Deconstructing quinine. Part 1. Toward an understanding of the remarkable performance of cinchona alkaloids in asymmetric phase transfer catalysis

Article abstract of DOI:10.3987/COM-10-S(E)108

A study of catalyst structure-activity/selectivity relationships for Cinchona alkaloid-based asymmetric phase transfer catalysis (APTC) is described. An array of substituent modifications at C(9) and the quinuclidine nitrogen were introduced to examine the role of steric and electronic effects on rate and selectivity. The synthesis of the catalysts began with manipulation of the C(9) hydroxyl group followed by alkylation of the quinuclidine nitrogen to generate the quaternary ammonium salt. Catalysts that contained large substituents attached to the quinuclidinium nitrogen were found to be the most selective and those in which the hydroxyl group was protected generally afforded faster catalysts. The presence of a polar group at C(9) significantly impacted catalyst activity. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-10-S(E)108

Denmark and Weintraub
page S1
Deconstructing Quinine. Part 1. Toward an Understanding of the Remarkable
Performance of Cinchona Alkaloids in Asymmetric Phase Transfer Catalysis
Scott E. Denmark* and Robert C. Weintraub
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801
SUPPORTING INFORMATION
TABLE OF CONTENTS
PAGE
S2
General Experimental
General Procedure I. N-Quaternization of Cinchona Alkaloids
General Procedure II. PTC Alkylation of N-(Diphenylmethylene)glycine tert-Butyl Ester
General Procedure III. Performing Kinetics and Enantioselectivity Measurements on PTC
Alkylations
S4
S4
S5
S6-S7
S7-S8
S8-S9
Preparation of epi-Cinchonidine (B)
Preparation of O-Benzyl-cinchonidine (C)
Preparation of O-Allyl-cinchonidine (D)
Preparation of O-Methyl-cinchonidine (E)
Preparation of O-Methyl-epi-cinchonidine (F)
Preparation of Deoxyfluorocinchonidine (G)
Preparation of Cinchonan-9-ol, 9-phenol thiocarbonate (H’)
Preparation of Deoxycinchonidine (H)
S10-S11
S11-S12
S13-S14
S14-S15
S15-S16
S17-S22
S23-S28
S28-S34
S35-S40
S41-S46
S47-S52
S53-S58
S59-S63
S63
Preparation of Cinchonidinium Salts in Series A
Preparation of Cinchonidinium Salts in Series B
Preparation of Cinchonidinium Salts in Series C
Preparation of Cinchonidinium Salts in Series D
Preparation of Cinchonidinium Salts in Series E
Preparation of Cinchonidinium Salts in Series F
Preparation of Cinchonidinium Salts in Series G
Preparation of Cinchonidinium Salts in Series H
References

Denmark and Weintraub
page S2
Kinetic Analyses of Catalysts in Series A
Kinetic Analyses of Catalysts in Series B
Kinetic Analyses of Catalysts in Series C
Kinetic Analyses of Catalysts in Series D
Kinetic Analyses of Catalysts in Series E
Kinetic Analyses of Catalysts in Series F
Kinetic Analyses of Catalysts in Series G
Kinetic Analyses of Catalysts in Series H
Tabular Summary of Kinetics Data
S64-S73
S74-S83
S84-S93
S94-S103
S104-S113
S114-S113
S124-S133
S134-S141
S142-S144
General Experimental
All reactions were performed in oven-dried (145 °C) or flame-dried glassware under an
inert atmosphere of dry argon. Reaction solvents THF (Fisher, HPLC grade), Et O (Fisher, BHT
2
stabilized ACS grade) and methylene chloride (Fisher, unstabilized HPLC grade) were dried by
percolation through two columns packed with neutral alumina under a positive pressure of argon.
Reaction solvents hexane (Fisher, OPTIMA grade) and toluene (Fisher, ACS grade) were dried
by percolation through a column packed with neutral alumina and a column packed with Q5
reactant, a supported copper catalyst for scavenging oxygen, under a positive pressure of argon.
Reactions were carried out at the temperature indicated (external temperature) as measured by an
thermocouple device unless otherwise indicated.
Column chromatography was performed using Merck grade 9385, 60 Å silica gel and
column diameter () was expressed in mm. Visualization was accomplished by UV light,
permanganate (KMnO
chromatography was performed on Merck silica gel plates with F-254 indicator.
Chromatography solvents EtOAc (Honeywell, HPLC grade), CH Cl (Sigma-Aldrich, ACS
4 2
), or iodine (I ) as indicated. Analytical and preparative thin-layer
2
2
grade), TBME (Sigma-Aldrich, ACS grade), and MeOH (Fisher, Optima grade) were used as
supplied.
1
13
19
H NMR, C NMR, F NMR spectra were acquired at 500 MHz, 126 MHz, and 376
1
13
MHz, respectively, and referenced to residual solvent [CHCl
3
at 7.26 ( H) and 77.00 ( C) or
1
13
1
13
MeOH 3.31 ( H), 49.00 ( C) or DMSO at 2.50 ( H) and 39.5 ( C) ppm]. Chemical shifts are
reported in ppm; multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), p,

Denmark and Weintraub
page S3
(pentet), m (multiplet) and br (broad). Coupling constants, J, are reported in Hertz. Mass
Spectrometry was performed by the University of Illinois Mass Spectrometer Center. ESI mass
spectra were performed on a Waters Q-Tof Ultima or a Waters ZMD Quadrupole instrument.
Data are reported in the form of m/z (intensity relative to base peak = 100). Analytical high
pressure liquid chromatography (HPLC) was performed using a Hewlett Packard 1090L
Chromatograph equipped with a variable wavelength diode array detector and an autosampler.
The chromatograph was equipped with a reverse phase Agilent Zorbax 300SB-C8 column (5 µm,
4
. 6x 200mm, lamp current = 1). Method 1: Linear Gradient; flow rate = 1.0 mL/min, l = 254 nm,
solvent = CH CN/H O (30:70) to CH CN/H O (90:10) over 10 min, then isocratic for 7 min. A 3
3
2
3
2
min re-equilibration time was utilized between runs. The water eluent contained 0.1% v/v acetic
acid. Chiral stationary phase HPLC (CSP-HPLC) Method 2: R,R-Welk-O, 1.0 mL/min,
IPA/hexanes 5:95. Melting points were obtained in vacuum-sealed glass tubes using a Thomas-
Hoover Uni-Melt™ melting point apparatus and are corrected.
Fitting of kinetic data was done with OriginPro 8 SR4 version 8.0951 (B951).
Interpolation of kinetic plots was done with Microsoft Excel 2008.
Cinchonidine and benzyl bromide were purchased from Acros Organics and Aldrich,
respectively, 3,5-bis(trifluoromethyl)benzyl bromide was purchased from Alfa-Aesar, 9-
i
ii
2
bromomethylanthracene , 2-bromomethylnaphthalene , 1-bromomethylnaphthalene , N-
iii,iv
v
(
diphenylmethylene)glycine tert-butyl ester,
and phenylchlorothionoformate were prepared
as described in the literature.

Denmark and Weintraub
page S4
General Procedure I. N-Quaternization of Cinchona Alkaloids
The cinchona alkaloid was placed in a single-neck,, round-bottomed flask containing a
magnetic stir bar and the arylmethylene bromide was then added (1.1 equiv). The flask was
then purged with dry argon and the contents were dissolved in MeCN (0.1 M). The reaction
mixture was allowed to stir until the starting material was consumed. Reactions were typically
1
monitored by H NMR spectroscopy of reaction aliquots (~100 μL). Solvent was removed on a
rotavap (20 mm Hg, 25 °C) and the residue was purified either by washing, chromatography or
recrystallization. On occasion the reaction mixtures could be diluted with CH
2 2
Cl and purified
directly by silica gel flash chromatography.
General Procedure II. PTC Alkylation of N-(Diphenylmethylene)glycine tert-Butyl Ester
A 2 mL scintillation vial was fitted with a Teflon lined rubber septum and tert-butyl 2-
diphenylmethyleneamino)acetate (100 mg, 0.34 mmol), and the phase transfer catalyst (8.48
(
μmol, 0.025 equiv) were added. The liquid reagents, benzyl bromide (800 μL, 0.51 M in
toluene, 1.2 equiv), internal standard (790 μL, 0.32 M in toluene, 0.75 equiv), and toluene (410
μL) were added via syringe. Then, a 1.5 cm egg-shaped magnetic stir bar was placed in the vial
and the contents were briefly agitated in an ultrasonic bath (10-20 s). Reaction vials were then
o
transferred to a cold room maintained at 2-4 C and were allowed to equilibrate for at least 1 h
with stirring while immersed in a water bath to control temperature fluctuations. Lastly, 50% aq.
(
w/w) KOH solution (670 μL, 11.9 mmol, 17.8 M, 35.0 equiv) was added to the rapidly stirred
1600 rpm) organic phase. Aliquots were taken at the indicated times and analyzed as follows.
The internal standard employed in these reactions was 1,1-diphenyl-1-heptene.
(

Denmark and Weintraub
page S5
General Procedure III. Performing Kinetics and Enantioselectivity Measurements on PTC
Alkylations
Three seconds prior to the indicated time interval, the stirrer was turned off. At the
indicated time interval a 10-µL aliquot of the organic layer was removed and then was injected
into MeCN (2.0 mL) containing glacial acetic acid (several drops). This clear solution was
filtered through a small plug of silica gel (0.5 x 1 cm) and the filtrate was analyzed by Reverse
Phase-HPLC Method 1.
For the PTC alkylations that reached near to full completion (70-85% conversion to
product), a 10-μL aliquot was taken from the organic phase and injected into i-PrOH (2 mL).
This aliquot was filtered through a small plug of silica gel (0.5 x 1 cm) and the filtrate was
analyzed by CSP-HPLC Method 2
For the PTC alkylations that did not reach full completion (<70% conversion to product),
the organic phase was first separated from the aqueous base via pipette. The alkylation product
was obtained by preparative thin-layer chromatography (8 x 10 cm plate) using 0.5 - 1.0 mL of
the organic phase directly. The product was eluted with 5:95 TBME/hexane. The product
band was removed, suspended in i-PrOH (4 mL), and the silica gel was removed by filtration.
The solvent was removed on a rotavap (20 mm Hg, 35-40 °C). The product was then dissolved
in an appropriate amount of i-PrOH (1 mg/mL) and then analyzed by CSP-HPLC Method 2.

Denmark and Weintraub
page S6
Preparation of epi-Cinchonidine (B)
Cinchonidine (2.94 g, 10.0 mmol), triphenylphosphine (2.89 g, 11.0 mmol, 1.1 equiv),
and 4-nitrobenzoic acid (5.18 g, 31.0 mmol, 3.1 equiv) were dissolved in THF (125 mL, 0.08 M)
in a 250-mL, three-neck round-bottomed flask fitted with an argon inlet, septum, and
thermocouple. The suspension was cooled to 0 °C (internal) in an ice-bath over 1 h, whereupon
diisopropyl azodicarboxylate (2.17 mL, 11.0 mmol, 1.1 equiv) was then added slowly over the
course of several minutes. The reaction mixture was stirred for an additional hour at 0 °C then
was allowed to warm to 22 °C over 1 h. The reaction mixture was diluted with Et
then was transferred to a 250-mL separatory funnel and was extracted with 1 N HCl aq. (3 x 50
mL). The combined aqueous extracts were basified with solid K CO to pH 9-11. This aqueous
phase was extracted with Et O (3 x 50 mL) then CH Cl (50 mL). The combined organic extracts
were dried over Na SO and then the solvent was removed on a rotavap (20 mm Hg, 25 °C) to
2
O (50 mL),
2
3
2
2
2
2
4
afford 2.50 g (85%) of B as a light-yellow solid. The entire product was further purified by
recrystallization from boiling i-PrOH (~150 mL) to afford B as a white, crystalline solid.
Data for B:
mp:
203-205 °C
1
H-NMR: (500 MHz, CDCl
3
)
8
7
6
.73 (d, J = 4.5 Hz, 1 H), 8.04 (dd, J = 8.5, 0.8 Hz, 1 H), 7.92 (d, J = 8.2 Hz, 1 H),
.60 (ddd, J = 8.3, 6.9, 1.2 Hz, 1 H), 7.55 (d, J = 4.4 Hz, 1 H), 7.30 (ddd, J = 8.3,
.9, 1.2 Hz, 1 H), 5.74 - 5.58 (m, 2 H), 5.12 (s, 1 H), 4.89 (ddt, J = 17.6, 10.3, 1.4
Hz, 2 H), 3.48 (tdd, J = 10.0, 4.8, 2.3 Hz, 1 H), 3.11 - 2.95 (m, 2 H), 2.66 - 2.47
m, 2 H), 2.22 (s, 1 H), 1.82 - 1.66 (m, 3 H), 1.52 - 1.40 (m, 2 H).
C-NMR: (126 MHz, CDCl
(
1
3
3
)
1
49.99, 149.61, 148.06, 141.77, 130.10, 128.95, 126.52, 125.61, 122.94, 118.19,
14.27, 71.76, 60.34, 56.95, 43.16, 39.90, 27.88, 27.58, 21.45.
1

Denmark and Weintraub
page S7
Analysis:
C
Calcd:
19
H
22
N
2
O (294.39)
C, 77.52;
H, 7.53;
H, 7.67;
N, 9.52
N, 9.47
Found:
C, 77.38;
+
LRMS: (ESI , Q-tof)
295.2 (100, M-Br+)
+
+
HRMS:
TLC:
C
19
H
23
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.11 (CH Cl /MeOH, 10:1) [silica gel, I ]
295.1810
295.1814
R
f
Preparation of O-Benzylcinchonidine (C)
Potassium hydride (164 mg, 4.08 mmol, 1.2 equiv) was placed in a 100-mL, single-neck,,
round-bottomed flask fitted with an argon inlet adapter and septum in a glove box. This flask
was then removed from the glove box and a solution of cinchonidine (1.00 g, 3.40 mmol) in THF
(43 mL, 0.08 M) was then added via syringe under argon. The reaction mixture was stirred for 15
min at 22 °C until it became a light orange solution and no further gas evolution was observed.
The mixture was cooled to 0 °C (external) on an ice bath over 2 h. Benzyl bromide (420 μL, 3.57
mmol, 1.05 equiv) was then added via syringe and the mixture was stirred for 4 h at 0 °C.
The reaction mixture was quenched with sat. aq. NH
diluted with Et O (30 mL). The quenched reaction mixture was transferred to a 125-mL
separatory funnel and then was extracted with 1 N aq. HCl solution (3 x 30 mL). The combined
aqueous extracts were washed with Et O (3 x 30 mL) then were basified with solid K CO until a
white suspension persisted with a pH of 9-11. The aqueous suspension was diluted with H O (20
mL) and then was extracted with CH Cl (3 x 30 mL). The combined organic extracts were
washed with brine (30 mL), dried over MgSO , and then concentrated on a rotavap (20 mm Hg,
5 °C) to afford 1.41 g of crude C as a light-amber oil. The product was purified by silica gel
4
Cl solution (~2 mL), and then was
2
2
2
3
2
2
2
4
2

Denmark and Weintraub
page S8
flash chromatography (50 g SiO
2
,  = 30, 20:1 to 5:1, EtOAc/MeOH gradient elution) to afford
1
.03 g (79%) of C as an off-white amorphous solid.
Data for C:
1
3
H-NMR: (500 MHz, CDCl )
8
.91 (d, J = 4.4 Hz, 1H), 8.22-8.09 (s, 1H), 8.17 (dd, J = 8.4, 0.9 Hz, 1H), 7.74
(
ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.62 – 7.55 (m, 1H), 7.53 (d, J = 4.3 Hz, 1H), 7.40
– 7.28 (m, 5H), 5.79 – 5.68 (m, 1H), 5.32 (s, 1H), 4.93 (ddd, J = 17.5, 9.5, 5.9 Hz,
2H), 4.43 (q, J = 11.5 Hz, 2H), 3.47 – 3.33 (m, 1H), 3.22 – 3.02 (m, 2H), 2.76 –
2.54 (m, 2H), 2.26 (s, 1H), 1.90 – 1.68 (m, 3H), 1.64 (s, 1H), 1.57 – 1.43 (m, 1H).
1
3
3
C-NMR: (126 MHz, CDCl )
1
1
2
50.17, 148.60, 146.38, 141.84, 137.81, 130.52, 129.09, 128.42, 127.73, 127.64,
26.69, 126.52, 123.21, 118.59, 114.25, 71.31, 60.80, 57.03, 43.15, 39.99, 27.92,
7.73.
+
LRMS: (ESI , Q-tof)
+
3
85.2 (100, M+H )
+
+
HRMS:
C
26
H
29
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.38 (CH Cl /MeOH, 10:1) [silica gel, I ]
385.2280
385.2278
TLC:
R
f
Preparation of O-Allylcinchonidine (D)
Potassium hydride (164 mg, 4.08 mmol, 1.2 equiv) was placed in a 100-mL, single-neck,,
round-bottomed flask fitted with an argon inlet adapter and septum in a glove box. This flask
was then removed from the glove box and a solution of cinchonidine (1.00 g, 3.40 mmol) in THF
(43 mL, 0.08 M) was then added via syringe under argon. The reaction mixture was stirred for 15
min at 22 °C until it became a light orange solution and no further gas evolution was observed.

Denmark and Weintraub
page S9
The reaction mixture was cooled to 0 °C (external) on an ice bath over 2 h. Allyl bromide (310
μL, 3.57 mmol, 1.05 equiv) was then added via syringe and the mixture was stirred for 4 h at
0
°C.
The reaction mixture was quenched with sat. aq. NH
diluted with Et O (30 mL). The quenched reaction mixture was transferred to a 125-mL
separatory funnel and then was extracted with 1 N aq. HCl solution (3 x 30 mL). The combined
aqueous extracts were washed with Et O (3 x 30 mL) then were basified with solid K CO until a
white suspension persisted with a pH of 9-11. The aqueous suspension was diluted with H O (20
mL) and then was extracted with CH Cl (3 x 30 mL). The combined organic extracts were
washed with brine (30 mL), dried over MgSO , and then concentrated on a rotavap (20 mm Hg,
5 °C) to afford 1.13 g (99+%) of crude D as a light-brown oil. The product was purified by
4
Cl solution (~2 mL), and then was
2
2
2
3
2
2
2
4
2
silica gel flash chromatography (40 g SiO ,  = 30, 20:1 to 10:1, EtOAc/MeOH) to afford 1.03 g
2
(
79%) of D as a light-amber oil.
Data for D:
1
3
H-NMR: (500 MHz, CDCl )
8
1
.90 (d, J = 4.4 Hz, 1 H), 8.13 (dd, J = 13.3, 8.5 Hz, 2 H), 7.72 (ddd, J = 8.3, 6.9,
.3 Hz, 1 H), 7.57 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.49 (d, J = 4.4 Hz, 1 H), 5.93
(
ddt, J = 17.1, 10.6, 5.4 Hz, 1 H), 5.77 - 5.65 (m, 1 H), 5.36 - 5.21 (m, 2 H), 5.21 -
.13 (m, 1 H), 4.99 - 4.84 (m, 2 H), 3.95 (ddt, J = 12.8, 5.1, 1.4 Hz, 1 H), 3.87 (dd,
J = 12.8, 5.7 Hz, 1 H), 3.44 (s, 1 H), 3.10 (dd, J = 13.5, 10.1 Hz, 2 H), 2.71 (dd, J
17.0, 7.3 Hz, 1 H), 2.63 (d, J = 13.4 Hz, 1 H), 2.27 (s, 1 H), 1.88 - 1.74 (m, 3 H),
.53 (ddd, J = 15.4, 12.7, 8.7 Hz, 2 H).
C-NMR: (126 MHz, CDCl
5
=
1
1
3
3
)
1
50.14, 148.54, 146.31, 141.73, 134.31, 130.49, 129.05, 126.68, 126.41, 123.12,
18.39, 116.95, 114.27, 70.14, 60.65, 57.09, 43.27, 39.98, 27.93, 27.69, 22.04.
1
Analysis:
C
22
H
26
N
2
O (334.45)
Calc:
C, 79.00;
H, 7.84;
H, 8.21;
N, 8.38
N, 8.11
Found:
C, 78.76;
+
LRMS: (ESI , Q-tof)
+
3
35.2 (100, M+H )

Denmark and Weintraub
page S10
+
+
HRMS:
C
22
H
27
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.34 (CH Cl /MeOH, 10:1) [silica gel, I ]
335.2123
335.2117
TLC:
R
f
Preparation of O-Methylcinchonidine (E)
Potassium hydride (164 mg, 4.08 mmol, 1.2 equiv) was placed in a 100-mL, single-neck,,
round-bottomed flask fitted with an argon inlet adapter and septum in a glove box. This flask
was then removed from the glove box and a solution of cinchonidine (1.00 g, 3.40 mmol) in THF
(43 mL, 0.08 M) was then added via syringe under argon. The reaction mixture was stirred for 15
min at 22 °C until it became a light orange solution and no further gas evolution was observed.
The reaction mixture was cooled to 0 °C (external) on an ice bath over 2 h. Methyl iodide (220
μL, 3.57 mmol, 1.05 equiv) was then added via syringe and the mixture was stirred for 4 h at
0
°C.
The reaction mixture was quenched with sat. aq. NH
diluted with Et O (30 mL). The quenched reaction mixture was transferred to a 125-mL
separatory funnel and then was extracted with 1 N aq. HCl solution (3 x 30 mL). The combined
aqueous extracts were washed with Et O (3 x 30 mL) then were basified with solid K CO until a
white suspension persisted with a pH of 9-11. The aqueous suspension was diluted with H O (20
mL) and then was extracted with CH Cl (3 x 30 mL). The combined organic extracts were
washed with brine (30 mL), dried over MgSO , and then concentrated on a rotavap (20 mm Hg,
5 °C) to afford 1.17 g of crude E as a light-yellow, crystalline solid.
The product was purified by silica gel flash chromatography (40 g SiO
0:1, CH Cl /MeOH ) to afford 781 mg (75%) of E as a white, crystalline solid. The entire
4
Cl solution (~2 mL), and then was
2
2
2
3
2
2
2
4
2
1
2
,  = 30, 20:1 to
2
2
product was further purified by recrystallization from boiling hexane.
Data for E:

Denmark and Weintraub
page S11
m.p.: 125-126 °C
1
3
H-NMR: (500 MHz, CDCl )
8
1
.90 (d, J = 4.4 Hz, 1 H), 8.12 (dd, J = 21.0, 8.4 Hz, 2 H), 7.72 (ddd, J = 8.3, 6.9,
.3 Hz, 1 H), 7.57 (ddd, J = 8.3, 6.9, 1.2 Hz, 1 H), 7.46 (d, J = 4.4 Hz, 1 H), 5.71
(
ddd, J = 17.7, 10.3, 7.7 Hz, 1 H), 5.07 (s, 1 H), 4.91 (ddt, J = 20.2, 10.3, 1.4 Hz,
2
2
H), 3.39 (t, J = 9.0 Hz, 1 H), 3.30 (s, 3 H), 3.09 (dd, J = 13.5, 10.2 Hz, 2 H),
.75 - 2.65 (m, 1 H), 2.65 - 2.55 (m, 1 H), 2.25 (s, 1 H), 1.84 - 1.69 (m, 3 H), 1.51
(
ddd, J = 16.8, 12.5, 7.7 Hz, 2 H).
1
3
C-NMR: (126 MHz, CDCl
3
)
1
50.14, 148.56, 146.07, 141.67, 130.49, 129.04, 126.69, 126.52, 123.16, 118.34,
14.34, 82.83, 60.57, 57.18, 56.96, 43.21, 39.92, 27.88, 27.59, 21.90.
1
Analysis:
C
20
H
24
N
2
O (308.42)
Calcd:
C, 77.89;
H, 7.84;
H, 7.95;
N, 9.08
N, 9.17
Found:
C, 77.96;
+
LRMS: (ESI , Q-tof)
+
+
3
09.2 (100, M+H )
+
HRMS:
TLC:
C
20
H
25
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.29 (CH Cl /MeOH, 10:1) [silica gel, I ]
309.1967
309.1960
R
f
Preparation of O-Methyl-epi-cinchonidine (F)
Potassium hydride (120 mg, 3.00 mmol, 1.2 equiv) was placed in a 50-mL, single-neck,
round-bottomed flask fitted with an argon inlet adapter and septum in a glove box. This flask
was then removed from the glove box and a solution of epi-cinchonidine (736 mg, 2.50 mmol) in
THF (31.0 mL, 0.08 M) was then added via syringe under argon. The reaction mixture was

Denmark and Weintraub
page S12
stirred for 15 min at 22 °C until it became a light orange solution and no further gas evolution
was observed. The reaction mixture was cooled to 0 °C (external) on an ice bath over 2 h. Methyl
iodide (164 μL, 2.63 mmol, 1.05 equiv) was then added via syringe and the mixture was stirred
for 4 h at 0 °C.
The reaction mixture was quenched with sat. aq. NH
diluted with Et O (30 mL). The quenched reaction mixture was transferred to a 125-mL
separatory funnel and then was extracted with 1 N aq. HCl solution (3 x 30 mL). The combined
aqueous extracts were washed with Et O (3 x 30 mL) then were basified with solid K CO until a
white suspension persisted with a pH of 9-11. The aqueous suspension was diluted with H O (20
mL) and then was extracted with CH Cl (3 x 30 mL). The combined organic extracts were
washed with brine (30 mL), dried over MgSO , and then concentrated on a rotavap (20 mm Hg,
5 °C) to afford 1.04 g of crude F as a light-yellow, crystalline solid.
The product was purified by silica gel flash chromatography (50 g SiO
:1, CH Cl /MeOH, gradient elution) to afford 665 mg (86%) of F as a white, crystalline solid.
4
Cl solution (~2 mL), and then was
2
2
2
3
2
2
2
4
2
5
2
,  = 30, 20:1 to
2
2
The entire product was further purified by recrystallization from boiling hexane.
Data for F:
m.p.: 125-126 °C
1
H-NMR: (500 MHz, CDCl
.90 (d, J = 4.4 Hz, 1 H), 8.18 - 8.06 (m, 2 H), 7.72 (ddd, J = 8.3, 6.9, 1.3 Hz, 1
H), 7.57 (ddd, J = 8.3, 6.9, 1.2 Hz, 1 H), 7.46 (d, J = 4.4 Hz, 1 H), 5.76 - 5.66 (m,
3
)
8
1
3
1
H), 5.07 (s, 1 H), 4.91 (ddt, J = 20.2, 10.3, 1.4 Hz, 2 H), 3.43 - 3.33 (m, 1 H),
.30 (s, 3 H), 3.08 (dt, J = 18.9, 9.6 Hz, 2 H), 2.75 - 2.64 (m, 1 H), 2.64 - 2.57 (m,
H), 2.26 (s, 1 H), 1.83 - 1.69 (m, 3 H), 1.51 (ddd, J = 16.4, 12.1, 7.7 Hz, 2 H).
1
3
3
C-NMR: (126 MHz, CDCl )
1
50.14, 148.51, 146.25, 141.85, 130.46, 129.00, 126.61, 126.51, 123.10, 118.33,
14.20, 83.09, 60.55, 57.17, 57.03, 43.16, 40.03, 27.87, 27.67, 21.98.
1
analysis:
C
20
H
24
N
2
O (308.42)
Calcd:
C, 77.89;
H, 7.84;
H, 7.95;
N, 9.08
N, 9.14
Found:
C, 77.90;
+
LRMS: (ESI , Q-tof)
+
3
09.2 (100, M+H )

Denmark and Weintraub
page S13
+
+
HRMS:
20 25 2
C H N O (ESI , Q-tof)
Calcd:
309.1967
Found:
309.1965
TLC:
f 2 2 2
R 0.30 (CH Cl /MeOH, 10:1) [silica gel, I ]
Preparation of Deoxyfluorocinchondine (G)
Cinchonidine (2.36 g, 8.00 mmol) was placed in a 50-mL, single-neck,, PTFE round-
bottomed flask fitted with a septum and was then suspended in THF (16.0 mL, 0.50 M). The
suspension was cooled to -20 °C (external) with a refrigerator unit in an i-PrOH bath over 2-3 h.
Diethylaminosulfur trifluoride (1.58 mL, 12.0 mmol, 1.50 equiv) was then added slowly over
several minutes via a polypropylene syringe under an argon atmosphere, and the mixture was
then stirred for 14 h at -20 °C. The reaction was quenched by transferring the brown solution to a
2
50-mL separatory funnel containing a sat. aq. NaHCO
extracted with CH Cl (3 x 60 mL). The combined organic extracts were washed with brine (60
mL), dried over MgSO , and then were concentrated on a rotavap (20 mm Hg, 25 °C) to afford
.75 g (116%) of G as an orange-amber, viscous oil.
The crude product was purified by three successive chromatographic separations on silica
gel. The first column (100 g SiO ,  = 40, 20:1 to 5:1, CH Cl /MeOH gradient elution) afforded
.42 g (60%) of crude G as a brown-amber oil. The second column (40 g SiO ,  = 30, 20:1 to
:1, EtOAc/MeOH gradient elution) afforded 521 mg (22%) of crude G as a yellow oil. The third
,  = 30, 10:1 to 8:1, TBME/MeOH) afforded 253 mg (11%) of G as a white,
3
solution (60 mL) which was then
2
2
4
2
2
2
2
1
5
2
column (50 g SiO
2
crystalline solid. The entire product was further purified by recrystallization from boiling
pentane.
Data for G:
m.p.: 78-81 °C

Denmark and Weintraub
page S14
1
3
H-NMR: (500 MHz, CD OD)
8
.81 (d, J = 4.6 Hz, 1 H), 8.03 (d, J = 8.3 Hz, 1 H), 7.98 (d, J = 8.4 Hz, 1 H), 7.75
ddd, J = 8.4, 6.9, 1.3 Hz, 1 H), 7.63 (ddd, J = 8.3, 6.9, 1.2 Hz, 1 H), 7.58 (d, J =
.6 Hz, 1 H), 6.40 (dd, J = 48.5, 2.2 Hz, 1 H), 5.70 (ddd, J = 17.6, 10.4, 7.5 Hz, 1
H), 4.91 (dd, J = 17.1, 1.5 Hz, 1 H), 4.87 - 4.81 (m, 1 H), 3.39 - 3.28 (m, 1 H),
(
4
3.10 (dd, J = 13.7, 10.2 Hz, 1 H), 2.80 - 2.70 (m, 1 H), 2.65 (ddd, J = 13.7, 5.1,
2.5 Hz, 1 H), 2.32 (s, 1 H), 1.80 - 1.69 (m, 3 H), 1.62 - 1.52 (m, 1 H), 1.46 (td, J =
10.4, 5.1 Hz, 1 H).
1
3
C-NMR: (126 MHz, CD
50.89, 148.81, 145.79 (d, J = 20.5 Hz), 142.31, 131.13, 130.33, 128.78, 125.91
d, J = 5.3 Hz), 124.09, 118.93 (d, J = 11.6 Hz), 115.15, 93.76 (d, J = 178.9 Hz),
0.81 (d, J = 21.9 Hz), 57.27, 44.22 (d, J = 5.4 Hz), 40.66, 29.03, 27.99, 21.27 (d,
3
OD)
1
(
6
J = 5.8 Hz).
1
9
3
F-NMR: (376 MHz, CD OD)
-
199.29 (dd, JH-F = 48.4, 27.4 Hz).
(296.38)
C, 77.00;
analysis:
19 2
C H21FN
Calcd:
H, 7.14;
H, 7.33;
N, 9.45
N, 9.47
Found:
C, 77.04;
+
LRMS: (ESI , Q-tof)
+
2
97.2 (100, M+H )
+
+
HRMS:
C
19
H
22FN
2
(ESI , Q-tof)
Calcd:
Found:
297.1767
297.1776
TLC:
f 2 2 2
R 0.42 (CH Cl /MeOH, 10:1) [silica gel, I ]
Preparation of Cinchonan-9-ol, 9-(phenol thiocarbonate) (H’)

Denmark and Weintraub
page S15
Cinchonidine (1.77 g, 6.00 mmol) and 4-dimethylaminopyridine (367 mg, 3.00 mmol,
.50 equiv) were added to a 100-mL, single-neck, round-bottomed flask fitted with an argon inlet
0
adapter and septum and followed by THF (67.0 mL, 0.09 M). Triethylamine (1.92 mL, 13.8
mmol, 2.30 equiv) was then added and the mixture was stirred until it became homogeneous.
Phenyl chlorothionoformate (1.67 mL, 12.0 mmol, 2.0 equiv) was then added via syringe to
afford a suspension with a yellow precipitate and the reaction mixture was stirred at room
temperature for 3 h. The reaction mixture was transferred to 125-mL separatory funnel followed
by the addition of a sat. aq. NaHCO
EtOAc (3 x 70 mL). The combined organic extracts were washed with brine (70 mL), dried over
Na SO , and concentrated on a rotavap (20 mm Hg, 30 - 35 °C) to afford 6.07 g of crude H’ as a
dark-brown liquid. The product was purified by silica gel flash chromatography (100 g SiO , 
40, 20:1 to 10:1, EtOAc/MeOH) to afford 2.18 g (85%) of H’ as an brown, amorphous solid.
3
solution (70 mL) and the suspension was extracted with
2
4
2
=
Data for H’:
1
3
H-NMR: (500 MHz, CDCl )
8
7
.94 (d, J = 4.5 Hz, 1 H), 8.20 (d, J = 8.2 Hz, 1 H), 8.16 (dd, J = 8.5, 0.8 Hz, 1 H),
.74 (ddd, J = 8.3, 6.9, 1.3 Hz, 1 H), 7.61 (ddd, J = 8.3, 6.9, 1.3 Hz, 1 H), 7.48 (d,
J = 4.5 Hz, 1 H), 7.42 - 7.35 (m, 2 H), 7.31 - 7.23 (m, 1 H), 7.09 - 7.00 (m, 3 H),
.81 (ddd, J = 17.6, 10.4, 7.5 Hz, 1 H), 4.99 (ddt, J = 10.3, 6.4, 1.4 Hz, 2 H), 3.43
dd, J = 16.9, 7.8 Hz, 1 H), 3.28 - 3.16 (m, 1 H), 3.07 (dd, J = 13.9, 10.1 Hz, 1 H),
5
(
2
1
.78 - 2.67 (m, 1 H), 2.60 (ddd, J = 13.7, 4.5, 2.4 Hz, 1 H), 2.30 (s, 1 H), 1.96 -
.85 (m, 2 H), 1.85 - 1.76 (m, 1 H), 1.76 - 1.68 (m, 1 H), 1.64 - 1.52 (m, 1 H).
+
LRMS: (ESI , ZMD)
+
2
77.2 (47), 431.1 (100, M+H )
Preparation of Deoxycinchonidine (H)
Azo bis(isobutyrodinitrile) (333 mg, 2.00 mmol, 0.40 equiv) and a solution of

Denmark and Weintraub
page S16
Cinchonan-9-ol, 9-(phenol thiocarbonate) (2.15 g, 5.00 mmol) in toluene (50 mL, 0.10 M) were
combined in a 100-mL, single-neck, round-bottomed flask fitted with a condenser and argon
inlet. Tributyltin hydride (2.73 mL, 10.0 mmol, 2.00 equiv) was then added via syringe and the
reaction mixture was stirred at reflux for 1 h. The reaction mixture was allowed to cool to 22 °C
and was then concentrated on a rotavap (20 mm Hg, 35-40 °C) to afford a yellow liquid.
The product was purified by silica gel flash chromatography [50 g SiO
2
,  = 30, 10:1,
EtOAc : (10% aq. NH OH in MeOH)] to afford 1.38 g (97%) of H as a light-brown, crystalline
4
solid. The product was further purified by recrystallization from concentrated pentane solution
and cooling overnight in a freezer to afford an off-white, crystalline solid.
Data for H:
m.p.: 58 – 59 °C
1
3
H-NMR: (500 MHz, CDCl )
8
7
.81 (d, J = 4.4 Hz, 1 H), 8.09 (dd, J = 19.7, 8.4 Hz, 2 H), 7.74 - 7.66 (m, 1 H),
.61 - 7.52 (m, 1 H), 7.28 (d, J = 4.4 Hz, 1 H), 5.79 (ddd, J = 17.8, 10.3, 7.6 Hz, 1
H), 4.97 (ddd, J = 13.7, 11.3, 1.2 Hz, 2 H), 3.41 (dd, J = 13.8, 5.8 Hz, 1 H), 3.28 -
.15 (m, 3 H), 3.08 (dd, J = 13.8, 8.5 Hz, 1 H), 2.85 - 2.74 (m, 1 H), 2.70 (ddd, J
3
=
1
13.8, 4.9, 2.4 Hz, 1 H), 2.33 - 2.22 (m, 1 H), 1.87 - 1.72 (m, 2 H), 1.71 - 1.62 (m,
H), 1.62 - 1.51 (m, 1 H), 1.17 (dd, J = 13.2, 6.6 Hz, 1 H).
1
3
3
C-NMR: (126 MHz, CDCl )
1
50.04, 148.37, 145.40, 141.77, 130.31, 128.95, 127.76, 126.38, 123.44, 121.52,
14.29, 56.25, 56.05, 41.06, 39.54, 38.18, 28.87, 27.96, 27.90.
1
analysis:
C
19
H
22
N
2
O (278.39)
Calcd:
C, 81.97;
H, 7.97;
H, 8.11;
N, 10.06
N, 10.13
Found:
C, 82.13;
+
LRMS: (ESI , Q-tof)
+
+
2
79.2 (100, M+H )
+
HRMS:
TLC:
C
19
H
23
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.28 (CH Cl /MeOH, 10:1) [silica gel, I ]
279.1861
279.1864
R
f

Denmark and Weintraub
page S17
Preparation of Cinchonidinium Salts in Series A
Preparation of N-9-Anthracenylmethylcinchonidinium Bromide (1a)
Following General Procedure I, cinchonidine (1.31 g, 4.4 mmol), MeCN (25 mL), and 9-
bromomethylanthracene (1.32 g, 4.84 mmol, 1.1 equiv) were combined in a 50-mL, single-neck,
round-bottomed flask fitted with an argon inlet, wrapped in aluminum foil and the mixture was
stirred overnight. Care was taken to avoid light exposure. The solvent was removed on a rotavap
(
2
20 mm Hg, 25 °C) and yellow solid residue was triturated with Et O (25-mL) and filtered to
afford 2.16 g (86%) of 1a as a light-yellow, crystalline solid. The entire product was further
2 2 2
purified by recrystallization from a concentrated CH Cl solution by slow diffusion of Et O in a
chamber.
Data for 1a:
m.p.: 154 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
9
8
7
.01 (d, J = 4.6 Hz, 1 H), 8.86 - 8.77 (m, 2 H), 8.66 - 8.56 (m, 2 H), 8.22 (d, J =
.5 Hz, 2 H), 8.20 - 8.14 (m, 1 H), 8.08 (d, J = 4.5 Hz, 1 H), 7.96 - 7.88 (m, 2 H),
.83 - 7.75 (m, 2 H), 7.63 (ddd, J = 8.4, 6.6, 4.1 Hz, 2 H), 7.11 (d, J = 1.8 Hz, 1
H), 6.50 (d, J = 14.0 Hz, 1 H), 5.93 (d, J = 14.0 Hz, 1 H), 5.71 (ddd, J = 17.4,
0.4, 7.2 Hz, 1 H), 5.01 (dd, J = 26.2, 13.8 Hz, 2 H), 4.74 - 4.63 (m, 1 H), 4.48 (t,
1
J = 9.0 Hz, 1 H), 3.86 (ddd, J = 12.5, 4.9, 3.2 Hz, 1 H), 3.24 (dd, J = 12.4, 10.9
Hz, 1 H), 2.80 (td, J = 11.7, 4.6 Hz, 1 H), 2.45 (s, 1 H), 2.30 (dd, J = 13.4, 8.2 Hz,
1
1
H), 2.18 - 2.07 (m, 1 H), 1.93 (d, J = 2.7 Hz, 1 H), 1.62 - 1.50 (m, 1 H), 1.50 -
.39 (m, 1 H).
1
3
3
C-NMR: (126 MHz, CD OD)
151.03, 148.72, 147.83, 138.79, 134.80, 134.71, 133.72, 133.04, 133.00, 131.35,
131.16, 131.08, 130.29, 129.29, 126.59, 126.32, 125.60, 125.12, 124.51, 121.55,
121.52, 119.25, 117.63, 69.95, 67.24, 63.74, 56.84, 53.37, 39.66, 27.29, 26.26,

Denmark and Weintraub
page S18
23.04.
+
LRMS: (ESI , Q-tof)
191.1 (35), 295.2 (25), 485.3 m/z (100, M-Br+)
+
+
HRMS:
TLC:
C
34
H
33
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.31 (CH Cl /MeOH, 5:1) [silica gel, I ]
485.2593
485.2598
R
f
Preparation of N-(2-Naphthylmethyl)cinchonidinium Bromide (2a)
Following General Procedure I, cinchonidine (1.47 g, 5 mmol), MeCN (50 mL), and 2-
bromomethylnaphthalene (2.35 g, 10.5 mmol, 2.1 equiv) were combined in a 100-mL, single-
neck, round-bottomed flask and the mixture was stirred overnight. The solvent was removed on a
2
rotavap (20 mm Hg, 25 °C) and the remaining off-white solid was triturated in Et O (3 x 25 mL)
then was filtered three times separately to afford 2.27 g (88%) of 2a as a white, crystalline solid.
Data for 2a:
m.p.: 236 °C (decomp.)
1
6
H-NMR: (500 MHz, d -DMSO)
9
8
.00 (d, J = 4.4 Hz, 1 H), 8.37 - 8.28 (m, 2 H), 8.12 (dd, J = 7.9, 6.0 Hz, 2 H),
.08 - 8.01 (m, 2 H), 7.89 - 7.80 (m, 3 H), 7.79 - 7.72 (m, 1 H), 7.69 - 7.61 (m, 2
H), 6.78 (d, J = 4.3 Hz, 1 H), 6.62 (s, 1 H), 5.69 (ddd, J = 17.2, 10.5, 6.5 Hz, 1 H),
5
1
1
.31 (d, J = 12.4 Hz, 1 H), 5.17 (dd, J = 14.5, 13.3 Hz, 2 H), 4.96 (d, J = 10.5 Hz,
H), 4.35 (t, J = 10.6 Hz, 1 H), 3.98 (t, J = 8.9 Hz, 1 H), 3.81 (dd, J = 8.9, 3.7 Hz,
H), 3.46 - 3.34 (m, 2 H), 2.64 (s, 1 H), 2.11 (dt, J = 22.9, 10.9 Hz, 2 H), 1.99 (d,
J = 2.3 Hz, 1 H), 1.79 (t, J = 10.4 Hz, 1 H), 1.31 (dd, J = 12.9, 10.3 Hz, 1 H).
C-NMR: (126 MHz, d -DMSO)
50.17, 147.62, 145.26, 138.13, 133.91, 133.27, 132.55, 130.15, 129.88, 129.45,
1
3
6
1

Denmark and Weintraub
page S19
128.38, 128.33, 127.65, 127.54, 127.17, 126.83, 125.41, 124.30, 123.64, 120.06,
116.36, 67.57, 64.20, 62.92, 59.29, 50.67, 36.93, 25.87, 24.25, 20.92.
+
LRMS: (ESI , Q-tof)
295.2 (10), 435.2 (100, M-Br+)
+
+
HRMS:
TLC:
C
30
H
31
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.25 (CH Cl /MeOH, 5:1) [silica gel, I ]
435.2436
435.2439
R
f
Preparation of N-(1-Naphthylmethyl)cinchonidinium Bromide (3a)
Following General Procedure I, cinchonidine (1.47 g, 5.00 mmol), MeCN (50.0 mL), and
1
-bromomethylnaphthalene (1.22 g, 5.50 mmol, 1.1 equiv) were combined in a 100-mL, single-
neck, round-bottomed flask fitted with an argon inlet and the reaction mixture was stirred
overnight. The solvent was removed on a rotavap (20 mm Hg, 25 °C) and remaining solid was
triturated with Et
solid. The entire crude product was further purified by recrystallization from a concentrated
CH Cl solution by slow diffusion of Et O in a chamber.
Data for 3a:
m.p.: 200 °C (decomp.)
H-NMR: (500 MHz, CD OD)
2
O (50 mL) then was filtered to afford 2.33 g (90%) of 3a as a white, crystalline
2
2
2
1
3
8.98 (d, J = 4.6 Hz, 1 H), 8.40 (d, J = 8.2 Hz, 2 H), 8.20 - 8.11 (m, 2 H), 8.09 -
7.99 (m, 3 H), 7.87 (dtd, J = 16.5, 6.9, 1.2 Hz, 2 H), 7.79 - 7.73 (m, 1 H), 7.73 -
7.67 (m, 1 H), 7.65 (t, J = 7.5 Hz, 1 H), 6.87 (s, 1 H), 5.91 (d, J = 13.1 Hz, 1 H),
5.70 (ddd, J = 17.3, 10.5, 6.8 Hz, 1 H), 5.37 (d, J = 13.1 Hz, 1 H), 5.14 (d, J =
17.2 Hz, 1 H), 5.00 (d, J = 10.5 Hz, 1 H), 4.68 - 4.57 (m, 1 H), 4.22 (t, J = 9.1 Hz,
1 H), 3.88 - 3.78 (m, 1 H), 3.56 (dd, J = 12.5, 10.8 Hz, 1 H), 3.16 (td, J = 11.4, 3.7

Denmark and Weintraub
page S20
Hz, 1 H), 2.65 (s, 1 H), 2.35 - 2.25 (m, 1 H), 2.24 - 2.14 (m, 1 H), 2.04 (s, 1 H),
.80 - 1.69 (m, 1 H), 1.42 (td, J = 10.2, 3.2 Hz, 1 H).
C-NMR: (126 MHz, CDCl
1
1
3
3
)
1
1
1
49.28, 146.89, 144.85, 135.77, 134.29, 133.01, 132.77, 130.27, 129.31, 128.64,
28.06, 127.41, 126.88, 125.70, 124.74, 124.11, 123.45, 123.25, 122.09, 119.48,
17.78, 65.92, 65.80, 59.49, 57.22, 50.99, 37.89, 25.93, 25.31, 22.81
+
LRMS: (ESI , Q-tof)
+
4
35.2 (100, M-Br )
+
+
HRMS:
TLC:
C
30
H
31
N
2
O (ESI , Q-tof)
435.2436
Calcd:
Found:
2 2 2
0.31 (CH Cl /MeOH, 5:1) [silica gel, I ]
435.2436
R
f
Preparation of N-(Benzyl)cinchonidinium Bromide (4a)
Following General Procedure I, cinchonidine (1.47 g, 5.00 mmol), MeCN (50.0 mL), and
benzyl bromide (650 μL, 5.50 mmol, 1.1 equiv) were combined in a 100-mL, single-neck, round-
bottomed flask fitted with an argon inlet and the mixture was stirred overnight. The reaction
mixture was filtered and the filter cake washed several times with MeCN (50 mL). The filtrate
2
was concentrated on a rotavap (20 mm Hg, 25 °C) and the solid residue triturated with Et O (50
mL) then filtered. Both filter cakes were combined to afford 2.25 g (97%) of 4a as a white,
crystalline solid. The entire crude product was further purified by recrystallization from a
2 2 2
concentrated CH Cl solution by slow diffusion of Et O in a chamber.
Data for 4a:
m.p.: 164 °C (decomp.)
H-NMR: (500 MHz, CD OD)
.95 (d, J = 4.6 Hz, 1 H), 8.28 (d, J = 8.2 Hz, 1 H), 8.13 (d, J = 8.2 Hz, 1 H), 7.97
d, J = 4.6 Hz, 1 H), 7.90 - 7.84 (m, 1 H), 7.84 - 7.77 (m, 1 H), 7.74 (dd, J = 6.5,
1
3
8
(

Denmark and Weintraub
page S21
2
1
1
1
2
.9 Hz, 2 H), 7.62 - 7.55 (m, 3 H), 6.66 (s, 1 H), 5.69 (ddd, J = 17.3, 10.5, 6.8 Hz,
H), 5.17 (dd, J = 21.7, 14.8 Hz, 2 H), 5.00 (d, J = 11.9 Hz, 2 H), 4.50 - 4.40 (m,
H), 4.00 (t, J = 9.1 Hz, 1 H), 3.66 (ddd, J = 12.7, 4.7, 3.3 Hz, 1 H), 3.48 (dd, J =
2.7, 10.8 Hz, 1 H), 3.41 (td, J = 11.3, 3.8 Hz, 1 H), 2.72 (s, 1 H), 2.33 - 2.19 (m,
H), 2.08 (d, J = 2.8 Hz, 1 H), 1.88 (ddd, J = 15.1, 5.2, 2.6 Hz, 1 H), 1.42 (ddd, J
=
13.4, 6.5, 3.4 Hz, 1 H).
1
3
C-NMR: (126 MHz, CDCl
3
)
1
1
2
49.42, 147.14, 144.42, 135.97, 134.02, 129.92, 129.58, 128.62, 128.34, 127.28,
26.90, 123.57, 122.88, 119.76, 117.77, 66.96, 65.06, 62.16, 60.04, 50.28, 37.79,
6.44, 25.08, 22.36
+
LRMS: (ESI , Q-tof)
+
3
85.2 (100, M-Br )
+
+
HRMS:
TLC:
C
26
H
29
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.27 (CH Cl /MeOH, 5:1) [silica gel, I ]
385.2280
385.2282
R
f
Preparation of N-(3,5-Bis-trifluoromethylbenzyl)cinchonidinium Bromide (5a)
Following General Procedure I, cinchonidine 589 mg (2.00 mmol), MeCN (20.0 mL),
and bis-(3,5-trifluoromethyl)benzyl bromide (404 μL, 2.20 mmol, 1.1 equiv) were combined in a
5
0-mL, single-neck, round-bottomed flask fitted with an argon inlet and the mixture was stirred
for 72 hours. The solvent was removed on a rotavap (20 mm Hg, 25 °C) and the solid residue
was triturated with Et O (30 mL) then filtered to afford 1.04 g (87%) of 5a as a white, crystalline
solid. The product was further purified by recrystallization from a concentrated CH Cl solution
by slow diffusion of Et O in a chamber.
2
2
2
2

Denmark and Weintraub
page S22
Data for 5a:
m.p.: 173 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
8
8
6
.95 (d, J = 4.6 Hz, 1 H), 8.45 (s, 2 H), 8.33 (d, J = 8.1 Hz, 1 H), 8.24 (s, 1 H),
.13 (dd, J = 8.4, 1.0 Hz, 1 H), 7.96 (d, J = 4.5 Hz, 1 H), 7.85 (dddd, J = 16.5, 8.2,
.9, 1.3 Hz, 2 H), 6.66 (s, 1 H), 5.69 (ddd, J = 17.3, 10.5, 6.8 Hz, 1 H), 5.34 (dd, J
=
63.7, 12.6 Hz, 2 H), 5.17 (d, J = 17.2 Hz, 1 H), 5.01 (d, J = 10.5 Hz, 1 H), 4.64 -
4.52 (m, 1 H), 4.05 (t, J = 8.4 Hz, 1 H), 3.83 - 3.70 (m, 1 H), 3.47 (dd, J = 12.3,
10.8 Hz, 1 H), 3.39 (td, J = 11.3, 3.8 Hz, 1 H), 2.74 (s, 1 H), 2.38 - 2.20 (m, 2 H),
2.10 (d, J = 2.4 Hz, 1 H), 1.96 - 1.84 (m, 1 H), 1.50 - 1.38 (m, 1 H).
1
3
3
C-NMR: (126 MHz, CD OD)
1
1
7
51.06, 148.76, 147.28, 138.52, 135.45, 133.68 (q, JC-F = 33.8 Hz), 132.03,
31.22, 130.41, 129.25, 126.06, 125.50 (m), 124.10, 123.43, 121.31, 117.69,
0.34, 66.32, 63.43, 61.93, 53.02, 39.13, 27.92, 25.86, 22.51.
+
LRMS: (ESI , Q-tof)
+
5
21.2 (100, M-Br )
+
+
HRMS:
TLC:
C
28
H
27
N
2
OF
6
(ESI , Q-tof)
521.2028
Calcd:
Found:
2 2 2
0.28 (CH Cl /MeOH, 5:1) [silica gel, I ]
521.2029
R
f
Preparation of Cinchonidinium Salts in Series B
Preparation of N-(9-Anthracenylmethyl)-epi-cinchonidinium Bromide (1b)
Following General Procedure I, epi-cinchonidine (100 mg, 0.340 mmol), MeCN (3.4 mL),
and 9-bromomethylanthracene (101 mg, 0.374 mmol, 1.10 equiv) were combined in a 10-mL,
single-neck, round-bottomed flask fitted with an argon inlet, wrapped in aluminum foil and the

Denmark and Weintraub
page S23
mixture was stirred overnight. Care was taken to avoid light exposure. The reaction mixture was
diluted with CH Cl (~5 mL) then was loaded directly on a silica gel column (15 g SiO ,  = 20,
00:0 to 10:1, CH Cl /MeOH gradient elution) to afford 169 mg (88%) of 1b as a light-yellow,
crystalline solid. The entire product was further purified by recrystallization from a concentrated
CH Cl solution by slow diffusion of Et O in a chamber.
Data for 1b:
mp: 154-162 °C (decomp.)
H-NMR: (500 MHz, CD OD)
.01 (d, J = 4.6 Hz, 1 H), 8.85 (s, 1 H), 8.80 (d, J = 9.0 Hz, 1 H), 8.63 (d, J = 9.0
Hz, 1 H), 8.61 - 8.56 (m, 1 H), 8.23 (d, J = 8.5 Hz, 2 H), 8.20 - 8.15 (m, 1 H),
2
2
2
1
2
2
2
2
2
1
3
9
8
7
.08 (d, J = 4.5 Hz, 1 H), 7.95 - 7.88 (m, 2 H), 7.80 (dtd, J = 7.7, 6.2, 1.1 Hz, 2 H),
.67 - 7.59 (m, 2 H), 7.11 (d, J = 1.9 Hz, 1 H), 6.51 (d, J = 14.0 Hz, 1 H), 5.93 (d,
J = 14.0 Hz, 1 H), 5.70 (ddd, J = 17.4, 10.4, 7.2 Hz, 1 H), 5.01 (dd, J = 23.7, 13.8
Hz, 2 H), 4.74 - 4.64 (m, 1 H), 4.46 (t, J = 9.0 Hz, 1 H), 3.85 (ddd, J = 12.5, 4.9,
3
2
2
.2 Hz, 1 H), 3.24 (dd, J = 12.4, 10.9 Hz, 1 H), 2.81 (td, J = 11.3, 4.2 Hz, 1 H),
.45 (s, 1 H), 2.30 (dd, J = 13.6, 8.1 Hz, 1 H), 2.19 - 2.08 (m, 1 H), 1.93 (d, J =
.7 Hz, 1 H), 1.62 - 1.52 (m, 1 H), 1.47 (ddd, J = 13.3, 8.3, 3.3 Hz, 1 H).
1
3
3
C-NMR: (126 MHz, CD OD)
1
1
1
2
51.10, 148.88, 147.65, 138.76, 134.82, 134.73, 133.74, 133.07, 133.03, 131.28,
31.17, 131.09, 130.44, 129.30, 129.25, 129.22, 126.60, 126.56, 126.32, 125.50,
25.07, 124.38, 121.50, 119.23, 117.61, 70.06, 67.24, 63.80, 56.89, 53.42, 39.66,
7.29, 26.27, 23.04
+
LRMS: (ESI , Q-tof)
+
4
85.2 (100, M-Br )
+
+
HRMS:
TLC:
C
34
H
33
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.58 (CH Cl /MeOH, 5:1) [silica gel, I ]
485.2593
485.2594
R
f

Denmark and Weintraub
page S24
Preparation of N-(2-Naphthylmethyl)-epi-cinchonidinium Bromide (2b)
Following General Procedure I, epi-cinchonidine (100 mg, 0.340 mmol), MeCN (3.4 mL),
and 2-bromomethylnaphthalene (83.0 mg, 0.374 mmol, 1.1 equiv) were combined in a 10-mL,
single-neck, round-bottomed flask fitted with an argon inlet and the mixture was stirred
overnight. Reaction was diluted with CH Cl (~5 mL) and MeOH (several drops) then was
2
2
loaded directly on a silica gel column (15 g SiO
2 2 2
,  = 20, 100:0 to 10:1, CH Cl /MeOH gradient
elution) to afford 125 mg (71%) of 2b as a pale-yellow, crystalline solid.
Data for 2b
m.p.: 198-210 °C (decomp.)
1
H-NMR: (500 MHz, d
.00 (d, J = 4.5 Hz, 1 H), 8.37 - 8.29 (m, 2 H), 8.15 - 8.08 (m, 2 H), 8.08 - 8.00
m, 2 H), 7.85 (ddd, J = 11.4, 8.3, 2.5 Hz, 3 H), 7.76 (ddd, J = 8.2, 6.9, 1.2 Hz, 1
H), 7.69 - 7.60 (m, 2 H), 6.82 (d, J = 4.3 Hz, 1 H), 6.62 (d, J = 2.9 Hz, 1 H), 5.69
ddd, J = 17.2, 10.6, 6.5 Hz, 1 H), 5.33 (d, J = 12.4 Hz, 1 H), 5.17 (t, J = 14.5 Hz,
H), 4.96 (d, J = 10.5 Hz, 1 H), 4.36 (t, J = 10.6 Hz, 1 H), 3.98 (t, J = 8.9 Hz, 1
6
-DMSO)
9
(
(
2
H), 3.86 - 3.76 (m, 1 H), 3.39 (ddd, J = 18.8, 12.1, 7.8 Hz, 2 H), 2.65 (d, J = 3.7
Hz, 1 H), 2.19 - 2.02 (m, 2 H), 1.99 (d, J = 2.5 Hz, 1 H), 1.79 (t, J = 9.3 Hz, 1 H),
1
.31 (dd, J = 12.9, 10.2 Hz, 1 H).
1
3
C-NMR: (126 MHz, d -DMSO)
6
1
1
1
50.11, 147.60, 145.21, 138.08, 133.86, 133.24, 132.51, 130.10, 129.84, 129.38,
28.33, 128.28, 127.60, 127.49, 127.12, 126.77, 125.38, 124.28, 123.59, 120.03,
16.31, 67.58, 64.14, 62.88, 59.33, 50.64, 36.90, 25.85, 24.22, 20.90, 19.27.
+
LRMS: (ESI , Q-tof)
+
4
35.2 (100, M-Br )

Denmark and Weintraub
page S25
+
+
HRMS:
C
30
H
31
N
2
O (ESI , Q-tof)
435.2436
Calcd:
Found:
2 2 2
0.51 (CH Cl /MeOH, 5:1) [silica gel, I ]
435.2432
TLC:
R
f
Preparation of N-(1-Naphthylmethyl)-epi-cinchonidinium Bromide (3b)
Following General Procedure I, epi-cinchonidine (100 mg, 0.340 mmol), MeCN (3.4 mL),
and 1-bromomethylnaphthalene (83.0 mg, 0.374 mmol, 1.1 equiv) were combined in a 10-mL,
single-neck, round-bottomed flask fitted with an argon inlet and the mixture was stirred
overnight. The reaction mixture was diluted with CH
2
Cl
2
(~5 mL) and then was loaded directly
Cl /MeOH gradient elution) to
on a silica gel column (15 g SiO ,  = 20, 100:0 to 10:1, CH
2
2
2
afford 141 mg (81%) of 3b as a white, crystalline solid.
Data for 3b:
m.p.: 189-197 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
8
8
1
.98 (d, J = 4.5 Hz, 1 H), 8.41 (dd, J = 8.0, 4.6 Hz, 2 H), 8.21 - 8.10 (m, 2 H),
.10 - 7.99 (m, 3 H), 7.93 - 7.80 (m, 2 H), 7.76 (t, J = 7.6 Hz, 1 H), 7.72 - 7.67 (m,
H), 7.64 (t, J = 7.5 Hz, 1 H), 6.87 (s, 1 H), 5.91 (d, J = 13.1 Hz, 1 H), 5.70 (ddd,
J = 17.2, 10.5, 6.8 Hz, 1 H), 5.39 (d, J = 13.1 Hz, 1 H), 5.14 (d, J = 17.2 Hz, 1 H),
5
3
1
1
.00 (d, J = 10.5 Hz, 1 H), 4.63 (t, J = 10.2 Hz, 1 H), 4.22 (t, J = 8.9 Hz, 1 H),
.89 - 3.79 (m, 1 H), 3.61 - 3.51 (m, 1 H), 3.16 (td, J = 11.3, 3.8 Hz, 1 H), 2.65 (s,
H), 2.35 - 2.24 (m, 1 H), 2.24 - 2.13 (m, 1 H), 2.04 (s, 1 H), 1.81 - 1.68 (m, 1 H),
.42 (td, J = 10.0, 2.8 Hz, 1 H).
1
3
3
C-NMR: (126 MHz, CD OD)
1
51.07, 148.81, 147.54, 138.73, 135.81, 135.65, 134.80, 133.10, 131.20, 130.64,
30.42, 129.18, 128.96, 127.60, 126.41, 126.16, 124.53, 124.14, 121.35, 117.52,
1

Denmark and Weintraub
9.68, 66.74, 62.70, 61.28, 53.30, 39.36, 27.64, 26.08, 22.74.
page S26
6
+
LRMS: (ESI , Q-tof)
+
4
35.2 (100, M-Br )
+
+
HRMS:
TLC:
C
30
H
31
N
2
O (ESI , Q-tof)
435.2436
Calcd:
Found:
2 2 2
0.55 (CH Cl /MeOH, 5:1) [silica gel, I ]
435.2444
R
f
Preparation of N-(Benzyl)-epi-cinchonidinium Bromide (4b)
Following General Procedure I, epi-cinchonidine (100 mg, 0.340 mmol), MeCN (3.4 mL),
and benzyl bromide (44.0 μL, 0.374 mmol, 1.10 equiv) were combined in a 10-mL, single-neck,
round-bottomed flask fitted with an argon inlet and the mixture was stirred overnight. The
reaction mixture was diluted with CH
column (15 g SiO ,  = 20, 100:0 to 10:1, CH
87%) of 4b as a white, crystalline solid.
Data for 4b:
m.p.: 165-169 °C (decomp.)
H-NMR: (500 MHz, CD OD)
2
Cl
2
(~5 mL) and then was loaded directly on a silica gel
2
2
Cl /MeOH gradient elution) to afford 137 mg
2
(
1
3
8.95 (d, J = 4.6 Hz, 1 H), 8.29 (d, J = 7.9 Hz, 1 H), 8.13 (dd, J = 8.4, 0.9 Hz, 1 H),
7.97 (d, J = 4.4 Hz, 1 H), 7.84 (dtd, J = 16.5, 7.0, 1.2 Hz, 2 H), 7.75 (dd, J = 6.4,
2.9 Hz, 2 H), 7.59 (dd, J = 4.7, 1.8 Hz, 3 H), 6.66 (s, 1 H), 5.69 (ddd, J = 17.2,
10.5, 6.8 Hz, 1 H), 5.17 (dd, J = 22.4, 14.8 Hz, 2 H), 5.01 (t, J = 11.5 Hz, 2 H),
4.46 (t, J = 10.5 Hz, 1 H), 4.01 (t, J = 9.1 Hz, 1 H), 3.68 (ddd, J = 12.7, 4.5, 3.1
Hz, 1 H), 3.48 (dd, J = 12.6, 10.9 Hz, 1 H), 3.41 (td, J = 11.2, 3.5 Hz, 1 H), 2.72
s, 1 H), 2.26 (ddd, J = 25.9, 14.7, 6.5 Hz, 2 H), 2.07 (s, 1 H), 1.94 - 1.81 (m, 1 H),
.42 (td, J = 10.1, 2.8 Hz, 1 H).
(
1

Denmark and Weintraub
page S27
1
3
3
C-NMR: (126 MHz, CD OD)
1
1
2
51.04, 148.78, 147.52, 138.73, 134.90, 131.76, 131.15, 130.40, 129.15, 128.72,
26.11, 124.08, 121.32, 117.50, 69.70, 66.32, 65.26, 62.10, 52.75, 39.13, 28.04,
5.95, 22.51.
+
LRMS: (ESI , Q-tof)
+
2
95.2 (40), 385.2 m/z (100, M-Br )
+
+
HRMS:
TLC:
C
26
H
29
N
2
O (ESI , Q-tof)
Calcd:
Found:
2 2 2
0.51 (CH Cl /MeOH, 5:1) [silica gel, I ]
385.2280
385.2285
R
f
Preparation of N-(3,5-Bis-trifluoromethylbenzyl)-epi-cinchonidinium Bromide (5b)
Following General Procedure I, epi-cinchonidine (100 mg, 0.340 mmol), MeCN (3.4 mL),
and bis-(3,5-trifluormethyl)-benzyl bromide (69.0 μL, 0.374 mmol, 1.10 equiv) were combined
in a 10-mL, single-neck, round-bottomed flask fitted with an argon inlet and the mixture was
stirred overnight. The reaction mixture was diluted with CH
2
Cl
2
(~5 mL) and then was loaded
Cl /MeOH gradient
directly on a silica gel column (15 g SiO ,  = 20, 100:0 to 10:1, CH
2
2
2
elution) to afford 200 mg (98%) of 5b as a white, crystalline solid.
Data for 5b:
m.p.: 200-212 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
8.96 (d, J = 4.6 Hz, 1 H), 8.45 (s, 2H), 8.32 (d, J = 8.5 Hz, 1 H), 8.25 (s, 1 H),
8.14 (dd, J = 8.4, 1.0 Hz, 1 H), 7.96 (d, J = 4.4 Hz, 1 H), 7.85 (dddd, J = 24.2, 8.2,
6.9, 1.3 Hz, 2H), 6.66 (s, 1 H), 5.69 (ddd, J = 17.3, 10.5, 6.8 Hz, 1 H), 5.40 (d, J =
12.6 Hz, 1 H), 5.27 (d, J = 12.6 Hz, 1 H), 5.17 (d, J = 17.2 Hz, 1 H), 5.01 (d, J =
10.5 Hz, 1 H), 4.63 - 4.52 (m, 1 H), 4.05 (t, J = 9.1 Hz, 1 H), 3.81 - 3.69 (m, 1 H),

Denmark and Weintraub
page S28
3.48 (dd, J = 12.3, 10.8 Hz, 1 H), 3.39 (td, J = 11.3, 4.2 Hz, 1 H), 2.74 (s, 1 H),
2.37 - 2.21 (m, 2H), 2.10 (d, J = 2.3 Hz, 1 H), 1.97 - 1.85 (m, 1 H), 1.45 (td, J =
10.3, 3.3 Hz, 1 H).
1
3
3
C-NMR: (126 MHz, CD OD)
1
1
6
51.07, 148.80, 147.24, 138.51, 135.43, 133.71 (q, JC-F = 33.7 Hz), 132.02,
31.21, 130.45, 129.23, 126.07, 125.59, 124.05, 123.42, 121.30, 117.70, 70.39,
6.34, 63.48, 62.00, 53.04, 39.14, 27.92, 25.87, 22.51.
+
LRMS: (ESI , Q-tof)
+
2
61.1 (15), 521.2 (100, M-Br )
+
+
HRMS:
TLC:
C
28
H
27
N
2
OF
6
(ESI , Q-tof)
Calcd:
Found:
2 2 2
0.55 (CH Cl /MeOH, 5:1) [silica gel, I ]
521.2028
521.2023
R
f
Preparation of Cinchonidinium Salts in Series C
Preparation of O-Benzyl-N-(9-Anthracenylmethyl)cinchonidinium Bromide (1c)
Following General Procedure I, a solution O-benzyl-cinchonidine (100 mg, 0.260 mmol)
in MeCN (2.60 mL, 0.1 M) was combined with 9-bromomethylanthracene (82.0 mg, 0.286 mmol,
1
.1 equiv) in a 5-mL, single-neck, round-bottomed flask fitted with an argon inlet, wrapped in
aluminum foil and the mixture was stirred overnight. Care was taken to avoid light exposure.
The reaction mixture was diluted with CH Cl (~5 mL) and then was loaded directly on a silica
gel column (15 g SiO ,  = 20, 100:0 to 2.5:1, TBME/MeOH, gradient elution) to afford 140 mg
82%) of 1c as a light-yellow, crystalline solid. The entire product was further purified by
recrystallization from a concentrated CH Cl solution via Et O slow diffusion in a chamber.
2
2
2
(
2
2
2

Denmark and Weintraub
page S29
Data for 1c:
m.p.: 185-188 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
9
8
.08 (d, J = 4.5 Hz, 1 H), 8.87 (s, 1 H), 8.69 (d, J = 9.0 Hz, 1 H), 8.59 (s, 1 H),
.28 - 8.16 (m, 3 H), 8.09 (dd, J = 10.3, 6.8 Hz, 2 H), 8.01 - 7.90 (m, 2 H), 7.79
(
ddd, J = 8.9, 6.6, 1.2 Hz, 1 H), 7.72 (d, J = 7.3 Hz, 2 H), 7.66 - 7.47 (m, 5 H),
7
1
.41 - 7.32 (m, 1 H), 7.06 (s, 1 H), 6.27 (d, J = 13.7 Hz, 1 H), 5.87 (d, J = 13.9 Hz,
H), 5.67 (ddd, J = 17.4, 10.2, 7.4 Hz, 1 H), 4.99 (ddd, J = 17.6, 14.9, 8.0 Hz, 4
H), 4.47 (t, J = 8.8 Hz, 1 H), 4.43 - 4.34 (m, 1 H), 3.69 (ddd, J = 12.6, 5.6, 3.0 Hz,
1
2
H), 3.21 - 3.09 (m, 1 H), 2.85 (td, J = 11.4, 5.6 Hz, 1 H), 2.61 - 2.50 (m, 1 H),
.40 (s, 1 H), 2.19 - 2.07 (m, 1 H), 1.97 (d, J = 2.8 Hz, 1 H), 1.71 - 1.50 (m, 2H ).
1
3
3
C-NMR: (126 MHz, CD OD)
1
1
1
3
50.46, 148.26, 144.28, 138.46, 138.11, 134.78, 134.43, 133.91, 133.02, 132.96,
32.15, 131.21, 131.15, 130.29, 129.86, 129.77, 129.45, 129.31, 129.17, 126.63,
26.44, 125.33, 124.75, 118.74, 117.82, 79.47, 72.73, 70.28, 63.31, 57.62, 53.82,
9.48, 27.33, 26.17, 23.31.
+
LRMS: (ESI , Q-tof)
+
5
75.3 (100, M-Br )
+
+
HRMS: C H N O (ESI , Q-tof)
4
1
39
2
Calcd:
Found:
575.3062
575.3059
TLC:
f 2 2 2
R 0.24 (CH Cl /MeOH, 10:1) [silica gel, I ]

Denmark and Weintraub
page S30
Preparation of O-Benzyl-N-(2-Naphthylmethyl)cinchonidinium Bromide (2c)
Following General Procedure I, a solution of O-benzyl-cinchonidine (100 mg, 0.260
mmol) in MeCN (2.60 mL, 0.1 M) was combined with 2-bromomethylnaphthalene (63.0 mg,
0
.286 mmol, 1.10 equiv) in a 5-mL, single-neck, round-bottomed flask fitted with an argon inlet
and the mixture was stirred overnight. The reaction mixture was diluted with CH Cl (~5 mL)
and then was loaded directly on a silica gel column (15 g SiO ,  = 20, 100:0 to 10:1,
CH Cl /MeOH, gradient elution) to afford 146 mg (93%) of 2c as a pale-yellow, crystalline solid.
2
2
2
2
2
2 2 2
The entire product was further purified by recrystallization from a CH Cl solution via Et O slow
diffusion in a chamber.
Data for 2c:
m.p.: 167-175 °C (decomp.)
1
3
H-NMR: (500 MHz, CD OD)
9
-
.03 (d, J = 4.4 Hz, 1 H), 8.26 (d, J = 7.6 Hz, 1 H), 8.20 (d, J = 8.4 Hz, 1 H), 8.08
7.95 (m, 5 H), 7.95 - 7.87 (t, J = 7.5 Hz, 1 H), 7.83 (t, J = 7.4 Hz, 1 H), 7.63
(
ddd, J = 21.1, 11.3, 6.2 Hz, 4 H), 7.58 - 7.49 (m, 3 H), 7.45 (t, J = 7.3 Hz, 1 H),
6
5
1
.51 (s, 1 H), 5.68 (ddd, J = 17.3, 10.4, 6.9 Hz, 1 H), 5.11 (d, J = 17.2 Hz, 1 H),
.00 (d, J = 10.5 Hz, 1 H), 4.93 (dd, J = 13.9, 12.1 Hz, 2 H), 4.80 (d, J = 12.3 Hz,
H), 4.67 (d, J = 11.5 Hz, 1 H), 4.20 (dd, J = 14.5, 7.2 Hz, 1 H), 4.01 (t, J = 9.0
Hz, 1 H), 3.63 (ddd, J = 12.6, 5.0, 3.0 Hz, 1 H), 3.57 - 3.46 (m, 1 H), 3.40 (td, J =
1
1.3, 4.8 Hz, 1 H), 2.65 (s, 1 H), 2.47 (dd, J = 13.1, 7.9 Hz, 1 H), 2.20 (dd, J =
8.9, 8.0 Hz, 1 H), 2.07 (d, J = 2.6 Hz, 1 H), 1.83 (t, J = 9.6 Hz, 1 H), 1.59 (dd, J
1
=
13.2, 10.7 Hz, 1 H).
1
3
C-NMR: (126 MHz, CD OD)
3
1
51.11, 149.29, 142.99, 138.50, 137.75, 135.37, 135.35, 134.44, 131.45, 130.72,
30.55, 130.49, 130.32, 130.12, 130.10, 129.47, 129.45, 129.02, 128.85, 128.26,
1