Enantioselective zinc-catalyzed hydrosilylation of ketones using pybox or pybim ligands

Article abstract of DOI:10.1002/asia.201100561

The combination of ZnEt₂ and chiral pyridinebisoxazoline (pybox) or pyridinebisimidazoline (pybim) ligands catalyzed the asymmetric hydrosilylation of aryl, alkyl, cyclic, heterocyclic, and aliphatic ketones. Under mild conditions, high yields and good enantioselectivities were achieved. ESI measurements allowed for the characterization of the active catalyst. Zincing outside of the pybox: A ZnEt₂/pybox catalyst promotes the hydrosilylation of carbonyl compounds under mild conditions to afford high yields and good ee values for a broad range of aryl, alkyl, cyclic, heterocyclic, and aliphatic ketones.

Full text of DOI:10.1002/asia.201100561

FULL PAPERS
DOI: 10.1002/asia.201100561
Enantioselective Zinc-Catalyzed Hydrosilylation of Ketones using Pybox or
Pybim Ligands**
Kathrin Junge,[a] Konstanze Mçller,[a] Bianca Wendt,[a] Shoubhik Das,[a] Dirk Gçrdes,[b]
Kerstin Thurow,[b] and Matthias Beller*[a]
Abstract: The combination of ZnEt2 and chiral pyridinebisoxazoline (pybox) or
pyridinebisimidazoline (pybim) ligands catalyzed the asymmetric hydrosilylation
of aryl, alkyl, cyclic, heterocyclic, and aliphatic ketones. Under mild conditions,
high yields and good enantioselectivities were achieved. ESI measurements al-
lowed for the characterization of the active catalyst.
Keywords: homogeneous catalysis ·
hydrosilylation · ketones · pybox ·
zinc
Introduction
polymethylhydrosiloxane (PMHS).[8b,c] Since then, an in-
creasing number of interesting publications on zinc-cata-
lyzed hydrosilylation reactions have been registered; how
ever, most of the known procedures exhibit limited func-
tional-group tolerance.[8m–s]
The asymmetric catalytic reduction of ketones to secondary
alcohols allows for the selective preparation of chiral alco-
hols,[1] which are used as versatile building blocks for phar-
maceuticals, agrochemicals, flavors, and fragrances. In addi-
tion to catalytic or transfer hydrogenation reactions, en
antioselective hydrosilylations are attractive for the reduc-
tion of prochiral ketones owing to their mild reaction condi-
tions and the ease of handling of the reagents, requiring no
high pressure equipment. Originally, rhodium–phosphine
complexes have been reported for asymmetric hydrosilyla-
tions.[2] Later on, it was shown that other transition metal
complexes based on ruthenium, iridium, titanium, palladi-
um, or copper can also be used for this purpose.[3] More re-
cently, the group of Nishiyama[4] as well as our group[5] dem-
onstrated that even iron complexes can be used as selective
Owing to the trend of applying bio-relevant metal cata-
lysts in organic synthesis and inspired by our previous ex
perience
using
the
so-called
pyridinebisoxazoline
(pybox)[9,10] and pyridinebisimidazoline (pybim)[11] ligands
(Scheme 1), we became interested in the zinc-catalyzed
asymmetric hydrosilylation of ketones. Herein, we report
our recent results in this area.
and active cataACHTUNGTRENNUNGlysts for the hydrosilylation of ketones.
Based on their availability and biomimetic nature, zinc-
based complexes also represent highly attractive candidates
for catalysis.[6] Surprisingly, since the first report on zinc-cata
lyzed hydrosilylation nearly two decades ago,[7] only few
studies have been performed in this field.[8a] Notably, a
breakthrough was reported by Mimoun et al. with the intro-
duction of ligated zinc catalysts that were able to efficiently
hydrosilylate simple ketones in the presence of inexpensive
Scheme 1. Structures of the pyridinebisoxazoline (pybox) 1 and pyridine-
bisimidazoline (pybim) 2 ligands.
Results and Discussion
At the start of our work, the reduction of acetophenone
into 1-phenylethanol with 1.5 equivalents of triethoxysilane
was investigated as a model reaction. Initially, the activity of
different zinc salts in the presence of 2,6-bis((R)-4-phenyl-
4,5-dihydrooxazol-2-yl)pyridine (pybox) 1a was studied at
608C (Table 1). In all experiments, the corresponding alco-
hol was detected after hydrolysis of the silylether, but most
zinc salts gave only low yields of product. Notably,
ZnACTHNUTRGNE(NUG OAc)2 and ZnEt2 showed conversions of around 70%
and enantioselectivities of up to 46% ee (Table 1, entries 6
and 7).
To improve these results further, different hydrosilanes
were tested in the presence of the two most-reactive zinc
[a] Dr. K. Junge, K. Mçller, B. Wendt, S. Das, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der
Universitꢁt Rostock
Albert-Einstein-Straße 29a, 18059 Rostock (Germany)
Fax : (+49)381-1281-51113
E-mail: matthias.beller@catalysis.de
Homepage: www.catalysis.de
[b] Dr. D. Gçrdes, Prof. Dr. K. Thurow
Center for Life Science Automation (CELISCA)
Universitꢁt Rostock
Friedrich-Barnewitz-Str. 8
18119 Rostock (Germany)
[**] Pybox=pyridinebisoxazoline, pybim=pyridinebisimidazoline.
salts, ZnACTHUGNTERNNU(G OAc)2 and ZnEt2. As shown in Table 2, the nature
314
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Chem. Asian J. 2012, 7, 314 – 320

Table 1. Asymmetric hydrosilylation of acetophenone: screening of dif-
ferent zinc precursors.[a]
Following our previous observations in the copper-cata-
lyzed hydrosilylation reactions of ketones,[12] the influence
of temperature on the hydrosilylation of acetophenone with
[Zn]/1a and PMHS was investigated in more detail
(Figure 1). Interestingly, opposite trends were observed for
Entry
Zinc precursor
Ligand
Yield [%]
ee [%]
1
2
3
4
5
6
7
ZnF2
ZnBr2
ZnI2
1a
1a
1a
1a
1a
1a
1a
43
23
20
16
28
74
73
20 (R)
3
AHCTUNGTRENNUNG
Zn
(ClO4)·6H2O
Zn(OAc)2
ZnEt2
ACHTUNGTRENNUNG(OTf)2
Zn
G
ACHTUNGTRENNUNG
G
33 (R)
46 (R)
[a] General conditions: 1 mol% zinc salt, 1 mol% pybox 1a, 1 mmol ace-
tophenone, 1.5 equiv (EtO)3SiH, 2 mL THF, 20 h, 608C. THF=tetrahy-
drofuran.
Table 2. Asymmetric hydrosilylation of acetophenone: screening of dif-
ferent silanes.[a]
Figure 1. Relation between temperature and enantioselectivity for the hy-
drosilylation of acetophenone with [Zn]/1a.
both zinc precursors. In the case of ZnACTHNUTRGENUG(N OAc)2, the yield and
Entry
Silane
ZnEt2
ZnACHTUNGTRENNUG
ee value decreased with increasing temperature, whilst when
using ZnEt2/1a, up to 59% ee and complete conversion of
the reactants was achieved at room temperature.
After identifying the optimized reaction parameters
(1 mol% ZnEt2/L=1:1, 5 equiv PMHS, THF, 20 h, RT) dif-
ferent pybox (1a–e) or pybim ligands (2a–c) were applied
to our model reaction (Scheme 2).[13] For all of the tested li-
Yield
[%]
ee (R)
[%]
Yield
[%]
(R)
1
2
3
4
5
6
7
8
PhSiH3
Ph2SiH2
MePh2SiH
Me2PhSiH
G
40
90
4
32
44
12
–
35
46
51
48
45
37
–
48
70
1
30
21
n.d.[f]
n.d.
42
–
<1
50
74
71
55
50
81
n.r.
22
80
73
85
54
33
87
n.r.[g]
75
C
33
37
48
51
37
–
17
PMHS
PMHS[b]
PMHS[c]
PMHS[d]
PMHS[e]
TMDS
9
10
11
12
12
[a] General conditions: 10À2 mmol zinc precursor, 10À2 mmol pybox 1a,
1 mmol acetophenone, 1.5 equiv silane, 2 mL THF, 20 h, 608C. [b] Ratio
of [Zn]/1a=1:2. [c] Ratio of [Zn]/1a=1:4. [d] 2 mol% NaOAc.
[e] 10 mol% NaOAc. [f] n.d.=not determined. [g] n.r.=no reaction.
TMDS=tetramethyldisiloxane.
of the reducing agent controls the catalytic activity and ste-
reoselectivity to a significant extent. In general, diethyl zinc
gave better conversions compared to zinc acetate. Alkoxysi-
lanes such as (EtO)2MeSiH and (EtO)3SiH gave good yields
(Table 2, entries 5 and 6), but the highest conversion was ob-
tained using Ph2SiH2 and ZnEt2 (Table 2, entry 2).
To our delight, inexpensive PMHS showed high activity
and the highest enantioselectivity (Table 2, entry 7). There-
fore this silane was chosen for further studies. Next, varia-
tion of the metal/ligand ratio was investigated (Table 2, en-
tries 7–9). The best performance was observed with a 1:1
ratio of ZnEt2/1a. In order to clarify the role of acetate
anion, 2 and 10 mol% NaOAc were added to both catalyst
precursors (Table 2, entries 10 and 11); these results showed
an adjustment and finally depletion of the catalytic activity.
Scheme 2. Screening of different pybox (1a—e) and pybim ligands (2a—
c) in the asymmetric hydrosilylation reaction. The yields and ee values of
acetophenone are shown.
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315

M. Beller et al.
FULL PAPERS
Table 3. Asymmetric hydrosilylation of different ketones catalyzed by
ZnEt2/pybox.[a]
gands, nearly full conversion was achieved except for the
pybim-based ligand 2c, which contained free NH groups in
the imidazole ring. Unfortunately, in most cases low en
antioselectivities were measured (6–32% ee), thus permit-
ting no general conclusions regarding structural effects to be
made. Using 2,6-bis((R)-4-phenyl-4,5-dihydrooxazol-2-yl)-
pyridine (1a), the highest ee value for the reduction of aceto
phenone was 59%. Therefore, this ligand was chosen to in-
estigate the substrate scope.
Entry
Substrate
Yield of 3
ee
[%]
[%]
As shown in Table 3, a broad range of aryl, alkyl, cyclic,
heterocyclic, and aliphatic ketones were investigated to
demonstrate the scope of our procedure. To our delight, for
most of the substrates, complete hydrosilylation was ach-
ieved in the presence of 1 mol% ZnEt2/1a within 20 hours
at room temperature. Among the different carbonyl com-
pounds, the highest enantioselectivity of 73% ee was ach-
ieved for aromatic ketones 1-(biphenyl-4-yl)ethanone (3j)
and 1-(4-ethylphenyl)propan-1-one (3k; Table 3, entries 10
and 11). An upscaling experiment for ketone 3j to 10 mmol
resulted in no problems and produced the corresponding al-
cohol in high yield and 70% enantioselectivity. Sterically
more-demanding alkyl chains (Table 3, entries 2 and 3) or
para- or meta-substitution on the aromatic ring of the
ketone gave higher enantioselectivities compared to aceto
phenone. On the other hand, ortho-substitution caused a de-
pletion of the enantioselective induction (Table 3, entry 14),
whilst heterocyclic carbonyl compounds showed comparable
ee values to the model substrate (Table 3, entries 17 and 18).
For a,b-unsaturated ketones, no general trend was evident,
with the enantiomeric excess ranging from 26–70%. Ali-
phatic ketones were transformed into the corresponding al-
cohols in good to excellent yields; however the enantioselec-
tivity did not exceed 30% (Table 3, entries 23–26). Other
classes of substrates like b-ketoesters or imines were tested
with this zinc catalyst showing only slight activity.
1
2
3
3a
3b
3c
99
97
59 (R)
68.5 (R)
<2
n.d.
67.5 (R)
98[b]
4
5
6
7
8
3d
3e
3 f
3g
3h
98
99
94
99
62 (R)
60 (R)
67 (R)
64 (R)
77
62 (R)
62 (R)
98[c]
After demonstrating the general applicability of the
ZnEt2/pybox catalyst for a number of different ketones, we
became interested in elucidating the active catalyst species.
Depending on the applied zinc-precursors and the type of
ligand, different catalytic cycles have been discussed in the
literature. For N-ligands containing zinc catalysts, Mimoun
et al. have presented three different mechanisms for
the PMHS hydrosilylation of carbonyl compounds
9
3i
97
52 (R)
99
71 (R)
73 (R)
70 (R)
10
11
3j
99[c]
88[d]
A
93
69 (+)
73 (+)
3k
76[b]
cies is assumed, whilst various ways of hydrogen activation
and transformation were postulated. Mechanism A involves
12
13
3l
99
98
69 (R)
53 (R)
À
hydrogen transfer from Zn H to the carbonyl compound
bound to the metal center. In mechanism B, the activation
À
of the Si H bond in a pentavalent hydridosilicate is as-
3m
sumed and a concerted transfer of hydrogen onto the C=O
group coordinated to the zinc is postulated. In mechanism C,
the nitrogen ligand is also involved in the substrate activa-
tion.
14
3n
99
45 (R)
By applying a diamine–zinc–diol complex, Ushio und
À
Mikami postulated a Si H bond activation caused by an
inter
A
316
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Chem. Asian J. 2012, 7, 314 – 320

Enantioselective Zinc-Catalyzed Hydrosilylation of Ketones
Table 3. (Continued)
Entry
Substrate
Yield of 3
ee
[%]
[%]
15
3o
3p
92
71 (R)
94
66.5 (R)
66 (R)
16
99[c]
37
58 (R)
55 (R)
17
18
19
20
3q
3r
3s
3t
99[c]
99
99
99
64 (R)
51 (R)
68 (R)
21
22
3u
3v
88
26 (R)
70 (S)
98[e]
99
ACHTUNGTNER(NUNG rac)
3 (R)
23
24
3w
3x
16[c]
99
30 (R)
Scheme 3. Proposed mechanism for the hydrosilylation of ketones ac-
cording to Mimoun and co-workers.
25
26
3y
3z
97
99
11 (R)
768.2613, 954.3505, and 1074.4114, which inferred the pres-
(rac)
ence of the free pybox ligand [(1a)+H]+ and [(1a)2+H]+
and zinc complexes such as [ZnEtCATHUNGTRENN(UNG 1a)AHCTNURTGENGN(NU Ph2SiH2)ACHTUNGTRENNUNG
(4a)]+,
[a] General conditions: 10À2 mmol% diethyl zinc (1.5m in toluene),
10À2 mmol (R,R)-pybox, 5 equiv PMHS, 1 mmol ketone, 2 mL THF, 20 h,
RT; [b] 608C; [c] ketone was added before PMHS; [d] 10 mmol of ketone
up-scaling; [e] 3v: 3% C=C hydrogenation; <1% completed hydrogena-
tion.
Subsequent addition of ketone is associated with the cleav-
À
age of Zn diol bond followed by hydride transfer to the
ketone. To confirm the catalytically active species, we per-
formed ESI-TOF-MS measurements of combinations of
ZnEt2, pybox 1a, Ph2SiH2, and ketone 3a. To facilitate the
interpretation of the analytical data, Ph2SiH2 was used in-
stead of PMHS. The spectrum of a freshly prepared solution
of ZnEt2/1a (1:1) in tetrahydrofuran showed signals at
m/z=462.1158 and 831.2626 corresponding to [ZnEt
(1a)]+
ACHTUNGTRENNUNG
and [ZnEt
ACHTUNGTRENNUNG
Following addition of Ph2SiH2 and acetophenone 3a, a
series of signals appeared at m/z=370.1556, 739.3050,
Figure 2. Characteristic ESI-MS spectrum for the Zn complex
[ZnEt
(1a)]+ as measured in the reaction mixture.
N
ACHTUNGTRENNUNG
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317

M. Beller et al.
FULL PAPERS
was detected in the spectrum when only pybox and Ph2SiD2
are mixed. Furthermore, the finding of [ZnEt
ACHUTGTNERN(NUG 1a)CAHTUNGTREN(NUGN Ph2SiH2)
AHCTUNGTRENNUNG
cies, which are responsible for the hydride transfer in the
catalytic cycle (mechanism B). Based on all of these results,
we postulate that [ZnEt
active catalyst, which exists in equilibrium with [ZnEt-
(1a)2]+. This postulation is also underlined by the fact that a
(1a)]+ is the stabilized form of the
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
1:1 ratio of Zn/1a was found to be optimal for the hydrosily-
lation of ketones, whilst a Zn/1a ratio of 1:2 led to a de-
crease in the catalyst activity (Table 2, entry 8).
Conclusions
In summary, a convenient catalyst composed of ZnEt2 and
commercially available pybox ligands is presented for the
enantioselective hydrosilylation of carbonyl compounds.
Under mild conditions, high yields and good enantioselectiv-
ities were achieved for a broad range of aryl, alkyl, cyclic,
heterocyclic, and aliphatic ketones. ESI measurements have
been performed to characterize the active catalyst.
Experimental Section
High-Resolution Mass Spectrometry
High-resolution mass spectrometry experiments were performed on an
Agilent 1969A time-of-flight mass spectrometer (Waldbronn, Germany).
The ESI-TOF-MS conditions (positive ion mode, 4 GHz instrument
mode, dual sprayer API-ES source) were as follows: nebulizer and
drying gas nitrogen; nebulizer pressure 45 psig; drying gas flow
10 LminÀ1; drying gas temperature 3508C; capillary voltage 4 kV; frag-
mentor voltage 175 V; skimmer voltage 60 V; octopole voltage 250 V;
mass reference (m/z) 121.050873 and 922.009798. The sample was imme-
diately injected via a 74900 Series syringe pump (Cole-Parmer Instru-
ment Company, Illinois, USA) without further dilution.
(4a)+H]+
Figure 3. ESI-MS spectra for the Zn complexes [ZnEtCATHNUGTREN(NNUG 1a)2ACHTUNRTGEG(NNUN 3a)ACHTNGUTRENNGUN
(top) and [ZnEt([D2]-1a)2ACHTNUTRGENUNG
(3a)([D2]-4a)+H]+ (bottom) measured in the
reaction mixture. Only one pybox ligand 1a is directly coordinated to the
Zn atom, whilst the second pybox ligand should form an aggregate in the
gas phase owing to the electrostatic interaction between the positively
charged complex and the electron-rich ligand.
[ZnEt
(1a)
E
and
(4a)+H]+
[ZnEtACHTNUGERTG(NUNN 1a)2ACHNUTRTGEG(NNUN 3a)CAHTNUGTRENNUGN
General Procedure for the Hydrosilylation of Ketones
(Figure 3, top).
A mixture of 10À2 mmol diethyl zinc (1.5m in toluene) or zinc precursor,
and 10À2 mmol (R,R)-pybox in 2 mL THF was purged with argon in a
Schlenk tube and stirred for 10 min at room temperature. This in situ
generated catalyst was transferred by syringe into 5 equiv of PMHS
placed under argon in a Schlenk tube; after 5 min of stirring, 1 mmol of
ketone was added. The red reaction mixture was stirred for 20 h at room
temperature, after which hexadecane (0.1 mL) was added as a standard,
the solution was diluted with 4 mL diethyl ether and quenched with 1 mL
NaOH (1m). After stirring for 30 min, the reaction mixture was washed
twice with distilled water and dried with Na2SO4. The yield was deter-
mined by GC (30 m HP 5 Agilent Technologies 50–3008C) and the enan-
tioselectivity was determined by HPLC or GC.
The same experiment was performed with ZnMe2 as the
zinc precursor, and led to corresponding signals at m/z=
448.1007, 754.2767, and 817.248 for [ZnMe
(1a)]+,
ACHTUNGTRENNUNG
G
A
E
N
ACHTUNGTRENNUNG
signals anticipated for zinc complexes at higher m/z values
were not detected.
When Ph2SiD2 is used in the reaction mixture instead of
Ph2SiH2 the signal pattern of the ESI-MS spectrum did not
change significantly. The aforementioned compounds were
observed, as well as signals at m/z=960.3870 and 1080.4441
corresponding to the deuterium-incorporated products
Enantioselectivities of the Hydrosilylation Products
[ZnEt([D2]-1a)2([D2]-4a)+H]+
and
[ZnEt([D2]-1a)2
3a: ee values were determined by GC (50 m Lipodex E), (S)-4a 35.7 min
and (R)-4a 36.9 min (85/35-6-180/2-8-200/15).
(3a)([D2]-4a)+H]+, respectively (Figure 3). Interestingly, a
signal was also observed at m/z=742.3255, which can be at-
tributed to [([D2]-1a)2+H]+, presumably owing to deuterium
incorporation into the pybox ligand (1a). This observation
can be regarded as evidence for the involvement of the dini-
trogen ligand in the substrate activation (mechanism C)
postulated by Mimoun et al.[8b,c] This assumption was under-
lined by the fact that no deuteration of the pybox ligand 1a
À
3b: ee values were determined by HPLC (Chiralcel OD H), (R)-4b
8.4 min and (S)-4b 9.7 min (eluent: n-heptane/ethanol 97:3; flow:
1.0 mLminÀ1).
À
3c: ee values were determined by HPLC (Chiralpak AD H), (R)-4c
9.4 min and (S)-4c 10.4 min (eluent: n-heptane/ethanol 99.5:0.5; flow:
1.0 mLminÀ1).
318
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Chem. Asian J. 2012, 7, 314 – 320

Enantioselective Zinc-Catalyzed Hydrosilylation of Ketones
À
3d: ee values were determined by HPLC (Chiracel OD H), (S)-4d
3z ee values were determined by GC (50 m Lipodex E), (S)-4z 25.9 min
and (R)-4z 29.4 min (40/35–6–180/2–8–200).
44.5 min and (R)-4d 52.7 min (eluent: n-heptane/ethanol 99:1; flow:
1.0 mLminÀ1).
À
3e: ee values were determined by HPLC (Chiralcel OD H), (S)-4e
26.4 min and (R)-4e 28.7 min (eluent: n-heptane/ethanol 98:2; flow:
0.5 mLminÀ1).
Acknowledgements
À
3 f: ee values were determined by HPLC (Chiralcel OD H), (S)-4 f
The authors thank Dr. Haijun Jiao for his fruitful discussions regarding
mechanistic problems and Dr. W. Baumann, Dr. C. Fischer, S. Buchholz,
S. Schareina, A. Koch, and S. Rossmeisl (all at the Leibniz-Institut fꢀr
Katalyse e.V.) for their excellent analytical and technical support.
30.9 min and (R)-4 f 33.7 min (eluent: n-heptane/ethanol 98:2; flow:
0.5 mLminÀ1).
3g: ee values were determined by HPLC (Reposil 100), (S)-4g 32.0 min
and (R)-4g 33.7 min (eluent: n-heptane/ethanol 99.75:0.25; flow:
0.5 mLminÀ1).
À
3h: ee values were determined by HPLC (Chiralcel OD H), (R)-4h
[1] a) T. Ohkuma, R. Noyori in Transition Metals for Organic Synthesis,
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[3] a) I. Ojima in The chemistry of Organic Silicon Compounds (Eds.: S.
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Marciniec, J. Gulinski, W. Urbaniak, Z. W. Kornetka in Comprehen-
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21.7 min and (S)-4h 24.7 min (eluent: n-heptane/ethanol 98:2; flow:
1.0 mLminÀ1).
À
3i: ee values were determined by HPLC (CHIRALCEL OB H), (S)-4i
12.2 min and (R)-4i 14.3 min (eluent: n-heptane/isopropanol 95:5; flow:
0.8 mLminÀ1).
À
3j: ee values were determined by HPLC (Chiralpak AD H), (S)-4j
19.4 min and (R)-4j 23.3 min (eluent: n-heptane/ethanol 97:3; flow:
1.0 mLminÀ1).
À
3k: ee values were determined by HPLC (Chiralpak AD H), (+)-4k
29.3 min and (À)-4k 31.7 min (eluent: n-heptane/ethanol 98:2; flow:
0.4 mLminÀ1).
À
3l: ee values were determined by HPLC (Chiralcel OD H), (R)-4l
42.8 min and (S)-4l 54.3 min (eluent: n-heptane/ethanol 97:3; flow:
0.2 mLminÀ1).
3m: ee values were determined by GC (Lipodex E), (R)-4m 41.0 min
and (S)-4m 41.5 min (70/20/6–180/30; flow: 1.0 mLminÀ1).
À
3n: ee values were determined by HPLC (Chiralcel OJ H), (S)-4n
34.4 min and (R)-4n 36.8 min (eluent: n-heptane/ethanol 98:2; flow:
pp. 111–126; d) “Hydrosilylation:
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À
3o: ee values were determined by HPLC (Chiralcel OD H), (S)-4o
19.0 min and (R)-4o 21.0 min (eluent: n-heptane/ethanol 97:3; flow:
1.0 mLminÀ1).
À
3p: ee values were determined by HPLC (Chiralpak AD H), (S)-4p
18.0 min and (R)-4p 20.0 min (eluent: n-heptane/ethanol 99:1; flow:
0.5 mLminÀ1).
À
3q: ee values were determined by HPLC (Chiralcel OB H), (R)-4q
22.1 min and (S)-4q 25.6 min (eluent: n-heptane/isopropanol 99:1; flow:
1.0 mLminÀ1).
À
3r: ee values were determined by HPLC (Chiralcel OB H), (S)-4r
27.64 min and (R)-4r 34.5 min (eluent: n-heptane/isopropanol 99:1; flow:
1.0 mLminÀ1).
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À
3s: ee values were determined by HPLC (Chiralcel OJ H), (S)-4s
13.7 min and (R)-4s 16.4 min (eluent: n-heptane/ethanol 95:5; flow:
0.7 mLminÀ1).
À
3t: ee values were determined by HPLC (Chiralcel OJ H), (S)-4t
13.8 min and (R)-4t 19.3 min (eluent: n-heptane/ethanol 95:5; flow:
0.7 mLminÀ1).
À
3u: ee values were determined by GC (Chirasil Dex CB), (S)-4u
37.3 min and (R)-4u 40.4 min (isotherm; 708C; flow: 1.2 mLminÀ1).
À
3v: ee values were determined by HPLC (Chiralcel OB H), (À)-4v
14.5 min and (+)-4v 16.1 min (eluent: n-heptane/i-propanol 98:2; flow:
0.6 mLminÀ1).
À
3w: ee values were determined by HPLC (Chiralcel OB H), (R)-4w
16.0 min and (S)-4w 17.2 min (eluent: n-heptane/ethanol 98:2; flow:
0.3 mLminÀ1).
À
3x: ee values were determined by HPLC (Chiralcel OD H), (S)-4x
21.4 min and (R)-4x 24.9 min (eluent: n-heptane/ethanol 99:1; flow:
1.0 mLminÀ1).
À
3y ee values were determined by GC (50 m Chiraldex ß PM), (R)-4y
62.4 min and (S)-4y 63.5 min (80/60–6–180/30).
Chem. Asian J. 2012, 7, 314 – 320
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Received: June 22, 2011
Published online: December 15, 2011
320
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Chem. Asian J. 2012, 7, 314 – 320