Highly enantioselective dynamic kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl group with a highly active lipoprotein lipase preparation

Article abstract of DOI:10.1016/j.tetasy.2015.06.010

Abstract The kinetic and dynamic kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl group with a highly active lipase preparation containing lipoprotein lipase, dextrin, and ionic surfactant 1 has been explored. It was found that all the trimethylsilyl-containing substrates were accepted by lipoprotein lipase-dextrin 1 (LPL-D1) with perfect enantioselectivity (E = >200). As a result, the dynamic kinetic resolution of these substrates with LPL-D1 in the presence of a Ru-based racemization catalyst provided single enantiomeric products (>99% ee) with good yields. Furthermore, the dynamic kinetic resolution products were readily desilylated or halodesilylated to yield enantiopure alkyl aryl carbinols. Thus a useful protocol for the highly enantioselective synthesis of alkyl aryl carbinols, particularly those carrying a long alkyl chain (C₆-C₁₀) has been established.

Full text of DOI:10.1016/j.tetasy.2015.06.010

Tetrahedron: Asymmetry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly enantioselective dynamic kinetic resolution of alkyl aryl
carbinols carrying a trimethylsilyl group with a highly active
lipoprotein lipase preparation
⇑
⇑
Jeonghun Cho , Jusuk Lee , Jaiwook Park , Mahn-Joo Kim
Department of Chemistry, Pohang University of Science and Technology, 77 Cheongam-ro, Pohang 790-784, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The kinetic and dynamic kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl group with a
highly active lipase preparation containing lipoprotein lipase, dextrin, and ionic surfactant 1 has been
explored. It was found that all the trimethylsilyl-containing substrates were accepted by lipoprotein
lipase–dextrin 1 (LPL–D1) with perfect enantioselectivity (E = >200). As a result, the dynamic kinetic res-
olution of these substrates with LPL–D1 in the presence of a Ru-based racemization catalyst provided sin-
gle enantiomeric products (>99% ee) with good yields. Furthermore, the dynamic kinetic resolution
products were readily desilylated or halodesilylated to yield enantiopure alkyl aryl carbinols. Thus a use-
ful protocol for the highly enantioselective synthesis of alkyl aryl carbinols, particularly those carrying a
long alkyl chain (C6–C10) has been established.
Received 13 May 2015
Accepted 5 June 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
CO2K
1. Introduction
Since the first report on a dynamic kinetic resolution employing
an enzyme and a metal-based racemization catalyst in combina-
tion,1 the metalloenzymatic dynamic kinetic resolution has been
intensively explored for enantioconvergent transformations of
racemic alcohols.2–4 Recently, we reported a highly active lipase
preparation (ionic-surfactant-coated Burkholderia cepacia lipase)
as the enzyme for the dynamic kinetic resolution of a wider range
of secondary alcohols.5 Later, our group also reported another
highly active lipase preparation containing lipoprotein lipase
(LPL), dextrin (D), and ionic surfactant 1 for the dynamic kinetic
resolution of sterically more demanding secondary alcohols such
as diarylmethanols.6 The lipoprotein lipase–dextrin 1 (LPL–D1) dis-
plays an aqueous-level turnover frequency in organic solvent,6a
and thus appears to be the most active lipase preparation that
has been reported to date for the application to dynamic kinetic
resolution. Herein we report the highly enantioselective dynamic
kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl
group as a new application of LPL–D1.
Et(OCH2CH2)3O
O(CH2CH2O)3Et
1
It is known that the enantioselectivity of a lipase in the transes-
terification of a secondary alcohol increases in general with an
increase in the difference in size between two substituents at the
hydroxymethine center of substrate.7 This implies that the enan-
tioselectivity of the lipase toward simple alkyl aryl carbinols is
high if the alkyl chain is small and decreases with an increase in
the length of the alkyl chain. However, the enantioselectivity of
lipase remains high for long alkyl aryl carbinols if a bulky group
such as t-butyl is present on the aromatic ring.5a This specificity
thus suggests that a readily removable bulky group on the
aromatic ring can serve as a steric auxiliary for inducing the high
enantioselectivity of lipase. Herein, we found that when the
trimethylsilyl group was used as a steric auxiliary, it induced
perfect enantioselectivity.
A variety of chemical methods have been developed for the
enantioselective synthesis of alkyl aryl carbinols. Some representa-
tive procedures include asymmetric reductions8 or hydrogena-
tions9 of alkyl aryl ketones, asymmetric arylations of aliphatic
aldehydes,10 and asymmetric alkylations of aromatic aldehydes.11
Enzymatic methods are also available as useful alternatives to
chemical procedures. Two well-known approaches are the reduc-
tase-catalyzed asymmetric reduction of ketones12 and the lipase-
⇑
Corresponding authors. Tel.: +82 54 279 2112; fax: +82 54 279 0654.
E-mail addresses: pjw@postech.ac.kr (J. Park), mjkim@postech.ac.kr (M.-J. Kim).
Contributed equally to this work.
http://dx.doi.org/10.1016/j.tetasy.2015.06.010
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Cho, J.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.06.010

2
J. Cho et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
catalyzed kinetic resolution of secondary alcohols.13 However, the
chemical and enzymatic methods often fail to provide high enan-
tiopurity in the synthesis of long alkyl aryl carbinols. In addition,
enzymatic kinetic resolutions suffer from the serious limitation
that the theoretical maximum yield for a single enantiomeric pro-
duct cannot exceed 50%. In contrast to this, the dynamic kinetic
resolution of long alkyl aryl carbinols with LPL–D1 described
herein provides high yields with excellent enantiopurities.
counterparts and thus required much longer reaction times
(entries 9 and 10). To reduce the reaction time, the dynamic kinetic
resolution of 3d was performed at a higher temperature (60 °C)
and provided a slightly lower enantiopurity (entry 11). On the
other hand, the dynamic kinetic resolution of 3e was unsuccessful
at 60 °C due to its low reactivity with enzyme and severe oxidation
to the corresponding ketone. The dynamic kinetic resolution was
thus carried out at a lower temperature (40 °C), took a much longer
reaction time, and gave a modest yield (entry 12). Overall, most of
the dynamic kinetic resolutions with LPL–D1 were straightforward
and provided excellent enantiopurities. This is compared to our
2. Results and discussion
previous result that the dynamic kinetic resolution of
a
2.1. Synthesis of trimethylsilyl-containing alkyl aryl carbinols
trimethylsilyl-free alkyl aryl carbinol (1-phenyl-1-heptanol) with
ionic-surfactant-coated Burkholderia cepacia lipase provided an
unsatisfactory enantiopurity (82% ee).5a We also found that the
dynamic kinetic resolution of its p-Br-substituted derivative, (1-
(p-bromophenyl)-1-heptanol), with LPL–D1 proceeded with
lower enantioselectivity to provide 95% ee.
A total of 12 different alkyl aryl carbinols 2a–g and 3a–e con-
taining a trimethylsilyl group at the m- or p-position were synthe-
sized from the corresponding Br-substituted benzaldehydes via
three steps according to the general protocol described in the liter-
ature14 (Scheme 1).
2.3. Desilylation and halodesilylation of dynamic kinetic
resolution products
2.2. Kinetic and dynamic kinetic resolution of trimethylsilyl-
containing alkyl aryl carbinols
Three dynamic kinetic resolution products (R)-4e–g with a C6 to
10 alkyl side chain were chosen for further transformations. First,
each of them was treated with TBAF in DMF at 70 °C to remove the
At first, the trimethylsilyl-substituted alkyl aryl carbinols were
tested as the substrates of LPL–D1 to determine the enantioselec-
tivity toward each of them in the kinetic resolution (Table 1).
The enzymatic enantioselectivity was determined with the trans-
esterification of each substrate with isopropenyl acetate (IPA) in
toluene. We found that all of the trimethylsilyl-substituted sub-
strates were accepted by LPL–D1 with the same perfect enantiose-
lectivity (E = >200), although their alkyl side chains ranged from C1
to C10. These results thus prove that the enantioselectivity of lipase
is high for long alkyl aryl carbinols if a bulky trimethylsilyl group is
present on the aromatic ring. On the other hand, the reactivity of
the substrate decreased in general when increasing the length of
the alkyl chain and going from p- to m-substituted derivatives.15
We performed the dynamic kinetic resolution of each
trimethylsilyl-substituted substrate with a solution containing a
substrate (0.1 mmol), LPL–D1 (10–50 mg/mmol), ruthenium com-
plex 6 (5 mol %) as the racemization catalyst, IPA (0.15 mmol) as
the acyl donor, and K2CO3 (0.1 mmol) in toluene (0.5 M) at 25–
60 °C. The dynamic kinetic resolution of 2a took place rapidly
and provided a good yield with excellent enantiopurity (entry 1,
Table 2). The dynamic kinetic resolutions of 2b–g took longer reac-
tion times because the enzymatic activity decreased when increas-
ing the length of alkyl chain in substrate. All of them, however,
afforded similarly good results (entries 2–7). The dynamic kinetic
resolutions of m-trimethylsilyl-substituted substrates were rather
sluggish relative to those of their p-trimethylsilyl-substituted
C
Table 1
The enantioselectivity in the lipase-catalyzed transesterification of alkyl aryl
carbinols
LPL-D1
AcOCH(Me)=CH2
OH
OH
OAc
Ar
+
R
Ar
R
Ar
toluene, 25 o
C
R
(R)-4-5
2-3
(S)-2-3
Entry Substrate LPL–D1 (mg/
Time
(h)
ees
eep
c
(%)
Ea
mmol)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
3a
3b
3c
3d
3e
10
10
10
10
20
20
20
10
10
10
20
20
3
7
>0.99 >0.99 50
0.85 >0.99 46
0.40 >0.99 29
0.62 >0.99 38
0.66 >0.99 40
0.71 >0.99 42
0.79 >0.99 44
>0.99 >0.99 50
0.61 >0.99 38
0.70 >0.99 41
0.75 >0.99 43
0.43 >0.99 31
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
>200
12
36
18
18
18
6
24
36
66
72
9
10
11
12
a
The
E
value was obtained using the equation: E = ln [1 À c(1 +eep)]/
ln [1 À c(1 À eep)] where c = ees/(ees +eep).
OH
O
OH
1) n-BuLi, THF, -78 oC, 2 h
RMgBr
R
H
R
Br
Br
TMS
THF, 0 oC to 25 o
C
2) TMSCl, -78 oC to 25 oC,
overnight
3) HCl (1 M), 25 oC, 1 h
OH
R
OH
TMS
R
TMS
2a
2c
2e
2g
2b
R = Me,
R = Et
3a
3b
R = Me, R = Et
2d
R = n-Pr,
R = n-Bu
3c R = n-Pr, 3d R = n-Bu
2f
3e
R = n-Hex
R = n-Hex, R = n-Oct
R = n-Dec
Scheme 1. Synthesis of alkyl aryl carbinols carrying a trimethylsilyl group.
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J. Cho et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
3
Table 2
Dynamic kinetic resolution of trimethylsilyl-substituted alkyl aryl carbinols
Ar
OH
OAc
LPL-D1, Ru
Ar
OCOAr
AcOCH(Me)=CH2
R
Ru =
R
Ar
OC
OC
Ar
Cl
Ru
TMS
TMS
K2CO3, toluene
2-3
(R)-4-5
6 Ar = Ph-p-OMe
Entry
Substrate
Product
LPL–D1 (mg/mmol)
Temp (°C)
Time (h)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
3a
3b
3c
3d
3e
(R)-4ac
(R)-4bc
(R)-4c
(R)-4d
(R)-4e
(R)-4f
(R)-4g
(R)-5ac
(R)-5bc
(R)-5c
(R)-5d
(R)-5e
10
10
20
30
30
30
30
10
20
20
30
50
25
25
25
25
25
25
25
25
25
25
60
40
6
82
84
91
89
86
90
85
81
78d
76e
83
65f
>99
>99
>99
>99
>99
>99
>99
>99
>99
>99
97
18
24
48
48
48
48
18
72
72
36
96
9
10
11
12
>99
a
b
c
d
e
f
Isolated yield.
Determined by HPLC.
Absolute configurations were confirmed by comparing their specific rotations with literature data.
The amount of ketone from the oxidation of substrate: 12%.
The amount of ketone from the oxidation of substrate: 15%.
The amount of ketone from the oxidation of substrate: 31%. At 60 °C, the amount of ketone was increased to 56%.
OH
TBAF
R
DMF, 70 oC, 3 d
(R)-7a R = n-Hex: 82% yield, >99% ee
(R)-7b R = n-Oct: 88% yield, >99% ee
7c
(R)-
R = n-Dec: 90% yield, >99% ee
OH
R
OAc
KCl, NCS
R
MeOH, 60 oC, 2 h
Cl
TMS
(R)-8a R = n-Hex: 90% yield, >99% ee
(R)-8b R = n-Oct: 79% yield, >99% ee
4e g
-
(R)-
8c
(R)- R = n-Dec: 83% yield, >99% ee
OH
R
KBr, NCS
MeOH, 60 oC, 2 h
Br
9a
(R)- R = n-Hex: 93% yield, >99% ee
(R)-9b R = n-Oct: 85% yield, >99% ee
(R)-9c R = n-Dec: 83% yield, >99% ee
Scheme 2. Deacetylation, desilylation, and halodesilylation of dynamic kinetic resolution products.
trimethylsilyl group. It was found that desilylation took place with
deacetylation to give free alcohols (R)-7a–c as the products
(Scheme 2). Next, the dynamic kinetic resolution products were
treated with KCl or KBr in the presence of N-chlorosuccinimide
(NCS) in MeOH at 60 °C to obtain halo-substituted alcohols (R)-
8a–c and (R)-9a–c.16 All of the transformations (desilylation and
halodesilylation) proceeded smoothly with no loss in the enantiop-
urity and provided good yields. We thus achieved the synthesis of
enantiopure long alkyl aryl carbinols via dynamic kinetic resolu-
tion. It should be noted that bromo-containing (R)-9a–c can be fur-
ther transformed into more complex compounds via metal-
catalyzed carbon–carbon coupling.17
3. Conclusion
Herein, we have explored the kinetic resolution and dynamic
kinetic resolution of alkyl aryl carbinols carrying a trimethylsilyl
group with a highly active lipoprotein lipase preparation of LPL–
D1. LPL–D1 was highly enantioselective and thus provided the
products of excellent enantiopurity in the dynamic kinetic resolu-
tion reactions. The dynamic kinetic resolution products were read-
ily desilylated or halodesilylated to yield enantiopure alkyl aryl
carbinols. We have thus developed a useful protocol for the highly
enantioselective synthesis of alkyl aryl carbinols via dynamic
kinetic resolution.
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4
J. Cho et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
J = 7.9 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 5.90–5.63 (m, 1H), 2.06 (s,
4. Experimental
3H), 1.53 (d, J = 6.6 Hz, 3H), 0.25 (s, 9H); 13C NMR (75 MHz,
CDCl3, ppm): 171.4, 143.3 141.3 134.7, 126.6, 73.5, 23.3, 22.5,
0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propanol = 97:3, flow
rate = 1.0 mL/min, UV = 217 nm, retention times 5.13 min (S),
9.96 min (R); TOF-MS (ESI+) calcd. for [C13H20O2Si-OAc]+
177.10995, found: 177.10783.
4.1. General procedure for the synthesis of trimethylsilyl-
substituted alkyl aryl carbinols
The synthesis of 1-(p-trimethylsilyl-phenyl)-1-undecanol 2g is
described as a representative procedure. In a two-neck round-bot-
tomed flask, 4-bromobenzaldehyde (5 mmol, 925 mg) was added
in distilled THF (20 mL) under an argon atmosphere. Next, a solu-
tion (1.0 M) of decylmagnesium bromide in diethyl ether (10.5 mL,
2.1 equiv) was added dropwise in an ice bath. The mixture was
stirred overnight at room temperature and then was quenched
by the addition of saturated aqueous NH4Cl. The solution was
extracted with ethyl acetate. The combined organic phase was
dried over magnesium sulfate and filtered through a Celite pad.
The filtrate was concentrated under reduced pressure and purified
by silica gel chromatography (hexane/EtOAc = 9:1) to give 4-bro-
mophenylundecanol (3.5 mmol, 1.15 g, 70% yield).
4.3.2. (R)-1-(4-(Trimethylsilyl)phenyl)propyl acetate 4b
[a] [a]
25 = +93.8 (c 0.8, CHCl3) >99% ee {lit.14 20 = +91.3 (c 1.0,
D D
CHCl3) >99% ee)}; 1H NMR (300 MHz, CDCl3, ppm): d 7.49 (d,
J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.65 (t, J = 6.84 Hz, 1H),
2.06 (s, 3H), 1.96-1.76 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H), 0.25 (s,
9H); 13C NMR (75 MHz, CDCl3, ppm): 171.5, 142.2, 141.1, 134.5,
127.0, 77.8, 30.4, 22.4, 11.1, 0.0; HPLC (R,R)Whelk-O1, n-hex-
ane/2-propanol = 97/3, flow rate = 1.0 mL/min, UV = 217 nm,
retention times 5.00 min (S), 11.3 min (R).
4.3.3. (R)-1-(4-(Trimethylsilyl)phenyl)butyl acetate 4c
A solution of n-butyllithium (2.5 equiv, 2.88 mL) was added
dropwise at À78 °C to 4-bromophenylundecanol (1.85 mmol,
605 mg) in distilled THF (8 mL). The resulting mixture was stirred
for 2 h and then trimethylsilyl chloride (2.8 equiv, 0.65 mL) was
added. After 30 min, the solution was allowed to warm to room
temperature and stirred overnight. The reaction was quenched
by the addition of aqueous acidic solution (1 M HCl, 3 mL) and stir-
red for 1 h. The organic layer was removed by evaporation and the
aqueous layer was extracted with ethyl acetate. The combined
organic phase was dried over magnesium sulfate and filtered
through a Celite pad. The filtrate was concentrated under reduced
pressure and purified by silica gel chromatography
(hexane/EtOAc = 9:1) to give the desired product (1.33 mmol,
426 mg, 72% yield).
[a]
25 = +86.8 (c 0.7, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.51 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 7.8 Hz, 2H), 5.75 (t,
J = 6.75 Hz, 1H), 2.08 (s, 3H), 1.96–1.74 (m, 2H), 1.38–1.27 (m,
2H), 0.94 (t, J = 7.3 Hz, 3H), 0.27 (s, 9H); 13C NMR (75 MHz,
CDCl3, ppm): 171.5, 142.5, 141.1, 134.6, 127.0, 77.0, 39.5, 22.4,
19.9, 14.9, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propanol = 97:3,
flow rate = 1.0 mL/min, UV = 217 nm, retention times 4.73 min
(S), 11.2 min (R); HRMS: [C15H24O2Si]+ 264.1546, found: 264.1548.
4.3.4. (R)-1-(4-(Trimethylsilyl)phenyl)pentyl acetate 4d
[a]
25 = +83.6 (c 0.75, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.49 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.71 (t,
J = 6.3 Hz, 1H), 2.06 (s, 3H), 1.97–1.75 (m, 2H), 1.48–1.10 (m, 4H),
0.87 (t, J = 6.93 Hz, 3H), 0.25 (s, 9H); 13C NMR (75 MHz, CDCl3,
ppm): 171.5, 142.5, 141.1, 134.6, 126.9, 77.2, 37.2, 28.8, 23.5,
22.4, 15.1, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propanol = 97:3,
flow rate = 1.0 mL/min, UV = 217 nm, retention times 4.46 min
(S), 7.41 min (R); HRMS: [C16H26O2Si]+ 278.1702, found: 278.1702.
4.2. General procedure for the kinetic resolution of
trimethylsilyl-substituted alkyl aryl carbinols
LPL–D1 was prepared according to the literature procedure.6
The enantioselectivity of each substrate was determined by per-
forming the transesterification as follows. The solution containing
the substrate (0.1 mmol), LPL–D1 (20 mg/mmol, 2 mg), and IPA
4.3.5. (R)-1-(4-(Trimethylsilyl)phenyl)heptyl acetate 4e
[a]
25 = +67.4 (c 1.2, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.48 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 5.71 (t,
J = 6.3 Hz, 1H), 2.06 (s, 3H), 1.96–1.71 (m, 2H), 1.45–1.08 (m, 8H),
0.86 (t, J = 6.5 Hz, 3H), 0.25 (s, 9H); 13C NMR (75 MHz, CDCl3,
ppm): 171.5, 142.5, 141.1, 134.5, 126.9, 77.3, 37.4, 32.8, 30.1,
26.2, 23.7, 22.4, 15.1, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propa-
nol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm, retention times
10.8 min (R), 13.1 min (S), ee was determined after deprotection
of trimethylsilyl and acetyl with TBAF (1.0 M solution in THF);
HRMS: [C18H30O2Si]+ 306.2015, found: 306.2019.
(0.15 mmol, 17 lL) in distilled toluene (0.5 M, 200 lL) was shaken
at 25 °C until the reaction reached near 50% conversion and then
filtered through a silica gel-pad. The organic layer was analyzed
by chiral HPLC to determine the enantiomeric excesses of the pro-
duct and remaining substrate.
4.3. General procedure for the dynamic kinetic resolution of
trimethylsilyl-substituted alkyl aryl carbinols
In a pear-shaped Schlenk flask, substrate (0.1 mmol), LPL–D1
(10–50 mg/mmol, 1–5 mg), and K2CO3 (0.1 mmol, 14 mg), ruthe-
nium complex 6 (5 mol %, 4 mg) was added under argon and dried
in vacuum for 30 min. Distilled toluene (0.5 M, 200 lL) was then
added into the flask under argon and stirred at 60 °C for the activa-
tion of the ruthenium complex. After 30 min, IPA (0.15 mmol,
17 lL) was added into the reaction mixture and the reaction mix-
ture was stirred at 25–60 °C for 6–96 h. After the reaction was
complete, the solution was filtered through a Celite pad. The fil-
trate was concentrated under reduced pressure and purified by sil-
ica gel chromatography (hexane/EtOAc = 9:1) to obtain the
product.
4.3.6. (R)-1-(4-(Trimethylsilyl)phenyl)nonyl acetate 4f
[a]
22 = +59.9 (c 1.5, CHCl3, >99% ee); 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.48 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 5.71 (t,
J = 6.4 Hz, 1H), 2.06 (s, 3H), 1.97–1.62 (m, 2H), 1.40–1.18 (m,
12H), 0.87 (t, J = 6.5 Hz, 3H), 0.25 (s, 9H); 13C NMR (75 MHz,
CDCl3, ppm): 171.6, 142.5, 141.1, 134.6, 127.0, 77.3, 37.4, 33.0,
30.5, 30.4, 30.3, 26.7, 23.8, 22.4, 15.2, 0.0; HPLC (R,R)Whelk-O1,
n-hexane/2-propanol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm,
retention times 3.98 min (S), 6.32 min (R); TOF-MS (ESI+) calcd
for C20H34Na1O2Si [M+Na]+: 357.22258, found: 357.22299.
4.3.7. (R)-1-(4-(Trimethylsilyl)phenyl)undecyl acetate 4g
[a]
24 = +53.4 (c 0.7, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
4.3.1. (R)-1-(4-(Trimethylsilyl)phenyl)ethyl acetate 4a
ppm): d 7.48 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 7.9 Hz, 2H), 5.71 (t,
J = 6.4 Hz, 1H), 2.06 (s, 3H), 1.95–1.67 (m, 2H), 1.40–1.17 (m,
16H), 0.87 (t, J = 6.5 Hz, 3H), 0.25 (s, 9H); 13C NMR (75 MHz,
[a] [a]
25 = +93.4 (c 1.0, CHCl3) >99% ee {lit.14 20 = +93.9 (c 1.0,
D D
CHCl3) >99% ee}; 1H NMR (300 MHz, CDCl3, ppm): d 7.51 (d,
Please cite this article in press as: Cho, J.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.06.010

J. Cho et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
5
CDCl3, ppm): 171.6, 142.5, 141.2, 134.6, 127.0, 77.3, 37.4, 33.0,
30.7, 30.6, 30.5, 30.4, 26.7, 23.8, 22.4, 15.2, 0.0; HPLC (R,R)Whelk-
72 h, then quenched with H2O, and extracted with CH2Cl2. The
organic layer was washed with brine, dried over magnesium sul-
fate, and filtered through a Celite pad. The filtrate was concen-
trated under reduced pressure and purified by silica gel
chromatography (hexane/EtOAc = 9:1) to give the product.
O1,
n-hexane/2-propanol = 97:3,
flow
rate = 1.0 mL/min,
UV = 217 nm, retention times 3.72 min (S), 5.72 min (R); HRMS:
[C22H38O2Si]+ 362.2641, found: 362.2640.
4.3.8. (R)-1-(3-(Trimethylsilyl)phenyl)ethyl acetate 5a
4.4.1. (R)-1-Phenylheptan-1-ol 7a
[
a
]
25 = +66.9 (c 0.65, CHCl3) >99% ee {lit.14
[
a
]
20 = +70.8 (c 1.0,
[a] [a]
25 = +31.8 (c 1.1, CHCl3) >99% ee {lit.8c 28 = +35.3 (c 1.04,
D D
D
D
CHCl3) >99% ee}; 1H NMR (300 MHz, CDCl3, ppm): d 7.47–7.42
(m, 2H), 7.35–7.25 (m, 2H), 5.92–5.81 (m, 1H), 2.07 (s, 3H), 1.56–
1.53 (m, 3H), 0.26 (s, 9H); 13C NMR (75 MHz, CDCl3, ppm): 171.4,
142.0, 141.9, 134.0, 132.1, 129.0, 127.7, 73.6, 23.3, 22.5, 0.0;
CHCl3, >99% ee)}; 1H NMR (300 MHz, CDCl3, ppm): d 7.23–7.37
(m, 5H), 4.67–4.63 (m, 1H), 1.83–1.70 (m, 3H), 1.43–1.21 (m,
8H), 0.89–0.83 (m, 3H); 13C NMR (75 MHz, CDCl3, ppm): 144.9,
128.4, 127.4, 125.8, 74.7, 39.1, 31.7, 29.1, 25.8, 22.5, 14.0; HPLC
Chiralcel-OD, n-hexane/2-propanol = 97:3, flow rate = 1.0 mL/min,
UV = 217 nm, retention times 10.9 min (R), 13.1 min (S).
HPLC
(R,R)Whelk-O1,
n-hexane/2-propanol = 97:3,
flow
rate = 1.0 mL/min, UV = 217 nm, retention times 4.78 min (S),
8.41 min (R); TOF-MS (ESI+) calcd for [C13H20O2SiÀOAc]+
177.10995, found: 177.10213.
4.4.2. (R)-1-Phenylnonan-1-ol 7b
[a] [a]
21 = +29.2 (c 0.55, CHCl3) >99% ee {lit.10a 25 = +27.3 (c 1.42,
D D
4.3.9. (R)-1-(3-(Trimethylsilyl)phenyl)propyl acetate 5b
CHCl3, 92% ee)}; 1H NMR (300 MHz, CDCl3, ppm): d 7.34–7.24 (m,
5H), 4.67–4.62 (m, 1H), 1.89–1.68 (m, 3H), 1.44–1.18 (m, 12H),
0.87 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm) 145.0,
128.4, 127.5, 125.9, 74.7, 39.1, 31.9, 29.5, 29.3, 25.8, 22.7, 14.1;
[a] [a]
25 = +73.5 (c 1.1, CHCl3) >99% ee {lit.14 20 = +76.8 (c 1.0,
D D
CHCl3) >99% ee}; 1H NMR (300 MHz, CDCl3, ppm): d 7.45–7.42
(m, 2H), 7.33–7.29 (m, 2H), 5.94–5.90 (m, 1H), 2.07 (s, 3H), 1.94–
1.78 (m, 2H), 0.91–0.86 (m, 3H), 0.26 (s, 9H); 13C NMR (75 MHz,
CDCl3, ppm): 171.5, 141.7, 140.8, 133.9, 132.5, 128.8, 128.0, 77.7,
30.5, 22.4, 11.1, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propa-
nol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm, retention times
4.22 min (S), 7.60 min (R).
HPLC
Chiralcel-OD,
n-hexane/2-propanol = 97:3,
flow
rate = 1.0 mL/min, UV = 217 nm, retention times 9.10 min (R),
10.4 min (S); HRMS: [C15H24O]+ 220.1827, found: 220.1825.
4.4.3. (R)-1-Phenylundecan-1-ol 7c
[a] [a]
23 = +23.7 (c 0.5, CHCl3) >99% ee {lit.11b 25 = +16.3 (c 2.2,
D D
CHCl3, 88% ee)}; 1H NMR (300 MHz, CDCl3, ppm): d 7.35–7.26 (m,
5H), 4.68–4.65 (m, 1H), 1.82–1.65 (m, 3H), 1.44–1.18 (m, 16H),
0.87 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm): 145.0,
128.4, 127.5, 125.9, 74.7, 39.1, 31.9, 29.6, 29.5, 29.3, 25.8, 22.7,
14.1; HPLC Chiralcel-OD, n-hexane/2-propanol = 97:3, flow
rate = 1.0 mL/min, UV = 217 nm, retention times 8.29 min (R),
9.36 min (S); HRMS: [C17H28O]+ 248.2140, found: 248.2140.
4.3.10. (R)-1-(3-(Trimethylsilyl)phenyl)butyl acetate 5c
[a]
25 = +69.0 (c 0.8, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.35–7.31 (m, 2H), 7.26–7.21 (m, 2H), 5.78–5.68 (m, 1H),
2.06 (s, 3H), 1.98–1.81 (m, 1H), 1.80–1.57 (m, 1H), 1.42–1.15 (m,
2H), 0.94–0.89 (m, 3H), 0.26 (s, 9H); 13C NMR (75 MHz, CDCl3,
ppm): 171.5, 141.8, 141.1, 133.9, 132.5, 128.9, 128.0, 77.1, 39.7,
22.4, 19.9, 14.9, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propa-
nol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm, retention times
4.11 min (S), 6.38 min (R); HRMS: [C15H24O2Si]+ 264.1546, found:
264.1543.
4.5. General procedure for halodesilylation of dynamic kinetic
resolution product
4.3.11. (R)-1-(3-(Trimethylsilyl)phenyl)pentyl acetate 5d
To a solution of dynamic kinetic resolution product (0.1 mmol,
>99% ee) in MeOH (0.1 M, 1 mL) were added N-chlorosuccinimide
(1.2 equiv, 16 mg) and KCl (1.2 equiv, 9 mg) or KBr (1.2 equiv,
14 mg). The resulting solution was stirred at 60 °C for 2 h and then
quenched with H2O. The mixture was then extracted with CH2Cl2.
The combined organic phase was dried over magnesium sulfate
and filtered through a Celite pad. The filtrate was concentrated
under reduced pressure and purified by silica gel chromatography
(hexane/EtOAc = 9:1) to give the product.
[a]
25 = +64.8 (c 1.0, CHCl3) 97% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.45–7.35 (m, 2H), 7.33–7.29 (m, 2H), 5.76–5.68 (m, 1H),
2.06 (s, 3H), 1.98–1.83 (m, 1H), 1.81–1.60 (m, 1H), 1.45-1.10 (m,
4H), 0.92–0.85 (m, 3H), 0.26 (s, 9H); 13C NMR (75 MHz, CDCl3,
ppm) 171.5, 141.8, 141.1, 133.9, 132.5, 128.8, 128.0, 77.4, 37.2,
28.8, 23.5, 22.4, 15.0, 0.0; HPLC (R,R)Whelk-O1, n-hexane/2-propa-
nol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm, retention times
4.29 min (S), 7.62 min (R); HRMS: [C16H26O2Si]+ 278.1702, found:
278.1704.
4.5.1. (R)-1-(4-Chlorophenyl)heptan-1-ol 8a
4.3.12. (R)-1-(3-(Trimethylsilyl)phenyl)heptyl acetate 5e
[a] [a]
25 = +26.1 (c 0.3, CHCl3) >99% ee {lit.11d 25 = +28.2 (c 1.0,
D D
[a]
25 = +32.3 (c 1.0, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
CHCl3) 96% ee}; 1H NMR (300 MHz, CDCl3, ppm): d 7.32–7.25 (m,
4H), 4.72–4.65 (m, 1H), 1.90–1.61 (m, 3H), 1.50–1.21 (m, 8H),
0.95–0.81 (m, 3H); 13C NMR (75 MHz, CDCl3, ppm): 143.4, 133.0,
128.4, 127.3, 73.9, 39.1, 31.7, 29.1, 25.6, 22.6, 14.0; HPLC
ppm): d 7.44–7.40 (m, 2H), 7.33–7.25 (m, 2H), 5.76–5.71 (m, 1H),
2.06 (s, 3H), 1.91–1.86 (m, 1H), 1.81–1.70 (m, 1H), 1.45–1.05 (m,
8H), 0.92–0.84 (m, 3H), 0.26 (s, 9H); 13C NMR (75 MHz, CDCl3,
ppm): 171.5, 141.7, 141.1, 133.9, 132.5, 128.8, 128.0, 77.4, 37.5,
32.7, 30.1, 26.6, 23.6, 22.4, 15.1, 0.0; HPLC (R,R)Whelk-O1, n-hex-
ane/2-propanol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm,
retention times 3.86 min (S), 7.29 min (R); HRMS: [C18H30O2Si]+
306.2015, found: 306.2018.
(R,R)Whelk-O1,
n-hexane/2-propanol = 97:3,
flow
rate = 1.0 mL/min, UV = 217 nm, retention times 4.21 min (S),
9.93 min (R), acetate-form.
4.5.2. (R)-1-(4-Chlorophenyl)nonan-1-ol 8b
4.4. General procedure for the desilylation of dynamic kinetic
resolution products
[a]
22 = +23.9 (c 0.6, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.33–7.25 (m, 4H), 4.66–4.61 (m, 1H), 1.91–1.61 (m, 3H),
1.45–1.19 (m, 12H), 0.87 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz,
CDCl3, ppm): 143.4, 133.1, 128.5, 127.3, 74.0, 39.2, 31.8, 29.5,
29.2, 25.7, 22.6, 14.1; HPLC (R,R)Whelk-O1, n-hexane/2-propa-
nol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm, retention times
To
(0.1 mmol, >99% ee) in DMF (1 mL) was added 1.0 M TBAF in THF
(6.0 equiv, 600 L). The resulting solution was stirred at 60 °C for
a solution of the dynamic kinetic resolution product
l
Please cite this article in press as: Cho, J.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.06.010

6
J. Cho et al. / Tetrahedron: Asymmetry xxx (2015) xxx–xxx
4.43 min (S), 10.7 min (R), acetate-form; HRMS: [C15H23ClO]+
254.1437, found: 254.1439.
3. For the dynamic kinetic resolution of secondary alcohols, see: (a) Persson, B. A.;
Larsson, A. L. E.; Le Ray, M.; Bäckvall, J. E. J. Am. Chem. Soc. 1999, 121, 1645–
1650; (b) Choi, J. H.; Kim, Y. H.; Nam, S. H.; Shin, S. T.; Kim, M.-J.; Park, J. Angew.
Chem., Int. Ed. 2002, 41, 2373–2376; (c) Kim, M.-J.; Chung, Y. I.; Choi, Y. K.; Lee,
H. K.; Kim, D.; Park, J. J. Am. Chem. Soc. 2003, 125, 11494–11495; (d) Martin-
Matute, B.; Edin, M.; Bogar, K.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2004, 43,
6535–6539; (e) Choi, J. H.; Choi, Y. K.; Kim, Y. H.; Park, E. S.; Kim, E. J.; Kim, M.-
J.; Park, J. J. Org. Chem. 2004, 69, 1972–1977; (f) Martin-Matute, B.; Edin, M.;
Bogar, K.; Kaynak, F. B.; Bäckvall, J.-E. J. Am. Chem. Soc. 2005, 127, 8817–8825;
(g) Berkessel, A.; Sebastian-Ibarz, M. L.; Müller, T. N. Angew. Chem., Int. Ed. 2006,
45, 6567–6570; (h) Hoyos, P.; Fernández, M.; Sinisterra, J. V.; Alcántara, A. R. J.
Org. Chem. 2006, 71, 7632–7637; (i) Akai, S.; Tanimoto, K.; Kanao, Y.; Egi, M.;
Yamamoto, T.; Kita, Y. Angew. Chem., Int. Ed. 2006, 45, 2592–2595; (j) Kim, M.-
J.; Choi, Y. K.; Kim, S.; Kim, D.; Han, K.; Ko, S.-B.; Park, J. Org. Lett. 2008, 10,
1295–1298; (k) Haak, R. M.; Berthiol, F.; Jerphagnon, T.; Gayet, J. A.; Tababiono,
C.; Postema, C. P.; Ritleng, V.; Pfeffer, M.; Janssen, D. B.; Minnaard, A. J.; Feringa,
B. L.; De Vries, J. G. J. Am. Chem. Soc. 2008, 130, 13508–13509; (l) Thalen, L. K.;
Sumic, A.; Bogar, K.; Norinder, J.; Persson, A. K. A.; Bäckvall, J.-E. J. Org. Chem.
2010, 75, 6842–6847; (m) Gang, X.; Chen, Y.; Wu, J.; Cheng, Y.; Yang, L.
Tetrahedron: Asymmetry 2011, 22, 1373–1378; (n) Ema, T.; Nakano, Y.; Yoshida,
D.; Kamata, S.; Sakai, T. Org. Biomol. Chem. 2012, 10, 6299–6630; (o) Egi, M.;
Sugiyama, K.; Saneto, M.; Hanada, R.; Kato, K.; Akai, S. Angew. Chem., Int. Ed.
2013, 52, 3654–3658.
4.5.3. (R)-1-(4-Chlorophenyl)undecan-1-ol 8c
[a]
21 = +20.5 (c 1.3, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.33–7.25 (m, 4H), 4.67–4.62 (m, 1H), 1.83–1.66 (m, 3H),
1.45–1.20 (m, 16H), 0.87 (t, J = 6.5 Hz, 3H); 13C NMR (75 MHz,
CDCl3, ppm): 143.4, 133.1, 128.5, 127.3, 74.0, 39.2, 31.9, 29.6,
29.5, 29.4, 29.3, 25.7, 22.7, 14.1; HPLC (R,R)Whelk-O1, n-hex-
ane/2-propanol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm,
retention times 4.08 min (S), 9.99 min (R), acetate-form; HRMS:
[C17H27ClO]+ 282.1750, found: 282.1752.
4.5.4. (R)-1-(4-Bromophenyl)heptan-1-ol 9a
[a]
25 = +23.3 (c 0.6, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.46 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 4.66–4.60
(m, 1H), 1.83–1.56 (m, 3H), 1.45–1.14 (m, 8H), 0.92–0.81 (m,
3H); 13C NMR (75 MHz, CDCl3, ppm): 143.8, 131.4, 127.6, 121.1,
74.0, 39.1, 31.7, 29.1, 25.6, 22.5, 14.0; HPLC (R,R)Whelk-O1, n-hex-
ane/2-propanol = 97:3, flow rate = 1.0 mL/min, UV = 217 nm,
retention times 4.19 min (S), 12.3 min (R), acetate-form; HRMS:
[C13H19BrO-H2O+H]+ 253.0586, found: 253.0589.
4. For applications of dynamic kinetic resolution to the synthesis of natural
products, see: (a) Jana, N.; Mahpatra, T.; Nanda, S. Tetrahedron: Asymmetry
2009, 20, 2622–2628; (b) Das, T.; Rnhuniya, R.; Nanda, S. Tetrahedron:
Asymmetry 2010, 21, 2206–2211; (c) Jana, N.; Nanda, S. Tetrahedron:
Asymmetry 2012, 23, 802–808; (d) Rej, R. K.; Jana, A.; Nanda, S. Tetrahedron
2014, 70, 2634–2642.
5. (a) Kim, H.; Choi, Y. K.; Lee, J.; Lee, E.; Park, J.; Kim, M.-J. Angew. Chem., Int. Ed.
2011, 50, 10944–10948; (b) Kim, C.; Lee, J.; Cho, J.; Oh, Y.; Choi, Y. K.; Choi, E.;
Park, J.; Kim, M.-J. J. Org. Chem. 2013, 78, 2571–2578.
6. (a) Lee, E.; Oh, Y.; Choi, Y. K.; Kim, M.-J. ACS Catal. 2014, 4, 3590–3592; (b) Lee,
J.; Oh, Y.; Choi, Y. K.; Choi, E.; Kim, K.; Park, J.; Kim, M.-J. ACS Catal. 2015, 5, 683–
689.
4.5.5. (R)-1-(4-Bromophenyl)nonan-1-ol 9b
[a]
22 = +20.5 (c 0.8, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.45 (d, J = 8.9 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 4.65–4.60
(m, 1H), 1.87–1.65 (m, 3H), 1.45–1.19 (m, 12H), 0.87 (t,
J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm): 143.9, 131.5,
127.6, 121.2, 74.0, 39.1, 31.8, 29.5, 29.2, 25.7, 22.6, 14.1; HPLC
7. Kazlauskas, R. J.; Weissfloch, A. N. E.; Rappaport, A. T.; Cuccia, L. A. J. Org. Chem.
1991, 56, 2656–2665.
8. (a) Hu, J.-B.; Zhao, G.; Ding, Z.-D. Angew. Chem., Int. Ed. 2001, 40, 1109–1111; (b)
Bandini, M.; Bottoni, A.; Cozzi, P. G.; Miscione, G. P.; Monari, M.; Pierciaccante,
R.; Umani-Ronchi, A. Eur. J. Org. Chem. 2006, 4596–4608; (c) Onodera, G.;
Nishibayashi, Y.; Uemura, S. Angew. Chem., Int. Ed. 2006, 45, 3819–3822; (d)
Yıldız, T.; Yusufog˘lu, A. Tetrahedron: Asymmetry 2010, 21, 2981–2987; (e)
Zhang, Z.; Jain, P.; Antilla, J. C. Angew. Chem., Int. Ed. 2011, 50, 10961–10964.
9. (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc.
1995, 117, 2675–2676; (b) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.;
Zanotti-Gerosa, A. Org. Lett. 2000, 2, 4173–4176; (c) Hu, A.; Yee, G. T.; Lin, W. J.
Am. Chem. Soc. 2005, 127, 12486–12487; (d) Huang, H.; Okuno, T.; Tsuda, K.;
Yoshimura, M.; Kitamura, M. J. Am. Chem. Soc. 2006, 128, 8716–8717.
10. (a) Yamamoto, Y.; Shirai, T.; Watanabe, M.; Kurihara, K.; Miyaura, N. Molecules
2011, 16, 5020–5034; (b) Carlos, A. M. M.; Contreira, M. E.; Martins, B. S.;
Immich, M. F.; Moro, A. V.; Lüdtke, D. S. Tetrahedron 2015, 71, 1202–1206.
11. (a) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. P. Tetrahedron Lett. 2000, 41,
57–60; (b) Yong, K. H.; Taylor, N. J.; Chong, J. M. Org. Lett. 2002, 4, 3553–3556;
(c) Muramatsu, Y.; Harada, T. Angew. Chem., Int. Ed. 2008, 47, 1088–1090; (d)
Kumar, R.; Kawasaki, H.; Harada, T. Org. Lett. 2013, 15, 4198–4201.
12. (a) Gröger, H.; Hummel, W.; Rollmann, C.; Chamouleau, F.; Hüsken, H.; Werner,
H.; Wunderlich, C.; Abokitse, K.; Drauz, K.; Buchholz, S. Tetrahedron 2004, 60,
633–640; (b) Zhu, D.; Malik, H. T.; Hua, L. Tetrahedron: Asymmetry 2006, 17,
3010–3014; (c) Musa, M. M.; Ziegelmann-Fjeld, K. I.; Vieille, C.; Zeikus, J. G.;
Phillips, R. S. Angew. Chem., Int. Ed. 2007, 46, 3091–3094.
(R,R)Whelk-O1,
n-hexane/2-propanol = 97:3,
flow
rate = 1.0 mL/min, UV = 217 nm, retention times 4.53 min (S),
11.8 min (R), acetate-form; HRMS: [C15H23BrO]+ 298.0932, found:
298.0930.
4.5.6. (R)-1-(4-Bromophenyl)undecan-1-ol 9c
[a]
23 = +19.0 (c 1.0, CHCl3) >99% ee; 1H NMR (300 MHz, CDCl3,
D
ppm): d 7.46 (d, J = 8.9 Hz, 2H), 7.22 (d, J = 8.3 Hz, 2H), 4.66–4.60
(m, 1H), 1.81–1.61 (m, 3H), 1.45–1.16 (m, 16H), 0.87 (t,
J = 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm): 143.9, 131.5,
127.6, 121.2, 74.0, 39.1, 31.9, 29.6, 29.5, 29.4, 29.3, 25.7, 22.7,
14.1; HPLC (R,R)Whelk-O1, n-hexane/2-propanol = 97:3, flow
rate = 1.0 mL/min, UV = 217 nm, retention times 4.16 min (S),
10.6 min (R), acetate-form; HRMS: [C17H27BrO]+ 326.1245, found:
326.1246.
Acknowledgments
13. (a) Jing, Q.; Kazlauskas, R. J. Chirality 2008, 20, 724–735; (b) Yıldız, T.;
Yusufog˘lu, A. Tetrahedron: Asymmetry 2011, 22, 1347–1352; (c) Kitamoto, Y.;
Kuruma, Y.; Suzuki, K.; Hattori, T. J. Org. Chem. 2015, 80, 521–527.
14. For the previous kinetic resolution of 1a, b and 2a, b with other lipases, see:
Palmerira, D. J.; Abreu, J. C.; Andrade, L. H. Molecules 2011, 16, 9697–9713.
15. It should be noted that o-trimethylsilyl-substituted alkyl aryl carbinols were
unreactive with LPL–D1.
We are grateful to the National Research Foundation of Korea
(Project numbers, 2012R1A1A2006595 and 2012-007235) for the
financial support of this work and Amano for the generous supply
of the lipoprotein lipase sample used in this work.
16. The halodesilylation of m-trimethylsilyl-substituted dynamic kinetic
resolution products can be achieved similarly to obtain the corresponding
alkyl aryl carbinols. For example, the bromodesilylation of (R)-5c afforded the
corresponding bromo-substituted alcohol: [
ee).
17. Metal-Catalyzed Cross-Coupling Reactions; Suzuki, A., Diederich, F., Stang, P. J.,
References
a]
23 = +30.7 (c 0.25, CHCl3, >99%
D
1. Dinh, P. M.; Howarth, J. A.; Hudnott, A. R.; Williams, J. M. J. Tetrahedron Lett.
1996, 37, 7623–7626.
2. (a) Lee, J. H.; Han, K.; Kim, M.-J.; Park, J. Eur. J. Org. Chem. 2010, 999–1015; (b)
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Please cite this article in press as: Cho, J.; et al. Tetrahedron: Asymmetry (2015), http://dx.doi.org/10.1016/j.tetasy.2015.06.010