temperature, the lesser resolution occurred. at room temperature, two clear peaks were assigned to...
TRANSCRIPT
S1
Dynamic Kinetic Resolution of Biaryl Atropisomers by Chiral Dialkylaminopyridine Catalysts Gaoyuan Ma,a Chao Deng,a Jun Deng,a and Mukund P. Sibia* aDepartment of Chemistry and Biochemistry, North Dakota State University, Fargo, North Dakota, USA 58108
Supporting Information
1. General S1 2. HPLC Analysis of Substrate S1 3. The Absolute Configuration Discussion S2 4. Experimental Details and Characterization S4 5. Crystal Structure of Catalyst L1 S17 6. References S18 7. NMR Spectra and HPLC Spectra S20 1. General
All solvents were dried and degassed by standard methods and stored
under nitrogen. Flash chromatography was performed using EM Science silica
gel 60 (230-400 mesh) or on an ISCO Combiflash. 1H NMR spectra were
recorded on Varian Unity/Inova-400 NB (400 MHz) spectrometer or Bruker
AscendTM 400 (400 MHz for 1H) spectrometer. 13C NMR spectra were recorded
on Varian Unity/Inova-400 NB (100 MHz) spectrometer or Bruker AscendTM 400
(100 MHz for 13H) spectrometer. HPLC analyses were carried out with Waters
515 HPLC pumps and a 2487 dual wavelength absorbance detector connected
to a PC with Empower workstation. Rotations were recorded on a JASCO-DIP-
370 polarimeter. High-resolution mass spectra were obtained at a Waters
ACQUITY UPLC with ESI Positive Mode.
2. HPLC Analysis of Substrate HPLC analysis (Figure S1) of biaryl rac-1a suggested that at higher
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2018
S2
temperature, the lesser resolution occurred. At room temperature, two clear
peaks were assigned to two enantiomers of rac-1a. When raising the
temperature, two peaks were getting close and started overlapping at 55 °C.
Finally a single peak was observed at 80 °C.
Figure S1. HPLC Analysis of Substrate
3. The Absolute Configuration Discussion Electronic circular dichroism (ECD or CD) is a powerful spectroscopic
method for solving stereochemical problems of chiral molecules.1 By using
quantum chemical calculations of time-dependent density functional theory (TD-
DFT), ECD has become a rapid and reliable way to establish the absolute
configuration of chiral compounds.2 In this study, we employed ECD spectra and
TD-DFT calculation to assign the absolute configuration of 2a.
The ECD spectra of 2a in methanol at a concentration of 0.8-0.9 mg/mL
were recorded in a 1mm path length quartz cuvette using a Jasco J-815 CD
spectrometer (Jasco Inc., Japan).
The ECD spectra were calculated by the TD-DFT method, which has been
proven to be reliable in predicting ECD spectra and assigning the absolute
configuration of organic molecules. Calculations of the ECD spectra of 3D
structure of S-2a (Figure S2) were carried out using the TD-M06/6-31+G** level
with Gaussian 09.3 Electronic excitation energies (nm) and rotational strengths
(Δε) were calculated for structures A. In order to cover the 200-400 nm range, 19
OHOMe
S3
transitions were calculated. As shown in Figure S2, the simulated spectra is in
good agreement with the experimental spectral data, and the S configuration
could be reliably assigned to compound 2a. The remaining configurations of
acylated products were assumed by analogy.
Experimental CD spectra of 2a
Simulated CD spectra of S-2a
Figure S2. TD-DFT Simulated Spectrum Calculated using B3LYP Method
(M06/6-31+G(d,p)optimization, the first 19 excited states were calculated. )
S4
5. Experimental Details and Characterization Solvents evaluation
Table S1. Evaluation of Solvents
General procedure for the preparation of biaryl compounds Condition A4 (rac-1a, rac-1b, rac-1c, rac-1d, rac-1f, rac-1g, rac-1h, rac-1i, rac-1j, rac-1k, rac-1l):
Under an atmosphere of argon, degassed dimethoxyethane solution was
added to a mixture of 1-bromo-2-methoxynaphthalene (1 equiv.), 2-[2-
(methoxymethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.1 equiv.),
CsF (3 equiv.) and Pd(PPh3)4 (7 mol%). After being stirred overnight at 95 oC, the
resulting suspension was filtered through a pad of celite and washed with ethyl
acetate. After evaporation in vacuo, the residue was purified by flash
OHOMe +
O
O OL1 (15 mol%)
40oC, solvent
OOMe
O
Solvents
CH2Cl2
Yield%a
95
e.r.b
87:13
Time
48h
64THF 3d 71:29
603dDMF 72:28
24h 87EtOAc 81:19
ClCH2CH2Cl 40h 92 86:14
CHCl3 48h 95 87:12
entry
1
2
6
7
3
5
Toluene 40h 95 84:164
rac-1a
a Conditions: racemic biaryl substrate rac-1 (1 equiv.) and anhydride (1.2 equiv.) in the presence of catalyst L1 (15 mol%), Solvent (2 ml), at 40 oC; b Determined by chiral HPLC analysis.
2a
BO O
OO
+R2
BrO
R
Pd(PPh3)4 (7mol%)CsF (3 eq.)
dimethoxyethane95oC R2
OR
O O Conc. HClMethanol, reflux
R2O
R
OH
R1
R1 R1
S5
chromatography on silica gel eluting with ethyl acetate/hexane (5/95) to yield
MOM protected product (60-80 %yield). Concentrated HCl was added to a
solution of MOM protected compound in methanol. The reaction mixture was
stirred overnight under reflux. After removal of the solvent, flash column
chromatography with ethyl acetate/hexane (5/95) gave the desired product. (70-
90 %yield).
Condition B5 (rac-1e) :
Under an atmosphere of argon, degassed toluene solution was added to a
mixture of 1-bromo-2-naphthol (1 equiv.), 2-methoxyphenylboronic acid (1.5
equiv.), 2-dicyclohexylphosphino-2’-(N,N’-dimethylamino)biphenyl (Davephos)
(2.4 mol%), Pd2(dba)3 (1 mol%) and K3PO4 (1.8 eq.). After being stirred overnight
at 70 oC, the resulting suspension was filtered through a pad of celite and
washed with ethyl acetate. After evaporation in vacuo, the residue was purified
by flash chromatography on silica gel eluting with ethyl acetate/hexane (5/95) to
yield product. (50-60 %yield).
rac-1a. Condition A. 1H NMR (CDCl3, 400 MHz) δ 3.92 (s, 3H),
4.97 (s, 1H), 7.1 (td, J = 7.6, 1.2 Hz, 1H), 7.14 (dd, J = 8, 1.2 Hz, 1H), 7.25 (dd, J
= 7.6, 2 Hz, 1H), 7.38-7.44 (m, 4H), 7.51-7.54 (m, 1H), 7.87-7.89 (m, 1H), 7.99
(d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 56.8, 113.5, 116.0, 118.5,
120.5, 122.4, 124.1, 125.0, 127.1, 126.6, 126.8, 128.1, 129.4, 129.4, 130.5,
BO
OHHO
+
BrOH
Pd2(dba)3 (1mol%)Davphos (2.4 mol%)K3PO4 (1.8 eq.)
Toluene, 70oCOHO
OHOMe
S6
132.1, 133.7, 153.8, 154.5; ESI-HRMS: m/z calcd. for (C17H14O2Na)+ 273.0886;
found 273.0894.
rac-1b. Condition A. 1H NMR (CDCl3, 400 MHz) δ 1.3 (t, J =
7.2 Hz, 3H), 4.1-4.2 (m, 2H), 5.18 (s, 1H), 7.08 (td, J = 7.2, 1.2 Hz, 1H), 7.14 (dd,
J = 8, 1.2 Hz, 1H), 7.26 (dd, J = 7.2, 2 Hz, 1H), 7.37-7.42 (m, 4H), 7.56-7.59 (m,
1H), 7.85-7.87 (m, 1H), 7.93 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ
15, 65.7, 115.4, 116.2, 119.9, 120.4, 122.7, 124.2, 125.2, 126.9, 128.1, 129.3,
129.7, 130.3, 132.3, 133.8, 153.7, 153.9; ESI-HRMS m/z calcd. for (C18H17O2)+
265.1229; found 265.1232.
rac-1c. Condition A. 1H NMR (CDCl3, 400 MHz) δ 4.96 (s, 1H),
5.12-5.19 (m, 2H), 7.07 (td, J = 7.2, 1.2 Hz, 1H), 7.13 (dd, J = 8, 1.2 Hz, 1H), 7.2-
7.25 (m, 3H), 7.25-7.31 (m, 3H), 7.37-7.42 (m, 4H), 7.51-7.55 (m, 1H), 7.82-7.86
(m, 1H), 7.9 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 71.8, 116, 120.2,
120.5, 122.5, 124.4, 125.1, 127.04, 127.05, 127.8, 128.1, 128.5, 129.4, 129.8,
130.4, 132.1, 133.7, 136.8, 153.6, 153.8; ESI-HRMS m/z calcd. for
(C23H18O2Na)+ 349.1205; found 349.1207.
rac-1d. Condition A. 1H NMR (CDCl3, 400 MHz) δ 3.33 (s, 3H),
4.34 (d, J = 10.8 Hz, 1H), 4.38 (d, J = 10.8 Hz, 1H), 5.44 (s, 1H), 7.05-7.14 (m,
OHO
OHO
Ph
OH
O
S7
3H), 7.38-7.45 (m, 3H), 7.48-7.52 (m, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.9 (d, J =
8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 58.6, 73.3,
116.8, 120.7, 124.9, 126.2, 126.3, 126.61, 126.64, 128, 128.9, 129.7, 131.4,
132.9, 133, 133.5, 134.8, 153.9; ESI-HRMS m/z calcd. for (C18H16O2Na)+
287.1048; found 287.1055.
rac-1e. Condition B. 1H NMR (CDCl3, 400 MHz) δ 3.78 (s, 3H),
5.32 (s, 1H), 7.15-7.21 (m, 2H), 7.29-7.4 (m, 5H), 7.51-7.55 (m, 1H), 7.83-7.85
(m, 2H); 13C NMR (CDCl3, 100 MHz) δ 55.8, 111.9, 117.7, 117.8, 121.5, 122.5,
123.2, 124.8, 126.3, 128, 129.1, 129.5, 130.2, 133.4, 133.5, 150.6, 157.8; ESI-
HRMS m/z calcd. for (C17H15O2)+ 251.1072; found 251.1077.
rac-1f. Condition A. 1H NMR (CDCl3, 400 MHz) δ 2.26 (s, 3H),
4.06 (s, 3H), 4.65 (s, 1H), 6.81 (s, 1H), 7.03-7.14 (m, 3H), 7.35-7.44 (m, 4H),
8.27-8.3 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 21.1, 55.8, 106.9, 115.4, 120.8,
122.2, 123.1, 124.7, 124.9, 125.3, 125.4, 127.4, 129.5, 131.7, 134.1, 136.4,
153.7, 155.8; ESI-HRMS m/z calcd. for (C18H17O2)+ 265.1229; found 265.1223.
rac-1g. Condition A. 1H NMR (CDCl3, 400 MHz) δ 3.87 (s, 3H),
OMeOH
OHOMe
OHOMe
OMe
S8
3.9 (s, 3H), 5.01 (s, 1H), 6.67 (td, J = 8.4, 2.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H),
7.35-7.42 (m, 3H), 7.52-7.55 (m, 1H), 7.83-7.86 (m, 1H), 7.94 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 55.5, 57, 101.6, 107.1, 113.7, 114.8, 118.6, 124.2,
125.3, 127.2, 128.2, 129.7, 130.5, 132.8, 134.3, 154.8, 154.9, 160.9; ESI-HRMS
m/z calcd. for (C18H17O3)+ 281.1178; found 281.1183.
rac-1h. Condition A. 1H NMR (CDCl3, 400 MHz) δ 3.9 (s, 3H),
5.09 (s, 1H), 6.8 (td, J = 8.4, 2.8 Hz, 1H), 6.84 (dd, J = 10, 2.4 Hz, 1H), 7.16 (dd,
J = 8.4, 6.8 Hz, 1H), 7.37-7.44 (m, 3H), 7.46-7.49 (m, 1H), 7.85-7.87 (m, 1H),
7.97 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 56.7, 103.6 (d, J = 25 Hz),
107.7 (d, J = 22 Hz), 113.4, 117.4, 118.3 (d, J = 4 Hz), 124.2, 124.7, 127.3,
128.2, 129.4, 130.8, 132.9 (d, J = 9 Hz), 133.8, 154.7, 155 (d, J = 12 Hz), 163.4
(d, J = 244 Hz); 19F NMR (CDCl3, 376 MHz) δ -112.7; ESI-HRMS m/z calcd. for
(C17H14FO2)+ 269.0978; found 269.0976.
rac-1i. Condition A. 1H NMR (CDCl3, 400 MHz) δ 2.35 (s, 3H),
3.91 (s, 3H), 4.8 (s, 1H), 7-7.03 (m, 2H), 7.17 (dd, J = 8.4, 2.4 Hz, 1H), 7.36-7.42
(m, 3H), 7.51-7.53 (m, 1H), 7.84-7.86 (m, 1H), 7.95 (d, J = 8.8 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ 20.6, 56.8, 113.4, 115.8, 118.7, 122.1, 124, 125.1, 127, 128,
129.4, 129.6, 130, 130.4, 132.4, 133.8, 151.6, 154.4; ESI-HRMS m/z calcd. for
(C18H17O2)+ 265.1229; found 265.1231.
OHOMe
F
OHOMe
Me
S9
rac-1j. Condition A.1H NMR (CDCl3, 400 MHz) δ 3.78 (s, 3H),
3.91 (s, 3H), 4.72 (s, 1H), 6.79 (d, J = 3.2 Hz, 1H), 6.95 (dd, J = 8.8, 3.2 Hz, 1H),
7.04 (d, J = 8.8 Hz, 1H), 7.37-7.43 (m, 3H), 7.55-7.57 (m, 1H), 7.84-7.87 (m, 1H),
7.95 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 55.8, 56.8, 113.5, 115.1,
116.81, 116.84, 118.7, 123.1, 124.1, 125, 127.1, 128.1, 129.4, 130.5, 133.6,
147.9, 153.4, 154.3; ESI-HRMS m/z calcd. for (C18H17O3)+ 281.1178; found
281.1181.
rac-1k. Condition A.1H NMR (CDCl3, 400 MHz) δ 3.91 (s, 3H),
4.82 (s, 1H), 6.95 (dd, J = 8.8, 2.8 Hz, 1H), 7.02-7.1 (m, 2H), 7.37-7.44 (m, 3H),
7.48-7.51 (m, 1H), 7.85-7.87 (m, 1H), 7.97 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 56.8, 113.3, 115.8 (d, J = 23 Hz), 116.9 (d, J = 8 Hz), 117.5, 118.2
(d, J = 23 Hz), 123.5 (d, J = 8 Hz), 124.2, 124.6, 127.4, 128.2, 129.4, 130.9,
133.3, 149.9 (d, J = 3 Hz), 154.4, 156.8 (d, J = 236 Hz); 19F NMR (CDCl3, 376
MHz) δ -124.5; ESI-HRMS m/z calcd. for (C17H14FO2)+ 269.0978; found
269.0976.
rac-1l. Condition A.1H NMR (CDCl3, 400 MHz) δ 3.91 (s, 3H),
5.57 (s, 1H), 7.17 (d, J = 9.2 Hz, 1H), 7.36-7.46 (m, 4H), 7.87-7.9 (m, 1H), 8.03
(d, J = 8.8 Hz, 1H), 8.18 (d, J = 2.8 Hz, 1H), 8.28 (dd, J = 9.2, 2.8 Hz, 1H); 13C
OHOMe
MeO
OHOMe
F
OHOMe
O2N
S10
NMR (CDCl3, 100 MHz) δ 56.6, 113, 115.1, 116.3, 123.1, 123.9, 124.5, 125.6,
127.9, 128.4, 128.5, 129.3, 131.8, 133.1, 141.6, 154.9, 159.5; ESI-HRMS m/z
calcd. for (C17H14NO4)+ 296.0923; found 296.0926.
General procedure for dynamic kinetic resolution of biaryl compounds
To a mixture of racemic biaryl compounds (0.05 mmol), catalyst (15 mol%),
Proton sponge (0.06 mmol) and Molecular sieves 13X (Aldrich), 2 ml dry CHCl3
was added. Under 40 °C, isobutyric anhydride (0.06 mmol) was added. After
stirring for indicated time in Scheme 2, the reaction mixture was purified by
column chromatography (hexane/ethyl acetate = 95/5) to afford the
corresponding ester. The optical purity of the obtained product was determined
by chiral HPLC.
2a (90:10 er) HPLC (UV 220 nm, Chiralpak AD-3, i-
PrOH/Hexane = 3/97, 0.5 mL/min), t1 (minor) = 12.8 min, t2 (major) = 14.8 min.
[α]D 22 12.1 (c 0.66, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.66 (d, J = 6.8 Hz,
3H), 0.7 (d, J = 6.8 Hz, 3H), 2.3 (m, 1H), 3.86 (s, 3H), 7.28-7.31 (m, 1H), 7.34-
7.43 (m, 6H), 7.48-7.52 (m, 1H), 7.81-7.83 (m, 1H), 7.9 (d, J = 9.2 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 18.2, 18.3, 33.8, 56.7, 113.4, 120.4, 122.8, 123.6,
125.2, 125.7, 126.4, 127.6, 128.6, 128.8, 129.4, 129.5, 132.5, 133.4, 149.3,
154.2, 174.7; ESI-HRMS: m/z calcd. for (C21H20O3Na)+ 343.1305; found
343.1302.
OO
O
S11
2b (89:11 er) HPLC (UV 220 nm, Chiralpak AD-3, i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (minor) = 14.7 min, t2 (major) = 20 min. [α]D 23 19.1 (c 0.69, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.63 (d, J = 6.8 Hz, 3H),
0.68 (d, J = 6.8 Hz, 3H), 1.24 (t, J = 6.8 Hz, 3H), 2.27 (m, J = 6.8 Hz, 1H), 4.04-
4.12 (m, 2H), 7.27 (d, J = 8 Hz, 1H), 7.3-7.42 (m, 6H), 7.45-7.49 (m, 1H), 7.78-
7.8 (m, 1H), 7.85 (d, J = 8.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 15, 18.2,
33.8, 65.4, 115.3, 121.3, 122.7, 123.6, 125.3, 125.5, 126.3, 127.6, 128.4, 129,
129.4, 129.5, 132.6, 133.5, 149.3, 153.6, 174.7; ESI-HRMS m/z calcd. for
(C22H22O3Na)+ 357.1467; found 357.1460.
2c (84:16 er) HPLC (UV 220 nm, Chiralpak AD-3, i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (minor) = 30.4 min, t2 (major) = 40.3 min.
[α]D 22 9.5 (c 0.71, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.55 (d, J = 7.2 Hz, 3H),
0.63 (d, J = 7.2 Hz, 3H), 2.24 (m, J = 7.2 Hz, 1H), 5.1 (s, 2H), 7.2-7.34 (m, 9H),
7.35-7.38 (m, 2H), 7.4-7.43 (m, 1H), 7.45-7.5 (m, 1H), 7.75-7.78 (s, 1H), 7.8 (d, J
= 8.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 18.3, 34, 71.7, 115.9, 121.9, 123,
124, 125.6, 125.9, 126.6, 127.1, 127.7, 127.8, 128.5, 128.8, 129.3, 129.6, 129.7,
132.8, 133.6, 137.7, 149.5, 153.5, 175; ESI-HRMS m/z calcd. for (C27H24O3Na)+
419.1623; found 419.1633.
OO
O
OO
O
Ph
S12
2d (56:44 er) HPLC (UV 220 nm, Chiralpak OD-3, i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (major) = 13.4 min, t2 (minor) = 16.1 min.
[α]D 22 -6.7 (c 0.6, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.51 (d, J = 7.2 Hz, 3H),
0.55 (d, J = 6.8 Hz, 3H), 2.2 (m, J = 7.2, 6.8 Hz, 1H), 3.3 (s, 3H), 4.32 (s, 2H),
7.25 (dd, J = 8, 1.2 Hz, 1H), 7.33-7.39 (m, 4H), 7.42-7.46 (m, 1H), 7.5-7.54 (m,
1H), 7.68 (d, J = 8.4 Hz, 1H), 7.84 (d, J = 8 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 18, 18.1, 33.7, 58.3, 72.3, 122.9, 125.5, 125.6, 125.9,
126.1, 126.3, 127.7, 128.2, 129.1, 131.3, 131.9, 132.4, 132.7, 133, 134.5, 149.1,
174.9; ESI-HRMS m/z calcd. for (C22H22O3)+ 357.1467; found 357.1472.
2e (61:39 er) HPLC (UV 220 nm, Chiralpak AD-H, i-
PrOH/Hexane = 0.5/0.995, 0.5 mL/min), t1 (minor) = 22.3 min, t2 (major) = 29.1
min. [α]D 25 5.5 (c 0.71, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.94 (d, J = 6.8 Hz,
3H), 0.99 (d, J = 6.8 Hz, 3H), 2.53 (m, J = 6.8 Hz, 1H), 3.68 (s, 3H), 7.02-7.07 (m,
2H), 7.16-7.19 (m, 1H), 7.3 (d, J = 8.8 Hz, 1H), 7.35-7.49 (m, 4H), 7.87-7.9 (m,
2H); 13C NMR (CDCl3, 100 MHz) δ 18.7, 18.8, 34.2, 55.9, 111.2, 120.6, 121.8,
124.1, 125.5, 126.2, 126.4, 127.7, 128.2, 129, 129.6, 131.9, 132.2, 133.6, 146.1,
157.8; ESI-HRMS m/z calcd. for (C21H20O3Na)+ 343.1310; found 343.1315.
O
O
O
OO O
S13
2f (63:37 er) HPLC (UV 220 nm, Whelk-(R,R), i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (major) = 18.2 min, t2 (minor) = 20.6 min.
[α]D 22 -7.4 (c 0.69, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.58 (d, J = 6.8 Hz, 3H),
0.61 (d, J = 6.8 Hz, 3H), 2.22 (s, 3H), 2.23 (m, J = 6.8 Hz, 1H), 4.03 (s, 3H), 6.73
(s, 1H), 7.23 (dd, J = 8, 1.2 Hz, 1H), 7.27-7.3 (m, 2H), 7.32-7.4 (m, 3H), 7.47 (td,
J = 7.6, 2 Hz, 1H), 8.21-8.23 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 18.1, 18.2,
21, 33.8, 55.5, 106.4, 121.5, 122.9, 123.9, 124.1, 125.5, 125.6, 126, 126.5, 128.5,
132.4, 132.8, 133.6, 134.4, 149.5, 154.9, 175; ESI-HRMS m/z calcd. for
(C22H22O3Na)+ 357.1467; found 357.1477.
2g (86:14 er) HPLC (UV 220 nm, Chiralpak AD-3, i-
PrOH/Hexane = 4/96, 0.5 mL/min), t1 (minor) = 16.7 min, t2 (major) = 20.7 min.
[α]D 23 4.7 (c 0.8, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.63 (d, J = 6.8 Hz, 3H),
0.66 (d, J = 6.8 Hz, 3H), 2.26 (m, J = 6.8 Hz, 1H), 3.84 (s, 3H), 3.89 (s, 3H), 6.83
(d, J = 2.8 Hz, 1H), 6.94 (dd, J = 8.8, 2.8 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.29-
7.36 (m, 3H), 7.42-7.44 (m, 1H), 7.77-7.79 (m, 1H), 7.86 (d, J = 9.2 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 18.21, 18.24, 33.8, 55.5, 56.7, 108.4, 111.9, 113.5,
120.2, 121.3, 123.5, 125.3, 126.4, 127.6, 128.9, 129.3, 132.8, 133.8, 150, 154.5,
159.8, 174.6; ESI-HRMS m/z calcd. for (C22H22O4Na)+ 373.1416; found
371.1423.
OO
O
Me
OO
O
OMe
S14
2h (83:17 er) HPLC (UV 220 nm, Chiralpak AD-3, i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (minor) = 15.8 min, t2 (major) = 23.2 min.
[α]D 23 8.7 (c 0.76, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.63 (d, J = 6.8 Hz, 3H),
0.67 (d, J = 7.2 Hz, 3H), 2.27 (m, J = 7.2, 6.8 Hz, 1H), 3.84 (s, 3H), 7.05 (dd, J =
9.2, 2.8 Hz, 1H), 7.1 (td, J = 8.4, 2.4 Hz, 1H), 7.31-7.38 (m, 5H), 7.78-7.81 (m,
1H), 7.89 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 18.15, 18.17, 33.8,
56.6, 110.8 (d, J = 24 Hz), 112.9 (d, J = 21 Hz), 113.3, 119.3, 123.6, 124.9, 125.3
(d, J = 3 Hz), 126.6, 127.8, 128.8, 129.8, 133.2 (d, J = 9 Hz), 133.5, 149.9 (d, J =
11 Hz), 154.3, 162.2 (d, J = 246 Hz), 174.4; 19F NMR (CDCl3, 376 MHz) δ -112.8;
ESI-HRMS m/z calcd. for (C21H19FO3Na)+ 361.1216; found 361.1207.
2i (89:11 er) HPLC (UV 220 nm, Whelk (R, R), i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (major) = 22.9 min, t2 (minor) = 26.6 min.
[α]D 23 36.2 (c 0.69, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.63 (d, J = 7.2 Hz,
3H), 0.67 (d, J = 6.8 Hz, 3H), 2.28 (m, J = 7.2, 6.8 Hz, 1H), 2.42 (s, 3H), 3.85 (s,
3H), 7.15 (d, J = 8.4 Hz, 1H), 7.17-7.18 (m, 1H), 7.26-7.37 (m, 4H), 7.41-7.44 (m,
1H), 7.78-7.81 (m, 1H), 7.87 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ
18.26, 18.28, 21, 33.8, 56.7, 113.4, 120.5, 122.4, 123.5, 125.3, 126.4, 127.6,
128.9, 129, 129.3, 129.4, 132.9, 133.5, 135.2, 147, 154.2, 174.9; ESI-HRMS m/z
calcd. for (C22H22O3Na)+ 357.1467; found 357.1475.
OO
O
F
OO
OMe
S15
2j (87:13 er) HPLC (UV 220 nm, Chiralpak IA, i-
PrOH/Hexane = 1/99, 0.5 mL/min), t1 (minor) = 20.5 min, t2 (major) = 27.7 min.
[α]D 23 28.3 (c 0.84, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.61 (d, J = 6.8 Hz,
3H), 0.65 (d, J = 6.8 Hz, 3H), 2.25 (m, J = 6.8 Hz, 1H), 3.82 (s, 3H), 3.85 (s, 3H),
6.9 (d, J = 2.8 Hz, 1H), 7 (dd, J = 8.8, 3.2 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 7.3-
7.37 (m, 3H), 7.42-7.45 (m, 1H), 7.78-7.8 (m, 1H), 7.87 (d, J = 9.2Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ 18.2, 18.3, 33.8, 55.6, 56.8, 113.4, 114, 117.3, 120.3,
123.4, 123.6, 125.2, 126.5, 127.6, 128.8, 129.6, 130.2, 133.3, 142.9, 154.1, 157,
175.1; ESI-HRMS m/z calcd. for (C22H22O4Na)+ 373.1416; found 373.1414.
2k (87:13 er) HPLC (UV 220 nm, Chiralpak IA, i-
PrOH/Hexane = 1/99, 0.4 mL/min), t1 (minor) = 16.6 min, t2 (major) = 22.5 min.
[α]D 22 -0.4 (c 0.83, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.61 (d, J = 6.8 Hz,
3H), 0.65 (d, J = 6.8 Hz, 3H), 2.25 (m, J = 6.8 Hz, 1H), 3.85 (s, 3H), 7.09 (dd, J =
8.8, 2.8 Hz, 1H), 7.13-7.23 (m, 2H), 7.31-7.4 (m, 4H), 7.79 (dd, J = 6.8, 1.6 Hz,
1H), 7.89 (d, J = 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 18.16, 18.19, 33.7,
56.7, 113.2, 115.2 (d, J = 23 Hz), 119.07 (d, J = 17 Hz), 119.2, 123.7, 124 (d, J =
9 Hz), 124.8, 126.7, 127.8, 128.8, 130, 131.2 (d, J = 8 Hz), 133.1, 145.2 (d, J = 2
Hz), 154.1, 160 (d, J = 243 Hz), 174.8; 19F NMR (CDCl3, 376 MHz) δ -117.6; ESI-
HRMS m/z calcd. for (C21H19FO3Na)+ 361.1216; found 361.1215.
OO
OMeO
OO
OF
S16
2l (51:49 er) HPLC (UV 220 nm, Chiralpak AD-H, i-
PrOH/Hexane = 5/95, 0.5 mL/min), t1 (major) = 28.2 min, t2 (minor) = 36 min. [α]D 23 2.5 (c 0.9, CH2Cl2). 1H NMR (CDCl3, 400 MHz) δ 0.66 (d, J = 7.2 Hz, 3H), 0.69
(d, J = 6.8 Hz, 3H), 2.3 (m, J = 7.2, 6.8 Hz, 1H), 3.85 (s, 3H), 7.27-7.3 (m, 1H),
7.33-7.4 (m, 3H), 7.44 (d, J = 9.2 Hz, 1H), 7.81-7.84 (m, 1H), 7.94 (d, J = 9.2 Hz,
1H), 8.29 (d, J = 2.8 Hz, 1H), 8.35 (dd, J = 8.8, 2.8 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ 18.08, 18.1, 33.9, 56.5, 112.9, 117.6, 123.8, 123.9, 124, 124.2,
127.1, 128, 128.4, 128.7, 130.6, 131.1, 132.8, 145.4, 154.2, 154.4, 174; ESI-
HRMS m/z calcd. for (C21H19NO5Na)+ 388.1161; found 388.1164.
OOMe
OO2N
S17
5. Crystal Structure of Catalyst L1
Figure S3. Crystal Structure of Catalyst L1
X-ray Structure determination: Single crystal X-ray diffraction data of L1
was collected on a Bruker APEX-II CCD diffractometer. The crystal was kept at
100K during data collection. Cu radiation was used for the sample. Using Olex2,6
the structure was solved with the ShelXS7 structure solution program using Direct
Methods and refined with the XL refinement package using Least Squares
minimization. Basic information pertaining to crystal parameters and structure
refinement is summarized in Table S2.
Identification code cu_gxm3_0m
Empirical formula C25H30N4O
Formula weight 402.53
S18
Temperature 100K
Crystal system orthorhombic
space group P212121
a/Å 11.2926(3)
b/Å 12.7919(3)
c/Å 15.5672(4)
α,deg 90
β,deg 90
γ,deg 90
V, Å3 2248.74(10)
Z 4
dcalcd, g.cm-3 1.189
µ, mm-1 0.580
F(000) 864.0
Crystal size/mm3 0.25 × 0.23 × 0.2
Radiation CuKa (l = 1.54178)
2Θ range for data collection 8.948 to 133.288
Index ranges -12 ≤ h ≤ 13, -15 ≤ k ≤ 11, -18 ≤ l ≤ 18
Reflections collected 15267
Independent reflections 3960 [Rint = 0.0252, Rsigma = 0.0209]
Data/restraints/parameters 3960/0/276
GOOF on F2 1.057
Final R indexes [I>=2σ (I)] R1 = 0.0279, wR2 = 0.0693
Final R indexes [all data] R1 = 0.0292, wR2 = 0.0702
Largest diff. peak/hole/e Å-3 0.15/-0.16
Flack parameter 0.00(8)
Table S2. Crystal Data and Structure Refinement 6. References
1. a) N. Berova, L. D. Bari and G. Pescitelli, Chem. Soc. Rev., 2007, 36, 914;
b) A. E. Nugroho and H. Morita, J. Nat. Med., 2014, 68, 1.
S19
2. a) Y.-H. Chen, D.-J. Cheng, J. Zhang, Y. Wang, X.-Y. Liu and B. Tan, J.
Am. Chem. Soc., 2015, 137, 15062; b) L. Li, L. Wang and Y. Si, Acta
Pharmaceutica Sinica B, 2014, 4, 167; c) L. Goerigk and S. Grimme, J.
Phys. Chem. A, 2009, 113, 767; d) S. Abbate, F. Lebon, G. Longhi, C. F.
Morelli, D. Ubiali and G. Speranza, RSC Adv., 2012, 2, 10200.
3. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J.
R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H.
Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G.
Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J.
Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T.
Vreven, J. A., Jr. Montgomery, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J.
Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L.
Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J.
Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V.
Ortiz, J. Cioslowski and D. J. Fox, Gaussian 09, Revision E.01, Gaussian,
Inc., Wallingford CT, 2009.
4. L. Chausset-Boissarie, R. Àrvai, G. R. Cumming, C. Besnard and E. P.
Kündig, Chem. Commun., 2010, 46, 6264.
5. S. Arseniyadis, M. Mahesh, P. McDaid, T. Hampel, S. G. Davey and A. C.
Spivey, Collect. Czech. Chem. Commun., 2011, 76, 1239.
6. O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and H.
Puschmann, J. Appl. Cryst., 2009, 42, 339.
7. G. M. Sheldrick, Acta Cryst., 2008, A64, 112.
S20
7. NMR Spectra and HPLC Spectra
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
60000
65000
70000
75000
80000
85000
3.0
4
1.0
2
0.9
80.9
70.9
94.0
11.0
0
0.9
91.0
0
3.9
23
4.9
69
7.0
75
7.0
78
7.0
94
7.0
97
7.1
12
7.1
15
7.1
24
7.1
27
7.1
44
7.1
47
7.2
34
7.2
39
7.2
53
7.2
57
7.2
84
7.3
84
7.3
88
7.3
98
7.4
00
7.4
04
7.4
07
7.4
10
7.4
12
7.4
20
7.4
22
7.4
25
7.4
27
7.4
36
7.4
43
7.5
08
7.5
10
7.5
12
7.5
14
7.5
16
7.5
22
7.5
24
7.5
35
7.8
68
7.8
75
7.8
79
7.8
87
7.8
92
7.8
94
7.9
75
7.9
98
OH
O
rac-1a
0102030405060708090100110120130140150160170180f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
500056.7
9
113.4
8116.0
0118.4
6120.4
9122.3
8124.0
8124.9
7127.0
7128.0
6129.4
1129.4
3130.5
2132.0
9133.7
1
153.7
6154.5
1
OH
O
rac-1a
S21
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
30000
3.0
8
2.0
5
0.9
6
0.9
91.0
01.0
74.0
31.0
10.9
91.0
0
1.2
78
1.2
95
1.3
13
4.1
04
4.1
10
4.1
21
4.1
28
4.1
43
4.1
45
4.1
60
4.1
63
4.1
78
4.1
84
4.1
95
4.2
02
5.1
81
7.0
81
7.0
84
7.1
00
7.1
03
7.1
27
7.1
30
7.1
47
7.1
50
7.2
47
7.2
51
7.2
65
7.2
70
7.3
70
7.3
76
7.3
93
7.4
00
7.4
04
7.4
07
7.4
12
7.4
18
7.5
59
7.5
61
7.5
72
7.5
75
7.5
84
7.8
50
7.8
58
7.8
74
7.9
15
7.9
38
OH
O
rac-1b
0102030405060708090100110120130140150160170180190f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
14.9
8
65.6
9
115.4
4116.2
4119.8
6120.3
8122.7
2124.1
8125.2
2126.9
5128.0
8129.2
8129.7
1130.3
3132.2
7133.8
1
153.7
3153.9
2
OH
O
rac-1b
S22
-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
-2000
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
19000
20000
21000
22000
0.9
72.0
2
1.0
10.9
73.2
03.3
14.0
41.0
41.0
11.0
0
4.9
64
5.1
48
5.1
56
7.0
53
7.0
56
7.0
72
7.0
75
7.0
90
7.0
93
7.1
14
7.1
17
7.1
34
7.1
37
7.2
01
7.2
03
7.2
05
7.2
07
7.2
10
7.2
14
7.2
19
7.2
23
7.2
25
7.2
38
7.2
42
7.2
45
7.2
56
7.2
60
7.2
65
7.2
67
7.2
71
7.2
79
7.2
81
7.2
85
7.2
88
7.3
01
7.3
72
7.3
76
7.3
81
7.3
88
7.3
91
7.3
96
7.3
99
7.4
06
7.4
11
7.4
15
7.5
16
7.5
18
7.5
20
7.5
23
7.5
25
7.5
29
7.5
31
7.5
35
7.5
41
7.5
43
7.8
28
7.8
36
7.8
41
7.8
46
7.8
52
7.8
86
7.9
09
OH
O
rac-1c
0102030405060708090100110120130140150160170f1 (ppm)
-200
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
1900
2000
2100
2200
2300
2400
71.7
6
116.0
3120.1
5120.4
9122.4
7124.3
8125.1
2127.0
4127.0
5127.8
1128.0
6128.4
6129.4
3129.8
0130.3
6132.1
1133.7
2136.8
4153.6
3153.8
1
OH
O
rac-1c
S23
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
2.9
1
1.9
7
0.9
5
2.9
33.0
01.0
20.9
81.0
01.0
0
3.3
34
4.3
24
4.3
51
4.3
68
4.3
95
5.4
36
7.0
72
7.0
75
7.0
90
7.0
93
7.1
16
7.1
21
7.1
35
7.1
38
7.3
82
7.3
87
7.3
96
7.4
00
7.4
05
7.4
08
7.4
12
7.4
15
7.4
26
7.4
28
7.4
45
7.4
80
7.4
84
7.4
95
7.5
00
7.5
04
7.5
16
7.6
64
7.6
85
7.8
89
7.9
10
7.9
39
7.9
60
OH
O
rac-1d
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
58.6
2
73.3
2
116.8
4120.7
0124.8
9126.2
2126.2
6126.6
1126.6
4128.0
4128.8
8129.7
0131.3
6132.9
0133.0
3133.5
4134.8
0153.8
8
OH
O
rac-1d
S24
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
5000
10000
15000
20000
25000
30000
2.9
9
0.9
1
1.9
55.3
01.1
92.0
0
3.7
80
7.1
55
7.1
58
7.1
67
7.1
69
7.1
78
7.1
85
7.1
88
7.2
04
7.2
07
7.2
86
7.2
96
7.3
18
7.3
34
7.3
38
7.3
43
7.3
48
7.3
50
7.3
52
7.3
57
7.3
60
7.3
63
7.3
72
7.3
77
7.3
83
7.3
91
7.5
10
7.5
14
7.5
28
7.5
31
7.5
33
7.5
35
7.5
49
7.5
54
7.8
29
7.8
51
OH
O
rac-1e
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
3200
3400
55.8
4
111.9
5117.7
2117.8
5121.5
4122.5
1123.1
9124.8
2126.2
5128.0
4129.1
1129.5
1130.2
4133.3
8133.4
6150.6
2
157.8
2
OH
O
rac-1e
S25
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
3.1
2
3.2
3
1.1
4
1.0
02.8
03.8
6
0.8
6
2.2
61
4.0
58
4.6
53
6.8
05
7.0
30
7.0
33
7.0
48
7.0
51
7.0
67
7.0
70
7.0
72
7.0
88
7.0
89
7.0
91
7.0
92
7.1
13
7.1
14
7.1
17
7.1
19
7.1
32
7.1
33
7.1
36
7.1
37
7.3
46
7.3
51
7.3
62
7.3
64
7.3
67
7.3
69
7.3
72
7.3
76
7.3
85
7.3
88
7.3
92
7.4
09
7.4
13
7.4
19
7.4
23
7.4
39
7.4
44
8.2
73
8.2
75
8.2
76
8.2
79
8.2
93
8.2
95
8.2
97
8.2
99
OH
O
rac-1f
-100102030405060708090100110120130140150160170180190200f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
650021.0
8
55.7
7
106.8
8
115.4
2120.8
5122.2
2123.1
2124.7
5124.9
3125.2
8125.3
6127.3
9129.4
8131.7
2134.1
2136.3
7153.7
4155.7
9
OH
O
rac-1f
S26
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
3.1
23.0
6
0.9
2
1.9
8
1.0
43.0
81.0
01.0
21.0
0
3.8
74
3.9
02
5.0
14
6.6
42
6.6
48
6.6
63
6.6
69
6.6
83
6.6
89
7.1
04
7.1
25
7.3
51
7.3
55
7.3
57
7.3
67
7.3
69
7.3
72
7.3
74
7.3
76
7.3
83
7.3
84
7.3
91
7.3
93
7.3
95
7.3
99
7.4
00
7.4
06
7.4
11
7.4
12
7.4
16
7.5
22
7.5
24
7.5
26
7.5
28
7.5
30
7.5
32
7.5
34
7.5
42
7.5
44
7.5
46
7.5
48
7.5
50
7.8
33
7.8
38
7.8
40
7.8
41
7.8
47
7.8
52
7.8
54
7.8
56
7.8
57
7.9
30
7.9
53
OH
O
O
rac-1g
-100102030405060708090100110120130140150160170180190200f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
55.5
457.0
3
101.6
2107.1
1113.7
1114.7
9118.5
6124.2
4125.2
7127.1
8128.2
4129.7
0130.5
0132.7
8134.2
5
154.8
4154.9
3160.9
5
OH
O
O
rac-1g
S27
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.5f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
60000
65000
70000
75000
80000
3.1
3
1.0
3
0.9
70.9
20.9
92.9
70.9
50.9
91.0
0
3.9
01
5.0
94
6.7
81
6.7
95
6.8
02
6.8
16
6.8
23
6.8
24
6.8
31
6.8
50
6.8
56
7.1
44
7.1
61
7.1
65
7.1
82
7.3
87
7.3
92
7.3
94
7.4
03
7.4
09
7.4
11
7.4
14
7.4
19
7.4
31
7.4
60
7.4
62
7.4
65
7.4
67
7.4
81
7.8
46
7.8
48
7.8
53
7.8
55
7.8
68
7.8
71
7.8
73
7.9
54
7.9
77
OH
O
F
rac-1h
0102030405060708090100110120130140150160170180190f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
56.7
4
103.4
4103.6
9107.5
4107.7
6113.3
8117.4
0118.2
3118.2
7124.1
7124.7
0127.2
6128.1
7129.4
3130.7
8132.8
2132.9
1133.7
9
154.6
9154.9
0155.0
2
162.2
2164.6
6
OH
O
F
rac-1h
S28
-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)
-2000
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
19000
20000
21000
22000
23000
-112.7
3
OH
O
F
rac-1h
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
3.0
0
3.0
5
1.0
2
1.9
51.0
12.9
61.0
30.9
91.0
0
2.3
47
3.9
05
4.8
04
6.9
96
7.0
17
7.0
19
7.0
20
7.0
24
7.0
26
7.1
61
7.1
67
7.1
82
7.1
88
7.3
71
7.3
76
7.3
86
7.3
88
7.3
95
7.4
01
7.4
11
7.5
06
7.5
08
7.5
10
7.5
12
7.5
25
7.5
27
7.5
30
7.5
32
7.8
35
7.8
37
7.8
43
7.8
45
7.8
49
7.8
57
7.8
60
7.8
62
7.9
37
7.9
59
OH
O
rac-1i
S29
-100102030405060708090100110120130140150160170180190f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
240020.6
4
56.7
9
113.4
3115.8
0118.7
3122.1
0124.0
3125.0
8127.0
1128.0
3129.4
4129.5
7130.0
0130.3
7132.3
6133.7
6
151.5
5154.4
0
OH
O
rac-1i
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
3.0
73.0
1
0.9
6
0.9
51.0
00.9
73.0
11.0
01.0
21.0
0
3.7
83
3.9
07
4.7
21
6.7
86
6.7
94
6.9
31
6.9
38
6.9
53
6.9
61
7.0
32
7.0
54
7.3
80
7.3
84
7.3
87
7.3
96
7.4
03
7.4
09
7.4
13
7.4
25
7.5
45
7.5
47
7.5
49
7.5
51
7.5
54
7.5
66
7.5
71
7.5
73
7.8
42
7.8
48
7.8
57
7.8
62
7.8
65
7.9
41
7.9
64
OH
O
O
rac-1j
S30
-100102030405060708090100110120130140150160170180190f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
55.7
756.8
3
113.4
9115.0
8116.8
1116.8
4118.7
2123.1
1124.1
0125.0
2127.1
2128.0
7129.4
3130.5
1133.5
8
147.8
6153.3
5154.3
4OH
O
O
rac-1j
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
30000
32000
34000
2.9
6
0.9
6
0.9
51.9
12.9
00.9
70.9
91.0
0
3.9
10
4.8
19
6.9
30
6.9
32
6.9
37
6.9
39
6.9
53
6.9
54
6.9
60
6.9
61
7.0
15
7.0
17
7.0
28
7.0
30
7.0
37
7.0
39
7.0
46
7.0
50
7.0
52
7.0
53
7.0
66
7.0
69
7.0
73
7.0
76
7.0
88
7.0
95
7.3
70
7.3
73
7.3
86
7.3
89
7.3
93
7.3
99
7.4
04
7.4
06
7.4
10
7.4
12
7.4
16
7.4
20
7.4
24
7.4
37
7.4
41
7.4
81
7.4
83
7.4
85
7.4
87
7.4
89
7.4
91
7.5
02
7.5
04
7.5
08
7.8
45
7.8
50
7.8
62
7.8
65
7.8
69
7.9
60
7.9
83
OH
O
F
rac-1k
S31
0102030405060708090100110120130140150160170f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
56.7
6
113.3
3115.7
2115.9
5116.8
6116.9
4117.4
5118.0
8118.3
1123.4
8123.5
6124.2
2124.6
0127.3
7128.1
8129.3
7130.9
3133.3
1149.9
0149.9
3154.4
3155.6
3157.9
9
OH
O
F
rac-1k
-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
-124.5
0
OH
O
F
rac-1k
S32
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
3.2
9
1.1
7
1.0
0
4.0
2
1.0
11.0
00.9
41.0
0
3.9
11
5.5
67
7.1
56
7.1
79
7.3
57
7.3
59
7.3
61
7.3
64
7.3
66
7.3
68
7.3
77
7.3
78
7.3
81
7.3
83
7.3
85
7.3
95
7.3
99
7.4
09
7.4
11
7.4
16
7.4
19
7.4
23
7.4
29
7.4
32
7.4
35
7.4
40
7.4
43
7.4
47
7.4
59
7.4
64
7.8
73
7.8
78
7.8
89
7.8
93
7.8
97
8.0
17
8.0
39
8.1
76
8.1
83
8.2
68
8.2
75
8.2
91
8.2
98
OH
O
N+
O
O-
rac-1l
0102030405060708090100110120130140150160170180190f1 (ppm)
-200
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
1900
2000
2100
2200
2300
2400
2500
56.5
9
113.0
1115.1
4116.2
5123.1
2123.9
2124.4
5125.5
9127.8
7128.4
4128.4
9129.2
9131.8
0133.1
1141.6
0
154.8
7
159.4
8
OH
O
N+
O
O-
rac-1l
S33
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
30000
32000
3.0
63.0
0
1.0
3
3.1
1
1.2
36.0
41.0
3
1.0
01.0
0
0.6
48
0.6
65
0.6
89
0.7
06
2.2
66
2.2
84
2.3
01
2.3
19
2.3
36
3.8
59
7.2
80
7.2
82
7.2
84
7.3
01
7.3
03
7.3
05
7.3
38
7.3
43
7.3
52
7.3
62
7.3
68
7.3
74
7.3
80
7.3
85
7.3
90
7.3
92
7.4
02
7.4
05
7.4
07
7.4
10
7.4
12
7.4
17
7.4
19
7.4
24
7.4
27
7.4
30
7.4
32
7.4
34
7.4
80
7.4
92
7.5
00
7.5
03
7.5
12
7.5
23
7.8
07
7.8
13
7.8
16
7.8
21
7.8
27
7.8
31
7.8
92
7.9
15
O
O
O
2a
0102030405060708090100110120130140150160170180190200f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
18.2
218.2
5
33.8
3
56.7
3
113.4
4120.3
5122.7
8123.5
5125.2
0125.6
7126.4
4127.6
4128.5
9128.8
3129.3
7129.5
2132.5
3133.4
1149.2
8154.2
0
174.6
9
O
O
O
2a
S34
OOMe
O
(±)-2a
OOMe
O
2a
S35
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
30000
32000
34000
2.9
32.9
4
2.9
4
1.0
0
2.0
4
1.1
46.0
01.0
50.9
71.0
0
0.6
21
0.6
38
0.6
75
0.6
92
1.2
20
1.2
37
1.2
55
2.2
57
2.2
74
2.2
92
4.0
46
4.0
57
4.0
60
4.0
63
4.0
78
4.0
81
4.0
85
4.0
96
4.0
98
4.1
02
4.1
13
7.2
56
7.2
76
7.3
01
7.3
11
7.3
14
7.3
17
7.3
24
7.3
32
7.3
35
7.3
39
7.3
49
7.3
51
7.3
54
7.3
63
7.3
67
7.3
70
7.3
82
7.3
90
7.3
92
7.3
95
7.3
98
7.4
06
7.4
10
7.4
11
7.4
15
7.4
17
7.4
45
7.4
52
7.4
61
7.4
65
7.4
68
7.4
73
7.4
81
7.4
88
7.7
75
7.7
82
7.7
86
7.7
94
7.7
99
7.8
35
7.8
57
O
O
O
2b
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
500014.9
718.2
3
33.8
4
65.3
7
115.2
6121.2
5122.6
8123.5
7125.3
1125.4
7126.3
3127.6
2128.4
1128.9
5129.3
7129.4
9132.5
5133.4
9149.2
9
153.6
0
174.6
8
O
O
O
2b
S36
OOEt
O
(±)-2b
OOEt
O
2b
S37
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
2.9
32.9
5
0.9
6
2.0
9
8.9
32.0
30.9
31.0
10.9
71.0
0
0.5
39
0.5
57
0.6
23
0.6
41
2.2
27
2.2
44
2.2
62
5.1
01
7.1
95
7.1
99
7.2
01
7.2
05
7.2
10
7.2
14
7.2
20
7.2
31
7.2
36
7.2
39
7.2
42
7.2
46
7.2
50
7.2
55
7.2
60
7.2
62
7.2
66
7.2
67
7.2
69
7.2
70
7.2
78
7.2
86
7.2
88
7.2
90
7.3
00
7.3
07
7.3
12
7.3
22
7.3
31
7.3
36
7.3
49
7.3
52
7.3
60
7.3
65
7.3
67
7.3
99
7.4
01
7.4
03
7.4
06
7.4
26
7.4
58
7.4
66
7.4
74
7.4
78
7.4
81
7.4
86
7.4
94
7.7
51
7.7
57
7.7
60
7.7
70
7.7
75
7.7
92
7.8
14
O
O
O
2c
-100102030405060708090100110120130140150160170180190200f1 (ppm)
-3000
-2000
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
18.3
4
33.9
9
71.7
1
115.8
8121.9
0122.9
6124.0
2125.6
1125.8
5126.6
0127.1
4127.7
2127.7
9128.5
0128.8
0129.3
2129.6
0129.6
8132.7
9133.6
4137.6
5149.5
2
153.4
9
174.9
9
O
O
O
2c
S38
OO
Ph
O
(±)-2c
OO
O
Ph2c
S39
-100102030405060708090100110120130140150160170180190200210
f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
4000
18.0
218.0
8
33.6
7
58.2
6
72.2
5
122.8
9125.5
0125.6
3125.9
3126.0
6126.2
7127.6
8128.1
5129.0
8131.2
7131.8
6132.3
5132.6
9132.9
9134.5
0149.0
5
174.9
2
O
O
O
2d
S40
O
OMe
O
(±)-2d
O
O
OMe
2d
S41
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
3.3
43.2
2
1.0
5
3.2
1
2.0
61.0
01.0
04.2
6
2.1
1
0.9
31
0.9
48
0.9
86
1.0
03
2.5
17
2.5
34
2.5
52
3.6
81
7.0
16
7.0
19
7.0
21
7.0
25
7.0
27
7.0
37
7.0
40
7.0
43
7.0
46
7.0
49
7.0
62
7.0
65
7.1
64
7.1
65
7.1
68
7.1
69
7.1
72
7.1
83
7.1
86
7.1
88
7.2
79
7.3
01
7.3
73
7.3
76
7.3
90
7.3
94
7.3
97
7.4
09
7.4
10
7.4
13
7.4
15
7.4
16
7.4
30
7.4
33
7.4
47
7.4
50
7.4
64
7.4
65
7.4
67
7.4
69
7.4
71
7.4
73
7.4
86
7.4
88
7.4
90
7.4
92
7.8
74
7.8
76
7.8
79
7.8
81
7.8
93
7.8
95
7.8
97
7.9
03
O O
O
2e
-100102030405060708090100110120130140150160170180190200f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
500018.6
618.8
2
34.2
0
55.8
9
111.2
2120.6
2121.7
9124.1
4125.4
8126.2
3126.4
3127.6
9128.2
2129.0
2129.5
5131.9
3132.2
3133.6
4146.1
4
157.8
2
O O
O
2e
S42
OMeO O
(±)-2e
OMeO O
2e
S43
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
0
5000
10000
15000
20000
25000
30000
35000
40000
3.0
93.1
4
4.2
1
3.1
7
1.0
4
1.0
02.0
43.1
81.1
2
1.0
0
0.5
67
0.5
84
0.6
05
0.6
22
2.1
93
2.2
11
2.2
17
2.2
28
2.2
46
2.2
63
4.0
27
6.7
29
7.2
22
7.2
25
7.2
42
7.2
45
7.2
60
7.2
71
7.2
73
7.2
77
7.2
83
7.2
91
7.2
94
7.2
97
7.3
01
7.3
21
7.3
25
7.3
38
7.3
42
7.3
46
7.3
58
7.3
62
7.3
64
7.3
74
7.3
78
7.3
80
7.3
83
7.3
95
7.3
99
7.4
47
7.4
52
7.4
66
7.4
71
7.4
86
7.4
90
8.2
07
8.2
09
8.2
12
8.2
14
8.2
28
8.2
32
8.2
34
O
O
O
2f
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-400
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
3200
3400
3600
3800
4000
18.1
218.1
920.9
5
33.7
5
55.5
2
106.4
0
121.4
5122.8
7123.9
0124.1
2125.4
7125.6
4125.9
8126.4
6128.5
1132.4
2132.7
5133.6
1134.4
4149.4
8154.8
5
174.9
5
O
O
O
2f
S44
OOMe
O
(±)-2f
OOMe
O
2f
S45
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
0
5000
10000
15000
20000
25000
30000
35000
2.8
92.9
5
1.0
1
2.9
62.9
5
0.9
40.9
81.3
73.0
31.0
00.9
81.0
0
0.6
20
0.6
37
0.6
51
0.6
68
2.2
10
2.2
27
2.2
45
2.2
62
2.2
79
2.2
97
2.3
14
3.8
36
3.8
87
6.8
23
6.8
30
6.9
27
6.9
33
6.9
48
6.9
55
7.2
53
7.2
74
7.2
90
7.2
94
7.3
07
7.3
12
7.3
18
7.3
24
7.3
30
7.3
35
7.3
39
7.3
43
7.3
55
7.3
60
7.4
16
7.4
18
7.4
20
7.4
22
7.4
24
7.4
26
7.4
36
7.4
38
7.4
42
7.7
71
7.7
76
7.7
87
7.7
91
7.7
94
7.8
46
7.8
69
O
O
O
O
2g
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
18.2
118.2
4
33.8
4
55.5
056.7
4
108.4
2111.9
3113.4
7120.1
7121.3
1123.4
9125.3
1126.3
5127.6
3128.8
8129.3
4132.8
2133.7
6
149.9
6154.4
6159.7
6
174.6
0
O
O
O
O
2g
S46
OOMe
O
OMe
(±)-2g
OOMe
O
OMe
2g
S47
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.5f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
60000
65000
70000
2.9
82.9
6
1.0
0
3.1
0
0.9
41.0
24.9
8
0.9
91.0
0
0.6
23
0.6
40
0.6
61
0.6
79
2.2
16
2.2
33
2.2
50
2.2
68
2.2
85
2.3
03
2.3
20
3.8
36
7.0
31
7.0
38
7.0
54
7.0
61
7.0
76
7.0
82
7.0
97
7.1
03
7.1
18
7.1
24
7.3
05
7.3
12
7.3
20
7.3
26
7.3
31
7.3
35
7.3
43
7.3
45
7.3
49
7.3
54
7.3
57
7.3
59
7.3
61
7.3
64
7.3
68
7.3
70
7.3
78
7.7
84
7.7
86
7.7
87
7.7
92
7.8
01
7.8
07
7.8
11
7.8
74
7.8
97
O
O
O
F
2h
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
18.1
518.1
7
33.7
9
56.6
3
110.6
7110.9
1112.7
9113.0
0113.2
8119.3
3123.6
1124.9
3125.2
4125.2
7126.5
9127.7
5128.8
3129.7
6133.1
7133.2
6133.4
5149.8
5149.9
6154.3
3160.9
6163.4
2
174.3
5
O
O
O
F
2h
S48
-210-200-190-180-170-160-150-140-130-120-110-100-90-80-70-60-50-40-30-20-10010f1 (ppm)
-2000
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000-112.7
6
O
O
O
F
2h
OOMe
O
F
(±)-2h
S49
OOMe
O
F
2h
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
-5000
0
5000
10000
15000
20000
25000
30000
35000
40000
45000
50000
55000
60000
2.9
82.9
8
1.0
23.0
3
3.0
2
1.0
10.9
34.2
21.0
00.9
91.0
0
0.6
24
0.6
42
0.6
64
0.6
81
2.2
23
2.2
40
2.2
58
2.2
75
2.2
93
2.3
10
2.3
27
2.4
21
3.8
48
7.1
43
7.1
64
7.1
73
7.1
75
7.1
76
7.1
79
7.1
81
7.2
60
7.2
62
7.2
64
7.2
68
7.2
70
7.2
83
7.2
85
7.2
88
7.2
90
7.3
17
7.3
21
7.3
25
7.3
27
7.3
34
7.3
41
7.3
48
7.3
52
7.3
64
7.4
09
7.4
11
7.4
13
7.4
15
7.4
18
7.4
29
7.4
31
7.4
36
7.7
82
7.7
87
7.8
02
7.8
05
7.8
60
7.8
83
O
O
O
2i
S50
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
7500
8000
8500
9000
18.2
618.2
821.0
3
33.8
3
56.7
4
113.4
2120.4
8122.4
2123.5
2125.2
9126.4
0127.6
3128.8
5128.9
6129.2
8129.4
3132.9
2133.4
7135.2
0147.0
4
154.1
7
174.9
1
O
O
O
2i
OOMe
OMe
(±)-2i
S51
OOMe
OMe
2i
-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.0f1 (ppm)
0
5000
10000
15000
20000
25000
30000
35000
40000
2.9
73.0
1
1.0
0
2.8
92.9
3
0.9
51.0
01.0
03.0
30.9
90.9
91.0
0
0.6
00
0.6
17
0.6
43
0.6
60
2.2
01
2.2
19
2.2
36
2.2
54
2.2
71
2.2
89
2.3
06
3.8
24
3.8
47
6.8
93
6.9
00
6.9
84
6.9
92
7.0
06
7.0
14
7.1
60
7.1
82
7.2
98
7.3
02
7.3
15
7.3
20
7.3
27
7.3
33
7.3
38
7.3
43
7.3
48
7.3
52
7.3
65
7.3
69
7.4
20
7.4
22
7.4
24
7.4
26
7.4
28
7.4
41
7.4
43
7.4
47
7.7
77
7.7
82
7.7
93
7.7
97
7.8
00
7.8
62
7.8
85
O
O
O
O
2j
S52
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
18.2
418.2
6
33.7
7
55.6
156.7
5
113.4
3113.9
7117.2
5120.2
6123.3
8123.5
7125.2
2126.5
0127.6
3128.8
0129.5
8130.1
9133.3
2142.8
5
154.1
3156.9
9
175.1
0O
O
O
O
2j
OOMe
OMeO
(±)-2j
S53
OOMe
OMeO
2j
-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.5f1 (ppm)
-2000
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
18000
19000
20000
21000
22000
23000
24000
25000
2.9
82.9
9
1.0
1
3.0
9
0.9
62.0
44.0
40.9
91.0
0
0.5
99
0.6
16
0.6
38
0.6
55
2.2
00
2.2
18
2.2
35
2.2
52
2.2
70
2.2
87
2.3
05
3.8
48
7.0
75
7.0
82
7.0
96
7.1
04
7.1
31
7.1
39
7.1
51
7.1
54
7.1
59
7.1
61
7.1
73
7.1
81
7.1
97
7.2
10
7.2
20
7.2
32
7.3
14
7.3
19
7.3
24
7.3
29
7.3
34
7.3
39
7.3
42
7.3
44
7.3
49
7.3
60
7.3
64
7.3
72
7.3
74
7.3
78
7.3
81
7.3
83
7.7
84
7.7
88
7.8
01
7.8
05
7.8
78
7.9
01
O
O
O
F
2k
S54
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
0
500
1000
1500
2000
2500
3000
3500
400018.1
618.1
9
33.7
4
56.6
5
113.2
4115.1
3115.3
6118.9
5119.1
2119.1
8123.6
8123.9
2124.0
1124.8
4126.7
1127.7
5128.7
5129.9
7131.1
7131.2
5133.0
5145.1
9145.2
1
154.1
2158.8
0161.2
3
174.7
8
O
O
O
F
2k
2k
S55
OOMe
OF
(±)-2k
OOMe
OF
2k
S56
-1.5-1.0-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.5f1 (ppm)
-2000
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
20000
22000
24000
26000
28000
2.9
72.9
6
1.0
5
2.9
7
1.0
13.0
31.0
31.0
11.0
00.9
10.9
7
0.6
49
0.6
67
0.6
86
0.7
03
2.2
50
2.2
67
2.2
84
2.3
02
2.3
19
2.3
37
2.3
54
3.8
46
7.2
74
7.2
76
7.2
78
7.2
81
7.2
83
7.2
94
7.2
96
7.2
98
7.3
01
7.3
02
7.3
31
7.3
37
7.3
47
7.3
52
7.3
55
7.3
60
7.3
65
7.3
71
7.3
75
7.3
78
7.3
83
7.3
95
7.4
00
7.4
28
7.4
51
7.8
13
7.8
19
7.8
29
7.8
34
7.8
37
7.9
27
7.9
50
8.2
90
8.2
97
8.3
33
8.3
40
8.3
55
8.3
62
O
O
O
N+
O
O-
2l
-100102030405060708090100110120130140150160170180190200210f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
18.0
818.1
0
33.8
6
56.4
5
112.8
6117.6
4123.7
9123.8
5124.0
0124.2
4127.1
2128.0
2128.4
2128.7
3130.6
3131.1
4132.7
8145.4
2
154.1
9154.4
2
173.9
9
O
O
O
N+
O
O-
2l
S57
OOMe
OO2N
(±)-2l
OOMe
OO2N
2l