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)
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
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)
1.001.091.021.101.00
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
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)
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
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)
1.001.031.021.010.97
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
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)
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
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)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
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)
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
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)
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
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)
1.001.970.980.99
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
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)
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
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)
1.000.990.950.990.97
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
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)
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
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)
1.011.000.990.99
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
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)
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
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)
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
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)
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
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)
1.061.001.010.880.80
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
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)
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
Figure S12. 1H and 13C NMR spectra of 1b
O
OHO
Br
S31
KDD400.30581.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)
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
Figure S13. 1H and 13C NMR spectra of 1c
O
OHO
F
S32
KDD389.24183.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)
1.011.001.020.980.95
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
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)
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
Figure S14. 1H and 13C NMR spectra of 1d
O
OHO
Cl
S33
KDD367.23509.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)
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
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)
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
Figure S15. 1H and 13C NMR spectra of 1e
O
OHO
MeO
S34
KDD368.23562.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)
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
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)
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
Figure S16. 1H and 13C NMR spectra of 1f
O
OHOOMe
S35
KDD399.24387.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)
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
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)
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
Figure S17. 1H and 13C NMR spectra of 1g
O
OHO
F
S36
KDD397.24383.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)
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
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)
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
Figure S18. 1H and 13C NMR spectra of 1h
S38
KDD401.30582.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)
1.041.911.000.97
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
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)
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
Figure S19. 1H and 13C NMR spectra of 1i
O
OHO
F
F
S39
KDD213.20323.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)
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
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)
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
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)
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
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)
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
Figure S21. 1H and 13C NMR spectra of 2b
CHO
F
S41
MS-M-003.24813.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)
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
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)
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
Figure S22. 1H and 13C NMR spectra of 2c
CHO
Cl
S42
MS-M-050.24725.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)
2.001.990.91
M03(s)
M02(m)
M01(m)7.
457.
467.
487.
557.
587.
58
9.43
MS-M-050.24726.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)
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
Figure S23. 1H and 13C NMR spectra of 2d
CHO
Br
S43
MS-M-045.29601.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)
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
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)
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
Figure S24. 1H and 13C NMR spectra of 2e
CHO
tBu
S44
MS-M-001.24726.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)
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
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)
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
Figure S25. 1H and 13C NMR spectra of 2f
CHO
MeO
S45
MS-M-043.29410.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)
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
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)
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
Figure S26. 1H and 13C NMR spectra of 2g
S47
MS-M-051.29621.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)
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
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)
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
Figure S27. 1H and 13C NMR spectra of 2h
CHO
F3C
S48
MS-M-007.24727.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)
1.001.990.980.86
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
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)
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
Figure S28. 1H and 13C NMR spectra of 2i
CHOCl
S49
MS-M-009.25110.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)
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
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)
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
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)
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
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)
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
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)
1.000.990.970.950.72
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
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)
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
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)
1.001.940.940.92
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
1.000.982.920.930.901.362.001.021.940.970.950.92
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
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)
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
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)
1.001.003.001.000.971.422.061.021.900.960.90
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
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)
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
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)
1.000.992.960.980.931.422.111.152.041.070.95
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
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)
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
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)
1.001.023.091.071.031.062.011.980.991.000.94
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
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)
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
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)
1.000.992.882.831.020.960.930.970.831.831.860.94
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
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)
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
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)
1.001.052.942.881.030.901.041.000.942.052.051.07
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
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)
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
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)
1.000.992.830.980.911.000.961.022.041.950.94
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
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)
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
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)
1.000.992.580.950.891.092.821.840.910.91
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
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)
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
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)
1.000.992.850.950.941.061.052.041.960.89
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
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)
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
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)
1.001.012.941.010.891.991.081.930.960.980.95
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
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)
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
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)
1.001.032.830.991.932.971.000.990.95
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
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)
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
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)
1.000.822.830.810.972.191.072.140.950.981.01
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
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)
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
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)
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
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)
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
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)
1.000.993.003.120.970.881.892.831.010.970.91
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
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)
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
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)
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
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)
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
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)
1.071.043.151.041.001.091.194.361.271.00
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
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)
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
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)
1.001.032.941.050.872.233.130.951.000.96
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
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)
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
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)
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
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)
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
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)
1.001.012.882.880.960.802.031.080.951.000.970.970.94
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
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)
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
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)
1.000.972.900.940.941.071.060.861.040.970.990.930.92
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
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)
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
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)
1.001.032.930.990.891.881.031.060.960.981.010.96
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
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)
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
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)
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
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)
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
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)
1.001.031.101.121.071.102.991.200.863.182.331.020.900.950.86
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
1.131.001.870.980.980.981.020.831.222.121.201.991.070.990.94
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
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)
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
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)
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
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)
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
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)
1.001.001.891.141.310.871.011.050.822.011.011.850.940.940.87
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
S128
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