Kinetic resolution of aryl alkenylcarbinols catalyzed by Fc-PIP

Article abstract of DOI:10.1002/cjoc.201200410

An effective kinetic resolution of a variety of aryl alkenylcarbinols catalyzed by nonenzymatic acyl transfer catalyst Fc-PIP was developed, affording corresponding unreacted alcohols in good to excellent ee value up to 99% and with selectivity factors up to 24.

Full text of DOI:10.1002/cjoc.201200410

FULL PAPER
DOI: 10.1002/cjoc.201200410
Kinetic Resolution of Aryl Alkenylcarbinols Catalyzed by
Fc-PIP†
Hu, Bin(胡斌)
Meng, Meng(孟萌)
Jiang, Shanshan(姜山山)
Deng, Weiping*(邓卫平)
Shanghai Key Laboratory of New Drug Design & School of Pharmacy, East China University of Science and
Technology, Shanghai 200237, China
An effective kinetic resolution of a variety of aryl alkenylcarbinols catalyzed by nonenzymatic acyl transfer
catalyst Fc-PIP was developed, affording corresponding unreacted alcohols in good to excellent ee value up to 99%
and with selectivity factors up to 24.
Keywords kinetic resolution, acyl transfer, Fc-PIP
Introduction
catalyst scaffolds, including cyclic phosphines by Ve-
dejs,[5] N-methyl imidazole (NMI)[6] by Miller and Ishi-
hara, 4-(dimethylamino)-pyridine (DMAP)[7] by Fu, Fuji
and Spivey et. al., and 2,3-dihydroimidazopyridine
(benzothiazole) derivatives[8] by Birman et al. incorpo-
rated with a variety of chiral elements, have been de-
veloped (Figure 1). A range of secondary alcohols, in-
cluding aryl alkyl carbinols,[3b-3d,6c,7a,8a,8b] allylic alco-
hols[3] and propargylic alcohols,[10] have been kineti-
cally resolved using aforementioned nucleophilic cata-
lysts with good to excellent stereoselectivities.
Chiral allylic alcohols are among the most versatile
synthetic intermediates.[1] Catalytic enantioselective syn-
thesis of these chiral building blocks currently relies on
three main methods: the kinetic resolution (KR) of cor-
responding racemic allylic alcohols through asymmetric
epoxidation[2a-2d] or acylative transformation,[2e-2g] asym-
metric addition of alkenylzinc reagents to carbonyl com-
pounds,[3] and asymmetric Baylis-Hillman reaction.[4]
Me2N
H
P
Cl
OH
Alk
OH
Alk
N
R2
R3
R2
R3
Fe
Ph
Kinetic resolution
H
Ar
Ph
Ph
Ph
N
N
previous work
R4
R4
Ph
[5c]
Ph
Ar = 3,5-t-Bu2C6H3
allylic alcohols
[7a]
[3c]
-Bu Ph-PBO (Vedejs)
t
Planar Chiral DMAP (Fu)
2
Cl-PIQ (Birman)
OH
OH
Ar
O
R2
R2
R3
Kinetic resolution
Ar
N
N
this work
N
O
R4
aryl alkenylcarbinols
H
R3
N
R4
Fe
Ph
Ph
N
N
Ph
O
H
Bn
N
N
Ph
Ph
O
Boc
H
Figure 2 The KR of different type of allylic alcohols
OMe
[6b]
Ph
Fc-PIP (Deng)
[13a]
β -hairpin tetrapeptide (Miller)
While the origin of enantioselectivity of nonenzy-
matic KR has still not been elucidated unambiguously,
it is generally accepted that π-cation and π-stacking in-
teractions between the arene ring π-electrons of sub-
strates and acylated catalysts play an important role in
the process of chiral recognition.[5d,7d,8c,11] Aryl alkenyl-
carbinols (Figure 2), which bear two sp2-hybridized
substituents, have received relatively little attention in
the field of asymmetric nonenzymatic acyl transforma-
Figure 1 Representative nonenzymatic acyl transfer catalysts.
Since the pioneering works of Vedejs and co-workers
in asymmetric acylation of secondary alcohols by
nonenzymatic catalysts,[5a,5b] significant progress has
been made in the development of nonenzymatic nu-
cleophilic catalysts for the kinetic resolution of secon-
dary alcohols.[5-9] To date, mainly four families of active
*
E-mail: weiping_deng@ecust.edu.cn
Received April 28, 2012; accepted June 4, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200410 or from the author.
Dedicated to Professor Jun Zhou on the occasion of his 80th birthday.
†
Chin. J. Chem. 2012, 30, 1289—1294
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Hu et al.
FULL PAPER
tion presumably due to its difficulty in distinguishing
the π-cation and π-stacking interactions arised from both
aryl or alkenyl substituents of aryl alkenylcarbinols. As
a consequence, the KR of aryl alkenylcarbinols remains
a great challenging task. It is notable that all the enan-
tioenriched allylic alcohols 1, which bear a simple alkyl
(not EWG group) group as R2, can not be prepared di-
rectly through asymmetric Baylis-Hillman reaction.
The only report that described the KR of aryl al-
kenylcarbinols is the Connon’s KR of Baylis-Hillman
adducts using chiral DMAP derivatives.[12] However,
the stereoselectivities in this case were found to be very
disappointing. Only one substrate was resolved with a
synthetically acceptable selectivity factor S＝13.1, and
the others were less than 4. In addition, the reaction
normally requires long reaction times (24 h) and low
temperature (－78 ℃).
Recently, we have developed a ferrocene-based acyl
transfer catalyst (Fc-PIP), which proved to be particu-
larly-effective in the KR of aryl alkylcarbinols (S up to
1892)[13a] and bulky (hetero)aryl alkylcarbinols[13b] af-
fording the unreacted alcohols with more than 99% ee
and good yields for all substrates. In this paper, we ex-
tended our catalytic system to the KR of a range of
challenging aryl alkenylcarbinol substrates, and moder-
ate to good selectivity factors were observed (up to 24)
with the enantiomeric excess up to 99% for corre-
sponding unreacted alcohols at reasonable yileds.
further screening of the reaction conditions revealed that
selectivity factor was not improved regardless of lowering
the reaction temperature to －20 ℃ or increasing the
catalyst loading to 5 mol% (Table 1, Entrries 2, 4, 7, 8).
Therefore, 2 mol% of Fc-PIP in toluene at 0 ℃ was
established as the optimal KR condition for our further
study.
With the optimized reaction condition, the generality
and substrate scope were then examined. It was found
that Fc-PIP can catalyze the kinetic resolution of all
tried aryl alkenylcarbinols with moderate to good selec-
tivities (Table 2). In contrast to aryl alkylcarbinols that
the selectivity factor increases as the size of alkyl group
increases, for the case of aryl alkenylcarbinols, the se-
lectivity factor decreases as the substituent R2 increases
(Table 2, Entries 1—3). To our delight, carbinols 1d and
1e in which a ortho-methyl group are attached to the
phenyl ring gave good selectivity factors up to 24 af-
fording corresponding unreacted alcohol with enanti-
omeric excess up to 99% (Table 2, Entries 4 and 5). The
presence of both electron-withdrawing and -donating
groups led to a slightly improved selectivity factors
(Table 2, Entries 6—8). Furthermore, naphthyl alkenyl-
carbinols 1j—1l also showed good selectivities (Table 2,
Entries 9—12) probably due to the reinforcement of
π-stacking interactions between aryl of substrate and
acylated catalyst, especially for 1-naphthyl substrates 1k
and 1l, the selectivity factor was found to be as high as the
that of carbinols with ortho-methyl group 1d and 1e pre-
sumably due to the similar ortho-steric hinderence (Entries
11, 12 vs. Entries 4, 5). The alcohol 1m containing
Results and Discussion
Initial investigation was carried out by chosing 1b, 1c
and 1j as model substrates using 2 mol% of Fc-PIP in
toluene at 0 ℃, providing the selectivity factor S＝5.6, 5.5,
10.5 respectively (Table 1, Entries 1, 3, 6). Surprisingly,
Table 2 The kinetic resolution of aryl alkenylcarbinols cata-
lyzed by Fc-PIP
2 mol% Fc-PIP
0.75 equiv. (EtCO)2O
OH
OH
OCOEt
R2
R2
R2
R1
R1
+
R1
0.75 equiv. i-Pr2NEt
Table 1 Optimization of reaction conditions
toluene, 0 oC
(R)
rac
(S)
Fc-PIP
0.75 equiv. (EtCO)2O
OH
OH
OCOEt
R2
R2
R2
a
Entry R1
R2 t/h eeE /% eeAb/% CHPLCc/% Sc
R1
R1
+
R1
0.75 equiv. i-Pr2NEt
1
Ph (1a)
H
8
61.7 76.6
53.2 55.6
55.4 10.0
51.1 5.6
59.7 5.5
62.3 24.0
61.1 23.0
59.2 11.0
68.8 9.0
65.6 6.0
62.1 11.0
65.1 10.5
62.0 21.4
64.0 18.0
50.4 3.0
toluene
(R)
rac
(S)
2
Ph (1b)
Me 7
d
e
Entry R1
R2 t/h eeE /% eeA /% CHPLCf/% Sf
3
Ph (1c)
Et 8.5 47.0 69.7
Me 13 60.4 99.7
Et 13 63.1 99.3
Me 12 59.5 86.2
Me 12 43.4 95.7
Me 10 42.5 80.9
Ph (1b)a
Ph (1b)b
Ph (1c)a
Ph (1c)b
Ph (1c)c
2-Naphthyl (1j)a Et 8 51.0
2-Naphthyl (1j)b Et 4 50.6
2-Naphthyl (1j)c Et 12 61.9
Me 7 53.2
Me 3.5 51.3
Et 8.5 47.0
Et 4 45.1
Et 14 63.8
55.6
71.2
69.7
76.6
51.9
95.0
95.4
86.4
51.1
58.1
59.7
62.9
55.1
65.1
65.3
58.3
5.6
4
o-MePh (1d)
o-MePh (1e)
p-MePh (1f)
p-ClPh (1g)
m-BrPh (1h)
1
2
3
4
5
6
7
8
5
6.4
6
5.5
7
5.8
8
5.9
9
2-Naphthyl (1i) Me 9.5 56.0 91.8
10.5
10.6
11.4
10
11
12
13
2-Naphthyl (1j) Et 8
1-Naphthyl (1k) Me 8
51.0 95.0
60.9 99.3
a Reaction was run at 0 ℃ using 2 mol% Fc-PIP. b Reaction was
1-Naphthyl (1l) Et 6.5 55.7 99.2
Thienyl (1m) Me 5.5 30.0 30.5
c
run at 0 ℃ using 5 mol% Fc-PIP. Reaction was run at －20
℃ using 5 mol% Fc-PIP. d ee value of the ester products. e ee
a ee value of the ester products. b ee value of the unreacted alco-
hols. c Calculated from the ees of the esters and the unreacted
alcohols.
f
value of the unreacted alcohols. Calculated from the ees of the
esters and the unreacted alcohols.
1290
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 1289—1294

Kinetic Resolution of Aryl Alkenylcarbinols Catalyzed by Fc-PIP
a heteroaromatic ring displayed lower selectivity factor
than that of phenyl alkenylcarbinols (Table 2, Entry 13,
S＝3).
column with hexane and i-propanol as mobile phase at a
flow rate of 1 mL/min and UV detection at 254 or 220
nm.
According to the π-stacking model proposed by
Birman and the exlusive stacked transition state in our
catalytic system proposed previously,[13] aryl alkenyl-
carbinols are believed to approach the acylated catalyst
also via π-cation and π-stacking interactions, however
with competition between aryl and alkenyl group of the
substrate due to their sp2 π-electron properties. The
moderate to good selectivity factors imply that our
Fc-PIP can discriminate the aforementioned competi-
tion of two π-stacking interactions effectively in the KR
of aryl alkenylcarbinols (Figure 3).
Preparation of racemic aryl alkenylcarbinols and
spectral data for new substrates
O
OH
IBX
1) BuLi
R
R
Ar-Br
N
Ar
Ar
EA, reflux
2) RCH2CHO
2
3
(2 equiv.)
N
O
NaBH4
CeCl3 7H2O
N
N
OH
.
R
R
Ar
Ar
Ac2O (3 equiv.)
MeOH
0 oC
4
1
R2
R2
The aryl alkyl ketones 3 were prepared according to
literature’s procedure, then substrates 1 could be ob-
tained through α-methylenation and Luche reduction as
follows:
H
HO
H
HO
O
O
N
N
+
+
N
N
Fe
Ph
Fe
Ph
Under nitrogen, 3 (21.4 mmol, 1.0 equiv.), hexa-
methylenetetramine (6.0 g, 42.8 mmol, 2.0 equiv.) and
acetic anhydride (6.07 mL, 64.2 mmol, 3.0 equiv.) were
added to a 50-mL Schlenk flask. After stirring at 80 ℃
for 5 h, the reaction mixture was cooled to 25 ℃ and
quenched into a stirred mixture of methylene chloride
R
Ph
Ph
Ph
R
Ph
Ph
Ph
H
H
Ph
Ph
Ph
Ph
favored
disfavored
Figure 3 Proposed transition state models.
and sodium hydroxide (20 mL of 2 mol•L－ solution).
1
Conclusions
The organic layer was separated and washed with
aqueous HCl (10 mL of 1 mol•L－ solution). The com-
1
In summary, we have developed an efficient KR of a
series of aryl alkenylcarbinols catalyzed by Fc-PIP,
providing moderate to good selectivity factors up to 24
and excellent enantiomeric excess of corresponding un-
reacted alcohols over 99%. It is noteworthy that it is the
first example for aryl alkenylcarbiols to give S value
over 20 by using nonenzymatic catalyst, which would
be of great benefit for the synthesis of a wide range of
chiral aryl alkenylcarbiols with excellent optical purity.
Further application of new type of substrates for the KR
using Fc-PIP is still in the progress in our laboratory.
bined organic layer was concentrated on a rotary
evaporator to afford the crude product which was suffi-
ciently pure for subsequent experiment. The resulting
colorless oil residue was dissolved in methanol (50 mL)
and cooled to 0 ℃, then treated with CeCl3•7H2O (7.45
g, 20.0 mmol, 1.0 equiv.). After stirring at 0 ℃ for a
few minutes, NaBH4 (757 mg, 20.0 mmol, 1.0 equiv.)
was added in several portions during 15 min. After the
reduction reaction was completed, it was quenched with
saturated aqueous NH4Cl. The organic layer was sepa-
rated and the water layer was extracted with CH2Cl2.
The combined organic layer was washed with brine,
dried over anhydrous Na2SO4, and concentrated on a
rotary evaporator, and this crude product was then puri-
fied by flash chromatography on silica gel (petro-
leum/EtOAc＝10/1, V/V) to afford pure carbinols 1b—
1m.
Experimental
General information
THF and toluene were distilled from sodium prior to
use, n-BuLi was available from Aldrich. The substrates
used in the kinetic resolution experiments were prepared
according to the literature procedures.[14,15] 1H NMR
spectra were recorded on a Bruker DPX 400 MHz spec-
trometer in chloroform-d3. Chemical shifts are reported
with the internal TMS signal at δ 0.0 as a standard. 13C
NMR spectra were recorded on a Bruker DPX 100 MHz
spectrometer in chloroform-d3. Chemical shifts are re-
ported with the internal chloroform signal at δ 77.0 as a
standand. Methods used for kinetic resolution experi-
ments, determination of ee’s and calculation of conver-
sions and selectivities were adopted from previously
published work.[8a] Enatiomeric ratios were determined
by HPLC, using a chiralpak OD-H, AS-H or OJ-H
Substrate 1a was prepared according to literature[16]
via Grignard reaction of benzaldehyde with vinyl mag-
nesium bromide.
Compouds 1b, 1c, 1f—1i, 1k and 1m are previously
reported.[17]
2-Methyl-1-(o-tolyl)prop-2-en-1-ol (1d)
Color-
1
less oil; H NMR (400 MHz, CDCl3) δ: 7.44—7.42 (m,
1H), 7.23—7.13 (m, 3H), 5.31 (d, J＝3.6 Hz, 1H), 5.12
(s, 1H), 5.00—4.98 (m, 1H), 2.35 (s, 3H), 1.87 (d, J＝
3.9 Hz, 1H), 1.64 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ: 146.0, 139.9, 135.8, 130.5, 127.5, 126.3, 126.1, 111.9,
74.3, 19.2, 18.9; IR (film) ν: 3141, 2982, 1672, 1481,
Chin. J. Chem. 2012, 30, 1289—1294
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1291

Hu et al.
FULL PAPER
1387, 1020, 901, 762 cm . HRMS calcd for C11H14O
－
J＝7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.2,
149.0, 138.9, 128.4, 128.0, 127.3, 110.0, 77.8, 27.8,
25.0, 11.9, 9.1; IR (film) ν: 2991, 1739, 1462, 1181,
1090, 1011, 901, 778, 700 cm－1. HRMS calcd for
C14H18O2 218.1307, found 218.1310.
1
162.1045, found 162.1052.
2-Methylene-1-(o-tolyl)butan-1-ol (1e) Colorless
oil; 1H NMR (400 MHz, CDCl3) δ: 7.42—7.40 (m, 1H),
7.23—7.12 (m, 3H), 5.36 (d, J＝4.0 Hz, 1H), 5.15—
5.14 (m, 1H), 5.01 (s, 1H), 2.34 (s, 1H), 2.06—1.84 (m,
1H), 1.01 (t, J＝7.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ: 151.9, 140.3, 135.9, 130.4, 127.4, 126.5,
126.1, 109.7, 73.7, 25.0, 19.2, 12.2; IR (film) ν: 3140,
2-Methyl-1-(o-tolyl)allyl propionate (5d)
1H
NMR (400 MHz, CDCl3) δ: 7.35—7.33 (m, 1H), 7.21—
7.13 (m, 3H), 6.38 (s, 1H), 4.98 (d, J＝1.1 Hz, 2H),
2.43—2.36 (m, 5H), 1.68 (s, 3H), 1.15 (t, J＝7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 173.4, 142.6,
136.7, 136.3, 130.5, 127.9, 127.0, 126.0, 112.9, 75.0,
27.8, 19.4, 19.3, 9.1; IR (film) ν: 2996, 1740, 1471,
－
1
2993, 1649, 1472, 1022, 902, 742 cm . HRMS calcd
for C12H16O 176.1201, found 176.1202.
2-Methylene-1-(naphthalen-2-yl)butan-1-ol (1j)
1
－
1
Colorless oil; H NMR (400 MHz, CDCl3) δ: 7.83—
1378, 1180, 1090, 1013, 902, 766 cm . HRMS calcd
7.79 (m, 4H), 7.49—7.43 (m, 3H), 5.32 (s, 2H), 5.02 (s,
1H), 2.11 (s, 1H), 2.04—1.83 (m, 2H), 0.99 (t, J＝7.4
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 152.5, 139.8,
133.3, 133.1, 128.2, 128.1, 127.8, 126.2, 126.0, 125.6,
124.8, 109.2, 77.6, 24.5, 12.1; IR (film) ν: 3145, 2992,
for C14H18O2 218.1307, found 218.1308.
2-Methylene-1-(o-tolyl)butyl propionate (5e) 1H
NMR (400 MHz, CDCl3) δ: 7.33 (m, 1H), 7.20—7.13
(m, 3H), 6.43 (s, 1H), 5.00 (d, J＝5.7 Hz, 2H), 2.43—
2.37 (m, 5H), 1.99 (q, J＝7.3 Hz, 2H), 1.15 (t, J＝7.6
Hz, 3H), 1.04 (t, J＝7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 173.3, 148.5, 136.9, 136.3, 130.5, 128.0,
127.2, 126.0, 110.8, 74.5, 27.8, 25.5, 19.3, 12.0, 9.2; IR
(film) ν: 2991, 1738, 1472, 1368, 1180, 1081, 1009, 902,
－
1
1655, 1469, 1379, 1283, 1024, 901, 820 cm . HRMS
calcd for C15H16O 212.1201, found 212.1205.
2-Methylene-1-(naphthalen-1-yl)butan-1-ol (1l)
1
Colorless oil; H NMR (400 MHz, CDCl3) δ: 8.17—
－
1
8.15 (m, 1H), 7.87—7.85 (m, 1H), 7.79 (d, J＝8.2 Hz,
1H), 7.60 (d, J＝7.0 Hz, 1H), 7.52—7.44 (m, 3H), 5.87
(d, J＝4.0 Hz, 1H), 5.31 (s, 1H), 5.10 (s, 1H), 2.10 (s,
1H), 2.03—2.01 (m, 1H), 1.92—1.90 (m, 1H), 1.01 (t,
J＝7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 152.3,
138.0, 134.1, 131.6, 129.0, 128.5, 126.2, 125.7, 125.6,
124.9, 124.3, 110.3, 74.1, 25.5, 12.3; IR (film) ν: 3142,
773 cm . HRMS calcd for C15H20O2 232.1463, found
232.1465.
2-Methyl-1-(p-tolyl)allyl propionate (5f)
1H
NMR (400 MHz, CDCl3) δ: 7.24 (d, J＝8.1 Hz, 2H),
7.14 (d, J＝8.0 Hz, 2H), 6.14 (s, 1H), 5.10 (s, 1H), 4.95
(m, 1H), 2.42—2.36 (m, 2H), 2.33 (s, 3H), 1.64 (s, 3H),
1.15 (t, J＝7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
173.3, 143.4, 137.8, 135.6, 129.1, 127.1, 112.1, 78.1,
27.9, 21.2, 19.0, 9.1; IR (film) ν: 2997, 1735, 1462,
－
1
2991, 1661, 1473, 1398, 1001, 901, 791 cm . HRMS
calcd for C15H16O 212.1201, found 212.1201.
－
1
1180, 1087, 1015, 906, 804 cm . HRMS calcd for
General procedure for the synthesis of corresponding
racemic esters
C14H18O2 218.1307, found 218.1310.
1-(4-Chlorophenyl)-2-methylallyl propionate (5g)
1H NMR (400 MHz, CDCl3) δ: 7.32—7.26 (m, 4H),
6.14 (s, 1H), 5.10 (s, 1H), 4.99—4.97 (m, 1H), 2.46—
2.33 (m, 2H), 1.63 (s, 3H), 1.16 (t, J＝7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 173.1, 142.7, 137.1, 133.8,
128.5, 128.4, 112.9, 77.4, 27.7, 18.7, 9.0; IR (film) ν:
2992, 1735, 1481, 1173, 1090, 1009, 902, 801 cm ;
HRMS calcd for C13H15ClO2 238.0761, found 238.0762.
1-(3-Bromophenyl)-2-methylallyl propionate (5h)
1H NMR (400 MHz, CDCl3) δ: 7.42—7.40 (m, 1H),
7.35—7.33 (m, 1H), 7.20—7.18 (m, 1H), 7.13—7.11
(m, 1H), 6.05 (s, 1H), 5.04 (d, J＝0.7 Hz, 1H), 4.91 (d,
J＝0.7 Hz, 1H), 2.37—2.31 (m, 2H), 1.55 (s, 3H), 1.08
(t, J＝7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
173.1, 142.6, 141.0, 131.1, 130.0, 125.7, 122.6, 113.3,
77.4, 27.8, 18.7, 9.1; IR (film) ν: 2996, 1742, 1418, 1183,
1079, 1027, 906, 790, 701 cm－ 1; HRMS calcd for
C13H15BrO2 282.0255, found 282.0252.
OH
30 mol% DMAP
1.2 equiv. (EtCO)2O
OCOEt
R
R
Ar
Ar
CH2Cl2, r.t.
1
5
A solution of aryl alkenylcarbinols 1 (1.01 mmol) in
5 mL of CH2Cl2 was treated with DMAP (37.1 mg, 30%
mmol) at room temperature. Then the reaction mixture
was treated with propionyl anhydride (0.17 mL, 1.31
mmol). After completion of the reaction, the solvent
was removed on a rotary evaporator and the residue was
purified by flash chromatography on silica gel (petro-
leum/EtOAc＝10/1, V/V), to afford racemic esters 5.
2-Methyl-1-phenylallyl propionate (5b) 1H NMR
(400 MHz, CDCl3) δ: 7.35—7.28 (m, 5H), 6.18 (s, 1H),
5.11 (s, 1H), 4.97 (s, 1H), 2.41 (q, J＝7.6 Hz, 2H), 1.64
(s, 3H), 1.16 (t, J＝7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 173.1, 143.3, 138.7, 128.4, 128.0, 127.1,
112.4, 78.2, 27.8, 18.9, 9.1; IR (film) ν: 2997, 1742,
－
1
2-Methyl-1-(naphthalen-2-yl)allyl propionate (5i)
1H NMR (400 MHz, CDCl3) δ: 7.82 (s, 4H), 7.49—7.44
(m, 3H), 6.35 (s, 1H), 5.19 (s, 1H), 5.02 (s, 1H), 2.44 (q,
J＝7.7 Hz, 2H), 1.67 (s, 3H), 1.18 (t, J＝7.5 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 173.4, 143.2, 136.0,
133.2, 128.3, 128.2, 127.8, 126.4, 126.3, 126.3, 124.9,
112.7, 78.3, 27.9, 19.1, 9.2; IR (film) ν: 2995, 1746,
－
1
1463, 1182, 1091, 1019, 902, 763, 700 cm . HRMS
calcd for C13H16O2 204.1150, found 204.1154.
2-Methylene-1-phenylbutyl propionate (5c) 1H
NMR (400 MHz, CDCl3) δ: 7.34—7.30 (m, 5H), 6.22 (s,
1H), 5.15 (s, 1H), 4.99 (s, 1H), 2.41 (q, J＝7.6 Hz, 2H),
1.95 (q, J＝7.2 Hz, 2H), 1.16 (t, J＝7.5 Hz, 3H), 1.01 (t,
1292
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Chin. J. Chem. 2012, 30, 1289—1294

Kinetic Resolution of Aryl Alkenylcarbinols Catalyzed by Fc-PIP
－
1
1469, 1370, 1181, 1086, 1023, 901, 815, 762 cm .
HRMS calcd for C17H18O2 254.1307, found 254.1308.
2-Methylene-1-(naphthalen-2-yl)butylpropionate
(5j) 1H NMR (400 MHz, CDCl3) δ: 7.81—7.79 (m,
4H), 7.47—7.44 (m, 3H), 6.40 (s, 4H), 5.23 (s, 3H),
5.03 (s, 1H), 2.45—2.39 (m, 2H), 1.97 (q, J＝7.1 Hz,
2H), 1.16 (t, J＝7.6 Hz, 3H), 1.01 (t, J＝7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 173.4, 149.0, 136.2,
133.2 (d), 128.3, 128.1, 127.7, 126.6, 126.3, 126.2,
125.1, 110.2, 77.9, 27.9, 25.2, 12.0, 9.2; IR (film) ν:
2994, 1747, 1471, 1369, 1188, 1091, 1017, 901, 818, 753
cm－ 1. HRMS calcd for C18H20O2 268.1463, found
268.1464.
(0.039 mL), resulting in a green solution. Then the reac-
tion mixture was strirred at 0 ℃ for a specified period
of time, at the end of which it was quenched by rapid
addition of 0.5 mL of methanol. The solution was al-
lowed to warm up to room temperature and stirred until
the solution color turned to red-orange again. The sol-
vent was removed in vacuo, and the residue was chro-
matographed (5% — 10% EtOAc/petroleum, V/V) to
separate the ester from the unreacted alcohol.
The enantiomeric excess values of the esters 5 were
determined according to corresponding alcohols after
hydrolysis (2 mL of 2 mol•L－ KOH in methanol, at
1
room temperature). The conversions and selectivities
were caculated as CHPLC＝eeA/(eeE＋eeA), S＝ln((1－
CHPLC)•(1－eeA))/ln((1－CHPLC)(1＋eeA)) from previ-
ously published work.[8a]
The absolute configurations of the unreacted alco-
hols were assigned by comparison of the sign of optical
rotation of 1c and 1k with literature data.[17c]
Methods used to assay enantiometric excess of cor-
responding unreacted alcohols are as follows:
1a: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝40/1, V/V, 1.0 mL/min) major: tR＝13.88
min, minor: tR＝18.77 min.
1b: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝33.96
min, minor: tR＝38.57 min.
1c: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝33.09
min, minor: tR＝37.32 min.
1d: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝29.53
min, minor: tR＝36.13 min.
1e: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝26.66
min, minor: tR＝32.37 min.
1f: HPLC (Daicel CHIRALCEL AS-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝14.67
min, minor: tR＝17.74 min.
1g: HPLC (Daicel CHIRALCEL AS-H, Hexane/iso-
propanol＝99.5/0.5, V/V, 1.0 mL/min) major: tR＝19.71
min, minor: tR＝22.52 min.
2-Methyl-1-(naphthalen-1-yl)allyl propionate (5k)
1H NMR (400 MHz, CDCl3) δ: 8.14 (d, J＝8.0 Hz, 1H),
7.84 (dd, J＝16.7, 7.9 Hz, 2H), 7.58 (d, J＝7.1 Hz, 1H),
7.53—7.44 (m, 3H), 6.93 (s, 1H), 5.12 (s, 1H), 5.08 (s,
1H), 2.48—2.37 (m, 2H), 1.70 (s, 3H), 1.16 (t, J＝7.5
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 173.5, 143.0,
134.0 (d), 131.3, 129.0, 128.9, 126.4, 125.8, 125.3,
123.9, 113.3, 75.3, 27.9, 19.9, 9.2; IR (film) ν: 2995,
－
1
1731, 1468, 1357, 1186, 1086, 1028, 907, 800, 790 cm .
HRMS calcd for C17H18O2 254.1307, found 254.1309.
2-Methylene-1-(naphthalen-1-yl)butyl propionate
(5l) 1H NMR (400 MHz, CDCl3) δ: 8.13 (d, J＝8.1 Hz,
1H), 7.84 (dd, J＝17.0, 7.9 Hz, 2H), 7.57 (d, J＝7.1 Hz,
1H), 7.53—7.43 (m, 3H), 6.98 (s, 1H), 5.14 (s, 1H),
5.10 (s, 1H), 2.47—2.36 (m, 2H), 2.01 (q, J＝7.3 Hz,
2H), 1.16 (t, J＝7.5 Hz, 3H), 1.04 (t, J＝7.4 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 173.5, 148.9, 134.3,
134.1, 131.5, 129.1, 128.9, 126.4, 126.0, 125.8, 125.3,
123.9, 111.1, 74.7, 27.9, 26.0, 12.2, 9.3; IR (film) ν:
2991, 1739, 1468, 1371, 1190, 1093, 1009, 910, 801,
－
1
789 cm . HRMS calcd for C18H20O2 268.1463, found
268.1466.
2-Methyl-1-(thiophen-2-yl)allyl propionate (5m)
1H NMR (400 MHz, CDCl3) δ: 7.26 (m, 1H), 7.03—
7.01 (m, 2H), 6.66 (s, 1H), 4.64 (s, 2H), 2.39 (q, J＝7.6
Hz, 2H), 2.01 (s, 3H), 1.17 (t, J＝7.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 174.3, 140.0, 130.9, 127.7, 126.9,
125.4, 121.6, 70.0, 27.6, 16.3, 9.2; IR (film) ν: 2995,
－
1
1732, 1470, 1181, 1089, 1009, 867, 701 cm . HRMS
calcd for C11H14O2S 210.0715, found 210.0718.
1h: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝60/1, V/V, 1.0 mL/min) major: tR＝15.42
min, minor: tR＝18.84 min.
1i: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝40/1, V/V, 1.0 mL/min) major: tR＝26.86
min, minor: tR＝31.07 min.
1j: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝40/1, V/V, 1.0 mL/min) major: tR＝25.62
min, minor: tR＝29.48 min.
General procedure for the kinetic resolution of aryl
alkenylcarbinols
2 mol% Fc-PIP
OH
OH
OCOEt
R2
R2
R2
0.75 equiv. (EtCO)2O
R1
+
R1
R1
0.75 equiv. i-Pr2NEt
toluene, 0 oC
(R)
rac
(S)
1k: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝40/1, V/V, 1.0 mL/min) major: tR＝26.23
min, minor: tR＝58.05 min.
1l: HPLC (Daicel CHIRALCEL OD-H, Hexane/iso-
propanol＝40/1, V/V, 1.0 mL/min) major: tR＝21.67
min, minor: tR＝42.38 min.
0.008 mmol of catalyst, 0.4 mmol of secondary al-
cohol, toluene (1 mL) and 0.3 mmol of N,N-diisopropyl
ethylamine (0.052 mL) were added in turn to a 10-mL
flask in a 0 ℃ ice bath, resulting in a red-orange solu-
tion. After stirring at 0 ℃ for 5 min, the reaction mix-
ture was treated with 0.3 mmol of propionyl anhydride
1m: HPLC (Daicel CHIRALCEL OJ-H, Hexane/iso-
Chin. J. Chem. 2012, 30, 1289—1294
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1293

Hu et al.
FULL PAPER
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Acknowledgement
This work was financially supported by the Funda-
mental Research Funds for the Central Universities, the
Natural Science Foundation of China (Nos. 20972047,
21172068), the ‘Shu Guang’ project of Shanghai Mu-
nicipal Education Commission, Shanghai Education
Development Foundation (No. 09SG28), and the
Shanghai Committee of Science and Technology (No.
11DZ2260600).
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 1289—1294