Sulfoxides derived from Cinchona alkaloids - Chiral ligands in palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tetasy.2010.04.032

Phenyl sulfides derived from Cinchona alkaloids, 9-PhS-epi-CD, 9-PhS-epi-QN, 9-PhS-epi-QD, and 9-PhSQN were oxidized into the corresponding sulfoxides. Regardless of the oxidation system used (NaIO₄, TEMPO/NaOCl, VO(acac)₂/chiral Schiff base/H₂O₂) a similar stereochemical outcome of the oxidation was observed. Four pure epimers of sulfoxides 9-PhSO-epi-CD and 9-PhSO-epi-QN were isolated and fully characterized (X-ray, CD, ¹H NMR-pattern). The chiral sulfoxides as well as the corresponding sulfides and sulfones were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. The sulfoxides obtained from Cinchona alkaloids bearing the additional stereogenic center gave the main product of configuration dependent on the chirality of alkaloid framework only. Similar ees (up to 60%) but significantly higher yields (90%) were obtained as compared to the reaction with the corresponding thioethers. The results were in agreement with nucleophilic attack directed at the allylic carbon located trans to the sulfur atom in the M-shaped intermediate η³-allylpalladium complex.

Full text of DOI:10.1016/j.tetasy.2010.04.032

Tetrahedron: Asymmetry 21 (2010) 853–858
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Tetrahedron: Asymmetry
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Sulfoxides derived from Cinchona alkaloids—chiral ligands
in palladium-catalyzed asymmetric allylic alkylation
a
a
b
a,
*
_
_
´
´
Elzbieta Wojaczynska , Mariola Zielinska-Błajet , Ilona Turowska-Tyrk , Jacek Skarzewski
a Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Technology, 50-370 Wrocław, Poland
b Institute of Physical and Theoretical Chemistry, Faculty of Chemistry, Wrocław University of Technology, 50-370 Wrocław, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Phenyl sulfides derived from Cinchona alkaloids, 9-PhS-epi-CD, 9-PhS-epi-QN, 9-PhS-epi-QD, and 9-PhS-
QN were oxidized into the corresponding sulfoxides. Regardless of the oxidation system used (NaIO4,
TEMPO/NaOCl, VO(acac)2/chiral Schiff base/H2O2) a similar stereochemical outcome of the oxidation
was observed. Four pure epimers of sulfoxides 9-PhSO-epi-CD and 9-PhSO-epi-QN were isolated and fully
characterized (X-ray, CD, 1H NMR-pattern). The chiral sulfoxides as well as the corresponding sulfides and
sulfones were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-
propenyl acetate. The sulfoxides obtained from Cinchona alkaloids bearing the additional stereogenic cen-
ter gave the main product of configuration dependent on the chirality of alkaloid framework only. Similar
ees (up to 60%) but significantly higher yields (90%) were obtained as compared to the reaction with the
corresponding thioethers. The results were in agreement with nucleophilic attack directed at the allylic
Received 5 April 2010
Accepted 20 April 2010
Available online 23 May 2010
carbon located trans to the sulfur atom in the M-shaped intermediate
g
3-allylpalladium complex.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
as chiral ligands in the Pd-catalyzed allylic alkylation in order to
examine the influence of sulfur oxidation state (comparison of sul-
fide, sulfoxide, and sulfone) and its configuration (sulfoxides) on
the yield and stereochemical outcome of the catalytic reaction.
Cinchona alkaloids (quinine QN, quinidine QD, cinchonine CN,
and cinchonidine QD) are well established powerful chiral auxilia-
ries and privileged catalysts, effective in numerous asymmetric
transformations.1 Because of their pseudoenantiomeric relation
(QN-QD and CN-CD), often the product with a desired configura-
tion at the newly created stereogenic center can be obtained. For
this purpose various C-9 functionalized derivatives of Cinchona
alkaloids have been developed.1 Since considerable attention has
been focused on the N, S-donating chiral ligands for the Pd-cata-
lyzed asymmetric allylic alkylation (AAA),2 the corresponding Cin-
chona C-9 aryl sulfides, selenides, disulfides, and mercaptanes have
been prepared and tested in our laboratory.3 Because two free elec-
tron pairs are available at the sulfur atom of sulfides, the metal-
complexation of a sulfanyl group can generate epimeric species,
possibly lowering stereochemical induction. On the other hand,
the chiral sulfoxide group (one electron pair only) can specifically
coordinate soft transition-metals and one may expect additional
enhancement of the stereoinduction exerted by such a ligand.4
Since the respective sulfoxides of Cinchona alkaloids have never
been reported, we undertook their synthesis. In this study, we de-
scribe the selective oxidation of chosen 9-phenylsulfanyl Cinchona
alkaloids into the corresponding sulfoxides, bearing an additional
sulfur stereogenic center. The separated diastereomers were used
2. Results and discussion
Previously, we have developed a simple method for the conver-
sion of alkaloids into their sulfanyl derivatives3a using the Hata
reaction.5 Previously the phenylsulfanyl derivatives of 9-epi-Cin-
chona alkaloids of like configurations [i.e., (8R,9R) or (8S,9S)] have
given in the Pd-catalyzed AAA much higher enantioselectivities
than those of unlike native configurations,3 the new compounds
of mostly a like-type were prepared. Thus, a one-step substitution
of the 9-hydroxy group of native QN, QD, CD, and epi-QN was
achieved in 60–70% yield with complete inversion of configuration
at the substitution center. The products obtained, (8S,9S)-9-PhS-
epi-QN, (8R,9R)-9-PhS-epi-QD, (8S,9S)-9-PhS-epi-CD, and (8S,9R)-
9-PhS-QN, were submitted to sulfoxidation.
At first, this reaction was carried out using an established
chemoselective oxidant, namely sodium periodate.6 Then, hoping
for better diastereoselectivity, we applied the optimized Bolm cat-
alytic system, based on vanadyl acetylacetonate, (S)-(ꢀ)-N-(3-phe-
nyl-5-nitrosalicylidene)valinol ((S)-L*) as a chiral ligand and 30%
aqueous hydrogen peroxide as a stoichiometric oxidant,7 and, fi-
nally, we often used diastereoselective TEMPO/sodium hypochlo-
rite system.8 The oxidation results are collected in Table 1.
* Corresponding author. Tel.: +48 71 320 2464; fax: +48 71 328 4064.
E-mail address: jacek.skarzewski@pwr.wroc.pl (J. Skarzewski).
_
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.04.032

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854
Table 1
Oxidation of sulfides derived from Cinchona alkaloids
Substrate
Oxidant
Yield (%)
dr (Rs):(Ss)
(8S,9S)-9-PhS-epi-CD
NaIO4
(S)-L*, VO(acac)2, H2O2
(R)-L*, VO(acac)2, H2O2
NaIO4
(S)-L*, VO(acac)2, H2O2
NaIO4
82
52
60
80
65
85
61
63
57:43
57:43
58:42
55:45
56:44
42:58
44:56
59:41
a
(8S,9S)-9-PhS-epi-QN
(8R,9R)-9-PhS-epi-QD
(8S,9R)-9-PhS-QN
NaOCl/TEMPO
NaIO4
a
(S)-L*: (S)-(ꢀ)-N-(3-phenyl-5-nitrosalicylidene)valinol, (R)-L*: (R)-(+)-N-(3-
phenyl-5-nitrosalicylidene)valinol.
The diastereomeric ratios shown in Table 1 clearly indicate that
for the substrates tested the vanadium-based chiral oxidation sys-
tem did not lead to the improvement of the outcome as compared
to the results obtained with sodium periodate. The comparable dr
values and the observed lower yield suggest that the chiral peroxo-
vanadium species have similar but limited excess to both prochiral
sides of the sulfanyl sulfur. For 9-PhS-epi-CD and 9-PhS-epi-QN
substrates, we found that all conversions yielded in excess the
(R)-sulfoxide (vide infra). Previously, a well-conserved tendency
of the (S)-L* ligand to oxidize alkyl-aryl sulfides leading to (SS)-
configuration and (R)-L* ligand giving (RS)-sulfoxides was noted.7b
Apparently, here it is the substrate that determines the configura-
tion of the newly created stereogenic center, though the asymmet-
ric induction is moderate.
From the reaction mixtures obtained in the oxidations of 9-PhS-
epi-CD and 9-PhS-epi-QN, enantiomerically pure sulfoxides were
isolated. In the first case, the epimers were separated by recrystal-
lization from CH2Cl2–n-hexane, while pure 9-PhS(O)-epi-QN dia-
stereomers were obtained by chromatography. The identity of all
sulfoxides was confirmed by 1H and 13C NMR, IR spectroscopy,
and high resolution mass spectrometry (see Section 3).
Figure 1. A view of the two independent (8S,9S,RS)-PhSO-epi-CD molecules found
in the X-ray structure of this compound. Thermal ellipsoids were drawn at 25%
probability level.
The absolute configuration of the main product obtained in the
course of (8S,9S)-9-PhS-epi-CD oxidation was established by X-ray
crystallography. The structure shown in Figure 1 is consistent with
(8S,9S,RS)-PhSO-epi-CD formulation of this isomer.
The configuration of all four separated sulfoxides was further
confirmed by CD spectroscopy. A correlation of the absolute config-
uration of the phenylsulfinyl chromophore and the sign of the Cot-
ton effects is well documented.9 Representative spectra are shown
in Figure 2. For the major diastereomers obtained in the course of
sulfide oxidation we observed a negative CE at ca. 220 nm and a
positive one at ca. 250–255 nm. The sign of Cotton effects indicates
the (R) absolute configuration of sulfur.
80
60
40
20
0
-20
-40
The 1H NMR spectra of the four separated sulfoxides also
showed characteristic patterns which could be used for their dif-
ferentiation. Chemical shifts of resonances assigned to 8-H, 9-H,
S-phenyl moieties, and identified quinoline signals are shown in
Figure 3. Remarkable differences (up to 1.4 ppm) between (RS)
and (SS) epimers caused by the magnetically anisotropic sulfinyl
group,10 and, on the other hand, similarities of chemical shifts
within (RS) and (SS) pairs are clearly visible. Quite similar spectral
patterns observed for (8R,9R)-9-PhSO-epi-QD and (8S,9R)-9-PhSO-
QN allowed for the quantification of their epimers (Table 1).
Using vanadyl acetylacetonate with racemic Schiff base and a
double amount of hydrogen peroxide, we converted (8S,9S)-9-
PhS-epi-CD and (8S,9S)-9-PhS-epi-QN into the corresponding sulf-
ones in 50–60% yield. Similar results were obtained using excess
of sodium periodate, while attempted oxidation with OxoneÒ led
to substrate degradation.
200
225
250
275
λ/nm
300
325
350
Figure 2. CD spectra of (8S,9S,RS)-PhSO-epi-CD (solid line), (8S,9S,SS)-PhSO-epi-CD
(dashed line), and (8S,9S)-PhS-epi-CD (dotted line) in acetonitrile solution in the
10ꢀ4 concentration range.
Clearly, the presence of the complexing sulfur atom is necessary
for the catalytic action and both sulfones hardly catalyzed the reac-
tion, leading to the racemic product. The higher yields obtained for
sulfoxides versus sulfides can be due to the more effective Pd-com-
plexation process, assisted by more favorable conformation of the
ligand. Moreover, the more p-accepting character of the sulfoxide
donating group may facilitate nucleophilic attack at the trans-lo-
cated allylic carbon. While the presence of a stereogenic sulfur
atom in 9-PhSO-epi-CD and 9-PhSO-epi-QN resulted in the high
yield of the catalytic reaction, the ee of product was in the range
observed for the parent sulfides. In all cases, an identical stereo-
With the chiral sulfides, sulfoxides, and sulfones in hands, we
performed the palladium-catalyzed asymmetric allylic alkylation
reaction (Scheme 1). The results are given in Table 2.

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E. Wojaczynska et al. / Tetrahedron: Asymmetry 21 (2010) 853–858
Table 2
Results of the AAA reaction with sulfur Cinchona derivatives as ligands
3.78(3.76)
H
3.18(3.20)
H
O
O
6.84-6.96
7.22-7.41
(7.25-7.49)
PhS
(6.89-7.03)
Entry
Ligand
Yield (%)
ee (%)
(S)
(R)
PhS
4.61(4.49)H
(S)
N
1
2
3
4
5
6
7
8
(8S,9S)-9-PhS-epi-CD
56
90
90
10
48
90
90
20
48 (R)
50 (R)
62 (R)
0
56 (R)
60 (R)
44 (R)
0
(S)
N
5.48(5.33)H
(S)
(S)
(8S,9S,RS)-9-PhSO-epi-CD
(8S,9S,SS)-9-PhSO-epi-CD
(8S,9S)-9-PhSO2-epi-CD
(8S,9S)-9-PhS-epi-QN
(8S,9S,RS)-9-PhSO-epi-QN
(8S,9S,SS)-9-PhSO-epi-QN
(8S,9S)-9-PhSO2-epi-QN
(4.00)
R
(3.72)
R
8.07(7.47)
6.90(6.39)
6.12(6.13)
8.57(8.44)
7.58(7.52)
8.91(8.78)
N
N
(RS)-9-PhSO-epi-CD: R = H
(RS)-9-PhSO-epi-QN: R = OMe
(SS)-9-PhSO-epi-CD: R = H
(SS)-9-PhSO-epi-QN: R = OMe
Figure 3. Selected 1H NMR resonances (d, ppm) distinguishing the isolated epimers.
Values for methoxy-substituted derivatives are given in parentheses.
spectra were measured on a Bruker CPX (1H, 300 MHz) or on a Bru-
ker Avance (1H, 500 MHz) spectrometer using TMS as an internal
standard. Optical rotations were measured using an Optical Activ-
ity Ltd Model AA-5 automatic polarimeter. High resolution mass
spectra were recorded using a microTOF-Q instrument utilizing
electrospray ionization mode. Separations of products by chroma-
tography were performed on Silica Gel 60 (230–400 mesh) pur-
chased from Merck. Thin layer chromatography analyses were
performed using Silica Gel 60 precoated plates (Merck).
X-ray data were collected at ambient temperature using a
KM4CCD diffractometer. Cystallographic data (excluding structure
factors) for the structure in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication no. 749302.
chemical preference was noted. Apparently, the configuration of
the newly formed stereogenic center is dependent on the configu-
ration of the alkaloid framework only, although the availability of
sulfur center capable of coordination is necessary. It is interesting
to note that the same stereochemical preference observed for both
sulfoxide epimers is in contrast to the recently obtained results for
the Pd-catalyzed AAA reaction with QN-9- and QD-9-phosphites of
C2-symmetric chiral diols.11 In these cases, the stereochemical out-
come depended only on the configuration of the diol, regardless of
the pseudoenantiomeric relation of the alkaloid frameworks.
For our ligand, the molecular model of [Pd(9-PhSO-epi-CD)(g3
-
1,3-diphenylallyl)]+ cation shows that the steric hindrance exerted
by the quinuclidine fragment is more pronounced for the W-
shaped complex (Fig. 4). The same outcome results for both (RS)-
and (SS)-epimers. Consequently, the M-shaped complexes are fa-
vored. The nucleophilic attack at the allylic carbon located trans
to the sulfur atom in the M complex leads to the product of (R)-
configuration, that indeed is preferred. This sense of induction is
the same as observed for the respective sulfide. Thus, regardless
of the configuration of the sulfoxide stereogenic center, quite sim-
Preparation of sulfides from commercially available Cinchona
alkaloids was described previously.3
3.2. Synthesis of sulfoxides
3.2.1. Oxidation of sulfides with VO(acac)2 and Schiff base
Vanadyl acetylacetonate (5.2 mg, 0.02 mmol) and (S)-(ꢀ)-N-(3-
phenyl-5-nitrosalicylidene)valinol (9.9 mg, 0.03 mmol) were dis-
solved in a test tube in dichloromethane (4 mL), and the solution
was stirred for 5 min at 25 °C. After the addition of the sulfide
(2 mmol) the solution was cooled to 0 °C and 30% H2O2 (0.26 mL,
2.3 mmol) was added dropwise during 10 min. The mixture was
stirred for 20 h at 0 °C and extracted with CH2Cl2 (2 ꢁ 5 mL). The
combined organic extracts were washed with H2O, brine, and dried
over Na2SO4. The solvent was removed in vacuo and the crude
product was submitted to chromatography on silica gel. n-Hex-
ane/ethyl acetate (1:1) mixture eluted the unreacted sulfide, and
the eluent was then changed to ethyl acetate. (8S,9S,RS)-9-PhSO-
epi-QN and (8S,9S,SS)-9-PhSO-epi-QN were eluted as subsequent
fractions; in case of 9-PhSO-epi-CD the final separation of epimers
was achieved by recrystallization of the solid products from meth-
ylene chloride/n-hexane.
ilar
g
3-allylic Pd complexes of an M-shape are formed.
The models were compiled under HyperChem8.0.3 software
using the available X-ray data for the ligand. The lower scheme
shows the reaction with a nucleophile.
Interestingly, the differences in ee observed for the AAA reac-
tion with both epimeric sulfoxides parallels the de value found
for the oxidation of the respective sulfide. It seems to reflect the
similar availability of each free electron pair for the oxidation of
prochiral sulfides (Table 1) and for the coordination to palladium.
Thus for both reactions, the stereochemical results seem to be
mostly influenced by the preferred conformation of 9-epi-Cinchona
alkaloids. For them, the lowest energy structures are considered as
anti-open-a
(for epi-QN) or -b (for epi-QD).12 In both cases the C-9
substituent is located at the less-hindered side of the molecule,
near the quinuclidine nitrogen atom. This is also observed in the
X-ray structure of PhSO-epi-CD presented in this paper.
For the preparation of sulfones, the amount of hydrogen perox-
ide was doubled, while the loadings of VO(acac)2 and racemic N-(3-
phenyl-5-nitrosalicylidene)valinol were kept identical as in the
synthesis of sulfoxides. The crude products were purified by col-
umn chromatography, using chloroform–methanol (6:1c v/v) as
eluent.
3. Experimental
3.1. General
3.2.2. Oxidation of sulfides with sodium periodate
Melting points were determined using a Boetius hot-stage
apparatus and are uncorrected. IR spectra were recorded on a Per-
kin–Elmer 1600 FTIR spectrophotometer. 1H NMR and 13C NMR
A solution of NaIO4 (0.28 g, 1.32 mmol) in water (3 ml) was
added to the solution of sulfide (1.2 mmol) in methanol (10 ml).
The reaction mixture was stirred at room temperature for 2 h
Ph
Ph
Ph
H2C(CO2Me)2, BSA (3 eq.), AcOK (3 mol%)
Ph
∗
Pd2(C3H5)2Cl2 (2.5 mol%), Ligand (10 mol%)
CH3CN,RT
OAc
MeO2C
CO2Me
Scheme 1.

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E. Wojaczynska et al. / Tetrahedron: Asymmetry 21 (2010) 853–858
856
Nu
Ph
N
N
Ph
Nu
Pd
Pd
S
S
Ph
Ph
Ph
Ph
O
O
η3
W-shaped -complex
η3
M-shaped -complex
Figure 4. Molecular models of the [Pd((8S,9S)-9-PhSO-epi-CD)(g
3-1,3-diphenylallyl)]+ complexes, upper: for (SS)–ligand, middle: for (RS)–ligand; left: W-shaped, right: M-
shaped.
and extracted with dichloromethane (2 ꢁ 15 ml). The combined
organic phases were dried with Na2SO4 and evaporated to dryness.
Further purification was performed as described above for the
vanadium-catalyzed oxidation.
well-stirred mixture a solution of NaOCl (0.36 M, 3.4 ml) together
with saturated NaHCO3 (1.5 ml) was added dropwise. The mixture
was stirred for 20–24 h at 0 °C (monitored by TLC) and the layers
were separated. The aqueous phase was extracted with CH2Cl2
(3 ꢁ 10 ml) and the combined organic phases were washed with
water, brine, and dried (Na2SO4).
3.2.3. Oxidation of sulfides with TEMPO/sodium hypochlorite
A 50 ml flask was charged with a solution of sulfide (1.16 mmol)
in 8 ml of CH2Cl2, TEMPO (0.034 mmol, 5.4 mg), and a saturated
aqueous solution of NaHCO3 (6.5 ml) containing 14.0 mg
(0.11 mmol) of KBr. To this cooled (0 °C, ice-water bath) and
3.2.4. (8S,9S,RS)-9-PhSO-epi-CD
Mp = 174–175 °C, (CH2Cl2/n-hexane), ½a D20
ꢃ 0 (c 0.20, CH2Cl2),
ꢂ
1H NMR (CDCl3): d = 0.66–0.73 (m, 1H), 1.50–1.74 (m, 4H), 2.28–

´
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E. Wojaczynska et al. / Tetrahedron: Asymmetry 21 (2010) 853–858
2.40 (m, 1H), 3.02–3.14 (m, 2H), 3.32–3.42 (m, 2H), 3.72–3.82 (m,
1H), 4.61 (d, 1H, J = 11.7 Hz), 4.98–5.14 (m, 2H), 5.76–5.92 (m, 1H),
6.84–6.96 (m, 5H, ArH), 7.10–7.23 (m, 2H, ArH), 7.43–7.49 (m, 1H,
ArH), 7.58 (d, 1H, ArH, J = 4.6 Hz), 7.90 (d, 1H, ArH, J = 8.5 Hz), 8.91
(d, 1H, ArH, J = 4.6 Hz) ppm. 13C NMR (CDCl3): d = 27.6, 27.7, 28.0,
39.4, 41.3, 55.2, 56.1, 64.8, 114.9, 121.2, 121.4, 123.8, 126.2,
127.9, 128.2, 128.4, 130.0, 130.5, 135.4, 141.3, 141.4, 147.7,
149.4 ppm. IR (KBr): 475, 753, 1039, 1049, 1086, 1444, 1580,
2863, 2942, 3059, 3443 cmꢀ1. HRMS (ESI): 403.1847 ([M+H]+);
for (C25H27N2OS)+ M = 403.1844.
128.2, 128.6, 129.2, 129.4, 130.8, 133.1, 134.2, 137.8, 141.5,
149.9 ppm. IR (KBr): 534, 544, 593, 687, 739, 1082, 1144, 1305,
1447, 1509, 1587, 1669, 1863, 1023, 3430 cmꢀ1. HRMS (ESI):
419.1769 ([M+H]+); for (C25H27N2O2S)+ M = 419.1793.
3.2.9. (8S,9S)-9-PhSO2-epi-QN
Yield = 60%, ½a 2D0
ꢂ
¼ ꢀ22:7 (c 1.23, CH2Cl2), 1H NMR (CDCl3):
d = 0.38–0.50 (m, 1H), 1.25–1.56 (m, 4H), 2.12–2.22 (m, 1H),
2.44–2.54 (m, 1H), 2.77–2.90 (m, 2H), 3.07–3.15 (m, 1H), 3.87–
3.90 (m, 1H), 3.89 (s, 3H, OMe), 4.94–4.99 (m, 2H), 5.08 (d, 1H,
J = 11.0 Hz), 5.71–5.83 (m, 1H), 7.05 (d, 1H, J = 2.6 Hz, ArH), 7.14–
7.19 (m, 2H, ArH), 7.23–7.31 (m, 2H, ArH), 7.49 (d, 1H, J = 4.6 Hz,
ArH), 7.63–7.66 (m, 2H, ArH), 7.89 (d, 1H, J = 9.2 Hz, ArH), 8.70
(d, 1H, ArH, J = 4.6 Hz) ppm. 13C NMR (CDCl3): d = 27.2, 27.5, 27.8,
39.1, 40.4, 55.4, 55.6, 57.2, 65.7, 101.2, 114.6, 120.9, 121.1, 127.9,
128.9, 129.1, 132.2, 133.0, 136.1, 139.6, 141.4, 144.6, 147.3,
158.2 ppm. IR (KBr): 525, 592, 687, 1028, 1081, 1143, 1231,
1243, 1305, 1446, 1474, 1508, 1586, 1620, 2863, 2939, 3069,
3433 cmꢀ1. HRMS (ESI): 449.1868 ([M+H]+); for (C26H29N2O3S)+
M = 449.1899.
3.2.5. (8S,9S,SS)-9-PhSO-epi-CD
Mp = 131–133 °C, (CH2Cl2/n-hexane), ½a D20
¼ ꢀ185:0 (c 0.26,
ꢂ
CH2Cl2), 1H NMR (CDCl3): d = 0.64–0.69 (m, 1H), 1.56–1.68 (m,
4H), 2.33–2.38 (m, 1H), 2.70–2.76 (m, 1H), 2.92–2.97 (m, 1H),
3.16–3.19 (m, 1H), 3.28–3.36 (m, 1H), 3.52–3.57 (m, 1H), 4.98–
5.04 (m, 2H), 5.48 (d, 1H, J = 11.6 Hz), 5.71–5.83 (m, 1H), 6.12 (d,
1H, J = 4.7 Hz), 7.22–7.24 (m, 2H, ArH), 7.30–7.35 (m, 2H, ArH),
7.38–7.41 (m, 1H, ArH), 7.57–7.63 (m, 1H, ArH), 7.68–7.73 (m,
1H, ArH), 8.07 (d, 1H, ArH, J = 8.4 Hz), 8.24 (d, 1H, ArH,
J = 8.4 Hz), 8.57 (d, 1H, ArH, J = 4.6 Hz) ppm. 13C NMR (CDCl3):
d = 27.3, 27.6, 27.7, 38.9, 41.1, 55.8, 56.0, 66.3, 114.8, 120.5,
124.1, 126.3, 126.9, 128.3, 129.4, 130.0, 131.3, 136.8, 139.8,
140.8, 141.2, 148.4, 148.7 ppm. IR (KBr): 693, 769, 899, 1043,
1440, 1508, 1508, 1584, 1744, 2943, 3069, 3438 cmꢀ1. HRMS
(ESI): 403.1840 ([M+H]+); for (C25H27N2OS)+ M = 403.1844.
3.2.10. (8R,9R)-9-PhSO-epi-QD (diastereomeric mixture)
1H NMR (CDCl3, selected peaks): major epimer: 3.70 (OMe),
4.33, 8.63 ppm; minor epimer: 3.83 (OMe), 4.82, 8.83 ppm. The
remaining signals overlap in the 0.4–8.5 ppm region. HRMS (ESI):
433.1953 ([M+H]+); for (C26H29N2O2S)+ M = 433.1949.
3.2.6. (8S,9S,RS)-9-PhSO-epi-QN
3.2.11. (8S,9R)-9-PhSO-QN (diastereomeric mixture)
Mp = 52–53 °C ½a 2D0
ꢂ
¼ ꢀ123 (c 0.86, CH2Cl2), 1H NMR (CDCl3):
1H NMR (CDCl3, selected peaks): major epimer: 3.60 (OMe),
4.42, 8.35 ppm; minor epimer: 3.82 (OMe), 5.31, 8.80 ppm. The
remaining signals overlap in the 0.4–8.5 ppm region. HRMS (ESI):
433.1936 ([M+H]+); for (C26H29N2O2S)+ M = 433.1949.
d = 0.60–0.72 (m, 1H), 1.51–1.80 (m, 4H), 2.32–2.41 (m, 1H),
2.98–3.10 (m, 2H), 3.30–3.42 (m, 2H), 3.72 (s, 3H, OMe), 3.70–
3.81 (m, 1H), 4.49 (d, 1H, J = 11.8 Hz), 4.99–5.13 (m, 2H), 5.81–
5.93 (m, 1H), 6.39 (d, 1H, J = 2.7 Hz, ArH), 6.89–7.03 (m, 5H, ArH),
7.11–7.17 (m, 1H, ArH), 7.52 (d, 1H, J = 4.8 Hz, ArH), 7.84 (d, 1H,
J = 9.3 Hz, ArH), 8.78 (d, 1H, ArH, J = 4.2 Hz) ppm. 13C NMR (CDCl3):
d = 27.7, 27.7, 28.0, 39.4, 41.3, 55.3, 55.3, 56.1, 65.3, 100.7, 114.9,
120.1, 121.7, 124.0, 128.2, 129.0, 130.7, 131.5, 133.8, 141.3, 141.8,
143.8, 147.0, 157.4 ppm. IR (KBr): 691, 746, 853, 917, 1045, 1086,
1230, 1319, 1359, 1443, 1473, 1507, 1583, 1620, 1722, 2865,
3.3. Catalytic reaction
The Pd-catalyzed allylic substitution reaction (Trost–Tsuji reac-
tion2) of dimethyl malonate with rac-1,3-diphenyl-2-propenyl ace-
tate was performed using 3 mol % of N,O-bis(trimethylsilyl)
acetamide–potassium acetate as a base, 2.5 mol % of [Pd(g3
-
2938, 3073, 3356 cmꢀ1
.
HRMS (ESI): 433.1900 ([M+H]+); for
C3H5)Cl]2, and 10 mol % of tested chiral ligand in acetonitrile
solution. The stereochemical effect of the catalytic reaction was
determined by 1H NMR measurement using Eu(hfc)3 as a chiral
shift reagent.
(C26H29N2O2S)+ M = 433.1949. Rf (ethyl acetate) = 0.16.
3.2.7. (8S,9S,SS)-9-PhSO-epi-QN
½
a 2D0
ꢂ
¼ ꢀ215 (c 0.52, CH2Cl2), 1H NMR (CDCl3): d = 0.62–0.71 (m,
1H), 1.58–1.72 (m, 4H), 2.30–2.43 (m, 1H), 2.72–2.82 (m, 1H),
2.90–3.05 (m, 1H), 3.18–3.29 (m, 1H), 3.30–3.38 (m, 1H), 3.51–
3.62 (m, 1H), 4.00 (s, 3H, OMe), 4.98–5.10 (m, 2H), 5.33 (d, 1H,
J = 11.4 Hz), 5.72–5.85 (m, 1H), 6.13 (d, 1H, J = 4.8 Hz, ArH), 7.25–
7.49 (m, 6H, ArH), 7.47 (d, 1H, J = 2.7 Hz, ArH), 7.96 (d, 1H,
J = 9.0 Hz, ArH), 8.44 (d, 1H, ArH, J = 4.8 Hz) ppm. 13C NMR (CDCl3):
d = 27.4, 27.7, 27.8, 39.0, 41.1, 55.8, 55.9, 56.3, 67.1, 102.9, 114.7,
120.7, 121.6, 126.3, 128.3, 131.0, 131.3, 131.5, 135.5, 139.9,
141.3, 144.7, 146.2, 158.1 ppm. IR (film): 917, 1043, 1082, 1230,
1473, 1621, 1724, 2864, 2929, 3073, 3399 cmꢀ1. HRMS (ESI):
433.1921 ([M+H]+); for (C26H29N2O2S)+ M = 433.1949. Rf (ethyl
acetate) = 0.08.
Acknowledgment
We are grateful to the Polish Ministry of Science and Higher
Education for financial support; Grant No. N204 161036.
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