Chromatography-free enzymatic kinetic resolution of secondary alcohols

Article abstract of DOI:10.1055/s-0029-1216997

Racemic secondary alcohols were resolved by enzymatic esterification using Candida antarctica lipase B (CAL B). After derivatization of the unreacted enantiomer with phthalic anhydride, the resulting phthalic acid monoesters could be easily separated from the corresponding acetates by precipitation and filtration or distillation, thus avoiding laborious column chromatography, which is a major obstacle for large-scale reactions. This method has been successfully applied to the multigram synthesis of enantiopure pyridyl alcohols.

Full text of DOI:10.1055/s-0029-1216997

3654
PAPER
Chromatography-Free Enzymatic Kinetic Resolution of Secondary Alcohols
E
nzymatic Kinetic Res
a
olution of
S
t
econda
t
ry
A
lc
h
ohols ias Maywald, Andreas Pfaltz*
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland
Fax +41(61)2671103; E-mail: andreas.pfaltz@unibas.ch
Received 18 May 2009; revised 9 July 2009
et. al. for the kinetic resolution of the structurally related
Abstract: Racemic secondary alcohols were resolved by enzymatic
esterification using Candida antarctica lipase B (CAL B). After de-
rivatization of the unreacted enantiomer with phthalic anhydride,
the resulting phthalic acid monoesters could be easily separated
5,6,7,8-tetrahydroquinolin-8-ol,7a the racemic alcohols 1
and 2 were treated with vinyl acetate in the presence of
Candida antarctica lipase B (CAL-B). After 30 hours at
from the corresponding acetates by precipitation and filtration or 60 °C the reactions were stopped at approximately 50%
distillation, thus avoiding laborious column chromatography, which
is a major obstacle for large-scale reactions. This method has been
successfully applied to the multigram synthesis of enantiopure py-
cohols (S)-1 and (S)-2 and their subsequent hydrolysis,
ridyl alcohols.
conversion (Scheme 1). After chromatographic separa-
tion of the acetates (R)-3 and (R)-4 from the unreacted al-
both enantiomers of 1 and 2 could be obtained in good
yield and excellent enantiomeric excess.
Key words: alcohols, asymmetric synthesis, enzymes, esterifica-
tion, kinetic resolution
cat CAL-B,
vinyl acetate,
n
The lipase-catalyzed enantioselective esterification of
i-Pr2O, 60 °C,
30 h
N
HO
secondary alcohols is an important method in asymmetric
synthesis with several industrial applications.1 However,
the separation of the ester from the remaining alcohol af-
ter enzymatic kinetic resolution can be laborious, espe-
cially if chromatography is necessary. We were
confronted with this challenge in the course of our work
on new ligands for the asymmetric iridium-catalyzed hy-
drogenation of unfunctionalized olefins,2,3 thus we be-
came interested in an enantioselective, multigram
synthesis of the pyridyl alcohols 1 and 2 (Figure 1), which
are backbones for an important ligand class.4 Herein we
report the development of a convenient and practical
method for the chromatography-free enzymatic kinetic
resolution of pyridyl alcohols 1 and 2 and its application
to different substrates.
1: n = 1
2: n = 2
n
n
+
N
N
HO
AcO
(S)-1: n = 1
41% yield, > 99% ee
(R)-3: n = 1
3
49% yield, > 99% ee
(S)-2: n = 2
45% yield, 99% ee
(R)-4: n = 2
45% yield, >99% ee
Scheme 1 Enantioselective acetylation of the pyridyl alcohols 1 and
2 with Candida antarctica lipase B
However, especially in the case of (S)-2 and (R)-4 the dif-
ficult separation by column chromatography was a major
drawback in reaction scale-up. In the literature, several
techniques have been reported to circumvent the need for
chromatography.9–11 Since we were interested in both
enantiomers of the pyridyl alcohols 1 and 2, dynamic ki-
netic resolution was not an option.9 Therefore, we focused
on the lipase-catalyzed esterification of alcohols with suc-
cinic anhydride followed by extraction of the acidic es-
ter.10 However, only low enantioselectivity was observed
with this acyl donor. Furthermore, complete separation of
the ester and the remaining alcohol by extraction was dif-
ficult. Next, vinyl stearate was used as an acyl donor in an
attempt to separate the esters from the alcohols based on
their solubility, since the alcohols 1 and 2 are barely solu-
ble in nonpolar solvents like n-hexane. Unfortunately, the
obtained enantioselectivities were again low.
N
N
HO
OH
1
2
Figure 1 Pyridyl alcohols 1 and 2
Recently, we described the kinetic resolution of these py-
ridyl alcohols through copper-catalyzed acylation.5
Asymmetric reduction of the corresponding ketones6 and
enzymatic kinetic resolution have been reported for struc-
turally related alcohols.7 Preliminary studies on the asym-
metric synthesis of 2 by enantioselective reduction or
enzymatic kinetic resolution have been carried out by S.
Kaiser in our laboratory.8 Using the procedure of Uenishi
Finally, we resorted to a two-step procedure that com-
bines enzymatic kinetic resolution with subsequent de-
rivatization of the unreacted alcohol 5 with a suitable
reagent followed by separation of the resulting derivative
7 from the acetate 6 (Scheme 2). This ‘phase-labeling’
SYNTHESIS 2009, No. 21, pp 3654–3660
x
x.
x
x
.
2
0
0
9
Advanced online publication: 08.09.2009
DOI: 10.1055/s-0029-1216997; Art ID: T10209SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Enzymatic Kinetic Resolution of Secondary Alcohols
3655
OAc
R1
R2
lipase-catalyzed
esterification
OH
OAc
R2
OH
6
1) derivatization
+
R1
R2
R1
R1
R2
X
2) facile separation
O
5
6
5
R1
R2
7
Scheme 2 Concept of chromatography-free enzymatic kinetic resolution
strategy12 has already been successfully applied to the ki- (Scheme 3).14a To ensure full conversion, excess of
netic resolution of secondary alcohols, which were modi- phthalic anhydride was used and the reaction mixture was
fied with polymer-supported acid chlorides and separated refluxed until TLC indicated complete disappearance of
by filtration or converted into sulfate esters followed by the starting alcohol. Subsequent extraction with saturated
acid–base extraction.13
ammonium chloride solution yielded the desired phthalic
acid monoesters (S)-8 or (S)-9 together with acetates (R)-
3 or (R)-4. As expected, they displayed a significantly dif-
ferent solubility profile than the acetates. After addition of
tert-butyl methyl ether to the residue the insoluble com-
pounds (S)-8 or (S)-9 could be easily separated by filtra-
tion from (R)-3 or (R)-4 on a five-gram scale. Hydrolysis
of the esters with 2 M sodium hydroxide and recrystalli-
zation from cyclohexane gave enantiopure alcohols 1 and
2 in high yield.
The solid-phase scavenging methodology is limited to
small-scale reactions, and according to our experience
with acid–base extractions of the pyridyl alcohols 1 and 2
we preferred separation by filtration. Hence, we chose
phthalic anhydride as the derivatizing reagent as the mo-
noesters of numerous alcohols are known to be crystalline
solids.14 Furthermore, derivatization with phthalic anhy-
dride was previously used to facilitate separation by liquid
chromatography.15
Next, we extended the method to octan-2-ol (10) and 1-
phenylethanol (11). The Candida antarctica lipase B cat-
alyzed transesterification was performed on a five-gram
scale according to literature methods with dichloro-
methane as solvent (Scheme 4),13b so that after enzymatic
kinetic resolution derivatization with phthalic anhydride
could be achieved without solvent change. Although the
Initial experiments showed that the esterification of the re-
sidual alcohols can be achieved under mild conditions us-
ing triethylamine as base and dichloromethane as solvent
1) cat CAL-B, vinyl acetate,
i-Pr2O, 60 °C, 30 h
n
N
2) phthalic anhydride (0.65 equiv)
Et3N (0.70 equiv), CH2Cl2, Δ, 6 h
3) sat NH4Cl
HO
1) cat CAL-B, vinyl acetate,
OH
4) separation by filtration
1: n = 1
2: n = 2
CH2Cl2, r.t., 16 h
2) phthalic anhydride (0.65 equiv)
Et3N (0.70 equiv), CH2Cl2, Δ, 7 h
3) 2 Μ HCl
R
10: R = n-Hept
11: R = Ph
n
n
4) separation by distillation
+
N
N
O
O
OH
O
AcO
O
O
O
R
OAc
+
OH
R
(S)-8: n = 1 49% yield
(S)-9: n = 2 43% yield
(R)-3: n = 1 49% yield
(R)-4: n = 2 39% yield
(R)-14: R = n-Hept
40% yield
(S)-12: R = n-Hept
49% yield
(R)-15: R = Ph
46% yield
(S)-13: R = Ph
50% yield
2 Μ NaOH,
2 Μ NaOH,
MeOH, Δ, 6 h
MeOH, r.t., 6 h
2 Μ NaOH,
2 Μ NaOH,
MeOH, Δ, 6 h
MeOH, r.t., 6 h
n
n
OH
OH
R
N
N
HO
HO
R
(S)-1: n = 1
(R)-1: n = 1
(R)-10: R = n-Hept
91% yield (36% over 2 steps),
> 99% ee
(S)-10: R = n-Hept
87% yield (43% over 2 steps),
> 99% ee
88% yield (43% over 2 steps), 91% yield (45% over 2 steps),
> 99% ee
> 99% ee
(R)-11: R = Ph
89% yield (41% over 2 steps),
95% ee
(S)-2: n = 2
(R)-2: n = 2
(S)-11: R = Ph
83% yield (42% over 2 steps),
99% ee
87% yield (37% over 2 steps) , 72% yield (28% over 2 steps),
> 99% ee
> 99% ee
Scheme 3 Enzymatic kinetic resolution of the pyridyl alcohols 1
and 2
Scheme 4 Enzymatic kinetic resolution of octan-2-ol (10) and 1-
phenylethanol (11)
Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York

3656
M. Maywald, A. Pfaltz
PAPER
(R)-7-Acetoxy-2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine
[(R)-3] and 2-{[(S)-2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyri-
din-7-yloxy]carbonyl}benzoic Acid [(S)-8]
phthalic acid monoesters (S)-12 and (S)-13 are solids, they
did not readily crystallize out of the reaction mixture.
However, since the boiling point differences between the
acetates and the phthalic acid monoesters are large, they
could be easily separated by bulb-to-bulb distillation. Af-
ter hydrolysis and distillation, alcohols 10 and 11 were ob-
tained in both high yield and high enantiomeric excess.
To a soln of 1 (4.50 g, 21.3 mmol, 1.00 equiv) in i-Pr2O (1 L) was
added vinyl acetate (9.82 mL, 107 mmol, 5.00 equiv) and Candida
antarctica lipase B [1.62 g, immobilized on acrylic resin from Sig-
ma (L4777)]. The resulting suspension was stirred at 60 °C for 30 h.
The enzyme was filtered off and washed with EtOAc (3 × 50 mL).
The solvent of the filtrate was removed and the resulting oily resi-
due was dissolved in CH2Cl2 (100 mL) and then phthalic anhydride
(2.05 g, 13.8 mmol, 0.65 equiv) and Et3N (2.10 mL, 15.0 mmol,
0.70 equiv) were added. The soln was heated to reflux for 6 h (TLC
monitoring). The mixture was washed with sat. NH4Cl
(2 × 100 mL) soln, the organic phase was dried (Na2SO4), and the
solvent was removed. t-BuOMe (100 mL) was added to the residue
and the obtained colorless solid was filtered off and washed with t-
BuOMe (3 × 100 mL) yielding (S)-8 (3.72 g, 49%). The filtrate was
concentrated and the yellow oil solidified at –18 °C. Recrystalliza-
tion (cyclohexane, 20 mL) yielded analytically pure (R)-3 (2.63 g,
49%) as an off-white solid.
In summary, we have developed a simple and convenient
two-step procedure that allows for facile enantiomer sep-
aration of secondary alcohols. The method is complemen-
tary to existing procedures and should be widely
applicable.13 Our method proved especially advantageous
in the multigram scale synthesis of the pyridyl alcohols 1
and 2.
NMR spectra were recorded on Bruker Avance 400 and Bruker
1
Avance 500 DRX spectrometers; references for H NMR: CHCl3
(d = 7.26) or DMSO (d = 2.50) and for 13C NMR: CDCl3
(d = 77.16) or DMSO (d = 39.51), assignment mc (centrosymmetric
multiplet). 13C spectra were acquired in broad band decoupled
mode. The multiplicity of the signals was determined by the DEPT
method (pulse angle of the last impulse: 135°). DEPT: + = primary
or tertiary carbon atom (positive DEPT signal), – = secondary car-
bon atom (negative DEPT signal), Cq = quaternary carbon atom
2-{[(S)-2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-
yloxy]carbonyl}benzoic Acid [(S)-8]
Mp 194–195 °C (dec).
IR: 1740 (s), 1695 (m), 1598 (m), 1570 (m), 1485 (w), 1460 (m),
1422 (w), 1354 (w), 1281 (s), 1260 (s), 1161 (m), 1145 (m), 1118
(s), 1073 (m), 1033 (m), 1020 (m), 951 (m), 885 (m), 841 (m), 798
(m), 791 (m), 759 (m), 747 (s), 737 (s), 646 cm–1 (m).
1
(DEPT signal intensity 0). The assignment of H and 13C spectra
was made using 2D NMR experiments (COSY, HMQC, HMBC).
IR spectra were recorded on a Shimadzu FTIR 8400S with neat sub-
stances using a Golden Gate ATR accessory. Mass spectra were
measured on VG70 250 (EI, 70 eV) and Finnigan MAT312 (FAB,
using 3-nitrobenzyl alcohol NBA as matrix) mass spectrometers.
The elemental analyses were carried out on a Leco CHN 900 ana-
lyzer (C, H, N detection). Gas chromatograms were collected on
Carlo Erba HRGB Mega2 Series 800 (HRGS Mega 2). For HPLC
analyses, Shimadzu systems with a SCL 10a System Controller,
CTO 10AC column oven, LC10-AD pump system, DGU 14a de-
gasser and a SPD M10A diode array detector were used. Chiralpak
column OD H (4.6 × 250 mm) from Daicel Chemical Industries Ltd.
was used. Optical rotations were measured on a Perkin Elmer Pola-
rimeter 341, Na lamp (l = 589 nm), 1-dm cuvette lengths, c in g/100
mL. Melting points were measured with a Büchi 535 melting point
apparatus and are not corrected. For TLC, TLC plates were obtained
from Macherey-Nagel (Polygram SIL G/UV254, 0.2 mm silica with
fluorescence indicator, 40 × 80 mm). For visualization UV light
(254 nm, 366 nm), basic permanganate soln [KMnO4 (3 g), K2CO3
(20 g), 5% aq NaOH (5 mL), H2O (300 mL)], Ce(SO4)2 soln [15%
(w/w) H2SO4 saturated with Ce(SO4)2] were used.
1H NMR (400 MHz, DMSO-d6): d = 2.31 (mc, J = 4.3 Hz, 1 H,
CH2), 2.60 (mc, J = 7.3 Hz, 1 H, CH2), 2.93–2.99 (m, 1 H, CH2),
3.07–3.17 (m, 1 H, CH2), 6.29 (dd, J1 = 3.5 Hz, J2 = 7.2 Hz, 1 H,
CHOOC), 7.39–7.48 (m, 3 H, HAr), 7.61–7.76 (m, 4 H, HAr), 7.83
(dd, J1 = 8.1 Hz, J2 = 16.9 Hz, 2 H, HAr), 8.04 (d, J = 7.1 Hz, 2 H,
HAr), 13.3 (br s, 1 H, CO2H).
13C NMR (101 MHz, DMSO-d6): d = 27.3 (–, CH2), 29.6 (–, CH2),
78.1 (+, CHOOC), 120.4 (+, CAr), 126.5 (+, CAr), 128.4 (+, CAr),
128.7 (+, CAr), 128.9 (+, CAr), 131.1 (+, CAr), 131.4 (+, CAr), 132.1
(Cq, CAr), 132.4 (Cq, CAr), 134.2 (+, CAr), 138.5 (Cq, CAr), 155.5 (Cq,
CAr), 160.0 (Cq, CAr), 167.2 (Cq, CHOCO), 168.0 (Cq, CO2H).
MS (EI, 70 eV, 200 °C): m/z (%) = 359 (1) [M]+, 211 (51) [M –
OCPhCO2H]+, 193 (26) [M – O2CPhCO2H]+, 182 (100) [M –
HCO2CPhCO2H]+, 155 (21), 104 (21), 76 (14).
Anal. Calcd for C22H17NO4 (359.37): C, 73.53; H, 4.77; N, 3.90.
Found: C, 72.55; H, 5.00; N, 3.68.
(R)-7-Acetoxy-2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine
[(R)-3]
Mp 98–100 °C
Reactions were performed under an argon atmosphere using stan-
dard Schlenk techniques. Glassware was oven dried and cooled un-
der vacuum prior to use. For enzymatic resolutions a sulfonation
flask equipped with a thermometer, a condenser, and a mechanical
stirrer was used.
IR: 2946 (w), 1726 (m), 1591 (m), 1566 (m), 1442 (m), 1430 (m),
1342 (w), 1323 (w), 1311 (w), 1218 (s), 1165 (m), 1156 (m), 1075
(w), 1020 (s), 979 (m), 961 (s), 945 (m), 925 (m), 889 (s), 846 (m),
760 (m), 739 (m), 729 (m), 713 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 2.10–2.18 (m, 4 H, CH3, CH2),
2.61–7.70 (m, 1 H, CH2), 2.88–2.95 (m, 1 H, CH2), 3.07–3.15 (m, 1
H, CH2), 6.15 (dd, J1 = 4.3 Hz, J2 = 7.3 Hz, 1 H, CHOAc), 7.37–
7.48 (m, 3 H, HAr), 7.61–7.67 (m, 2 H, HAr), 7.97 (d, J = 7.3 Hz, 2
H, HAr).
13C NMR (101 MHz, CDCl3): d = 21.5 (+, CH3), 27.8 (–, CH2),
31.1 (–, CH2), 77.5 (+, CHOAc), 120.8 (+, CAr), 127.2 (+, CAr),
128.8 (+, CAr), 128.9 (+, CAr), 120.8 (+, CAr), 133.8 (+, CAr), 136.2
(Cq, CAr), 139.5 (Cq, CAr), 157.4 (Cq, CAr), 160.7 (Cq, CAr), 171.0
(Cq, O2CCH3).
Solvents were purchased from Fluka or Merck and dried using stan-
dard laboratory methods.16 Chemicals were obtained from Acros,
Sigma-Aldrich, Fluka, and Merck. Candida antarctica Lipase B im-
mobilized on acrylic resin was purchased from Sigma (L4777). Py-
ridyl alcohols 1 and 2 were prepared according to literature
procedures.4c The absolute configurations of the pyridyl alcohols 1
and 2 were determined by conversion into the corresponding
[Ir(COD)]BArF complexes which were analyzed by X-ray diffrac-
tion.8
MS (EI, 70 eV, 100 °C): m/z (%) = 253 (6) [M]+, 210 (62) [M –
OCCH3]+, 193 (100) [M – O2CCH3]+, 182 (7) [M – HCO2CCH3]+.
Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York

PAPER
Enzymatic Kinetic Resolution of Secondary Alcohols
3657
Anal. Calcd for C16H15NO2 (253.30): C, 75.87; H, 5.97; N, 5.53.
Found: C, 75.78; H, 6.03; N, 5.45.
139.2 (Cq, CAr), 153.2 (Cq, CAr), 155.1 (Cq, CAr), 170.7 (Cq,
CHOCO).
MS (EI, 70 eV, 100 °C): m/z (%) = 267 (4) [M]+, 224 (100) [M –
(R)-8-Acetoxy-2-phenyl-5,6,7,8-tetrahydroquinoline [(R)-4]and
2-{[(S)-2-Phenyl-5,6,7,8-tetrahydroquinolin-8-yloxy]carbon-
yl}benzoic Acid [(S)-9]
OCCH3]+, 207 (38) [M – HOOCCH3]+, 169 (5).
Anal. Calcd for C17H17NO2 (267.33): C, 76.38; H, 6.41; N, 5.24.
Found: C, 76.18; H, 6.41; N, 5.19.
To a soln of 2 (5.00 g, 22.2 mmol, 1.00 equiv) in i-Pr2O (1 L) was
added vinyl acetate (10.3 mL, 107 mmol, 5.00 equiv) and Candida
antarctica lipase B [1.80 g, immobilized on acrylic resin from Sig-
ma (L4777)]. The resulting suspension was stirred at 60 °C for 30 h.
The enzyme was filtered off and washed with EtOAc (3 × 50 mL).
The solvent of the filtrate was removed and the resulting oily resi-
due was dissolved in CHCl3 (100 mL) and then phthalic anhydride
(2.14 g, 14.4 mmol, 0.65 equiv) was added. The soln was heated to
reflux for 6 h (TLC monitoring). The solvent was removed and t-
BuOMe (100 mL) was added to the residue. The colorless solid was
filtered off and washed with t-BuOMe (3 × 100 mL) to yield analyt-
ically pure (S)-9 (3.60 g, 43%) as a colorless solid. The filtrate was
concentrated and the yellow oil solidified at –18 °C. Recrystalliza-
tion (cyclohexane, 15 mL) yielded analytically pure (R)-4 [2.31 g,
39%, >99% ee (HPLC)] as a colorless solid.
2-{[(S)-Octan-2-yloxy]carbonyl}benzoic Acid [(S)-12] and (R)-
Octan-2-yl Acetate [(R)-14]; Typical Procedure
To a soln of 10 (5.00 g, 38.4 mmol) in CH2Cl2 (30 mL) was added
vinyl acetate (3.53 mL, 38.4 mmol, 1.00 equiv) and Candida ant-
arctica lipase B [880 mg, immobilized on acrylic resin (L4777)].
The resulting suspension was stirred at r.t. for 16 h. The enzyme
was filtered off and washed with CH2Cl2 (2 × 10 mL). To the filtrate
was added phthalic anhydride (3.70 g, 25.0 mmol, 0.65 equiv) and
Et3N (3.74 mL, 26.9 mmol, 0.70 equiv) and the soln was heated to
reflux for 7 h (TLC monitoring). The mixture was washed with 2 M
HCl (50 mL) and the aqueous phase was extracted with CH2Cl2
(2 × 50 mL). The combined organic phases were dried (Na2SO4)
and the solvent was removed. Bulb-to-bulb distillation of the resi-
due (120 °C/15 mbar) yielded (S)-12 (5.19 g, 49%) as a brown solid
and analytically pure (R)-14 [2.67 g, 40%, >99% ee (GC)] as a col-
orless liquid.
2-{[(S)-2-Phenyl-5,6,7,8-tetrahydroquinolin-8-yloxy]carbon-
yl}benzoic Acid [(S)-9]
Mp 81–82 °C
2-{[(S)-Octan-2-yloxy]carbonyl}benzoic Acid [(S)-12]
IR: 2931 (w), 2872 (w), 1728 (m), 1699 (w), 1467 (m), 1285 (m),
1250 (s), 1113 (s), 1068 (m), 1057 (m), 959 (m), 916 (w), 846 (m),
798 (w), 777 (w), 734 (s), 702 cm–1 (s).
1H NMR (400 MHz, DMSO-d6): d = 1.82–1.93 (m, 2 H, CH2),
2.05–2.31 (m, 2 H, CH2), 2.72–2.92 (m, 2 H, CH2), 6.16 (mc,
J = 1.2 Hz, 1 H, CHOCO), 7.36–7.49 (m, 3 H, HAr), 7.52–7.68 (m,
4 H, HAr), 7.70–7.77 (m, 1 H, HAr), 7.83 (d, J = 8.1 Hz, 1 H, HAr),
8.30 (d, J = 7.3 Hz, 2 H, HAr), 13.3 (br s, 1 H, CO2H).
13C NMR (101 MHz, DMSO-d6): d = 14.3 (–, CH2), 23.3 (–, CH2),
24.0 (–, CH2), 67.5 (–, CHOCO), 115.7 (+, CAr), 122.3 (+, CAr),
124.2 (+, CAr), 124.7 (+, CAr), 124.9 (+, CAr), 124.9 (+, CAr), 126.9
(+, CAr), 122.3 (+, CAr), 127.0 (+, CAr), 127.3 (+, CAr), 128.2 (Cq,
CAr), 128.3 (Cq, CAr), 134.3 (+, CAr), 134.3 (+, CAr), 148.4 (Cq, CAr),
149.8 (Cq, CAr), 162.8 (Cq, CHOCO), 164.1 (Cq, CO2H).
Mp 72–74 °C (AcOH–H2O) [Lit.14a mp 74–75 °C (AcOH–H2O)].
1H NMR (400 MHz, CDCl3): d = 0.82–0.89 (m, 3 H, CH3), 1.23–
1.43 (m, 12 H, CH2, CH3CHO), 1.52–1.61 (m, 1 H, CH2CHO),
1.69–1.75 (m, 1 H, CH2CHO), 5.18 (sextet, J = 6.3 Hz, 1 H, CHO),
7.52–7.64 (m, 2 H, HAr), 7.69 (d, J = 7.3 Hz, 1 H, HAr), 7.96 (d,
J = 7.6 Hz, 1 H, HAr).
13C NMR (101 MHz, CDCl3): d = 14.2 (+, CH3), 19.7 (+,
OHCCH3), 22.7 (–, CH2), 25.5 (–, CH2), 29.3 (–, CH2), 31.9 (–,
CH2), 35.9 (–, CH2), 73.3 (+, CH2CHO), 128.9 (+, CAr), 130.0 (+,
CAr), 130.1 (+, CAr), 130.8 (+, CAr), 132.3 (Cq, CAr), 134.0 (Cq, CAr),
167.9 (Cq, CHOCO), 172.2 (Cq, CO2H).
MS (FAB, NBA): m/z (%) = 279.1 (57) [M + H]+, 167 (78), 149
(100) [Ph(CO2H)2]+, 77 (16), 43 (20).
MS (EI, 70 eV, 300 °C): m/z (%) = 224 (15) [M – OCPhCO2H]+,
196 (32), 169 (100), 104 (29), 76 (22), 50 (10).
Anal. Calcd for C16H22O4 (278.34): C, 69.04; H, 7.97. Found: C,
69.08; H, 7.87.
MS (FAB, NBA): m/z (%) = 374 (100) [M]+, 224 (26) [M –
OCPhCO2H]+, 208 (67) [M – OOCPhCO2H]+, 77 (35) [Ph]+, 39
(37).
(R)-Octan-2-yl Acetate [(R)-14]
GC [b-cyclodextrin Brechbühler SE54 (25 m × 0.25 mm ×
0.25 mm), 60 kPa He; 240 °C (injector); 270 °C (detector); temper-
ature program: 90 °C (20 min), 20 °C/min, 160 °C (10 min)]:
tR = 13.4 min.
Anal. Calcd for C23H19NO4 (373.40): C, 73.98; H, 5.13; N, 3.75.
Found: C, 73.72; H, 5.19; N, 3.61.
1H NMR (400 MHz, CDCl3): d = 0.82–0.89 (m, 3 H, CH3), 1.16 (d,
J = 5.8 Hz, 3 H, CH3CHO), 1.20–1.32 (m, 8 H, CH2), 1.37–1.46 (m,
1 H, CH2CHO), 1.49–1.56 (m, 1 H, CH2CHO), 2.02 (s, 3 H,
OOCCH3), 4.86 (sextet, J = 6.3 Hz, 1 H, CHO).
13C NMR (101 MHz, CDCl3): d = 14.2 (+, CH3), 20.1 (+,
OHCCH3), 21.5 (+, OOCCH3), 22.7 (–, CH2), 25.5 (–, CH2), 29.2
(–, CH2), 31.9 (–, CH2), 36.0 (–, CH2), 71.2 (+, CH2CHO), 170.9
(Cq, OOCCH3).
(R)-8-Acetoxy-2-phenyl-5,6,7,8-tetrahydroquinoline [(R)-4]
Mp 79–80 °C (cyclohexane); Rf = 0.24 (n-hexane–EtOAc, 4:1);
HPLC (Chiracel OD-H, 0.5 mL/min, 20 °C, detection at 220 nm, n-
heptane–i-PrOH, 98:2): tR = 24.6 min.
[a]D20 +42.6 (c 1.03, CHCl3).
IR: 3031 (w), 2831 (w), 1717 (s), 1595 (w), 1562 (w), 1460 (m),
1446 (m), 1425 (w), 1373 (s), 1236 (s), 1198 (m), 1128 (w), 1951
(m), 1016 (m), 999 (s), 960 (s), 930 (m), 908 (m), 874 (m), 851 (s),
775 (s), 760 (s), 741 (s), 696 cm–1 (s).
1H NMR (400 MHz, CDCl3): d = 1.81–1.91 (m, 2 H, CH2), 1.93–
2.25 (m, 5 H, CH2, CH3), 2.72–2.95 (m, 2 H, CH2), 6.08 (t,
J = 4.8 Hz, 1 H, CHOCO), 7.34–7.50 (m, 3 H, HAr), 7.60 (d,
J = 8.1 Hz, 2 H, HAr), 7.99 (d, J = 7.1 Hz, 2 H, HAr).
MS (EI, 70 eV, r.t.): m/z (%) = 112 (17) [M – AcOH]+, 87 (49) [M –
CH3CH2OAc]+, 43 (100) [M – CH2CH2CH3]+.
Anal. Calcd for C10H20O2 (172.26): C, 69.72; H, 11.70. Found: C,
69.90; H, 11.51.
2-{[(S)-1-Phenylethoxy]carbonyl}benzoic Acid [(S)-13] and (R)-
1-Phenylethyl Acetate [(R)-15]
According to the typical procedure for (S)-12 and (R)-14, enzymat-
ic kinetic resolution was performed with 11 (5.00 g, 40.9 mmol).
13C NMR (101 MHz, CDCl3): d = 18.8 (–, CH2), 21.6 (+, CH3), 28.2
(–, CH2), 29.2 (–, CH2), 71.2 (–, CHOCO), 120.7 (+, CAr), 126.8 (+,
CAr), 128.7 (+, CAr), 128.8 (+, CAr), 131.8 (Cq, CAr), 137.9 (+, CAr),
Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York

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M. Maywald, A. Pfaltz
PAPER
Bulb-to-bulb distillation (100 °C/0.1 mbar) of the residue yielded
(S)-13 (5.58 g, 50%) as a brown solid residue and (R)-15 (3.05 g,
46%) as a colorless liquid, which were hydrolyzed without further
purification. An analytical sample of (S)-13 was prepared by recrys-
tallization (AcOH–H2O).
MS (EI, 70 eV, 100 °C): m/z (%) = 211 (50) [M]+, 182 (100), 155
(28), 115 (8), 77 (9) [Ph]+.
Anal. Calcd for C14H13NO (211.26): C, 79.59; H, 6.20; N, 6.63.
Found: C, 79.38; H, 6.19; N, 6.42.
(S)-8-Hydroxy-2-phenyl-5,6,7,8-tetrahydroquinoline [(S)-2]
Compound (S)-2 was prepared from (S)-9 (3.60 g, 9.64 mmol) ac-
cording to the typical procedure for hydrolysis to give (S)-1. Re-
crystallization (cyclohexane, 25 mL) yielded (S)-2 [1.89 g, 87%,
>99% ee (HPLC)] as a colorless solid; mp 81–82 °C (n-hexane);
Rf = 0.17 (n-hexane–EtOAc, 9:1); HPLC (Chiracel OD-H, 0.5 mL/
min, 20 °C, detection at 220 nm, n-heptane–i-PrOH, 98:2):
tR = 35.1 min.
2-{[(S)-1-Phenylethoxy]carbonyl}benzoic Acid [(S)-13]
Mp 80–81 °C (AcOH–H2O) [Lit.18 mp 108 °C (AcOH)].
1H NMR (400 MHz, CDCl3): d = 1.67 (d, J = 6.6 Hz, 3 H, CH3),
6.15 (q, J = 6.6 Hz, 1 H, PhCH), 7.25–7.34 (m, 1 H, HAr), 7.36 (t,
J = 7.1 Hz, 2 H, HAr), 7.41 (d, J = 7.3 Hz, 2 H, HAr), 7.57 (mc,
J = 7.0 Hz, 2 H, HAr), 7.70 (dd, J1 = 1.8 Hz, J2 = 7.7 Hz, 1 H, HAr),
7.89 (dd, J1 = 1.8 Hz, J2 = 7.2 Hz, 1 H, HAr), 12.1 (br s, 1 H, CO2H).
13C NMR (101 MHz, CDCl3): d = 21.8 (+, CH3), 74.3 (+, PhCH),
126.4 (+, CAr), 128.1 (+, CAr), 128.7 (+, CAr), 129.0 (+, CAr), 130.1
(+, CAr), 131.0 (Cq, CAr), 132.3 (+, CAr), 133.6 (+, CAr), 141.1 (Cq,
CAr), 167.4 (Cq, CHOCO), 172.8 (Cq, CO2H).
[a]D20 +142 (c 1.00, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.76–1.95 (m, 2 H, CH2), 1.98–
2.11 (m, 1 H, CH2), 2.28–2.45 (m, 1 H, CH2), 2.72–2.91 (m, 2 H,
CH2), 4.40 (br s, 1 H, OH), 4.76 (mc, J = 5.1 Hz, 1 H, CHOH),
7.39–7.50 (m, 5 H, HAr), 7.58 (d, J = 7.3 Hz, 1 H HAr), 8.00 (d,
J = 7.3 Hz, 1 H, HAr).
MS (EI, 70 eV, r.t.): m/z (%) = 150 (58) [M – PhCOO]+, 121 (82)
[PhCO2H]+, 105 (100) [M – OOCPhCO2H]+, 77 (30) [Ph]+.
MS (FAB, NBA): m/z (%) = 271 (18) [M + H]+, 167 (59) [M –
13C NMR (101 MHz, CDCl3): d = 20.0 (–, CH2), 28.46 (–, CH3),
31.1 (–, CH2), 69.2 (+, CHOH), 119.9 (+, CAr), 127.3 (+, CAr), 129.2
(+, CAr), 129.6 (+, CAr), 130.7 (Cq, CAr), 138.7 (+,CAr), 154.5 (Cq,
CAr), 158.0 (Cq, CAr).
PhCHCH3]+, 105 (100) [M – OOCPhCO2H]+.
(R)-1-Phenylethyl Acetate [(R)-15]
HPLC (Chiracel OD-H, 0.5 mL/min, 20 °C, detection at 210 nm, n-
heptane–i-PrOH, 99:1): tR = 10.2 min.
[a]D20 –106 (c 1.01, CHCl3) [Lit.14b [a]D20 –102 (c 1.00, CHCl3).
Anal. Calcd for C15H15NO (225.29): C, 79.97; H, 6.71; N, 6.22.
Found: C, 79.84; H, 6.72; N 6.05.
(S)-Octan-2-ol [(S)-10]
1H NMR (400 MHz, CDCl3): d = 1.58 (d, J = 6.6 Hz, 3 H, CH3),
2.09 (s, 3 H, OOCCH3), 5.92 (q, J = 6.6 Hz, 1 H, PhCH), 7.29–7.38
(m, 5 H, HAr).
13C NMR (101 MHz, CDCl3): d = 21.3 (+, OOCCH3), 22.2 (+,
CH3), 72.3 (+, PhCH), 126.1 (+, CAr), 127.9 (+, CAr), 128.5 (+, CAr),
141.7 (Cq, CAr), 170.3 (Cq, OOCCH3).
MS (EI, 70 eV, r.t.): m/z (%) = 164 (22) [M]+, 122 (86) [M –
OCCH3]+, 104 (100) [M – HOOCCH3]+, 77 (32) [Ph]+, 43 (51)
[OCCH3]+.
Compound (S)-10 was prepared from (S)-12 (5.17 g, 18.6 mmol)
according to the typical procedure for hydrolysis to give (S)-1.
Bulb-to-bulb distillation (100 °C/15 mbar) yielded (S)-10 [2.10 g,
87%, >99% ee (GC)] as a colorless liquid.
GC determination of ee after derivatization as acetate [b-cyclodex-
trin Brechbühler SE54 (25 m × 0.25 mm × 0.25 mm), 60 kPa He;
240 °C (injector); 270 °C (detector); temperature program: 90 °C
(20 min), 20 K/min, 160 °C (10 min)]: tR = 8.03 min.
[a]D20 +10.3 (c 2.00, EtOH) [Lit.14b [a]D20 +9.8 (c 5.95, EtOH)].
(S)-2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol [(S)-1];
Typical Procedure for 2-Carboxybenzoate Hydrolysis
To a soln of (S)-8 (3.72 g, 10.4 mmol) in MeOH (25 mL) was added
2 M NaOH (50 mL) and the mixture was heated to reflux for 6 h.
MeOH was removed under reduced pressure and the aqueous soln
was extracted with CH2Cl2 (3 × 50 mL). The combined organic
phases were dried (Na2SO4) and the solvent was removed. The oil
obtained solidified after drying under vacuum for 4 h. Recrystalli-
zation (cyclohexane, 20 mL) yielded (S)-1 [1.94 g, 88%, >99% ee
(HPLC)] as a colorless solid; mp 118–119 °C (cyclohexane);
Rf = 0.07 (n-hexane–EtOAc, 4:1); HPLC (Chiracel OD-H, 0.5 mL/
min, 20 °C, detection at 210 nm, n-heptane–i-PrOH, 95:5):
tR = 37.1 min.
1H NMR (400 MHz, CDCl3): d = 0.82–0.88 (m, 3 H, CH3), 1.15 (d,
J = 6.0 Hz, 3 H, CH3CHOH), 1.20–1.45 (m, 10 H, CH2), 1.77 (br s,
1 H, OH), 4.86 (sextet, J = 5.6 Hz, 1 H, CHOH).
13C NMR (101 MHz, CDCl3): d = 14.2 (+, CH3), 22.7 (–, CH2),
23.5 (+,CH3), 25.8 (–, CH2), 29.4 (–, CH2), 39.5 (–, CH2), 68.2 (+,
CH2CHOH).
Anal. Calcd for C8H18O (130.23): C, 73.78; H, 13.93. Found: C,
73.56; H, 13.68.
(S)-1-Phenylethanol [(S)-11]
Compound (S)-11 was prepared from (S)-13 (5.58 g, 20.6 mmol)
according to the typical procedure for hydrolysis to give (S)-1.
Bulb-to-bulb distillation (60 °C/0.1 mbar) yielded (S)-11 [2.10 g,
83%, 99% ee (HPLC)] as a colorless liquid; HPLC (Chiracel OD-
H, 0.5 mL/min, 20 °C, detection at 220 nm, n-heptane–i-PrOH,
98:2): tR = 38.7 min.
[a]D20 –60.0 (c 1.00, CHCl3) [Lit.17 [a]D20 –57 (c 5.12, CHCl3)].
1H NMR (400 MHz, CDCl3): d = 1.49 (d, J = 6.3 Hz, 3 H, CH3),
2.16 (br s, 1 H, OH), 4.87 (q, J = 6.6 Hz, 1 H, CHOH), 7.26–7.36
(m, 5 H, HAr).
[a]D20 +40.7 (c 1.04, CHCl3).
IR: 3167 (br s), 2968 (m), 1588 (m), 1572 (m), 1458 (s), 1445 (s),
1307 (m), 1238 (m), 1163 (w), 1053 (s), 1021 (m), 961 (m), 908
(m), 852 (m), 768 (s), 695 (s), 563 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 2.04 (q, J = 7.3 Hz, 1 H, CH2),
2.57 (mc, J = 4.3 Hz, 1 H, CH2), 2.85 (q, J = 8.1 Hz, 1 H, CH2),
3.00–3.08 (m, 1 H, CH2), 3.37 (br s, 1 H, OH), 5.24 (t, J = 6.8 Hz,
1 H, CHOH), 7.37–7.40 (m, 3 H, HAr), 7.41 (d, J = 8.1 Hz, 1 H,
HAr), 7.46 (d, J = 7.8 Hz, 1 H, HAr), 7.95 (d, J = 7.3 Hz, 2 H, HAr).
13C NMR (101 MHz, CDCl3): d = 27.2 (–, CH2), 33.0 (–, CH2), 74.8
(+, CH), 120.0 (+, CAr), 127.0 (+, CAr), 128.7 (+, CAr), 133.7 (+,
CAr), 134.7 (Cq, CAr), 139.4 (Cq, CAr), 156.6 (Cq, CAr), 164.7 (Cq,
CAr).
13C NMR (101 MHz, CDCl3): d = 25.3 (+, CH3), 70.4 (+, CHOH),
125.5 (+, CAr), 127.5 (+, CAr), 128.5 (+, CAr), 145.9 (Cq, CAr).
Anal. Calcd for C8H10O (122.17): C, 78.65; H, 8.25. Found: C,
78.10; H, 8.23.
Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York

PAPER
Enzymatic Kinetic Resolution of Secondary Alcohols
3659
(R)-2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ol [(R)-
1]; Typical Procedure for Acetate Hydrolysis
1H NMR (400 MHz, CDCl3): d = 0.82–0.88 (m, 3 H, CH3), 1.15 (d,
J = 6.0 Hz, 3 H, CH3CHOH), 1.20–1.45 (m, 10 H, CH2), 1.77 (br s,
1 H, OH), 4.86 (sextet, J = 5.6 Hz, 1 H, CHOH).
13C NMR (101 MHz, CDCl3): d = 14.2 (+, CH3), 22.7 (–, CH2),
23.5 (+,CH3), 25.8 (–, CH2), 29.4 (–, CH2), 39.5 (–, CH2), 68.2 (+,
CH2CHOH).
To a soln of (R)-3 (2.63 g, 10.4 mmol) in MeOH (25 mL) was added
2 M NaOH (25 mL) and the mixture was stirred at r.t. for 6 h.
MeOH was removed under reduced pressure and the aqueous soln
was extracted with CH2Cl2 (3 × 25 mL). The combined organic
phases were dried (Na2SO4) and the solvent was removed. The oil
obtained solidified after drying under vacuum for 4 h. Recrystalli-
zation (cyclohexane, 20 mL) yielded (R)-1 [2.10 g, 91%, >99% ee
(HPLC)] as a colorless solid; mp 118–119 °C (cyclohexane); HPLC
(Chiracel OD-H, 0.5 mL/min, 20 °C, detection at 210 nm, n-hep-
tane–i-PrOH, 95:5): tR = 25.0 min.
Anal. Calcd for C8H18O (130.23): C, 73.78; H, 13.93. Found: C,
73.53; H, 13.70.
(R)-1-Phenylethanol [(R)-11]
Compound (R)-11 was prepared from (R)-13 (3.05 g, 18.6 mmol)
according to the typical procedure for acetate hydrolysis to give (R)-
1. Bulb-to-bulb distillation (60 °C/0.1 mbar) yielded (R)-11 [2.02 g,
89%, 95% ee (HPLC)] as a colorless liquid; HPLC (Chiracel OD-
H, 0.5 mL/min, 20 °C, detection at 220 nm, n-heptane–i-PrOH,
98:2): tR = 31.0 min.
[a]D20 –39.8 (c 1.01, CHCl3).
IR: 3167 (br s), 2968 (m), 1588 (m), 1572 (m), 1458 (s), 1445 (s),
1307 (m), 1238 (m), 1163 (w), 1053 (s), 1021 (m), 961 (m), 908
(m), 852 (m), 768 (s), 695 (s), 563 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 2.04 (q, J = 7.3 Hz, 1 H, CH2),
2.57 (mc, J = 4.3 Hz, 1 H, CH2), 2.85 (q, J = 8.1 Hz, 1 H, CH2),
3.00–3.08 (m, 1 H, CH2), 3.37 (br s, 1 H, OH), 5.24 (t, J = 6.8 Hz,
1 H, CHOH), 7.37–7.40 (m, 3 H, HAr), 7.41 (d, J = 8.1 Hz, 1 H,
HAr), 7.46 (d, J = 7.8 Hz, 1 H, HAr), 7.95 (d, J = 7.3 Hz, 2 H, HAr).
13C NMR (101 MHz, CDCl3): d = 27.2 (–, CH2), 33.0 (–, CH2), 74.8
(+, CH), 120.0 (+, CAr), 127.0 (+, CAr), 128.7 (+, CAr), 133.7 (+,
CAr), 134.7 (Cq, CAr), 139.4 (Cq, CAr), 156.6 (Cq, CAr), 164.7 (Cq,
CAr).
[a]D20 +58.5 (c 1.00, CHCl3) [Lit.17 [a]D20 +54.2 (c 1.00, CHCl3)].
1H NMR (400 MHz, CDCl3): d = 1.49 (d, J = 6.3 Hz, 3 H, CH3),
2.16 (br s, 1 H, OH), 4.87 (q, J = 6.6 Hz, 1 H, CHOH), 7.26–7.36
(m, 5 H, HAr).
13C NMR (101 MHz, CDCl3): d = 25.3 (+, CH3), 70.4 (+, CHOH),
125.5 (+, CAr), 127.5 (+, CAr), 128.5 (+, CAr), 145.9 (Cq, CAr).
Anal. Calcd for C8H10O (122.17): C, 78.65; H, 8.25. Found: C,
78.09; H, 8.26.
MS (EI, 70 eV, 100 °C): m/z (%) = 211 (50) [M]+, 182 (100), 155
(28), 115 (8), 77 (9) [Ph]+.
Acknowledgment
Anal. Calcd for C14H13NO (211.26): C, 79.59; H, 6.20; N, 6.63.
Found: C, 79.46; H, 6.20; N, 6.50.
Financial support from the Swiss National Science Foundation and
the Federal Commission for Technology and Innovation (KTI) is
gratefully acknowledged.
(R)-8-Hydroxy-2-phenyl-5,6,7,8-tetrahydroquinoline [(R)-2]
Compound (R)-2 was prepared from 4 (2.42 g, 9.05 mmol) accord-
ing to the typical procedure for acetate hydrolysis to give (R)-1. Re-
crystallization (cyclohexane, 20 mL) yielded (R)-2 [1.42 g, 72%,
>99% ee (HPLC)] as a colorless solid; mp 98 °C (cyclohexane);
HPLC (OD-H, 0.5 mL/min, 20 °C, detection at 220 nm, n-heptane–
i-PrOH, 98:2): tR = 33.1 min.
References
(1) (a) Schmid, A.; Dordick, J. S.; Hauer, B.; Kiener, A.;
Wubbolts, M.; Witholt, B. Nature 2001, 409, 258.
(b) Schmid, R. D.; Verger, R. Angew. Chem. Int. Ed. 1998,
37, 1608; Angew. Chem. 1998, 110, 1694. (c) Chênevert,
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[a]D20 –148 (c 0.98, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.76–1.95 (m, 2 H, CH2), 1.98–
2.11 (m, 1 H, CH2), 2.28–2.45 (m, 1 H, CH2), 2.72–2.91 (m, 2 H,
CH2), 4.40 (br s, 1 H, OH), 4.76 (mc, J = 5.1 Hz, 1 H, CHOH),
7.39–7.50 (m, 5 H, HAr), 7.58 (d, J = 7.3 Hz, 1 H HAr), 8.00 (d,
J = 7.3 Hz, 1 H, HAr).
13C NMR (101 MHz, CDCl3): d = 20.0 (–, CH2), 28.46 (–, CH3),
31.1 (–, CH2), 69.2 (+, CHOH), 119.9 (+, CAr), 127.3 (+, CAr), 129.2
(+, CAr), 129.6 (+, CAr), 130.7 (Cq, CAr), 138.7 (+, CAr), 154.5 (Cq,
CAr), 158.0 (Cq, CAr).
Anal. Calcd for C15H15NO (225.29): C, 79.97; H, 6.71; N, 6.22.
Found: C, 79.81; H, 6.78; N, 6.02.
(R)-Octan-2-ol [(R)-10]
Compound (R)-10 was prepared from (R)-12 (2.67 g, 15.5 mmol)
according to the typical procedure for acetate hydrolysis to give (R)-
1. Bulb-to-bulb distillation (100 °C/15 mbar) yielded (R)-10
[1.83 g, 91%, >99% ee (GC)] as a colorless liquid.
(5) (a) Roseblade, S. J.; Pfaltz, A. Synthesis 2007, 3751.
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(6) Liu, Q. B.; Yu, C. B.; Zhou, Y. G. Tetrahedron Lett. 2006,
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GC determination of ee after derivatization as acetate [b-cyclodex-
trin Brechbühler SE54 (25 m × 0.25 mm × 0.25 mm), 60 kPa He;
240 °C (injector); 270 °C (detector); temperature program: 90 °C
(20 min), 20 K/min, 160 °C (10 min)]: tR = 13.4 min.
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Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York

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M. Maywald, A. Pfaltz
PAPER
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Synthesis 2009, No. 21, 3654–3660 © Thieme Stuttgart · New York