A green resolution-separation process for aliphatic secondary alcohols

Article abstract of DOI:10.1016/j.tetasy.2013.01.018

In order to obtain both enantiomers of aliphatic secondary alcohols via a greener method, the four-step resolution-separation process involving lipase-catalyzed enantioselective esterification and hydrolysis as well as two separation procedures both via heterogeneous azeotropic distillation was developed. (S)-2-Pentanol (ee = 98.6%), (R)-2-pentanol (ee >99%), (S)-2-octanol (ee = 98.2%), and (R)-2-octanol (ee = 98.5%) were all produced in high purity (>98%) and high yield (>90%). In addition to the two model substrates, this method could also be applied to the resolution of other aliphatic secondary alcohols.

Full text of DOI:10.1016/j.tetasy.2013.01.018

Tetrahedron: Asymmetry 24 (2013) 249–253
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A green resolution–separation process for aliphatic secondary alcohols
Liwei Ren a, Tian Xu a, Ruoping He a, Zhenhua Jiang a, Hua Zhou a,b, , Ping Wei a,b
⇑
a College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 211816, PR China
b State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing 210009, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
In order to obtain both enantiomers of aliphatic secondary alcohols via a greener method, the
four-step resolution–separation process involving lipase-catalyzed enantioselective esterification and
hydrolysis as well as two separation procedures both via heterogeneous azeotropic distillation was
developed. (S)-2-Pentanol (ee = 98.6%), (R)-2-pentanol (ee >99%), (S)-2-octanol (ee = 98.2%), and
(R)-2-octanol (ee = 98.5%) were all produced in high purity (>98%) and high yield (>90%). In addition to
the two model substrates, this method could also be applied to the resolution of other aliphatic secondary
alcohols.
Received 13 November 2012
Accepted 21 January 2013
Available online 26 February 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
recovery of the other esterified enantiomer.19 The combination of
the lipase-catalyzed resolution and the separation process enables
Green chemistry is the design of chemical products and pro-
cesses that reduces or eliminates the use and generation of hazard-
ous or toxic substances and minimizes the requirement for
energy.1,2 The application of biocatalysis, which possesses many
green features, contributes to the development of modern chemi-
cal industries.3–5 More importantly, the enantioselectivity of
enzymes gives biocatalysis an unparalleled advantage in asymmet-
ric synthesis.6–9
Enantiomerically pure secondary alcohols are pivotal synthons
for pharmaceuticals and other fine chemicals. For example, (S)-2-
pentanol is an important chiral intermediate for the synthesis of
potential anti-Alzheimer’s drugs,10 while (S)- and (R)-2-octanol
are both employed as versatile precursor compounds for the prep-
aration of agrochemicals, pharmaceuticals, and liquid crystals.11,12
The lipase-catalyzed kinetic resolution of secondary alcohols is still
a practical method for obtaining both enantiomers, compared with
the oxidoreductase-catalyzed asymmetric reduction of prochiral
ketones.13 The two major disadvantages of oxidoreductases are
their low activity and poor stability in organic solvents or sol-
vent-free systems, as well as their dependence on coenzymes or
cofactor regeneration systems.14 Both of these factors complicate
the preparation and separation of enantiopure alcohols. Lipases
are independent of coenzymes and are highly active and stable
both in aqueous media and organic solvents.15 Recently, some res-
olution processes have been designed to facilitate the separation of
free alcohol enantiomers and enantiomerically enriched esters.16–18
Several efforts have also been made with regard to the subsequent
us to gain both enantiomers of secondary alcohols more easily and
efficiently.
However, the resolution–separation process still has several
limitations. In order to perform the asymmetric transesterification
in solvent-free systems and to offer the prospect of product isola-
tion, middle and long chain fatty acid-derived esters, such as ethyl
octanoate and ethyl tetradecanoate, are usually employed as acyl-
ating agents for lipases.16,20 These esters are generally prepared
from the corresponding fatty acids and ethanol via acid–base catal-
ysis. By comparison, the original fatty acids, which are the natural
substrates for lipases and can avoid substrate inactivation, will be
greener and more available acyl donors.21 Furthermore, the subse-
quent deacylation step should also be greener and more efficient.
In order to bypass the insolubility of the enantiomerically enriched
esters in water, the enzymatic aminolysis can be carried out in an
organic solvent; for example enzymatic alcoholysis in ethanol has
been adopted in some resolution–separation processes.13,16 How-
ever, they are still two reversible processes, besides the possible
inhibition to the activity and the enantioselectivity of the lipase
from free ammonia and excessive ethanol. More importantly, it is
necessary to establish a new separation method. Enantiopure sec-
ondary alcohols are currently separated from their reaction sys-
tems using silica gel chromatography or HPLC.13,22,23 However,
the use of either a mobile phase or an eluent for chromatographic
separation, which is usually a mixture of two or three organic sol-
vents, makes the solvent-free reactions meaningless. It has been
reported that secondary alcohols can be separated from the
remaining acyl donors and the generated esters by vacuum distil-
lation,16 but this approach relies heavily on a large difference in the
boiling points of the three substances and the formation of azeo-
⇑
Corresponding author. Tel./fax: +86 25 5813 9916.
E-mail address: zhouhua@njut.edu.cn (H. Zhou).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.01.018

250
L. Ren et al. / Tetrahedron: Asymmetry 24 (2013) 249–253
CH3
OH
O
CH3
O
CH3
OH
Novozyme 435
+
+
Step 1:
45 °C, solvent free
R1
R2
OH
R1
O
R2
R1
Step 2:
+ H2O, heterogeneous azeotropic distillation
CH3
+ H2O
R1
OH
O
CH3
O
CH3
OH
O
Step 3:
Novozyme 435
37 °C, pH 8.0-8.5 R1
+
+ NaHCO3 + H2O
+
+ CO2
R2
OH
R1
O
R2
R2
ONa
Step 4:
heterogeneous azeotropic distillation
R
1 = C3H7 R2 = C5H11
C6H13
C7H15
C9H19
C11H23
CH3
+ H2O
R1
OH
O
R2
ONa
Scheme 1. The four-step resolution–separation process, using 2-pentanol and 2-octanol as the model substrates and fatty acids as the acylating agent.
Table 1
tropes must be prevented. In addition, it has been found that res-
olution–separation processes have scarcely been applied to ali-
phatic secondary alcohols. The lack of a reasonable separation
method for aliphatic examples may be partly responsible for this
situation.
Kinetic resolution of 2-pentanol 1 and 2-octanol 2 with middle chain fatty acids in
solvent-free systemsa
Ed
b
c
Entry
Acid
Alcohol
Time
(h)
Conv.
(%)
ees
eep
(%, S)
(%, R)
1
2
3
4
5
6
7
8
Hexanoic
Octanoic
Decanoic
Dodecanoic
Hexanoic
Octanoic
1
1
1
1
2
2
2
2
12
8
8
49.6
49.7
49.7
49.7
47.7
49.9
49.5
49.0
97.7
98.6
98.6
98.6
89.9
98.2
96.5
94.8
>99
>99
>99
>99
98.5
98.5
98.5
98.5
895
991
991
991
409
626
541
491
Herein we report a green resolution–separation process, which
is appropriate for aliphatic secondary alcohols. A simpler first
step, the lipase-catalyzed resolution of a racemic secondary alco-
hol, was carried out at atmospheric pressure, using a middle
chain fatty acid as the solvent and acylating agent. In the recovery
step for the other enantiomer via enzymatic hydrolysis from the
enantiomerically enriched ester, a solution of sodium bicarbonate
was used to facilitate mixing of the ester with water and to effec-
tively shift the reaction equilibrium constantly to the hydrolytic
side by forming a sodium salt with the residual and released fatty
acid. Moreover, the ability of aliphatic secondary alcohols to form
an azeotrope with water was exploited in order to distill their
two enantiomers from solvent-free systems and aqueous media,
respectively, at a lower temperature and atmospheric pressure
(Scheme 1).
8
16
12
12
12
Decanoic
Dodecanoic
a
Reactions were carried out with 36 mmol of racemic secondary alcohols and
54 mmol of fatty acid at 45 °C, in the presence of Novozyme 435 (0.18 g) and 4 Å
molecular sieves (6.0 g).
b
The enantiomeric excesses of the unreacted alcohols (ees) were measured by
derivatization with (R)-1-phenylethyl isocyanate (ee >99.5%), followed by GC
analysis using the capillary column Agilent DB-1.
c
The enantiomeric excesses of the generated esters (eep) were measured by GC
using the capillary column Varian CP-chirasil-Dex CB.
d
E = ln[(1 ꢀ ees)/(1 + ees/eep)]/ln[(1 + ees)/(1 + ees/eep)], c = ees/eep + ees.
three acids tested gave similar results and, for the resolution of
2-octanol, the results of octanoic acid (logP = 2.43) were slightly
better than those of decanoic (logP = 3.27) and dodecanoic
(logP = 4.10) acids, which are both solid at room temperature. In
view of the solid catalyst mass transfer, the lower viscosity of these
reaction systems might help octanoic acid cover the shortage in
hydrophobicity. Therefore, octanoic acid was chosen as the acylat-
ing agent for further tests.
Higher temperatures afforded improved reaction rates. Novo-
zyme 435 remained active at 60 °C in this solvent-free system,
but the stereoselectivity decreased. As a result, the reaction tem-
perature was optimized to 45 °C. The special condition that the
molar ratio of octanoic acid to secondary alcohol was 0.5:1, was
investigated in order to facilitate the subsequent separation. In
theory, only the (S)-enantiomers of the alcohols and the (R)-esters
should be obtained at 50% conversion of the secondary alcohols.
However, we were unable to reach 50%, even though the by-prod-
uct (water) was continually removed by 4 Å molecular sieves. This
indicated that the excess octanoic acid, which acted as the solvent
and propelled the esterification, was essential for the solvent-free
systems; the optimal molar ratio of acid to alcohol was proved to
be 1.5:1 (Table 2).
2. Results and discussion
2.1. Enzymatic kinetic resolution of secondary alcohols
For the sake of comparison with other methods, the four-step
resolution–separation process was evaluated using two model sub-
strates (2-pentanol and 2-octanol) and employed Novozyme 435
as the catalyst. For the lipase-catalyzed resolution of aliphatic sec-
ondary alcohols, the immoderate acidity and the insufficient
hydrophobicity restricted the short chain fatty acids from acylating
the alcohols in solvent-free systems. Conversely, the high hydro-
phobicity of long chain fatty acids that are a viscous liquid or even
a solid at room temperature made them inappropriate as well.
Commonly available middle chain fatty acids were also investi-
gated herein (Table 1). Hexanoic acid needed more time to achieve
similar conversions to the other acylating agents, but the enantio-
meric purities of the unreacted alcohols were always less, perhaps
because its acidity was still too strong for the lipase or because
hexanoic acid (logP = 1.91) could not create a suitably hydrophobic
environment for the lipase-catalyzed esterifications. The other

L. Ren et al. / Tetrahedron: Asymmetry 24 (2013) 249–253
251
Table 2
yield of (S)-2-pentanol was still above 90%. When (S)-2-pentanol
was dried, the purities of (S)-2-pentanol and (S)-2-octanol were
both >98% while the impurity was only a slight amount of octanoic
acid. In addition, the colorless alcohols were separated from the
pale yellow reaction systems, meaning that the procedure of the
decoloration was accomplished simultaneously by this low-energy
and high-efficiency separation process.
Study of the reaction conditions for the enzymatic kinetic resolution of 2-pentanola
b
c
Entry
Temp (°C)
Acid/alcohol
ratio
Time
(h)
Conv.
(%)
ees
eep
(%, S)
(%, R)
1
2
3
4
5
6
30
45
60
45
45
45
1.5:1
1.5:1
1.5:1
0.5:1
1:1
10
8
7
14
8
8
48.3
49.8
51.0
45.4
48.7
49.8
93.0
98.6
96.3
82.8
94.2
98.6
>99
>99
94.7
>99
>99
>99
2.3. Lipase-catalyzed hydrolysis of esters
2:1
a
Reactions were carried out with 36 mmol of 2-pentanol and 18–72 mmol of
The distillation residues of step 2 were directly mixed with a
solution of sodium bicarbonate at 37 °C for 30 min. With the re-
lease of carbon dioxide, the residual octanoic acid was irreversibly
converted into sodium octanoate, while the esters were not hydro-
lyzed by the weak base under these conditions. As a type of stabi-
lizer for albumin production, sodium octanoate did not inhibit the
activity of the lipase,25 the pH of 8.0–8.5 was measured in a solu-
tion of sodium octanoate, which was almost the optimal pH for
Novozyme 435. More importantly, the esters and water were
mixed efficiently, due to the existence of sodium octanoate, which
acted as a surfactant. Novozyme 435, in which Candida antarctica
lipase B is physically adsorbed by the hydrophobic macroporous
support, generally floats on the aqueous media together with the
hydrophobic substrates. Moreover, due to the generated sodium
octanoate, Novozyme 435 was evenly distributed through the reac-
tion solution and the enzymatic hydrolysis of the esters changed
from an interfacial reaction to a homogeneous reaction.
The concentration of sodium bicarbonate was a crucial factor in
this procedure. In addition to forming sodium octanoate with the
residual octanoic acid, sodium bicarbonate should be left to dis-
place the reaction equilibrium constantly to the hydrolytic side
by forming the new sodium salt with the released octanoic acid.
However, it should be noticed that too much sodium bicarbonate
could inactivate the catalyst. Contrarily, the enlarged volume of
the reaction systems would decrease the efficiency of biocatalytic
hydrolysis at lower concentrations. Finally, the concentration of
sodium bicarbonate was optimized to 0.60 mol/L. Under these con-
ditions, the esters were completely hydrolyzed at 37 °C within
6–8 h and the final concentrations of sodium octanoate and
sodium bicarbonate were 0.59 and 0.01 mol/L, respectively (Fig. 1).
octanoic acid at 30–60 °C, in the presence of Novozyme 435 (0.18 g) and 4 Å
molecular sieves (6.0 g).
b
The enantiomeric excesses of the unreacted alcohols (ees) were measured by
derivatization with (R)-1-phenylethyl isocyanate (ee >99.5%), followed by GC
analysis using the capillary column Agilent DB-1.
c
The enantiomeric excesses of the generated esters (eep) were measured by GC
using the capillary column Varian CP-chirasil-Dex CB.
2.2. Separation of the (S)-enantiomers via azeotropic distillation
The esterification was stopped at about 50% conversion by fil-
tering out the lipase and molecular sieves. When the two (S)-enan-
tiomers were separated from the filtrates by vacuum distillation,
there was always approximately 20% of octanoic acid and 3% of
the generated esters in the distillates. It was found in our previous
work that such problems had been near-universal for most other
aliphatic secondary alcohols, whether using the original acids or
the derived esters as acylating agents.
However, only the secondary alcohols in the filtrates can form
an azeotrope with water (36.5 wt%, 91.7 °C for 2-pentanol and
73.0 wt%, 98.0 °C for 2-octanol).24 When a certain amount of water,
according to the azeotropic proportions, was added and the mix-
tures were heated to the advisable temperatures, both the majority
of the two alcohols were purified without any damage to the enan-
tiomeric excesses (ee). We had also attempted to complete the sep-
aration of the alcohols through accelerated stirring and ultrasound
emulsification; however both methods were unsuccessful. The
main reason might be that there was no method to make the added
water contact only with the secondary alcohol, instead of all the
three components. As a solution, the amount of water was multi-
plied. When 4.0 and 12.8 mL of water were added, respectively,
(S)-2-pentanol and (S)-2-octanol were both distilled completely
and the ee values were perfectly preserved (Table 3). At room tem-
perature the distillates changed to two layers automatically, due to
the insolubility of 2-octanol and the poor solubility of 2-pentanol
in water. For the same reason, the water content of the obtained
(S)-2-pentanol was approximately 6% and approximately 5% of
(S)-2-pentanol was contained in the layer of water. However, the
Table 3
Effect of the amount of added water on the distillation of (S)-2-pentanol 1 and
(S)-2-octanol 2
Watera (mL)
Efficiencyb (%)
ees (%, S)
c
Entry
Alcohol
1
2
3
4
5
6
1
1
1
1
2
2
1.0
2.0
3.0
4.0
6.4
65.1
81.4
93.0
100
75.6
100
98.6
98.6
98.6
98.6
98.2
98.2
Figure 1. Hydrolytic processes of (R)-2-pentyl octanoate (triangle) and (R)-2-octyl
octanoate (circle) with (solid) or without (hollow) sodium bicarbonate.
12.8
a
The initial amount of water was added according to the azeotropic proportion,
then it was multiplied gradually.
2.4. Separation of the (R)-enantiomers via azeotropic
distillation
b
The efficiency of the distillation was calculated from the amount of the residual
alcohol in the distillation residue, which was measured by GC using the capillary
column Agilent DB-225.
c
The (R)-2-pentanol and (R)-2-octanol could also be directly sep-
The enantiomeric excesses of the separated alcohols were measured by GC,
following dilution with n-hexane.
arated from the hydrolyzates of step 3 by azeotropic distillation, as

252
L. Ren et al. / Tetrahedron: Asymmetry 24 (2013) 249–253
long as Novozyme 435 was filtered out. The existence of sodium
octanoate and sodium bicarbonate merely raised the azeotropic
temperatures by 5–8 °C, meaning that an ee >99% and an
ee = 98.5% were obtained for (R)-2-pentanol and (R)-2-octanol,
respectively, which were equal to the ee values of their corre-
sponding esters (Table 1). Due to the superabundant water in the
hydrolyzates, the azeotropic distillations were immediately ended
when the organic layer of the distillates stopped expanding. We
found that no alcohol was omitted in the distillation residues
and that the final yields of (R)-2-pentanol and (R)-2-octanol were
both over 90%. Moreover, their purities were almost 100%, because
octanoic acid, which was the impurity of the distillates in step 2,
was completely converted into sodium octanoate before the azeo-
tropic distillation, which has a high boiling point. The distillation
residue of this step was a solution of sodium octanoate with a
small amount of sodium bicarbonate. As a type of valuable bio-
chemical, the purified sodium octanoate could be easily obtained
by drying and recrystallization. Alternatively, all of the used octa-
noic acid could precipitate out from the distillation residue by add-
ing hydrochloric acid, then, it could be reused as the acylating
agent for the resolution–separation process. Both methods ensure
no harmful emission to the environment during the whole process.
in n-hexane at 40 °C for 45 min, followed by GC analysis using a
capillary column Agilent DB-1 (30 m ꢁ 0.25 mm ꢁ 0.25 m).
l
2-Pentanol: oven temperature: 110 °C for 1 min and ramp
10 °C/min to 190 °C, followed by 190 °C for 1 min and ramp
1 °C/min to 215 °C; tr(S) = 10.8 min, tr(R) = 11.1 min. 2-Octanol:
oven temperature: 110 °C for 1 min and ramp 15 °C/min to
210 °C, followed by 210 °C for 1 min and ramp 1 °C/min to
225 °C; tr(S) = 12.4 min, tr(R) = 13.1 min. The enantiomeric ex-
cesses of the enantiomerically enriched esters were analyzed by
GC using the capillary column Varian CP-chirasil-Dex CB
(25 m ꢁ 0.25 mm ꢁ 0.25
lm). Oven temperature: 60 °C for 1 min
and ramp 3 °C/min to 200 °C.
4.3. General procedure for the green resolution–separation
process
4.3.1. Enzymatic kinetic resolution of secondary alcohols
(step 1)
Racemic 2-pentanol or 2-octanol (36 mmol), fatty acid
(54 mmol), and 4 Å molecular sieves (6.0 g) were added to a conical
flask with a stopper. The reaction was started by the addition of
Novozyme 435 (0.18 g). Samples (15 lL) were withdrawn at regu-
lar intervals, diluted with n-hexane (0.5 mL) and analyzed as de-
scribed above.
3. Conclusion
Both enantiomers of 2-pentanol and 2-octanol were obtained in
high purity and yield without using or generating any hazardous or
toxic substances while the requirement for energy was reduced by
avoiding a longstanding vacuum both in the resolution and the
separation procedures. We have demonstrated that this approach
can also be applied to the resolutions of other aliphatic secondary
alcohols, such as 2-hexanol, 2-heptanol, 3-methy-2-butanol,
4-methy-2-pentanol, 3-hexanol, and so on, in our later work. The
simplicity, green properties, and scalability of this efficient resolu-
tion–separation process give it great potential for industrial appli-
cations. Novozyme 435 can duplicate the esterification more than
eight times, but it takes more time to completely hydrolyze the es-
ters with the increase of reuse. This is because of the leaching of
the lipase; the reusability of the immobilized lipase in an aqueous
media needs to be enhanced in further work.
4.3.2. Separation of (S)-enantiomers via azeotropic distillation
(step 2)
The esterification reaction was stopped at approximately 50%
conversion of the alcohol by filtering out the lipase and molecular
sieves. The filtrate and a certain amount of deionized water were
added to a 50 mL round bottom flask. Under lab conditions, the
azeotropic distillation was carried out with ordinary distillation
apparatus. With sufficient stirring, the temperature of the vapor
at the outlet was heated to 92.0 °C for 2-pentanol or 98.0 °C for
2-octanol. When the distillates went through the condenser, it
changed into two layers automatically and only the layer of
2-pentanol needed to be dried by 4 Å molecular sieves.
4.3.3. Lipase-catalyzed hydrolysis of esters (step 3)
The distillation residue of step 2 was mixed with a solution of
sodium bicarbonate (0.60 mol/L, 90 ml) at 37 °C for 30 min. The
hydrolysis of the enantiomerically enriched ester was started by
the addition of Novozyme 435 (0.3 g). Samples (0.5 mL) were with-
drawn at regular intervals, extracted with n-hexane (1.5 mL) and
analyzed as described above.
4. Experimental
4.1. Enzyme and chemicals
Novozyme 435Ò was purchased from Novozymes Co. (Den-
mark). The 4 Å molecular sieves and n-hexane (HPLC grade) were
purchased from Sinopharm (China). Other chemicals were all pur-
chased from Sigma–Aldrich or TCI. Deionized water was used. The
logP-values were calculated using Chemdraw Ultra 7.0 software
(Cambridgesoft Corp., Cambridge).
4.3.4. Separation of the (R)-enantiomers via azeotropic
distillation (step 4)
The hydrolysis reaction was stopped at 100% conversion by fil-
tering out the lipase. The hydrolyzate was directly added to a
250 mL round bottom flask. Other conditions were the same as
for the separation of (S)-enantiomers, but the azeotropic tempera-
tures were increased by approximately 5–8 °C.
4.2. Analytical methods
1H NMR spectra were recorded on a Bruker AV-300 instrument
operating at a frequency of 300 MHz. All chemical shifts (d) are
quoted in parts per million (ppm) and reported relative to an inter-
nal tetramethylsilane (br = broad signal). Optical rotations were
determined on a Jasco P-1020 Polarimeter at room temperature
using a cell of 1 dm length and k = 589 nm. The course of reactions
and the purity of the products were monitored by GC analysis,
performed on an Agilent 6890, FID detection, using the capil-
4.3.5. (S)-2-Pentanol and (R)-2-pentanol
(S)-2-Pentanol (16.4 mmol, 92.1% yield, 98.6% purity):
½
a 2D8:2
ꢂ
¼ þ18:0 (c 0.97, CHCl3) for 98.6% ee. (R)-2-Pentanol
(16.3 mmol, 91.6% yield, >99% purity): ½a D28:0
¼ ꢀ20:1 (c 0.97,
ꢂ
CHCl3) for > 99% ee; 1H NMR (CDCl3): d 0.92 (3H, t, J = 6.0), 1.17
(3H, d, J = 6.2), 1.31–1.48 (4H, br), 2.34 (1H, d, J = 2.6), 3.78 (1H, m).
4.3.6. (S)-2-Octanol and (R)-2-octanol
lary column Agilent DB-225 (30 m ꢁ 0.32 mm ꢁ 0.25
lm). Oven
(S)-2-Octanol (16.6 mmol, 93.2% yield, 98.4% purity):
temperature: 60 °C for 1 min and ramp 10 °C/min to 210 °C. The
enantiomeric excesses of the secondary alcohols were measured
by derivatization with (R)-1-phenylethyl isocyanate (ee >99.5%)
½
a 2D8:3
ꢂ
¼ þ10:4 (c 0.98, CHCl3) for 98.2% ee. (R)-2-Octanol
(17.0 mmol, 94.4% yield, >99% purity): ½a D28:3
¼ ꢀ12:3 (c 0.98,
ꢂ

L. Ren et al. / Tetrahedron: Asymmetry 24 (2013) 249–253
253
CHCl3) for 98.5% ee; 1H NMR (CDCl3): d 0.87 (3H, t, J = 6.2), 1.18
(3H, d, J = 6.2), 1.29–1.43 (10H, br), 1.58 (1H, s), 3.80 (1H, m).
11. Liese, A.; Zelinski, T.; Kula, M. R.; Kierkels, H.; Karutz, M.; Kragl, U.; Wandrey, C.
J. Mol. Catal. B Enzym. 1998, 4, 91–99.
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745.
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Financial support for this research from the National Program
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