C21H21O5 353.1389; found: 353.1389.

Butyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanoate (3aad). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 79.32 mg (0.22 mmol), isolated yield of 87%, 84% ee; 1H NMR (700 MHz, CDCl3) δ 8.22 (ddd, J = 0.4, 1.8, 7.9 Hz, 1H), 7.67 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.52 (dd, J = 0.4, 8.6 Hz, 1H), 7.48 (dd, J = 0.9, 8.1 Hz, 2H), 7.40 (ddd, J = 1.0, 7.0, 8.0 Hz, 1H), 7.36-7.33 (m, 2H), 7.28-7.26 (m, 1H), 6.43 (s, 1H), 5.01 (dd, J = 7.0, 9.0 Hz, 1H), 4.05 (t, J = 6.6 Hz, 2H), 3.38 (dd, J = 9.2, 16.3 Hz, 1H), 3.15 (dd, J = 7.0, 16.3 Hz, 1H), 1.53-1.47 (m, 2H), 1.26 (qd, J = 7.4, 15.1 Hz, 2H), 0.84 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 171.0, 155.5, 150.8, 139.2, 137.8, 133.2, 128.8, 127.8, 127.5, 125.5, 124.5, 121.3, 118.1, 64.7, 41.0, 36.9, 30.5, 19.0, 13.6; IR νmax: 3285, 2959, 1731, 1611, 1568, 1469, 1422, 1290, 1230, 756, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C22H23O5 367.1545; found: 367.1547.

Allyl (R)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanoate (3aae). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 51.96 mg (0.15 mmol), isolated yield of 59%, 90% ee; 1H NMR (700 MHz, CDCl3) δ 8.18 (dd, J = 1.7, 8.0 Hz, 1H), 7.64 (ddd, J = 1.7, 7.0, 8.7 Hz, 1H), 7.51-7.47 (m, 1H), 7.46-7.43 (m, 2H), 7.37 (ddd, J = 1.1, 7.0, 8.0 Hz, 1H), 7.34-7.30 (m, 2H),

7.25-7.23 (m, 1H), 6.29 (s, 1H), 5.78 (tdd, J = 5.8, 10.4, 17.2 Hz, 1H), 5.20 (qd, J = 1.5, 17.2 Hz, 1H), 5.14 (qd, J = 1.3, 10.4 Hz, 1H), 4.98 (dd, J = 7.0, 9.1 Hz, 1H), 4.52 (td, J = 1.4, 5.8 Hz, 2H), 3.39 (dd, J = 9.2, 16.3 Hz, 1H), 3.15 (dd, J = 6.9, 16.3 Hz, 1H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 170.6, 155.5, 150.4, 139.1, 137.7, 133.2, 131.7, 128.8, 127.8, 127.6, 125.5, 124.5, 121.2, 118.4, 118.2, 65.4, 41.0, 36.8; IR νmax: 3282, 3064, 1733, 1610, 1569, 1482, 1469, 1422, 1290, 1229, 757, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C21H19O5 351.1232; found: 351.1231.

(R)-N-Butyl-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanamide (3aaf). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid,

O

OHO

O

O

O

OHO

O

O

O

OHO

O

O

O

OHO

HN

O

S17

63.46 mg (0.17 mmol), isolated yield of 69%, 87% ee; 1H NMR (700 MHz, CDCl3) δ 8.17 (dd, J = 1.3, 8.0 Hz, 1H), 7.63 (ddd, J = 1.7, 7.0, 8.5 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.45-7.43 (m, 2H), 7.35 (ddd, J = 1.0, 7.1, 8.1 Hz, 1H), 7.33-7.29 (m, 2H), 7.25-7.22 (m, 1H), 5.62 (s, 1H), 4.94 (dd, J = 7.0, 9.1 Hz, 1H), 3.23 (dd, J = 9.1, 14.7 Hz, 1H), 3.18-3.11 (m, 2H), 2.95 (dd, J = 7.0, 14.7 Hz, 1H), 1.32-1.26 (m, 2H), 1.14 (qd, J = 7.4, 15.0 Hz, 2H), 0.77 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 170.0, 155.6, 151.2, 139.7, 137.9, 133.2, 128.8, 127.9, 127.5, 125.5, 124.5, 121.3, 118.1, 42.3, 39.4, 39.3, 31.5, 19.8, 13.5; IR νmax: 3301, 2960, 2927, 1622, 1610, 1545, 1469, 1423, 1291, 1277, 1236, 752, 696 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C22H24NO4 366.1705; found: 366.1705; mp 154.1−163.4 °C.

(R)-N-Allyl-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanamide (3aag). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 86.56 mg (0.25 mmol), isolated yield of 99%, 91% ee; 1H NMR (700 MHz, CDCl3) δ 8.21 (dd, J = 1.5, 7.9 Hz, 1H), 7.67 (ddd, J = 1.7, 7.1, 8.6 Hz, 1H), 7.50 (d, J = 8.6 Hz, 1H), 7.48 (dd, J = 1.0, 8.3 Hz, 2H), 7.40 (ddd, J = 1.0, 7.1, 8.0 Hz,

1H), 7.37-7.33 (m, 2H), 7.28-7.27 (m, 1H), 6.38 (s, 1H), 5.69 (tdd, J = 5.7, 10.3, 17.1 Hz, 1H), 5.62 (s, 1H), 5.04-5.01 (m, 1H), 5.00-4.97 (m, 1H), 3.82 (tt, J = 1.5, 5.7 Hz, 2H), 3.30 (dd, J = 9.0, 15.0 Hz, 1H), 3.00 (dd, J = 6.9, 14.9 Hz, 1H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 169.9, 155.5, 150.9, 139.6, 137.8, 133.8, 133.2, 128.9, 127.8, 127.5, 125.5, 124.5, 121.2, 118.2, 116.3, 42.2, 41.9, 39.2; IR νmax: 3280, 3065, 2919, 1632, 1609, 1538, 1469, 1421, 1293, 1235, 1221, 750, 697 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C21H20NO4 350.1392; found: 350.1393; mp 170.1−177.6 °C.

(3R)-N-(sec-Butyl)-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropan-amide (3aah). GP4. A scale of 0.25 mmol, opening time was equal to 24 h, solid, 83.99 mg (0.23 mmol), isolated yield of 92%, 92% ee, dr 1:1; 1H NMR (700 MHz, CDCl3) δ 8.19-8.15 (m, 1H), 7.63 (qt, J = 0.9, 7.8 Hz, 1H), 7.49-7.43 (m, 3H), 7.36 (tdd, J = 0.9, 7.1, 8.0 Hz, 1H), 7.33-7.28 (m, 2H), 7.25-7.22

(m, 1H), 6.40 (s, 1H), 5.33 (s, 1H), 4.93 (ddd, J = 2.8, 7.4, 8.8 Hz, 1H), 3.83-3.78 (m, 1H), 3.20 (td, J = 8.8, 14.5 Hz, 1H), 2.93 (ddd, J = 5.5, 7.2, 14.6 Hz, 1H), 1.32-1.24 (m, 2H), 0.94 (dd, J = 6.6, 10.3 Hz, 3H), 0.70 (td, J = 7.5, 9.2 Hz, 3H); 13C{1H} NMR (176 MHz, CDCl3) δ 172.9, 169.3, 169.3, 155.6, 150.9, 150.9, 139.7, 139.6, 137.9, 133.2, 128.9, 127.9, 127.5, 125.5, 124.5, 121.2, 118.1, 46.6, 42.5, 42.5, 39.7, 39.7, 29.5, 29.5, 20.2, 20.2, 10.0; IR νmax: 3301, 2963, 2929, 1633, 1621, 1612, 1568, 1548, 1470, 1425, 1275, 1238,

751, 696 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C22H24NO4 366.1705; found: 366.1704; mp 183.8−191.3 °C.

(R)-N,N-Diethyl-3-(3-hydroxy-4-oxo-4H-chromen-2-yl)-3-phenylpropanamide (3aai). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 44.89 mg

(0.12 mmol), isolated yield of 49%, 66% ee; 1H NMR (700 MHz, CDCl3) δ 8.20 (dd, J = 1.5, 7.9 Hz, 1H), 7.64 (ddd, J = 1.8, 7.0, 8.6 Hz, 1H), 7.51-7.45 (m, 3H), 7.39-7.32 (m, 3H), 7.28-7.25 (m, 1H), 6.47 (s, 1H), 5.06 (dd, J = 5.4, 10.0 Hz, 1H), 3.51 (dd, J = 10.1, 16.1 Hz, 1H), 3.42-3.34 (m, 3H), 3.30 (qd, J = 7.0, 13.8 Hz, 1H), 3.00 (dd, J = 5.5, 16.1 Hz, 1H), 1.23 (t, J = 7.2 Hz, 3H), 1.04 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.8, 169.2, 155.4, 151.9, 140.3, 137.9, 132.9, 128.8, 127.9, 127.3, 125.5, 124.4, 121.4, 118.1, 42.2, 41.9, 40.3, 36.1, 14.3, 12.9; IR νmax: 3281, 2974, 2931, 1609, 1568, 1481, 1467, 1426, 1289, 1265, 755, 699 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C22H24NO4 366.1705; found: 366.1705.

(R)-3-Hydroxy-2-(3-oxo-1-phenyl-3-(pyrrolidin-1-yl)propyl)-4H-chromen-4-one (3aaj). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 60.75 mg (0.17 mmol), isolated yield of 67%, 72% ee; 1H NMR (700 MHz, CDCl3)

O

OHO

HN

O

O

OHO

HN

O

O

OHO

NEt2

O

O

OHO

N

O

S18

δ 8.18 (ddd, J = 0.4, 1.7, 8.2 Hz, 1H), 7.61 (ddd, J = 1.7, 7.0, 8.5 Hz, 1H), 7.49-7.43 (m, 3H), 7.36-7.28 (m, 3H), 7.25-7.22 (m, 1H), 6.42 (s, 1H), 5.03 (dd, J = 5.7, 9.6 Hz, 1H), 3.50

(s, 1H), 3.45-3.37 (m, 4H), 2.97 (dd, J = 5.7, 16.0 Hz, 1H), 1.92 (s, 2H), 1.81 (s, 2H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.9, 168.7, 155.5, 151.7, 140.3, 137.9, 132.9, 128.8, 127.9, 127.3, 125.5, 124.3, 121.4, 118.1, 46.6, 45.7, 41.8, 37.5, 26.0, 24.3; IR νmax: 3260, 2927, 2872, 1608, 1567, 1467, 1423, 1288, 757, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C22H22NO4 364.1549; found: 364.1550.

(R)-3-Hydroxy-2-(3-oxo-1-phenyl-3-(piperidin-1-yl)propyl)-4H-chromen-4-one (3aak). GP4. A scale of 0.25 mmol, opening time was equal to 72 h, oil, 46.88 mg (0.12 mmol), isolated yield of 50%, 91% ee; 1H NMR (700 MHz, CDCl3) δ 8.18 (ddd, J = 0.4, 1.7, 8.0 Hz, 1H), 7.62 (ddd, J = 1.6, 7.0, 8.6 Hz, 1H), 7.49-7.43 (m, 3H), 7.35 (ddd, J = 1.1, 7.0, 8.0 Hz, 1H), 7.33-7.29 (m, 2H), 7.25-7.22 (m, 1H), 5.00 (dd, J = 5.5, 9.8 Hz, 1H), 3.52-3.42 (m, 5H), 3.01 (dd, J = 5.6, 16.1 Hz, 1H), 1.71-1.58 (m, 6H); 13C{1H} NMR (75 MHz, CDCl3) δ 172.9, 168.4, 155.5, 151.8, 140.3, 137.8, 132.9, 128.8, 127.9, 127.3, 125.5, 124.3, 121.4, 118.1, 46.6, 42.9, 42.1, 36.0, 26.4, 25.5, 24.5; IR νmax: 3271, 2930, 2854, 1608, 1567, 1468, 1441, 1288, 1231, 757, 698 cm-1; HRMS (ESI-TOF) m/z: (M + H)+ calcd for C23H24NO4 378.1705; found: 378.1705.

3. X-Ray Crystallography Data

The diffraction data of the studied compounds were collected at room temperature for the single crystal using Oxford Sapphire CCD diffractometer, MoKα radiation λ = 0.71073 Å. The numerical absorption correction was applied.14 The structure was solved by the direct methods and refined with full-matrix least-squares procedure on F2 (SHELX-9715). All heavy atoms were refined with anisotropic displacement parameters. Positions of hydrogen atoms attached to carbon atoms were assigned at calculated positions with thermal displacement parameters fixed to a value of 20% or 50% higher than those of the corresponding carbon atoms, whereas positions of hydrogen atoms from hydroxyl groups were found from difference electron density synthesis. To maintain reasonable geometry and to keep stable refinement process atoms from positionally disordered O44 ester group were refined with constraints (DFIX and EADP). All figures were prepared in DIAMOND16 and ORTEP-3.17 The results of

O

OHO

N

O

S19

the data collections and refinement have been summarized in Table 1. CCDC 2088560 contain the supplementary crystallographic data for 3daa. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk.data_request/cif.

Table 1. Crystal data and structure refinement

Identification code 3daa

Empirical formula C19H15O5Br

Formula weight 403.22

Temperature [K] 293(2)

Wavelength [Å] 0.71073

Crystal system, space group monoclinic, P21

Unit cell dimensions [Å] and []

a 17.401(8) 90b 5.9984(13) 115.06(5)

c 18.889(6) 90

Volume [Å3] 1786.1(13)

Z, Calculated density [Mgm–3] 4, 1.500

Absorption coefficient [mm–1] 2.327

F(000) 816

Crystal size [mm] 0.550 x 0.120 x 0.050

Theta range for data collection [] 2.095 to 26.372

Limiting indices-21<=h<=16-7<=k<=7-22<=l<=23

Reflections collected/unique 11460 / 6739 [R(int) = 0.0431]

Completeness [%] to theta [°] 25.242° 99.9 %

Absorption correction Analytical

Max. and min. transmission 0.869 and 0.320

Refinement method Full-matrix least-squares on F2

Data/restraints/parameters 6739 / 17 / 466

Goodness-of-fit on F2 1.004

Final R Indices [I>2sigma(I)] R1a 0.0551, wR2b 0.1122

R indices (all data) R1a 0.1233, wR2b 0.1451

Absolute structure parameter -0.014(13)

http://www.ccdc.cam.ac.uk.data_request/cif

S20

Largest diff. peak and hole [eÅ–3] 0.247 and -0.254

a R1 F0– Fc/F0 b wR2 [w(F02 – Fc

2)2/(w(F02)2)]1/2

4. NMR Spectra

Figure S1. Structure of C19H15O5Br 3daa with thermal ellipsoids at 20% of probability. There are two crystallographically (both occurring in R configuration) independent molecules in the asymmetric unit. O5 molecule is presented to the left and O35 one to the right.

Figure S2. Packing of 3daa along c axis shows bc double layers (left) composed solely of O5 or O35 molecules. View along b axis show interlayer interactions assured by hydrogen bonds (green, right). However, intralayer interactions differ significantly and weak halogen bond (cyan) occurs only between O35 molecules due to subtle conformational changes in torsion angles around C6-C11 (C36-C41) bonds.

S21

KDD359.23365.esp

11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

1.000.990.990.990.96

M04(d)

M05(dd)

M03(dd)

M02(dd)

M01(d)

6.356.

36

7.357.

357.36

7.74

7.747.75

7.85

7.85

8.33

8.33

KDD359.2632.esp

200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)

M07(s)

M08(s)

M03(s)

M05(s)M06(s)

M04(s)

M09(s)

M01(s)

M02(s)

113.

00

118.

7012

0.18

126.

1212

8.41

136.

74

155.

2315

5.46

176.

19

Figure S3. 1H and 13C NMR spectra of 0b

O

OBr

S22

KDD364.32034.esp


1.001.091.021.101.00

M05(d)

M01(dd)

M04(ddd)

M03(ddd)

M02(ddd)

6.36

6.37

7.417.42

7.42

7.43

7.49

7.50

7.87

7.87

7.88

7.89

KDD364.2637.esp


M09(d)

M07(s)

M06(d)

M05(d)

M03(d)

M02(s)

M04(d)

M01(d)

M08(d)

110.

4711

0.79

112.

22

120.

28120.

3912

1.83

122.

1712

5.95

152.

7015

5.46

157.

8516

1.13

176.

7817

6.81

Figure S4. 1H and 13C NMR spectra of 0c

O

OF

S23

KDD360.23366.esp


1.001.031.021.010.97

M05(m)

M01(d)M04(d)

M02(dd)

6.346.

35

7.42

7.42

7.43

7.61

7.62

7.85

7.85

8.17

8.17

KDD360.2633.esp


M04(s)

M07(s)

M05(s)

M09(s)

M03(s)

M08(s)

M01(s)

M02(s)M06(s)

112.

90

119.

95125.

1912

5.7413

1.22

133.

98

154.

7915

5.45

176.

34

Figure S5. 1H and 13C NMR spectra of 0d

O

OCl

S24

KDD356.23362.esp

11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5Chemical Shift (ppm)

3.000.990.970.980.960.96

M03(d)

M01(s)

M05(d)

M02(d)

M06(m)

M04(dd)

3.90

6.276.28

6.84

6.966.97

7.77

7.78

8.108.12

KDD356.2630.esp


M07(s)M05(s)

M08(s)

M02(s)

M01(s)

M03(s)

M06(s)

M09(s)

M10(s)

M04(s)

55.7

9

100.

33112.

9111

4.50

118.

74

127.

16

154.

8415

8.23

164.

07

176.

99

Figure S6. 1H and 13C NMR spectra of 0e

O

O

MeO

S25

KDD357.23363.esp


3.000.991.001.001.021.02

M01(d)

M02(dd)M03(d)

M06(dd)

M04(m)

M05(td)

3.96

3.97

6.236.23

6.796.806.

997.

00

7.527.

527.

537.

667.67

KDD357.2631.esp


M09(s)

M02(s)

M05(s)

M10(s)

M06(s)

M08(s)

M03(s)

M01(s)M07(s)

M04(s)

56.4

5

106.

3711

0.16

114.

5711

5.57

133.

72

153.

09

158.

4815

9.80

177.

39

Figure S7. 1H and 13C NMR spectra of 0f

O

OOMe

S26

KDD363.23441.esp


1.001.970.980.99

M03(d)

M01(d)

M04(dd)

M02(m)

6.326.33

7.12

7.12

7.13

7.157.

827.

838.

218.

228.

228.

23

KDD363.2635.esp


M04(d)

M09(s)

M02(s)

M06(s)

M05(d)

M07(d)

M03(d)

M01(d)

M08(d)

104.

6410

4.97

113.

1211

3.92

114.

22

121.

7112

1.74

128.

32128.

46

155.

4015

7.36

157.

53163.

9016

7.2817

6.58

Figure S8. 1H and 13C NMR spectra of 0g

O

O

F

S27

KDD361.23389.esp


1.000.990.950.990.97

M03(d)

M05(m)

M01(d)

M02(dd)

6.336.34

7.367.

377.

377.38

7.47

7.48

7.82

7.82

8.13

8.138.14

KDD361.2634.esp


M03(s)

M02(s)

M06(s)

M01(s)

M09(s)

M04(s)

M07(s)

M08(s)

M05(s)

113.

26

118.

21

123.

3612

6.1312

7.20

139.

82

155.

3215

6.54

176.

68

Figure S9. 1H and 13C NMR spectra of 0h

O

O

Cl

S28

KDD365.24382.esp


1.011.000.990.99

M04(d)

M01(d)

M03(ddd)

M02(ddd)

6.366.

37

7.237.

237.247.

267.

647.657.65

7.88

7.89

KDD365.2638.esp


M09(dd) M04(d)

M03(s)

M05(dd)

M07(s)

M01(dd)

M02(dd)

M06(dd)

M08(dd)

105.

8410

6.15

109.

1710

9.55

112.

73

126.

9112

7.02

149.

7514

9.90

153.

1715

3.31

155.

0415

6.74

159.

9316

0.0517

5.47

Figure S10. 1H and 13C NMR spectra of 0i

O

OF

F

S29

KDD232.27990.esp


0.771.000.960.980.920.97

M05(s)

M03(d)

M02(t)

M06(ddd)

M04(m)

M01(s)

7.42

7.437.52

7.53

7.70

7.71

7.72

8.04

8.288.29

KDD232.2629.esp


M06(s)

M08(s)

M05(s)

M02(s)

M03(s)

M01(s)

M07(s)

M09(s)

118.

4812

1.91

124.

5912

5.55

133.

51

138.

5414

1.7715

6.28

173.

42

Figure S11. 1H and 13C NMR spectra of 1a

O

OHO

S30

KDD386.24528.esp


1.061.001.010.880.80

M05(d)

M04(s)

M03(dd)

M02(d)

M01(s)

6.07

7.41

7.43

7.767.77

7.79

8.02

8.40

8.41

KDD386.2641.esp


M01(s)

M02(s)

M07(s)

M03(s)

M09(s) M08(s)

M04(s)

M06(s)

M05(s)

118.

0412

0.43

123.

14

128.

01

136.

5613

8.56

141.

85

155.

00

172.

12


O

OHO

Br

S31

KDD400.30581.esp


0.921.000.950.950.90

M05(s)

M03(m)

M04(ddd)

M02(ddd)

M01(s)

7.45

7.467.

537.

547.

907.

907.

917.

918.

05

KDD400.30798.esp

200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

M07(s)

M04(d)

M06(s)

M09(s)

M05(s)

M02(d)

M01(d)

M03(d)

M08(d)

109.

9511

0.08

120.

64120.

6812

2.08

122.

2312

2.88

138.

5614

1.43

152.

69

158.

42159.

83

172.

68


O

OHO

F

S32

KDD389.24183.esp


1.011.001.020.980.95

M05(dd)

M04(s)

M02(d)

M03(dd)

M01(s)

7.45

7.47

7.61

7.61

7.62

8.00

8.22

KDD389.2642.esp


M07(s)

M02(s)

M08(s)

M04(s)

M05(s)

M01(s)

M09(s)

M06(s)

M03(s)

120.

2212

2.71

124.

75

130.

6613

3.86

138.

5714

1.81

154.

59

172.

27


O

OHO

Cl

S33

KDD367.23509.esp


3.000.840.960.980.950.99

M03(d)

M05(s)

M01(s)

M06(d)

M04(dd)

M02(s)3.

90

6.846.84

6.98

6.98

6.99

7.91

8.13

8.14

KDD367.2639.esp


M04(s)

M08(s)

M01(s)M06(s)

M09(s)

M02(s)M05(s)

M10(s)

M03(s)

M07(s)

55.8

0

99.9

6

114.

9111

5.83

126.

80

137.

7514

1.50

158.

22164.

09

172.

75


O

OHO

MeO

S34

KDD368.23562.esp


3.000.880.970.951.010.94

M06(s)

M03(dd)

M04(dd)

M01(s)

M05(t)

M02(s)4.

01

6.41

6.776.78

7.037.

04

7.54

7.55

7.57

7.87

KDD368.2640.esp


M06(s)

M03(s)

M07(s)

M01(s)

M08(s)

M02(s)

M09(s)

M04(s)

M10(s)

M05(s)

56.4

1

105.

01110.

4811

2.62

133.

8213

5.67

142.

01

158.

3015

9.80

172.

76


O

OHOOMe

S35

KDD399.24387.esp


0.672.000.970.99

M03(s)

M04(ddd)

M02(m)

M01(s)

6.13

7.14

7.14

7.16

7.167.

187.

18

7.98

8.25

8.268.27

8.28

KDD399.2644.esp


M06(s)

M09(s)

M05(d)M03(d)

M04(d)

M07(d)

M02(d)

M01(d)

M08(d)

104.

72105.

05113.

8011

4.11

118.

74

127.

99128.

13

138.

3813

8.39

141.

70

157.

2015

7.39

163.

9316

7.32

172.

61


O

OHO

F

S36

KDD397.24383.esp


0.771.000.970.970.99

M03(d)

M04(s)

M02(dd)

M05(dd)

M01(s)

7.37

7.377.38

7.52

7.52

7.97

8.18

8.19O

OHO

Cl

S37

KDD397.2643.esp


M08(s)

M04(s)

M06(s)

M03(s)

M02(s)

M07(s)

M01(s)

M05(s)

M09(s)11

8.44

120.

40

125.

6712

6.87

138.

3914

1.91

156.

29

172.

73


S38

KDD401.30582.esp


1.041.911.000.97

M04(s)

M03(ddd)

M02(m)

M01(s)

6.12

7.277.287.29

7.307.

717.

717.72

7.72

8.09

KDD401.30810.esp


M09(t)

M04(s)

M05(s)

M03(d)

M01(dd)

M06(d)

M02(dd)

M07(dd)

M08(dd)

105.

33105.

4610

8.90

109.

0710

9.18

123.

8312

3.88

138.

5114

1.77

142.

2215

1.03

151.

1015

2.50

152.

5715

7.23

157.

2815

8.64

158.

69171.

86


O

OHO

F

F

S39

KDD213.20323.esp


2.001.011.980.96

M04(s)

M01(m)

M02(ddt)

M03(m)

7.40

7.40

7.417.

417.

427.

487.

607.60

7.61

7.62

9.43

KDD213.20324.esp


M03(s)

M01(s)

M05(s)

M07(s)

M02(s)

M06(s)

M04(s)

88.0

594.7

3119.

03

128.

3613

0.92

132.

89

176.

38

Figure S20. 1H and 13C NMR spectra of 2a

CHO

S40

MS-M-053.29710.esp


2.001.980.94

M03(s)

M01(m)

M02(m)7.

127.

127.

137.

147.

157.62

7.637.

637.

647.

657.

65

9.43

MS-M-053.29719.esp


M07(s)

M01(s)

M03(d)

M02(s)

M05(d)

M06(d)

88.3

8

93.8

4

115.

6111

6.24

116.

36

135.

61

163.

5916

5.03

176.

42


CHO

F

S41

MS-M-003.24813.esp


2.001.930.91

M03(s)

M01(m)

M02(m)

7.38

7.40

7.53

7.54

9.41

MS-M-003.2383.esp


M02(s)

M01(s)

M07(s)

M03(s)

M06(s)M04(s)

M05(s)

88.9

7

93.5

1117.

87

129.

23

134.

4113

7.78

176.

45


CHO

Cl

S42

MS-M-050.24725.esp


2.001.990.91

M03(s)

M02(m)

M01(m)7.

457.

467.

487.

557.

587.

58

9.43

MS-M-050.24726.esp


M06(s)

M01(s)

M04(s)M03(s)

M02(s)

M05(s)

M07(s)

89.0

8

93.5

2

118.

37

126.

21

132.

1813

4.48

176.

42


CHO

Br

S43

MS-M-045.29601.esp


9.002.011.970.88

M04(s)

M01(s)

M02(m)

M03(m)

1.35

7.447.

467.

577.

58

9.44

MS-M-045.29605.esp


M01(s)

M08(s)

M03(s)M05(s)

M02(s)

M07(s)

M06(s)

M04(s)M09(s)

31.0

3

35.1

6

88.4

6

95.9

2116.

36

125.

85

133.

26

155.

20

176.

84


CHO

tBu

S44

MS-M-001.24726.esp


3.001.991.940.89

M04(s)

M01(s)

M03(m)M02(m)

3.85

6.90

6.90

6.92

6.92

7.55

7.55

7.57

7.57

9.39

MS-M-001.2381.esp


M04(s)

M07(s)

M02(s)

M03(s)

M08(s)

M01(s)

M05(s)

M06(s)

55.4

4

88.7

2

96.5

2111.

1211

4.49

135.

40

162.

13

176.

65


CHO

MeO

S45

MS-M-043.29410.esp


3.001.971.930.85

M04(s)

M01(s)

M03(m)

M02(m)

2.42

7.237.24

7.51

7.52

7.53

9.43

CHO

Me

S46

MS-M-043.29417.esp


M04(s)

M02(s)

M07(s)

M06(s)

M05(s)

M01(s)

M03(s)M08(br. s.)

21.7

9

88.5

0

95.9

8

116.

29

129.

5813

3.36

142.

23

176.

85


S47

MS-M-051.29621.esp


2.001.910.88

M03(s)

M02(d)

M01(d)

7.69

7.71

7.74

7.75

9.47

MS-M-051.29717.esp


M08(s)

M07(s)

M03(s)

M01(s)

M02(s)

M05(q)

M06(q)

M04(q)

89.2

392

.09

121.

1512

2.6912

3.3012

5.62

125.

6713

2.65

132.

8413

3.31

176.

17


CHO

F3C

S48

MS-M-007.24727.esp


1.001.990.980.86

M04(s)

M01(m)

M03(ddd)

M02(m)7.

307.

30

7.337.34

7.43

7.447.457.

477.

487.

627.

647.

65

9.50

MS-M-007.24728.esp


M01(s)

M02(s)

M04(s)

M05(s)

M03(s)

M08(s)

M06(s)

M07(s)

M09(s)

90.9

392.1

1

119.

80

126.

8212

9.76

132.

2013

4.96

137.

65

176.

43


CHOCl

S49

MS-M-009.25110.esp


3.001.020.980.980.960.91

M06(s)

M03(ddt)

M05(ddd)

M01(s)

M02(m)

M04(m)

2.50

7.20

7.21

7.267.

277.

377.38

7.39

7.55

7.56

9.46

MS-M-009.2387.esp


M04(s)

M05(s)

M01(s)

M09(s)

M07(s)

M08(s)

M03(s)

M10(s)

M06(s)

M02(s)

20.5

5

92.2

494

.40

119.

21

125.

96

129.

9113

1.34

133.

80

142.

60

176.

82

Figure S29. 1H and 13C NMR spectra of 2j

CHOMe

S50

MS-M-049.29604.esp


3.001.071.011.030.980.89

M06(s)

M01(s)

M05(ddd)M02(d)

M03(td)M04(ddd)

3.93

6.946.95

6.97

6.98

6.99

7.46

7.47

7.487.

547.

557.

55

9.47

MS-M-049.29607.esp


M01(s)

M02(s)

M09(s)

M03(s)

M06(s)

M05(s)

M07(s)

M08(s)

M04(s)

M10(s)

55.7

5

92.5

392

.68

108.

4411

1.04

120.

65

133.

2513

5.13

161.

72

176.

78

Figure S30. 1H and 13C NMR spectra of 2k

CHOOMe

S51

MS-M-052.29689.esp


1.000.990.970.950.72

M05(s)

M02(td)

M04(ddd)

M01(m)

M03(m)

7.167.16

7.17

7.21

7.22

7.22

7.51

7.527.

597.60

7.60

9.47

MS-M-052.29718.esp


M01(s)

M02(d)

M07(s)

M05(d)

M06(d)

M03(d)

M04(d)

M09(s)

M08(d)

88.0

892.5

3

108.

3810

8.46

115.

9411

6.0512

4.43

133.

3213

3.36

134.

80

162.

9816

4.44

176.

30

Figure S31. 1H and 13C NMR spectra of 2l

CHOF

S52

MS-M-006.24942.esp


1.001.940.940.92

M04(s)

M03(m)

M01(m)

M02(m)

7.33

7.34

7.47

7.58

7.58

9.41

MS-M-006.2385.esp


M05(s)

M06(s)

M07(s)

M08(s)

M09(s)

M01(s)

M02(s)

M03(s)

88.6

3

92.7

1121.

14

129.

9913

1.4813

2.79

134.

67

176.

38

Figure S32. 1H and 13C NMR spectra of 2m

CHOCl

S53

MS-M-044.29593.esp


3.002.042.040.88

M04(s)

M01(s)

M02(m)

M03(m)

2.39

7.30

7.31

7.32

7.45

9.44

MS-M-044.29602.esp


M09(s)

M05(s)

M02(s)

M06(s)

M03(s)

M08(s)

M07(s)

M01(s)

M04(s)M10(s)

21.1

3

88.3

0

95.6

1

119.

23

128.

6613

0.45

132.

2813

3.75

138.

63

176.

84

Figure S33. 1H and 13C NMR spectra of 2n

CHOMe

S54

MS-M-005.29407.esp


2.002.003.091.910.85

M05(t)

M04(m)

M02(t)

M01(td)

M03(m)

2.73

2.74

2.93

2.94

2.95

7.25

7.26

7.35

7.36

9.18

MS-M-005.29416.esp


M01(s)

M02(s)

M06(s)

M07(s)

M04(s)

M05(s)

M08(s)

M03(s)

M09(br. s.)

21.2

1

33.8

0

82.1

7

97.9

0

126.

76128.

3612

8.64

139.

47

176.

94

Figure S34. 1H and 13C NMR spectra of 2o

CHO

S55

KDD485.27930.esp


1.000.982.920.930.901.362.001.021.940.970.950.92

M10(m)

M09(m)

M08(ddd)

M06(m)

M12(ddd)

M11(ddd)

M07(m)

M04(dd)M05(s)

M02(dd)

M03(s)

M01(dd)

3.14

3.153.

173.

183.

373.

393.

403.

66

5.005.01

5.01

5.02

6.36

7.27

7.28

7.29

7.35

7.47

7.48

7.517.

677.

687.

688.21

8.22

O

OHO

OMe

O

S56

KDD485.2621.esp


M08(s)

M09(s)

M16(s)

M17(s)

M15(s)

M07(s)

M02(s)M12(s)

M13(s)

M04(s)

M05(s)

M10(s)

M14(s)

M06(s)

M01(s)

M11(s)

M03(s)

36.5

6

40.9

7

51.9

2118.

1612

1.28

124.

51125.

4912

7.57

127.

7612

8.85

133.

20

137.

7513

9.21

150.

49

155.

48171.

4417

2.82

Figure S35. 1H and 13C NMR spectra of 3aaa

S57

KDD501.27757.esp


1.001.003.001.000.971.422.061.021.900.960.90

M11(d)

M08(d)

M06(m)

M09(m)

M10(dd)

M07(t)

M04(dd)

M02(dd)

M05(s)

M01(dd)

M03(s)

3.103.

113.

123.

333.

343.

353.

373.

62

4.944.95

4.96

4.97

6.327.25

7.25

7.32

7.39

7.41

7.42

7.697.70

7.71

8.30

KDD501.27759.esp


M08(s)

M07(s)

M10(s)

M12(s)

M14(s)M17(s)

M13(s)

M16(s) M15(s)

M11(s)

M02(s)M05(s)

M01(s)

M03(s)

M04(s)

M06(s)

36.5

3

41.1

4

51.9

0

117.

9212

0.09

122.

67

127.

7312

8.92

136.

2113

7.97

138.

99

151.

01154.

24

171.

3017

1.61

Figure S36. 1H and 13C NMR spectra of 3baa

O

OHO

OMe

O

Br

S58

KDD503.26301.esp


1.000.992.960.980.931.422.111.152.041.070.95

M09(dd)

M10(dd)

M08(ddd)

M06(m)

M07(m)

M11(dd)

M03(s)

M02(dd)

M01(dd)M04(dd)

M05(br. s.)

3.113.12

3.13

3.34

3.35

3.36

3.38

3.63

4.964.97

4.97

4.98

6.31

7.257.

257.

257.

327.

427.

437.

497.

507.80

7.80

7.81

7.81

KDD503.26601.esp


M08(s)

M10(s)

M11(s)

M12(s)

M14(s)M16(s)

M17(d)M13(s)

M07(d)M01(s)

M05(d)

M06(d)M02(s)

M03(s)M04(d)

M15(d)

36.5

6

41.1

6

51.8

9

109.

9511

0.08

120.

3112

1.67

121.

8112

2.28

127.

6612

7.74

128.

91

137.

5213

9.07

150.

9815

1.83

158.

41

171.

3317

2.14

Figure S37. 1H and 13C NMR spectra of 3caa

O

OHO

OMe

O

F

S59

KDD513.27590.esp


1.001.023.091.071.031.062.011.980.991.000.94

M06(m)

M09(dd)

M11(d)

M08(m)

M10(dd)

M07(t)

M05(s) M01(dd)

M02(dd)

M04(dd)

M03(s)

3.09

3.103.11

3.12

3.33

3.34

3.36

3.63

4.94

4.95

4.95

4.96

6.23

7.26

7.277.

317.

32

7.41

7.447.

457.

577.

587.58

8.14

8.15

KDD513.27600.esp


M08(s)

M07(s)

M15(s)

M12(s)

M10(s)

M17(s)

M09(s)

M13(s)

M14(s)

M11(s)

M16(s)

M05(s)

M04(s)

M06(s)

M01(s)

M02(s)

M03(s)

36.5

4

41.1

4

51.9

0119.

8712

2.24

124.

7512

7.73

128.

9213

0.58

133.

49

137.

9213

9.0115

0.99

153.

83

171.

3117

1.75

Figure S38. 1H and 13C NMR spectra of 3daa

O

OHO

OMe

O

Cl

S60

KDD497.27611.esp


1.000.992.882.831.020.960.930.970.831.831.860.94

M09(m)

M07(d)M10(t)

M11(m)

M12(d)

M08(dd)

M06(s)

M04(s) M02(dd)

M03(s)

M05(dd) M01(dd)

3.103.103.12

3.13

3.32

3.33

3.34

3.62

3.90

4.914.92

4.936.

26

6.84

6.94

7.24

7.25

7.31

7.32

7.42

7.43

8.05

8.07

O

OHO

OMe

OMeO

S61

KDD497.27612.esp


M10(s)

M09(s)

M17(s)

M06(s)

M12(s)

M11(s)

M08(s)

M07(s)

M16(s)

M02(s)

M04(s)

M05(s)M18(s)

M03(s)

M13(s)

M14(s)M15(s)

M01(s)

36.7

0

41.1

0

51.8

3

55.7

9

100.

01114.

6611

5.19

126.

7812

7.73

128.

82

137.

4613

9.48

149.

52

157.

45164.

01

171.

4217

2.29

Figure S39. 1H and 13C NMR spectra of 3eaa

S62

KDD499.27740.esp


1.001.052.942.881.030.901.041.000.942.052.051.07

M09(m)

M08(dd)

M04(s)

M03(s)

M07(d)

M11(m)

M10(m)

M05(dd)

M12(t)

M01(dd)

M02(dd)M06(s)

3.08

3.093.11

3.12

3.30

3.31

3.33

3.61

3.97

4.874.88

4.88

4.89

6.58

6.73

6.747.

027.

037.

247.30

7.31

7.31

7.41

7.427.

517.

52

KDD499.2607.esp


M09(s)

M18(s)

M08(s)

M10(s)

M14(s)

M12(s)

M17(s)

M03(s)

M15(s)

M16(s)

M11(s)

M13(s)

M06(s)M01(s)

M02(s)M07(s)

M04(s)M05(s)

36.6

4

40.9

7

51.8

9

56.4

2

105.

07110.

2511

1.91

127.

5012

7.73

128.

80

133.

4913

8.00

139.

32

147.

59

157.

4615

9.66

171.

4417

2.36

Figure S40. 1H and 13C NMR spectra of 3faa

O

OHO

OMe

O

OMe

S63

KDD495.27991.esp


1.000.992.830.980.911.000.961.022.041.950.94

M08(m)

M07(dd)

M10(m)

M03(s)

M09(t)

M06(ddd)

M11(dd) M04(dd)

M02(dd)

M01(dd)M05(s)

3.12

3.133.14

3.15

3.36

3.37

3.39

3.66

4.964.97

4.97

4.98

6.287.

197.

207.

217.297.34

7.35

7.44

7.45

8.21

8.22

8.22

8.23

KDD495.2628.esp


M07(s)

M08(s)

M02(s)

M01(s)

M06(d)

M03(s)

M13(d)

M16(s) M11(s)

M17(s) M12(s)

M10(s)

M09(d)

M14(d)

M05(d)M04(d)

M15(d)

36.4

3

40.9

9

51.9

3

104.

5110

4.85

113.

6211

3.93

118.

1311

8.16

127.

6912

8.90

137.

6513

9.01

150.

69

156.

3215

6.50

163.

7616

7.14

171.

3617

2.11

Figure S41. 1H and 13C NMR spectra of 3gaa

O

OHO

OMe

OF

S64

KDD515.27682.esp


1.000.992.580.950.891.092.821.840.910.91

M09(d)

M06(m)

M03(s)

M08(m)

M10(d)

M04(dd)

M07(m)

M05(s)

M02(dd)

M01(dd)

3.08

3.093.10

3.11

3.32

3.34

3.36

3.63

4.93

4.94

4.95

6.22

7.26

7.277.

317.

337.

337.

527.

52

8.10

8.12

KDD515.2601.esp


M09(s)

M08(s)

M17(s)

M16(s)

M12(s)

M13(s)

M11(s)

M10(s)

M15(s)

M14(s)

M07(s)

M06(s)

M05(s)

M04(s)

M02(s)

M01(s)

M03(s)

36.4

1

40.9

7

51.9

3118.

1811

9.81

125.

5312

6.80

127.

6912

8.90

137.

8813

8.95

139.

49

150.

66

155.

46

171.

3217

2.14

Figure S42. 1H and 13C NMR spectra of 3haa

O

OHO

OMe

OCl

S65

KDD505.27931.esp


1.000.992.850.950.941.061.052.041.960.89

M07(m)

M10(ddd)

M08(m)

M06(ddd)

M09(m)

M03(s)

M04(dd)

M02(dd)

M01(dd)

M05(s)

3.133.16

3.173.40

3.41

3.42

3.43

3.67

4.995.00

5.01

5.02

6.307.

247.

257.

307.

317.

357.

367.

477.

487.

637.

637.

647.

65

KDD505.2623.esp


M07(s)

M08(s)

M09(s)

M11(s)

M13(s)

M16(s)M10(s)

M03(s)

M06(d)

M12(dd)

M01(s)

M02(s)

M04(dd)

M05(dd)

M15(dd)

M14(dd)

36.3

9

40.9

0

51.9

6

105.

2410

5.55

108.

3310

8.59

108.

7110

8.98

123.

3412

3.46

127.

7612

7.86

128.

95

137.

84138.

6814

1.09

141.

2814

9.75

149.

9115

1.44

153.

3215

6.11

156.

24

159.

54

171.

38

Figure S43. 1H and 13C NMR spectra of 3iaa

O

OHO

OMe

O

F

F

S66

KDD613.29705.esp


1.001.012.941.010.891.991.081.930.960.980.95

M07(ddd)

M08(m)

M09(dd)

M11(dd)

M10(ddd)

M03(s)

M01(dd)

M02(dd)

M04(t)

M06(m)

M05(s)

3.13

3.143.15

3.16

3.33

3.34

3.35

3.66

4.984.

995.

00

6.40

7.02

7.03

7.05

7.39

7.40

7.44

7.45

7.507.52

7.68

7.698.

218.

22

KDD613.29773.esp


M01(s)

M17(s)

M16(s)

M02(s)

M03(s)

M12(s)

M06(s)

M11(d)

M13(s)

M10(s)M08(s)

M05(s)

M07(s)

M04(d)

M14(s)

M09(d)

M15(d)

36.7

140

.4151

.86

115.

6411

5.76

118.

0912

1.34

124.

5812

5.58

129.

37

133.

2813

5.02

137.

71

150.

20

155.

54

161.

4916

2.88

171.

2117

2.84

Figure S44. 1H and 13C NMR spectra of 3aba

O

OHO

OMe

O

F

S67

MS-M-015 I 016.28667.esp


1.001.032.830.991.932.971.000.990.95

M07(m)

M09(m)

M03(s)

M05(m)

M08(ddd)

M06(m)

M04(t)M01(dd)

M02(dd)

3.13

3.143.

153.

163.

323.

333.

353.

66

4.964.

974.

99

7.31

7.33

7.40

7.41

7.51

7.68

7.698.

218.

22

MS-M-015 I 016.28674.esp


M15(s)M14(s)

M11(s)

M13(s)

M16(s)

M10(s)

M01(s)

M02(s)

M12(s) M03(s)M04(s)

M07(s)

M05(s)

M06(s)

36.4

6

40.5

351.9

2

118.

1112

1.28

124.

6312

5.58

129.

0212

9.15

133.

3413

3.5413

7.74

149.

80155.

54

171.

1317

2.80

Figure S45. 1H and 13C NMR spectra of 3aca

O

OHO

OMe

O

Cl

S68

MS-M-071 I 072.30494.esp


1.000.822.830.810.972.191.072.140.950.981.01

M03(s)

M09(m)

M08(d)

M11(ddd)

M07(m)

M10(ddd)

M06(s)

M04(t) M01(dd)

M02(dd)

M05(s)

3.143.15

3.16

3.32

3.33

3.34

3.35

3.66

4.964.

974.

98

6.417.34

7.347.

367.

477.

487.

687.

687.

698.21

8.22

O

OHO

OMe

O

Br

S69

MS-M-071 I 072.24730.esp


M16(s)

M04(s)

M07(s)

M03(s)

M06(s)

M01(s)

M08(s)

M11(s)

M12(s)

M10(s)

M13(s)

M05(s)

M15(s)

M02(s)

M14(s)

M09(s)

M17(s)

36.3

7

40.5

2

51.9

7118.

1112

1.60

124.

6412

5.59

127.

7812

9.52

131.

9813

3.36

137.

79138.

26

149.

84155.

50

171.

1517

2.86

Figure S46. 1H and 13C NMR spectra of 3ada

S70

KDD611.29638.esp


9.000.990.962.740.970.861.952.760.940.950.85

M11(dd)

M07(m)

M08(m)

M04(s)

M09(dd)

M10(ddd)

M03(dd)

M06(s) M05(dd)

M01(s)

M02(dd)

1.30

3.123.13

3.14

3.38

3.39

3.40

3.42

3.65

4.96

4.97

4.97

4.98

6.287.

357.

367.

367.38

7.39

7.53

7.667.67

7.678.20

8.21

KDD611.29772.esp


M15(s)

M10(s)

M09(s)

M16(s)

M11(s)

M13(s)

M12(s)

M17(s)

M06(s)

M08(s)

M07(s)

M19(s)

M14(s)

M18(s)

M02(s)

M05(s)

M01(s)

M03(s)

M04(s)

31.2

634

.4536.6

9

40.6

5

51.7

9

118.

1812

1.36

124.

4312

5.52

125.

7512

7.38

133.

1013

6.19

137.

76150.

4715

0.71

155.

56

171.

4917

2.82

Figure S47. 1H and 13C NMR spectra of 3aea

O

OHO

OMe

O

tBu

S71

MS-M-017 I 018.28299.esp


1.000.993.003.120.970.881.892.831.010.970.91

M11(dd)

M07(m)M08(m)

M10(ddd)

M09(d)

M03(s)

M05(t)

M04(s)

M02(dd)M06(s)

M01(dd)

3.123.14

3.153.33

3.34

3.35

3.37

3.65

3.79

4.954.96

4.97

6.39

6.876.89

6.897.

387.

397.

407.

527.

657.66

7.688.21

8.21

MS-M-017 I 018.28300.esp


M17(s)

M07(s)

M09(s)M12(s)

M18(s)M16(s)

M10(s)

M01(s)

M04(s)

M08(s)

M14(s)

M03(s)

M06(s)

M11(s)

M15(s)

M02(s)M13(s)

M05(s)

36.8

040

.35

51.8

255

.23

114.

30

118.

1412

1.34

124.

4912

5.52

128.

8213

1.32

133.

14

137.

56

150.

84

155.

54159.

06

171.

4417

2.84

Figure S48. 1H and 13C NMR spectra of 3afa

O

OHO

OMe

O

OMe

S72

MS-M-059 I 060.30312.esp


3.001.051.022.931.000.902.062.001.061.031.010.98

M08(m)

M10(dd)

M01(s)

M09(ddd)

M07(d)

M12(dd)M06(s)

M11(ddd)

M04(s)

M05(dd)M02(dd)

M03(dd)

2.33

3.12

3.133.14

3.15

3.35

3.36

3.37

3.65

4.964.97

4.97

4.98

6.39

7.157.167.

357.

367.

397.

667.66

7.678.

208.20

8.21

8.21

MS-M-059 I 060.30577.esp


M13(s)

M15(s)

M14(s)

M12(s)

M11(s)

M18(s)

M07(s)

M17(s)

M06(s)

M09(s)

M05(s)

M16(s)

M10(s)

M03(s)

M01(s)

M04(br. s.)

M02(s)

21.0

1

36.6

8

40.6

9

51.8

5

118.

1512

1.40

124.

48125.

5312

7.66

129.

5413

3.14

136.

3013

7.77

151.

00155.

52

171.

5017

2.89

Figure S49. 1H and 13C NMR spectra of 3aga

O

OHO

OMe

O

Me

S73

MS-M-069 I 070.30493.esp


1.071.043.151.041.001.091.194.361.271.00

M07(d)

M10(dd)

M03(s)

M09(ddd)

M06(ddd)

M08(m)

M02(dd)

M04(t) M01(dd)M05(s)

3.193.20

3.213.36

3.37

3.39

3.40

3.67

5.075.

085.

09

6.507.

407.

417.41

7.517.52

7.61

7.69

7.708.21

8.22

8.23

MS-M-069 I 070.30570.esp


M07(s)

M08(s)

M13(s)

M14(s)

M10(s)

M12(s)

M15(s)

M09(q)

M16(s)M18(s)

M17(s)

M05(s)M02(s)

M04(s)

M11(d)

M03(s)

M01(s)M06(q)

36.2

8

40.9

2

51.9

8

118.

0912

1.29

123.

2112

4.70

125.

6212

8.21

130.

0613

3.44

137.

92

143.

23149.

36

155.

56171.

0017

2.82

Figure S50. 1H and 13C NMR spectra of 3aha

O

OHO

OMe

O

CF3

S74

MS-M-025 I 026.27557.esp


1.001.032.941.050.872.233.130.951.000.96

M08(dd)

M10(dd)

M03(s)

M09(ddd)

M04(dd)

M07(m)

M06(m)

M01(dd)

M02(dd)

M05(s)

3.06

3.073.08

3.09

3.31

3.33

3.34

3.35

3.64

5.415.42

5.42

5.43

6.267.

197.19

7.22

7.24

7.38

7.397.

397.40

7.47

7.65

7.65

7.668.

208.

21

MS-M-025 I 026.27563.esp


M09(s)

M10(s)

M11(s)

M13(s)

M12(s)

M15(s)M17(s)

M16(s)

M18(s)

M19(s)

M14(s)

M07(s)

M08(s)

M05(s)

M01(s)M04(s)

M02(s)

M03(s)

36.2

638

.60

51.8

8

118.

1712

1.29

124.

5912

5.58

127.

1812

8.82

130.

0313

3.27

133.

8713

6.94

138.

49

149.

18

155.

61

171.

1317

2.82

Figure S51. 1H and 13C NMR spectra of 3aia

O

OHO

OMe

OCl

S75

MS-M-027 I 028.28643.esp


3.001.031.052.981.080.953.251.141.071.071.070.98

M12(dd)M09(m)

M10(d)

M01(s)

M04(s)

M11(ddd)

M08(ddd)

M02(dd)

M03(dd)

M07(m)

M06(s)

M05(dd)

2.56

3.10

3.113.12

3.13

3.33

3.34

3.35

3.65

5.235.25

5.26

6.337.

177.

187.18

7.19

7.21

7.40

7.477.517.52

7.67

7.68

7.688.

218.

22

MS-M-027 I 028.28651.esp


M02(s)

M03(s)

M16(s)

M04(s)

M18(s)

M10(s)

M11(s)

M17(s)

M08(s)

M09(s)

M05(s)

M13(s)

M15(s)

M01(s)

M14(s)

M20(s)

M07(s)

M06(s)

M19(s)

19.7

1

36.8

837

.02

51.8

5118.

1412

1.33

124.

5112

5.54

126.

3812

7.05

127.

3713

0.77

133.

1813

6.53

137.

5713

7.82

150.

50155.

60

171.

4817

2.83

Figure S52. 1H and 13C NMR spectra of 3aja

O

OHO

OMe

OMe

S76

MS-M-063 I 064.30360.esp


1.001.012.882.880.960.802.031.080.951.000.970.970.94

M04(s)

M09(dd)

M03(s)

M11(dd)

M13(m)

M10(ddd)

M12(ddd)

M08(ddd)

M05(dd)M06(s)

M07(qd)

M01(dd)

M02(dd)

3.06

3.063.08

3.093.33

3.34

3.35

3.37

3.65

3.87

5.345.35

5.36

5.37

6.31

6.916.916.

926.92

6.93

6.93

7.307.

407.

517.66

7.66

7.67

7.678.

238.

24

MS-M-063 I 064.30571.esp


M12(s)

M13(s)

M01(s)

M07(s)

M11(s)

M08(s)

M09(s)

M17(s)

M02(s)

M10(s)

M14(s)M06(s)

M15(s)

M20(s) M16(s)

M19(s)M05(s)

M03(s)

M04(s)

M18(s)

35.5

035

.98

51.7

4

55.7

0

111.

05

118.

1812

0.77

121.

3512

4.41

125.

5012

8.26

128.

60

133.

03

138.

36

150.

76155.

5815

6.92

171.

8317

2.81

Figure S53. 1H and 13C NMR spectra of 3aka

O

OHO

OMe

OMeO

S77

MS-M-065 I 066.30313.esp


1.000.972.900.940.941.071.060.861.040.970.990.930.92

M08(m)

M07(td)

M09(ddd)

M10(td)

M11(dd)

M12(ddd)

M13(dd)

M06(ddd)

M03(s)

M05(s)

M04(dd) M01(dd)

M02(dd)

3.13

3.143.15

3.16

3.39

3.41

3.42

3.66

5.275.28

5.28

5.29

6.46

7.08

7.127.

137.

13

7.39

7.40

7.517.52

7.67

7.688.

228.

23

O

OHO

OMe

OF

S78

MS-M-065 I 066.30576.esp


M11(d)

M10(d)

M03(s)

M15(s)

M13(s)

M12(s)

M02(s)

M18(s)

M17(s)

M05(s)

M08(s)

M09(d)

M01(s)

M06(s)

M14(s)

M04(d)

M16(d)

35.1

635

.91

51.8

9

115.

79115.

9211

8.19

121.

3412

4.41

124.

5512

5.55

126.

1012

9.25

129.

38

133.

27

138.

21

149.

37

155.

5615

9.85

161.

27

171.

2517

2.87

Figure S54. 1H and 13C NMR spectra of 3ala

S79

MS-M-019 I 020.29365.esp


1.001.032.930.990.891.881.031.060.960.981.010.96

M09(t)

M07(dt)

M10(dd)

M03(s)

M12(dd)

M06(m)

M08(ddd)

M11(ddd)

M04(dd) M01(dd)

M02(dd)

M05(s)

3.133.143.15

3.16

3.34

3.35

3.37

3.67

4.964.97

4.97

4.98

6.387.

267.

267.

277.

277.417.

457.

527.53

7.69

7.70

7.708.

218.

228.

23

MS-M-019 I 020.29386.esp


M10(s)

M09(s)

M11(s)

M08(s)

M07(s)

M13(s)

M19(s)

M14(s)

M18(s)

M12(s)

M15(s)M03(s)

M16(s)

M05(s)

M04(s)

M02(s)

M01(s)

M17(s)

36.3

9

40.7

4

51.9

7

118.

1612

1.35

124.

6512

5.60

127.

9513

0.09

133.

3713

4.66

137.

9214

1.23

149.

78155.

52

171.

1217

2.88

Figure S55. 1H and 13C NMR spectra of 3ama

O

OHO

OMe

O

Cl

S80

MS-M-061 I 062.30311.esp


3.001.011.013.071.010.931.013.201.081.011.050.99

M01(s)

M10(dd)

M12(dd)

M07(d)

M09(ddd)

M11(ddd)

M04(s)

M08(m)

M06(s)

M03(dd)

M05(dd) M02(dd)

2.35

3.12

3.123.14

3.15

3.37

3.38

3.39

3.66

4.954.96

4.97

6.317.097.10

7.22

7.24

7.25

7.26

7.40

7.527.

537.

677.

688.21

8.21

8.22

8.22

MS-M-061 I 062.30580.esp


M11(s)

M12(s)

M08(s)

M09(s)

M07(s)

M04(s)

M13(s)

M20(s)

M06(s)

M17(s)

M15(s)

M14(s)

M05(s)

M16(s)

M18(s)

M19(s)

M01(s)

M02(s)

M03(s)

21.4

2

36.6

5

41.0

8

51.8

3

118.

1812

1.31

124.

4812

4.66

125.

5112

8.3412

8.71

133.

15

137.

7613

8.53

139.

21

150.

52

155.

56

171.

4517

2.81

Figure S56. 1H and 13C NMR spectra of 3ana

O

OHO

OMe

O

Me

S81

MS-M-057 I 058.30314.esp


1.001.031.101.121.071.102.991.200.863.182.331.020.900.950.86

M15(ddd)

M13(ddd)

M11(m)

M14(ddd)

M12(ddd)

M09(s)M05(dd)

M08(m)

M06(dd)

M10(m)

M04(ddd)

M03(ddd)

M07(s)

M02(dtd)

M01(dddd)

2.06

2.072.22

2.23

2.23

2.622.

752.

762.77

2.78

2.89

2.90

2.91

2.92

3.65

3.75

3.786.29

7.12

7.12

7.15

7.157.

167.

217.23

7.23

7.42

7.49

7.507.50

7.687.

69

8.23

8.24

8.24

MS-M-057 I 058.30578.esp


M12(s)

M11(s)

M19(s)

M13(s)

M16(s)M18(s)

M05(s)

M17(s)

M15(s)

M14(s)

M09(s)

M01(s)

M08(s)

M10(s)

M07(s)

M06(s)

M02(s)

M04(s)

M03(s)33

.56

33.8

035

.91

36.9

1

51.7

7

118.

1112

1.37

124.

4812

5.55

128.

30

133.

17

138.

62141.

15

151.

66155.

61

171.

7917

2.64

Figure S57. 1H and 13C NMR spectra of 3aoa

O

OHO

OMe

O

S82

MS-M-041 I 042.29395.esp


3.006.171.081.010.990.982.841.050.900.970.930.980.93

M11(dd)

M07(s)

M13(ddd) M09(s)

M10(ddd)

M12(ddd)

M06(dd)

M05(dd)

M08(dddd)

M01(t)

M03(m)

M04(m) M02(m)

0.85

0.86

0.87

1.26

1.271.28

1.29

1.29

1.33

1.34

1.701.84

1.852.

722.

732.74

2.75

2.86

2.87

2.88

2.90

3.66

3.70

3.71

3.72

3.73

6.21

7.40

7.41

7.497.50

7.677.

687.

687.

698.24

8.25

MS-M-041 I 042.29401.esp


M12(s)

M05(s)

M06(s)

M18(s)

M07(s)M04(s)

M11(s)

M17(s)

M10(s)

M16(s)

M08(s)M01(s)

M02(s)

M15(s)

M03(s)

M13(s)

M14(s)

M09(s)

13.8

8

22.3

8

26.7

4

31.4

932

.29

35.8

836

.79

51.6

9

118.

1112

1.33

124.

3912

5.53

133.

07

138.

45

152.

12155.

64

171.

9817

2.58

Figure S58. 1H and 13C NMR spectra of 3apa

O

OHO

OMe

O

S83

MS-M-047 I 048.30263.esp


2.001.982.820.921.040.980.980.94

M03(s)

M08(ddd)M07(ddd)

M06(ddd)

M05(ddd) M02(t) M01(t)

M04(s)

2.83

2.84

2.853.

213.22

3.23

3.74

6.26

7.40

7.41

7.48

7.677.

687.

698.23

8.25

MS-M-047 I 048.30288.esp


M13(s)

M12(s)

M08(s)

M03(s)

M07(s)

M05(s)

M04(s)

M02(s)

M10(s)

M09(s)

M11(s)

M06(s)

M01(s)

24.5

3

30.5

8

51.8

5

118.

0512

1.47

124.

43125.

55

133.

14

138.

39

149.

71

155.

62

172.

4117

2.55

Figure S59. 1H and 13C NMR spectra of 3aqa

O

OHO

OMe

O

S84

KDD519.27897.esp


3.001.081.072.051.020.880.892.461.272.121.081.070.98

M07(m)

M11(ddd)

M10(m)

M13(ddd)

M09(m)

M08(m)

M12(ddd)

M01(t)

M05(dd)

M04(q)

M03(dd)

M02(dd)

M06(s)

1.15

1.16

1.17

3.13

3.143.

153.

163.35

3.37

3.38

3.394.

084.

094.10

4.11

4.995.00

5.00

5.01

6.337.

277.27

7.287.

347.

357.

477.

487.

487.

527.53

7.67

7.678.

218.21

8.22

8.22

KDD519.27915.esp


M11(s)

M10(s)

M03(s)

M09(s)

M12(s)

M14(s)

M08(s)

M02(s)M01(s)M13(s)

M16(s)

M06(s)

M17(s)

M05(s)

M18(s)

M15(s)

M04(s)

14.0

3

36.9

4

41.1

560.7

2

118.

1512

1.32

124.

5012

5.53

127.

8112

8.82

133.

18

137.

8013

9.31

150.

60155.

55

170.

8917

2.82

Figure S60. 1H and 13C NMR spectra of 3aab

O

OHO

OEt

O

S85

KDD521.27958.esp


3.002.041.021.021.920.980.850.882.171.142.000.991.000.95

M08(m)

M12(d)

M11(dd)

M14(dd)

M10(ddd)

M06(dd)

M09(m)

M13(ddd)

M01(t)

M05(t)

M03(dd)

M04(dd)

M02(sxt)

M07(s)

0.84

0.85

0.86

1.53

1.54

1.55

1.56

1.57

1.58

3.143.153.

163.

173.

373.38

3.39

3.40

3.99

4.00

4.01

4.995.

015.

02

6.337.

277.

287.34

7.35

7.47

7.48

7.53

7.67

7.68

8.218.21

8.22

8.22

KDD521.2624.esp


M11(s)

M15(s)M19(s)

M13(s)

M16(s)

M14(s)

M12(s)

M17(s)

M18(s)

M09(s)

M06(s)

M08(s)

M03(s)

M04(s)

M01(s)

M07(s) M02(s)M05(s)

10.2

1

21.8

4

36.8

5

40.9

8

66.4

1

118.

1212

1.32

124.

49125.

5012

7.80

128.

8213

3.19

137.

8013

9.27

150.

77

155.

44171.

0617

2.85

Figure S61. 1H and 13C NMR spectra of 3aac

O

OHO

O

O

S86

KDD523.27959.esp


3.002.081.980.980.991.870.950.910.892.341.151.910.990.960.88

M09(m)

M13(dd)

M15(ddd)

M12(dd)

M11(ddd)

M10(m)

M14(ddd)

M06(t)

M07(dd)

M04(dd)

M05(dd) M03(m)

M01(t)

M02(dq)

M08(s)

0.83

0.84

0.85

1.23

1.24

1.25

1.26

1.27

1.28

1.491.50

1.51

1.52

3.133.143.

163.

173.

363.38

3.39

3.40

4.04

4.05

4.06

5.005.

015.

015.

02

6.43

7.27

7.27

7.28

7.34

7.35

7.47

7.48

7.53

7.67

7.67

7.68

8.21

8.21

8.22

KDD523.2625.esp


M12(s)

M16(s)

M13(s)

M11(s)

M19(s)

M14(s)

M15(s)M20(s) M01(s)M08(s)

M10(s)

M18(s)

M09(s)

M17(s)M04(s)

M03(s)M06(s)

M05(s)

M07(s)

M02(s)

13.5

618.9

6

30.5

1

36.8

7

41.0

0

64.6

7

118.

1412

1.28

124.

5412

5.49

127.

5512

7.78

128.

82

133.

21

137.

7613

9.22

150.

83

155.

45171.

0517

2.83

Figure S62. 1H and 13C NMR spectra of 3aad

O

OHO

O

O

S87

KDD541.27831.esp


1.131.001.870.980.980.981.020.831.222.121.201.991.070.990.94

M09(m)

M15(dd)

M12(m)

M11(ddd)

M03(dt)

M13(m)

M05(dq)

M10(m)

M14(ddd)

M06(dq)

M04(dd)

M02(dd)

M01(dd)

M08(s)M07(ddt)

3.143.153.

163.

173.

373.38

3.39

3.40

4.514.52

4.52

4.974.98

4.98

4.99

5.13

5.15

5.185.21

5.21

5.75

5.76

5.775.78

5.80

5.81

6.297.24

7.24

7.25

7.25

7.32

7.44

7.45

7.63

7.64

7.65

7.65

8.17

8.19

KDD541.2614.esp


M07(s)

M05(s)

M17(s)

M19(s)

M18(s)

M04(s)

M08(s)

M10(s)

M15(s)

M16(s)

M12(s)

M14(s)

M11(s)

M06(s)

M09(s)

M13(s)

M02(s)

M01(s)M03(s)

36.7

6

40.9

965.4

3

118.

1711

8.42

121.

2512

4.53

125.

4812

7.58

127.

7812

8.85

131.

74133.

21

137.

7313

9.15

150.

41

155.

47170.

6417

2.79

Figure S63. 1H and 13C NMR spectra of 3aae

O

OHO

O

O

S88

KDD535.27704.esp


3.002.062.021.012.051.061.030.960.982.051.061.980.991.020.98

M13(d)

M12(m)

M15(dd)

M09(m)

M11(ddd)

M10(m)

M14(ddd)

M04(dd)

M01(t)

M03(m)

M07(dd)

M06(dd)

M05(m)

M02(dq)

M08(s)

0.76

0.77

0.78

1.11

1.12

1.131.141.28

1.29

1.30

1.31

2.93

2.942.96

2.97

3.13

3.153.

223.

233.

243.

25

4.934.94

4.94

4.96

5.62

7.23

7.24

7.247.

307.

317.

447.

457.

467.

637.

637.

64

8.17

8.18

KDD535.27729.esp


M05(s)

M04(s)

M11(s)

M15(s)

M13(s)

M18(s)

M09(s)

M20(s)M17(br. s.)

M10(s)

M16(s)

M19(s)

M12(s)

M08(s)M14(s)

M07(s)

M06(s)

M02(s)

M01(s)

M03(s)

13.5

4

19.8

4

31.5

4

39.2

639

.39

42.3

5118.

1412

1.33

124.

4812

5.48

127.

8612

8.83

133.

18

137.

9113

9.72

151.

16

155.

56

170.

0417

2.92

Figure S64. 1H and 13C NMR spectra of 3aaf

O

OHO

HN

O

S89

KDD537.27960.esp


1.001.001.891.141.310.871.011.050.822.011.011.850.940.940.87

M09(m)

M13(d)

M15(dd)

M04(m)

M12(dd)

M05(m)

M11(ddd)

M14(ddd)

M10(m)

M06(s)

M03(tt)

M01(dd)

M02(dd)M07(ddt)

M08(s) 2.99

3.003.

013.

023.28

3.30

3.31

3.32

3.81

3.81

3.82

3.83

4.98

4.99

5.02

5.03

5.03

5.62

5.66

5.67

5.68

5.69

5.71

5.72

6.38

7.27

7.27

7.28

7.28

7.34

7.35

7.47

7.48

7.51

7.66

7.67

7.67

7.68

8.20

8.21

KDD537.2626.esp


M13(s)

M02(s)

M16(s)

M03(s)

M09(s)

M15(s)

M12(s)

M06(s)

M08(s)

M14(s)

M11(s)

M17(s)

M07(s)

M05(s)

M18(s)

M01(s)

M19(s)

M04(s)

39.2

441

.89

42.2

2116.

2911

8.18

121.

2212

4.52

125.

4712

7.55

127.

8412

8.88

133.

2413

3.85

137.

8313

9.58

150.

95

155.

51

169.

9217

2.89

Figure S65. 1H and 13C NMR spectra of 3aag

O

OHO

HN

O

S90

KDD539.27742.esp


3.002.962.090.981.010.960.980.931.080.982.151.143.101.050.99

M10(m)

M12(ddt)

M15(m)

M14(tq)

M11(m)

M02(dd)

M07(ddd) M06(m)

M04(ddd)

M13(m)

M05(dt)

M01(dt)

M08(s)

M03(m)

M09(s)

0.69

0.70

0.71

0.72

0.94

0.94

0.95

1.25

1.26

1.27

1.28

1.29

1.30

1.31

1.32

2.932.94

2.942.95

3.17

3.19

3.21

3.22

3.783.783.

793.80

3.81

3.82

4.91

4.92

4.93

4.93

4.94

4.94

5.33

6.40

7.237.23

7.247.

247.

307.30

7.31

7.44

7.45

7.45

7.467.

477.

637.

648.17

8.17

8.18

KDD539.27760.esp


M25(s)

M26(s) M07(s)

M23(s)

M06(s)

M22(s)M21(s)

M02(s)

M03(s)

M09(s)

M20(s)

M05(s)

M08(s)

M04(s)

M10(s)

M24(s)M27(s)

M15(s)

M17(s)

M16(s)

M12(s)

M14(s)M18(s)

M19(s)

M13(s)

M11(s)

M01(s)

9.98

20.2

3

29.5

3

39.6

639

.68

42.5

146

.62

118.

1312

1.24

124.

5112

7.52

127.

8712

8.85

133.

2213

7.87

139.

68

150.

94

155.

57

169.

2816

9.30

172.

86

Figure S66. 1H and 13C NMR spectra of 3aah

O

OHO

HN

O

S91

KDD531.27898.esp


3.003.011.001.113.011.010.950.701.013.062.991.000.93

M09(m)

M13(dd)

M07(dd)

M12(ddd)

M11(m)

M02(t)

M04(dq)

M06(dd) M03(dd)

M10(m)

M01(t)

M05(m)

M08(s)

1.03

1.04

1.05

1.23

1.24

2.993.003.

013.

023.

273.

283.

303.36

3.373.38

3.51

3.52

3.53

5.055.

065.

075.

07

6.47

7.26

7.26

7.27

7.33

7.34

7.47

7.48

7.48

7.49

7.64

7.64

7.65

8.20

8.21

KDD531.2619.esp


M06(s)

M13(s)

M12(s)

M14(s)

M15(s)

M07(s)

M16(s)

M05(s)

M11(s)

M20(s)

M09(s)

M10(s)

M19(s)

M04(s)

M18(s)

M02(s)

M03(s)

M17(s)

M01(s)

M08(s)

12.9

414

.29

36.1

140

.32

41.9

142

.17

118.

0712

1.41

124.

3612

5.49

127.

9012

8.79

132.

94

137.

9114

0.34

151.

9115

5.43

169.

2317

2.84

Figure S67. 1H and 13C NMR spectra of 3aai

O

OHO

NEt2

O

S92

KDD545.27832.esp


2.342.321.003.861.110.960.831.073.183.001.040.95

M08(m)

M12(ddd)

M06(dd)

M11(ddd)

M10(m)

M03(dd)

M05(s)

M01(s)

M04(m)

M02(s)

M09(m)

M07(s) 1.81

1.922.

962.

962.98

2.993.383.

393.

403.

413.

423.

43

3.50

5.025.035.04

5.04

6.42

7.23

7.247.

307.

317.46

7.61

7.62

8.178.18

KDD545.2615.esp


M12(s)

M13(s)

M15(s)

M14(s)

M06(s)

M09(s)

M03(s)M04(s)

M05(s)

M10(s)

M07(s)M16(s)

M02(s)M08(s)

M01(s)

M19(s)M17(s)

M20(s)M18(s) 24

.30

26.0

4

37.4

841.7

645

.71

46.5

7

118.

1312

1.42

124.

3512

5.48

127.

3312

7.92

128.

7713

2.94

137.

8614

0.27

151.

7515

5.4716

8.73

172.

89

Figure S68. 1H and 13C NMR spectra of 3aaj

O

OHO

N

O

S93

KDD547.27833.esp


6.001.015.261.021.072.141.113.131.091.01

M05(m)

M07(ddd)

M06(m)

M10(ddd)M04(dd)

M09(ddd)

M02(dd)

M08(m)

M03(m)M01(m)

1.59

1.601.61

1.62

1.63

1.67

1.682.

993.

003.02

3.02

3.453.46

3.473.

483.

493.

503.

51

4.995.00

5.00

5.01

7.23

7.24

7.24

7.257.

307.

317.

447.

457.

477.487.

627.

637.

638.17

8.17

8.188.18

KDD547.2616.esp


M01(s)

M02(s)

M03(s)

M13(s)

M12(s)

M15(s)

M18(s)

M11(s)

M19(s)M16(s)M21(s)

M09(s)

M10(s)

M04(s)M07(s)M17(s)

M14(s)

M05(s)

M08(s)

M20(s)

M06(s)

24.4

625

.49

26.4

335.9

5

42.0

942

.89

46.6

2

118.

1212

1.42

124.

3512

5.48

127.

9212

8.79

132.

93

137.

8214

0.31

151.

8315

5.46

168.

40

172.

85

Figure S69. 1H and 13C NMR spectra of 3aak

O

OHO

N

O

S94

5. HPLC Chromatograms

Figure S70. HPLC chromatograms of 3aaa

S95

Figure S71. HPLC chromatograms of 3baa

S96

Figure S72. HPLC chromatograms of 3caa

S97

Figure S73. HPLC chromatograms of 3daa

S98

Figure S74. HPLC chromatograms of 3eaa

S99

Figure S75. HPLC chromatograms of 3faa

S100

Figure S76. HPLC chromatograms of 3gaa

S101

Figure S77. HPLC chromatograms of 3haa

S102

Figure S78. HPLC chromatograms of 3iaa

S103

Figure S79. HPLC chromatograms of 3aba

S104

Figure S80. HPLC chromatograms of 3aca

S105

Figure S81. HPLC chromatograms of 3ada

S106

Figure S82. HPLC chromatograms of 3aea

S107

Figure S83. HPLC chromatograms of 3afa

S108

Figure S84. HPLC chromatograms of 3aga

S109

Figure S85. HPLC chromatograms of 3aha

S110

Figure S86. HPLC chromatograms of 3aia

S111

Figure S87. HPLC chromatograms of 3aja

S112

Figure S88. HPLC chromatograms of 3aka

S113

Figure S89. HPLC chromatograms of 3ala

S114

Figure S90. HPLC chromatograms of 3ama

S115

Figure S91. HPLC chromatogram of 3ana

S116

Figure S92. HPLC chromatograms of 3aoa

S117

Figure S93. HPLC chromatograms of 3apa

S118

Figure S94. HPLC chromatograms of 3aab

S119

Figure S95. HPLC chromatograms of 3aac

S120

Figure S96. HPLC chromatograms of 3aad

S121

Figure S97. HPLC chromatograms of 3aae

S122

Figure S98. HPLC chromatograms of 3aaf

S123

Figure S99. HPLC chromatograms of 3aag

S124

Figure S100. HPLC chromatograms of 3aah

S125

Figure S101. HPLC chromatograms of 3aai

S126

Figure S102. HPLC chromatograms of 3aaj

S127

Figure S103. HPLC chromatograms of 3aak

S128

6. Literature

(1) Hardman-Baldwin, A. M.; Visco, M. D.; Wieting, J. M.; Stern, C.; Kondo, S. I.; Mattson, A. E. Org. Lett. 2016, 18, 3766–3769.

(2) Balakrishna, C.; Kandula, V.; Gudipati, R.; Yennam, S.; Devi, P. U.; Behera, M. Synlett 2018, 29, 1087–1091.

(3) Damodar, K.; Lee, J. T.; Kim, J. K.; Jun, J. G. Bioorganic Med. Chem. Lett. 2018, 28, 2098–2102.(4) Stubbing, L. A.; Li, F. F.; Furkert, D. P.; Caprio, V. E.; Brimble, M. A. Tetrahedron 2012, 68, 6948–6956.(5) Wang, X.; Liu, B.; Searle, X.; Yeung, C.; Bogdan, A.; Greszler, S.; Singh, A.; Fan, Y.; Swensen, A. M.;

Vortherms, T.; Balut, C.; Jia, Y.; Desino, K.; Gao, W.; Yong, H.; Tse, C.; Kym, P. J. Med. Chem. 2018, 61, 1436–1449.

(6) Zhou, Y.; Liang, H.; Sheng, Y.; Wang, S.; Gao, Y.; Zhan, L.; Zheng, Z.; Yang, M.; Liang, G.; Zhou, J.; Deng, J.; Song, Z. J. Org. Chem. 2020, 85, 9230–9243.

(7) Rao, P.; Srimannarayana, G. Synth. Commun. 1987, 17, 1507–1512.(8) Ahmad-Junan, S. A.; Whiting, D. A. J. Chem. Soc. Perkin Trans. 1 1992, No. 6, 675.(9) Hueber, D.; Teci, M.; Brenner, E.; Matt, D.; Weibel, J. M.; Pale, P.; Blanc, A. Adv. Synth. Catal. 2018, 360,

2453–2459.(10) Xu, Y.; Wang, Q.; Wu, Y.; Zeng, Z.; Rudolph, M.; Hashmi, A. S. K. Adv. Synth. Catal. 2019, 361,

2309–2314.(11) Zhou, B.; Wu, Q.; Dong, Z.; Xu, J.; Yang, Z. Org. Lett. 2019, 21, 3594–3599.(12) Kim, S. M.; Lee, D.; Hong, S. H. Org. Lett. 2014, 16, 6168–6171.(13) Kwong, C. K. W.; Fu, M. Y.; Law, H. C. H.; Toy, P. H. Synlett 2010, No. 17, 2617–2620.(14) CrysAlis RED and CrysAlis CCD. Oxford Diffraction Ltd., Abingdon, Oxfordshire, England, 2000. (15) Sheldrick, G. M. Acta Crystallogr. Sect. C Struct. Chem. 2015, 71, 3–8.(16) K. Brandenburg, DIAMOND, Release 2.1e. Crystal Impact GbR, Bonn, Germany, 2001. (17) Farrugia, L. J. J. Appl. Crystallogr. 2012, 45, 849–854.

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3-Hydroxychromenones via α,β-Unsaturated Acylazoliums NHC