Asymmetric organocatalytic Michael addition of anthrone to enone

Article abstract of DOI:10.1039/b927421a

Catalyzed by the bifunctional tertiary amino-thiourea organocatalyst derived from epicinchona alkaloid, the asymmetric Michael addition of anthrone to enone was achieved in high yield with excellent enantioselectivity. The Royal Society of Chemistry 2010.

Full text of DOI:10.1039/b927421a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Asymmetric organocatalytic Michael addition of anthrone to enone†
Chunlin Wu, Wenjun Li, Juanjuan Yang, Xinmiao Liang* and Jinxing Ye*
Received 7th January 2010, Accepted 4th May 2010
First published as an Advance Article on the web 21st May 2010
DOI: 10.1039/b927421a
Catalyzed by the bifunctional tertiary amino–thiourea organocatalyst derived from epicinchona
alkaloid, the asymmetric Michael addition of anthrone to enone was achieved in high yield with
excellent enantioselectivity.
Table 1 Screening of catalysts
Introduction
As one of the most important approaches to carbon–carbon bond
forming, the Michael addition has drawn significant attention
in organic chemistry,1 as well as asymmetric organocatalysis.2
The past decade has witnessed explosive growth in the field of
asymmetric organocatalysis with a catalytic amount of a small
organic molecule.3 Bifunctional organocatalysts bearing tertiary
amine and thiourea, which are able to simultaneously bind and
activate two reactants, have exhibited enormous potential in a
broad range of enantioselective reactions.4 Up to now, a variety
of bifunctional catalysts have been developed for the asymmetric
Michael addition of nitroolefins5 and enones.6
As a reactive diene, anthrone has been successfully applied in
the Diels–Alder reaction, which makes it a promising synthetic
Entry a
Catalyst
Time/h
Conv. b(%)
ee b(%)
tool for the formation of cyclic compounds.7 Effective catalytic
asymmetric Diels–Alder reactions of phenylmaleimide activated
olefin with anthrone have been reported in the presence of chiral
Brønsted base.7i However, the Michael addition of anthrone with
a,b-unsaturated ketone is still a great challenge due to the Diels–
Alder reaction byproducts.8 So we envisioned the corresponding
Michael addition could be exclusively produced in good yield
and excellent enantioselectivity in the presence of bifunctional
organocatalyst.
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
24 h
24 h
24 h
24 h
24 h
24 h
78
91
97
97
94
99
-39
-78
86
86
-71
-78
a In each case, the reaction was carried out with 2a (0.1 mmol), 3a
(0.2 mmol) and catalyst (0.02 mmol) in toluene (0.2 mL). b Detected by
HPLC analysis on chiral column.
Herein we presented a catalytic asymmetric Michael addition
of anthrone to a,b-unsaturated ketones for the first time with
bifunctional catalyst 1c developed from cinchona alkaloid.9
was employed (Entry 2). In order to obtain excellent conversion
and enantioselectivity, we next promoted the Michael reaction in
the presence of cinchona alkaloid derived tertiary amino–thiourea
organocatalysts 1c–1f, which have exhibited high catalytic activity
in the Michael addition of enone. Gratifyingly, the Michael addi-
tion of 2a with 3a proceeded to 97% conversion with 86% ee with
1c as the organocatalyst (Entry 3). The same result was observed
when the methoxyl group on the quinoline was removed, using 1d
instead of 1c (Entry 4). However, when the stereo-configuration of
organocatalysts (1c–1d) was reversed, replacing 1c and 1d with 1e
and 1f, the enantioselectivity decreased to 71% and 78% (Entries
5–6). It also indicated that 9-amino(9-deoxy)epiquinine would be
more helpful to control the enantioselectivity. After screening the
catalysts, the conclusion was arrived at that the Michael addition
of 2a and 3a could be efficiently catalyzed by tertiary amino–
thiourea organocatalysts 1c and 1d. Therefore, we next conducted
the Michael addition using 1c as the bifunctional organocatalyst.
A survey of solvents revealed that the reaction medium played
an important role in the Michael addition. The results are
Results and discussion
In the initial investigation of screening organocatalysts, the
Michael addition of anthrone 2a to a,b-unsaturated ketone 3a
(2.0 equiv) was carried out in toluene (0.5 M) in the presence
of tertiary amine–thiourea organocatalysts (1a–1f) at room tem-
perature. As illustrated in Table 1, the 1a-catalyzed reaction
afforded 78% conversion with only 39% ee (Entry 1). To our
delight, the conversion increased to 91% with 78% ee when 1b
Engineering Research Centre of Pharmaceutical Process Chemistry, Min-
istry of Education, School of Pharmacy, East China University of Science
and Technology, 130 Meilong Road, Shanghai 200237, China. E-mail: yejx@
ecust.edu.cn, liangxm@ecust.edu.cn
† Electronic supplementary information (ESI) available: General proce-
dure for the synthesis of substrate and chiral catalyst; HPLC analysis of
Michael addition products; 1H and 13C NMR spectra of Michael addition
products. CCDC reference number 764606. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b927421a
3244 | Org. Biomol. Chem., 2010, 8, 3244–3250
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Table 2 Optimization of Michael addition conditions
Table 3 The Michael addition of 2 to 3 in the presence of 1c
Entrya R1
R2
R3 adduct Yieldb(%) eec(%)
Entrya
Catalyst
Solvent
Time/h
Conv. b(%)
ee b(%)
1
2
3
4
5
6
7
8
H (2a)
C6H5 (3a)
Me 4aa
Me 4ab
Me 4ac
Me 4ad
Me 4ae
Me 4af
Me 4ag
Me 4ah
Me 4ai
Me 4aj
95
98
97
97
97
97
74
97
98
88
90
80
85
83
97
83
81
92
83
86
91
91
91
90
86
87
91
91
90
90
91
90
93
90
84
70
90
57
1
2
3
4
1c
1c
1c
1c
1c
1c
1c
1c
1c
1c
Toluene
MTBEh
CH2Cl2
THF
Acetone
Toluene
Toluene
Toluene
Toluene
Toluene
24 h
24 h
24 h
24 h
24 h
72 h
24 h
48 h
60 h
120 h
97
97
97
72
97
17
96
94
89
98
86
84
76
78
56
59
89
91
91
89
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
H (2a)
Cl (2b)
2-ClC6H4 (3b)
3-ClC6H4 (3c)
4-ClC6H4 (3d)
2-FC6H4 (3e)
3-FC6H4 (3f)
4-FC6H4 (3g)
2-BrC6H4 (3h)
3-BrC6H4 (3i)
4-BrC6H4 (3j)
5
6c
7d
8e
9f
10g
9
10
11
12
13
14
15
16
17
18
19
2-OMeC6H4 (3k) Me 4ak
3-OMeC6H4 (3l) Me 4al
4-OMeC6H4 (3m) Me 4am
a In each case, the reaction was carried out with 2a (0.1 mmol), 3a
(0.2 mmol) and catalyst 1c (0.02 mmol) in solvent (0.2 mL) under room
temperature. b Detected by HPLC analysis on chiral column. c Reaction
was carried out at -30 ◦C. d Reaction was carried out with 0.5 ml solvent.
e Reaction was carried out with 1 mL solvent. f Reaction was carried out
with 10 mol% catalyst in 1 mL solvent. g Reaction was carried out with
5 mol% catalyst in 1 mL solvent. h MTBE means methyl tert-butyl ether.
2-MeC6H4 (3n)
3-MeC6H4 (3o)
4-MeC6H4 (3p)
C6H5 (3q)
Me 4an
Me 4ao
Me 4ap
Et 4aq
Me 4ba
Me 4ci
C6H5 (3a)
OH (2c) 3-BrC6H4 (3i)
a In each case, the reaction was carried out with 2 (0.5 mmol), 3 (1.0 mmol)
and 1c (10 mol%) in toluene (2.5 mL) under room temperature for 72 h.
b Isolated yield. c Detected by chiral HPLC analysis on chiral column.
summarized in Table 2. Full conversions and excellent ee values
were observed in nonpolar solvents, such as toluene and MTBE
(Entries 1–2). In contrast, use of dichloromethane, THF or acetone
led to a significant decrease in enantioselectivity (Entries 3–5).
For THF and acetone, this might be attributed to the hydrogen
bonding interaction between catalyst 1c and the solvents. Screen-
ing solvents revealed that toluene was the best medium in terms
of conversion and enantioselectivity. Nevertheless, the reaction
became sluggish with lower enantioselectivity if the temperature
was reduced to -30 ◦C (Entry 6). Further investigations revealed
that improvement of enantioselectivity was observed when the
reactions were carried out in 0.2 M and 0.1 M solutions of the
substrate. For example, up to 89% ee value was obtained when the
reaction took place in 0.5 mL toluene (Entry 7) and the same level
of ee value was observed in 1.0 mL toluene with a slight decrease in
conversion (Entry 8). Besides, studies demonstrated that as low as
10 mol% 1c in 0.1 M solution of the substrate afforded the Michael
adduct in 89% conversion with 91% ee in prolonged reaction time
(Entry 9). Even when the catalyst loading was reduced to 5 mol%,
up to 98% of conversion with 89% ee was obtained after 120 h
(Entry 10).
70% ee could still be obtained (Entry 17). Further investigations
revealed that the Michael addition of 1,8-dichloroanthracen-9-
one (2b) to 4-phenylbut-3-en-2-one (3a) also proceeded in 92%
yield and 90% ee value (Entry 18). However, only 57% ee value
was obtained when using 1,8-dihydroxyanthracen-9-one (2c) as the
nucleophile (Entry 19). This might be attributed to the competitive
activation with 3i of catalyst 1c and anthrone derivate 2c. However,
less than 30% enantioselectivities were obtained in the Michael
addition of anthrone to alkyl enones (not shown in Table 3).
The asymmetric Michael additions of anthrone 2a to cyclic
enones 5 catalyzed by 1c were also investigated. The results are
shown in Table 4. To our delight, the Michael reaction of cyclohex-
2-enone (5a) with anthrone 2a afforded the desired adduct 6aa with
85% yield and 78% ee (Entry 1). However, the Michael addition of
Table 4 The Michael addition of 2a to 5 in the presence of 1c
After establishing the optimal reaction conditions, the gener-
ality of this Michael addition was explored. The representative
results are displayed in Table 3. We first carried out the Michael
additions of anthrone 2a to various aryl enones (3a–3p). To
our great delight, aryl enones bearing electron-withdrawing and
donating groups in the o-, m-, p-positions of the aromatic ring all
afforded the desired adducts in high yields (74–98%) with excellent
enantioselectivities (84–93%) (Entries 1–16). It appeared that the
position and the electronic property of the substituent group
on the aromatic ring played a limited role in the yields and the
enantioselectivities. If a highly sterically hindered substrate such
as 1-phenylpent-1-en-3-one (3q) was used, up to 81% yield with
Entrya
n(5)
adduct
yieldb(%)
ee (%)c
1
2
1 (5a)
2 (5b)
6aa
6ab
85
91
78
44
a In each case, the reaction was carried out with 2 (0.5 mmol), 5 (1.0 mmol)
and 1c (10 mol%) in toluene (2.5 mL) under room temperature for 72 h.
b Isolated yield. c Detected by chiral HPLC analysis on chiral column
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anthrone 2a to other cyclic enones produced low enantioselectivity.
For example, only 44% ee with 91% yield was obtained when
cyclohept-2-enone (5b) reacted with anthrone 2a (Entry 2). The
absolute configuration of 4ad was determined to be S by X-ray
crystal structural analysis (Scheme 1),† and a working model of
the reaction transition state was proposed based on the stereo-
outcome (Scheme 2).
are referenced to the carbon resonances of the solvent (CDCl3: d
77.16). Data are represented as follows: chemical shift, integration,
multiplicity (br = broad, s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet), coupling constants in Hertz (Hz).
Mass spectra (ESI) were measured on a Waters Micromass LCT
spectrometer. High performance liquid chromatography (HPLC)
was performed on an Agilent 1200 Series chromatographs using
a Daicel Chirapak AS-H column (0.46 cm x 25 cm), Chiralpak
IA-H, IC–H column (0.46 cm x 25 cm), and Regis (R, R)-Whelk
O1 column (0.46 cm x 25 cm) as noted.
Crystal structure determination of compound of 4ad:
C24H19ClO2, M = 374.84; a block crystal (0.20 ¥0.15 ¥ 0.10 mm),
˚
T = 298(2), l(Mo-Ka) = 0.71073 A, Orthorhombic, space group:
˚
˚
˚
P212121, a = 12.5855(10) A, b = 14.0795(11) A, c = 21.9701(17) A,
3
˚
V = 3893.0(5) A , 16570 total reflections, 5543 unique, Rint
=
0.0315, , R1 = 0.0535 [I > 2s(I)], wR2 = 0.1440, min/max residual
-3
˚
electron density -0.298/+0.464 e A , Flack parameter: 0.04(14).
General procedure for asymmetric Michael addition
To a solution of a,b-unsaturated ketone 3 (1.0 mmol) and catalyst
1c (0.05 mmol) in toluene (2.5 mL) was added anthrone 2a
(0.5 mmol). The reaction mixture was stirred at room temperature
for 72 h and then the solvent was removed under vacuum. The
residue was purified by column chromatography on silica gel to
yield the desired addition product.
Scheme 1 X-Ray structure of enantiopure 4ad. Thermal ellipsoids are
shown with 50% ellipsoids.
(S)-9-(3-Oxo-1-phenylbutyl)anthracen-10(9H)-one
(4aa).
◦
White solid, Mp: 110–112 C, 95% yield. [a]2D3 +2.88 (c 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.07 (d, J =
7.6 Hz, 1H), 8.01(d, J = 7.6 Hz, 1H), 7.60 (t, J = 6.8 Hz, 1H),
7.53-7.49 (m, 1H), 7.47–7.37 (m, 3H), 7.26–7.25 (m, 1H), 7.12 (t,
J = 7.6 Hz, 1H), 6.98 (t, J = 7.6 Hz, 2H), 6.24 (d, J = 7.6 Hz,
1H), 4.56–4.55 (m, 1H), 3.81–3.77 (m, 1H), 2.83 (dd, J = 7.2,
17.2 Hz, 1H), 2.69 (dd, J = 7.6, 17.2 Hz, 1H), 2.08 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 206.67, 183.97, 143.04,
141.42, 138.07, 134.09, 133.31, 132.21, 131.93, 128.69, 128.62,
128.56, 127.71, 127.47, 127.22, 127.13, 126.89, 126.48, 60.41,
48.34, 44.84, 30.60. HRMS: exact mass calculated for [M+NH4]+
(C24H20O2) require m/z 358.1807, found m/z 358.1801. 86% ee,
determined by Chiral HPLC. [Regis (R, R)-Whelk O1 column,
l = 254 nm, n-Hexane: EtOH = 15 : 1, flow rate = 0.8 mL min-1]:
36.0 min (major), 40.3 min (minor).
Scheme 2 Proposed working model of the reaction transition state.
Conclusions
In conclusion, a new organocatalytic methodology has been
developed for the asymmetric Michael addition of anthrone to
enone. This methodology could afford the required Michael
adducts in high yields and excellent enantioselectivities with
10 mol% catalyst loading. It is noteworthy that the Michael
addition of anthrone to enone has not been reported yet. Further
investigations on anthrone chemistry are underway and results
from these studies will be presented in the future.
(S)-9-(1-(2-Chlorophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4ab). White solid, Mp: 147–149 C, 98% yield. [a]2D4 +19.58 (c
1
1.0, CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.22–8.20
(m, 2H), 7.77–7.75 (m, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.49 (t, J =
7.6 Hz, 1H), 7.44–7.41 (m, 2H), 7.32–7.29 (m, 1H), 7.21–7.18 (m,
1H), 7.01 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 7.6 Hz, 1H), 6.26 (d, J =
7.6 Hz, 1H), 4.66–4.65 (m, 1H), 4.42–4.38 (m, 1H), 2.41 (dd, J =
9.6, 17.2 Hz, 1H), 2.32 (dd, J = 5.6, 17.2 Hz, 1H), 1.86 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 205.53, 184.72, 143.02,
140.29, 137.41, 134.82, 133.45, 133.41, 133.02, 131.51, 129.98,
129.92, 129.20, 128.40, 128.37, 127.63, 127.55, 126.98, 126.90,
126.16, 46.17, 45.86, 41.89, 30.06. HRMS: exact mass calculated
for [M+NH4]+ (C24H19ClO2) require m/z 392.1417, found m/z
392.1399. 91% ee, determined by Chiral HPLC. [Daicel Chiralpak
IC–H column, l = 254 nm, n-Hexane: EtOH = 15 : 1, flow rate =
0.8 mL min-1]: 28.0 min (major), 30.9 min (minor).
Experimental
General methods
Proton nuclear magnetic resonance (1H NMR) spectra and carbon
nuclear magnetic resonance (13C NMR) spectra were recorded on a
Bruker AV-400 spectrometer (400 MHz and 100 MHz). Chemical
shifts for protons are reported in parts per million downfield from
tetramethylsilane and are referenced to residual protium in the
NMR solvent (CDCl3: d 7.26). Chemical shifts for carbon are
reported in parts per million downfield from tetramethylsilane and
3246 | Org. Biomol. Chem., 2010, 8, 3244–3250
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(S)-9-(1-(3-Chlorophenyl)-3-oxobutyl)anthracen-10(9H)-one
(ppm) 206.192, 183.89, 163.31; 160.86, 142.69, 141.06, 140.92;
140.86, 134.00, 133.24, 132.37, 132.07, 129.20; 129.11, 128.49,
128.50, 127.67, 127.43, 127.01, 126.60, 124.38; 124.36, 115.68;
115.46, 114.08; 113.87, 49.99, 48.09, 44.70, 30.59. HRMS: exact
mass calculated for [M+NH4]+ (C24H19FO2) require m/z 376.1713,
found m/z 376.1697. 86% ee, determined by Chiral HPLC. [Daicel
Chiralpak AS-H column, l = 254 nm, n-Hexane: EtOH = 8 : 1,
flow rate = 0.8 mL min-1]: 11.1 min (major), 14.0 min (minor).
◦
(4ac). White solid, Mp: 129–131 C, 97% yield. [a]2D3 +11.58 (c
1
1.0, CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.12–8.10
(m, 1H), 8.05–8.03 (m, 1H), 7.63–7.60 (m, 1H), 7.55–7.52 (m, 1H),
7.49–7.46 (m, 1H), 7.43–7.40 (m, 2H), 7.27–7.25 (m, 1H), 7.10–
7.09 (m, 1H), 6.91 (t, J = 8.0 Hz, 1H), 6.18 (s, 1H), 6.12 (d, J =
8.0 Hz, 1H), 4.53– 4.52 (m, 1H), 3.78–3.74 (m, 1H), 2.82 (dd, J =
7.2, 17.6 Hz, 1H), 2.65 (dd, J = 7.6, 17.6 Hz, 1H), 2.10 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 206.10, 183.71, 142.64,
140.95, 140.32, 133.98, 133.49, 133.21, 132.38, 132.08, 128.88,
128.83, 128.53, 128.48, 127.60, 127.43, 127.18, 126.97, 126.78,
126.57, 50.01, 48.03, 44.60, 30.60. HRMS: exact mass calculated
for [M+NH4]+ (C24H19ClO2) require m/z 392.1417, found m/z
392.1402. 91% ee, determined by Chiral HPLC. [Regis (R, R)-
Whelk O1 column, l = 254 nm, n-Hexane: EtOH = 15 : 1, flow
rate = 0.8 mL min-1]: 40.3 min (major), 46.4 min (minor).
(S)-9-(1-(4-Fluorophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4ag). White solid, Mp: 142–144 C, 74% yield. [a]2D3 +7.18 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.09 (d, J =
7.6 Hz, 1H), 6.02 (d, J = 7.6 Hz, 1H), 7.60 (t, J = 7.2 Hz, 1H), 7.54
(t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.2 Hz, 1H), 7.42–7.39 (m, 2H),
7.32–7.30 (m, 1H), 6.69–6.64 (m, 2H), 6.17–6.14 (m, 2H), 4.53–
4.52 (m, 1H), 3.80–3.75 (m, 1H), 3.50–3.49 (m, 1H), 5.70 (dd, J =
7.2, 17.2 Hz, 1H), 2.67 (dd, J = 7.6, 17.6 Hz, 1H), 2.09 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 206.43, 183.82, 163.06;
160.61, 143.05, 141.06, 134.07, 133.74; 133.70, 133.23, 132.36,
131.95, 130.15, 130.07, 128.49, 128.50, 127.58, 127.31, 127.01,
126.57, 114.67, 114.46, 49.69, 48.16, 45.28, 30.60. HRMS: exact
mass calculated for [M+NH4]+ (C24H19FO2) require m/z 376.1713,
found m/z 376.1695. 87% ee, determined by Chiral HPLC. [Daicel
Chiralpak AS-H column, l = 254 nm, n-Hexane: EtOH = 8 : 1,
flow rate = 0.8 mL min-1]: 12.2 min (major), 18.9 min (minor).
(S)-9-(1-(4-Chlorophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4ad). White solid, Mp: 113–115 C, 97% yield. [a]2D3 -2.72 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.10 (d, J =
8.0 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.62–7.59 (m, 1H), 7.54–
7.50 (m, 1H), 7.47 (t, J = 7.2 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H),
7.26–7.24 (m, 1H), 6.98 (m, 1H), 6.96 (m, 1H), 6.20 (m, 1H), 6.18
(m, 1H), 4.52–4.51 (m, 1H), 3.79–3.75 (m, 1H), 2.80 (dd, J =
7.2, 17.6 Hz, 1H), 2.64 (dd, J = 8.0, 17.6 Hz, 1H), 2.07 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 206.23, 183.85, 142.72,
141.12, 136.86, 133.93, 133.17, 132.96, 132.34, 132.07, 129.90,
128.57, 128.53, 127.86, 127.63, 127.39, 127.07, 126.68, 49.815,
48.10, 44.85, 30.59. HRMS: exact mass calculated for [M+NH4]+
(C24H19ClO2) require m/z 392.1417, found m/z 392.1410. 91% ee,
determined by Chiral HPLC. [Regis (R, R)-Whelk O1 column,
l = 254 nm, n-Hexane: EtOH = 30 : 1, flow rate = 0.8 mL min-1]:
55.2 min (major), 66.5 min (minor).
(S)-9-(1-(2-Bromophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4ah). White solid, Mp: 159–161 C, 97% yield. [a]2D3 +33.22 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.24–8.21 (m,
2H), 7.85–7.83 (m, 1H), 7.67–7.63 (m, 2H), 7.49 (t, J = 7.2 Hz,
1H), 7.43 (t, J = 7.2 Hz, 1H), 7.30–7.28 (m, 1H), 7.14–7.10 (m, 1H),
7.08–7.04 (m, 1H), 6.42 (d, J = 7.6 Hz, 1H), 6.25–6.23 (m, 1H),
4.68 (m, 1H), 4.39–4.37 (m, 1H), 2.39 (dd, J = 10.0, 17.2 Hz, 1H),
2.28 (dd, J = 4.2, 17.2 Hz, 1H), 1.84 (s, 3H). 13C NMR (100 MHz,
CDCl3): d (ppm) 205,48, 184.85, 143.10, 139.95, 138.99, 133.54,
133.47, 133.42, 133.10, 131.40, 130.15, 129.47, 128.74, 128.33,
127.66, 127.60, 127.02, 126.94, 126.76, 125.87, 48.37, 46.10, 41.91,
30.03. HRMS: exact mass calculated for [M+NH4]+ (C24H19BrO2)
require m/z 436.0912, found m/z 436.0888. 91% ee, determined
by Chiral HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-
Hexane: EtOH = 8 : 1, flow rate = 0.8 mL min-1]: 9.0 min (major),
10.5 min (minor).
(S)-9-(1-(2-Fluorophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4ae). white solid, Mp: 94–95 C, 97% yield. [a]2D4 +1.28 (c 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.16–8.11 (m,
2H), 7.61 (t, J = 7.2 Hz, 1H), 7.55–7.53 (m, 1H), 7.47 (t, J =
7.6 Hz, 1H), 7.43–7.41 (m, 2H), 7.21–7.16 (m, 1H), 6.98–6.90 (m,
2H), 6.83 (t, J = 7.6 Hz, 1H), 6.19 (t, J = 7.2 Hz, 1H), 4.58–4.57
(m, 1H), 4.17–4.13 (m, 1H), 2.63–2.51 (m, 2H), 1.99 (s, 3H). 13C
NMR (100 MHz, CDCl3): d (ppm) 205.98, 184.35, 162.27, 159.82,
142.19, 141.74, 133.59, 133.14, 132.48, 132.01, 129.43, 129.39,
129.10, 128.91, 128.83, 128.66, 127.60, 127.44, 126.93, 126.78,
126.53, 126.40, 123.47, 123.42, 115.50, 115.27, 47.29, 43.33, 42.80,
30.27. HRMS: exact mass calculated for [M+NH4]+ (C24H19FO2)
require m/z 376.1713 found m/z 376.1706. 90% ee, determined by
Chiral HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-
Hexane: EtOH = 8 : 1, flow rate = 0.8 mL min-1]: 10.3 min (major),
14.2 min (minor).
(S)-9-(1-(3-Bromophenyl)-3-ox◦obutyl)anthracen-10(9H)-one
(4ai). White solid, Mp: 120–121 C, 98% yield. [a]2D3 +14.22 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.12 (d, J =
7.6 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H),
7.56–7.52 (m, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.44–7.40 (m, 2H),
7.27–7.24 (m, 2H), 6.86–6.83 (m, 1H), 6.32 (m, 1H), 6.17–6.15 (d,
J = 7.6 Hz, 1H), 4.53–4.52 (m, 1H), 3.77–3.73 (m, 1H), 2.82 (dd,
J = 7.6, 17.6 Hz, 1H), 2.65 (dd, J = 7.6, 17.6 Hz, 1H), 2.10 (s, 3H).
13C NMR (100 MHz, CDCl3): d (ppm) 206.08, 183.68, 142.61,
140.92, 140.59, 134.00, 133.22, 132.38, 132.07, 131.75, 130.10,
129.16, 128.53, 128.47, 127.69, 127.45, 127.21, 126.99, 126.69,
121.78, 50.03, 48.04, 44.58, 30.62. HRMS: exact mass calculated
for [M+NH4]+ (C24H19BrO2) require m/z 436.0912, found m/z
436.0906. 91% ee, determined by Chiral HPLC. [Regis (R, R)-
Whelk O1 column, l = 254 nm, n-Hexane: EtOH = 15 : 1, flow
rate = 0.8 mL min-1]: 43.0 min (major), 49.8 min (minor).
(S)-9-(1-(3-Fluorophenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4af). White solid, Mp: 112–114 C, 97% yield. [a]2D3 +5.16 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.11 (d, J =
7.6 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.61 (t, J = 7.2 Hz, 1H),
7.53 (t, J = 7.2 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.43–7.40 (m,
2H), 7.27–7.25 (m, 1H), 6.98–6.93 (m, 1H), 6.84–6.79 (m, 1H),
6.05 (d, J = 7.6 Hz, 1H), 5.95–5.92 (m, 1H), 4.55–4.54 (m, 1H),
3.81–3.77 (m, 1H), 2.82 (dd, J = 7.2, 17.6 Hz, 1H), 2.66 (dd, J =
8.0, 17.6 Hz, 1H), 2.09 (s, 3H). 13C NMR (100 MHz, CDCl3): d
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(S)-9-(1-(4-Bromophenyl)-3-oxobutyl)anthracen-10(9H)-one
129.62, 128.65, 128.55, 127.39, 127.14, 126.90, 126.51, 113.15,
55.12, 49.81, 48.55, 45.12, 30.56. HRMS: exact mass calculated for
[M+NH4]+ (C25H22O3) require m/z 388.1913, found m/z 388.1893.
90% ee, determined by Chiral HPLC. [Regis (R, R)-Whelk O1
column, l = 254 nm, n-Hexane: EtOH = 15 : 1, flow rate =
0.8 mL min-1]: 48.2 min (major), 54.9 min (minor).
◦
(4aj). White solid, Mp: 132–134 C, 88% yield. [a]2D3 -4.04 (c
1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 8.11 (d, J =
6.8 Hz, 1H), 8.05 (d, J = 6.8 Hz, 1H), 7.62–7.58 (m, 1H), 7.54–
7.50 (m, 1H), 7.49–7.45 (m, 1H), 7.43–7.39 (m, 2H), 7.23 (d, J =
7.6 Hz, 1H), 7.13–7.11 (m, 2H), 6.16–6.14 (m, 2H), 4.51 (d, J =
3.6 Hz, 1H), 3.78–3.73 (m, 1H), 2.78 (dd, J = 7.2, 17.6 Hz, 1H),
2.63 (dd, J = 8.0, 17.2 Hz, 1H), 2.06 (s, 3H). 13C NMR (100 MHz,
CDCl3): d (ppm) 206.18, 183.83, 142.64, 141.14, 137.46, 133.88,
133.14, 132.33, 132.10, 130.81, 130.26, 128.59, 128.53, 127.63,
127.39, 127.07, 126.69, 121.09, 49.87, 48.03, 44.73, 30.59. HRMS:
exact mass calculated for [M+NH4]+ (C24H19BrO2) require m/z
436.0912, found m/z 436.0897. 90% ee, determined by Chiral
HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-Hexane:
EtOH = 8 : 1, flow rate = 0.8 mL min-1]: 13.0 min (major), 16.6 min
(minor).
(S)-9-(3-Oxo-1-o-tolylbut◦yl)anthracen-10(9H)-one
(4an).
White solid, Mp: 123–125 C, 83% yield. [a]2D4 -21.28 (c 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.12–8.09 (m,
2H), 7.57–7.53 (m, 1H), 7.47–7.40 (m, 3H), 7.37 (d, J = 7.6 Hz,
1H), 7.08–7.04 (m, 2H), 7.01–6.99 (m, 1H), 6.86 (t, J = 7.2 Hz,
1H), 6.08 (d, J = 7.6 Hz, 1H), 4.43–4.42 (m, 1H), 4.05–4.00 (m,
1H), 2.70–2.58 (m, 2H), 1.94 (s, 3H), 1.92 (s, 3H). 13C NMR
(100 MHz, CDCl3): d (ppm) 206.46, 184.41, 142.40, 142.23,
137.33, 137.25, 134.10, 133.36, 132.13, 131.73, 130.41, 129.67,
128.25, 127.69, 127.46, 127.41, 126.93, 126.88, 126.85, 126.17,
48.10, 45.32, 45.27, 30.57, 19.14. HRMS: exact mass calculated
for [M+NH4]+ (C25H22O2) require m/z 372.1964, found m/z
372.1946. 93% ee, determined by Chiral HPLC. [Daicel Chiralpak
AS-H column, l = 254 nm, n-Hexane: EtOH = 8 : 1, flow rate =
0.8 mL min-1]: 8.4 min (major), 9.6 min (minor).
(S)-9-(1-(2-Methoxyphenyl)-3-oxobutyl)anthracen-10(9H)-one
(4ak). White foamy solid, 90% yield. [a]2D3 -26.46 (c 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): d (ppm) 8.18–8.14(m, 2H), 7.65–
7.60 (m, 2H), 7.48–7.44 (m, 1H), 7.41–7.35 (m, 2H), 7.23–7.20
(m, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.75 (d, J = 7.2 Hz, 1H),
6.70 (t, J = 7.6 Hz, 1H), 6.21–6.20 (m, 1H), 4.61–4.60 (m, 1H),
(S)-9-(3-Oxo-1-m-to◦lylbutyl)anthracen-10(9H)-one
(4ao).
4.33–4.29 (m, 1H), 3.74 (s, 3H), 2.47–2.34 (m, 2H), 1.91 (s, 3H). 13
C
White solid, Mp: 96–98 C, 97% yield. [a]2D3 +8.54 (c 1.0, CH2Cl2).
1H NMR (400 MHz, CDCl3): d (ppm) 8.08 (d, J = 7.6 Hz, 1H),
8.01 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.2 Hz, 1H), 7.52–7.48 (m,
1H), 7.47–7.43 (m, 2H), 7.39 (t, J = 7.2 Hz, 1H), 7.23 (d, J =
7.6 Hz, 1H), 6.94–6.92 (m, 1H), 6.86 (t, J = 7.6 Hz, 1H), 6.04 (d,
J = 7.2 Hz, 1H), 6.00 (m, 1H), 4.54–4.53 (m, 1H), 3.77–3.72(m,
1H), 2.78 (dd, J = 7.2, 17.2 Hz, 1H), 2.66 (dd, J = 7.6 Hz, 17.2 Hz,
1H), 2.07 (m, 6H). 13C NMR (100 MHz, CDCl3): d (ppm) 206.76,
183.86, 143.05, 141.55, 137.91, 137.16, 134.13, 133.36, 132.11,
131.89, 129.68, 128.68, 128.55, 127.73, 127.55, 127.39, 127.15,
126.76, 126.38, 125.55, 50.34, 48.41, 44.74, 30.60, 21.18. HRMS:
exact mass calculated for [M+NH4]+ (C25H22O2) require m/z
372.1964, found m/z 372.1956. 90% ee, determined by HPLC.
[Regis (R, R)-Whelk O1 column, l = 254 nm, n-Hexane: EtOH =
15 : 1, flow rate = 0.8 mL min-1]: 30.8 min (major), 34.2 min
(minor).
NMR (100 MHz, CDCl3): d (ppm) 206.70, 184.69, 157.11, 143.50,
141.99, 133.46, 133.21, 132.52, 131.47, 129.54, 128.63, 128.37,
128.23, 127.87, 127.27, 127.09, 126.67, 126.61, 119.81, 110.27,
55.30, 46.69, 43.08, 42.37, 30.15. HRMS: exact mass calculated for
[M+NH4]+ (C25H22O3) require m/z 388.1913, found m/z 388.1895.
90% ee, determined by Chiral HPLC. [Daicel Chiralpak IA-H
column, l = 254 nm, n-Hexane: EtOH = 15 : 1, 0.8 mL min-1]:
16.4 min (major), 18.5 min (minor).
(S)-9-(1-(3-Methoxyphenyl)◦-3-oxobutyl)anthracen-10(9H)-one
(4al). White solid, 108–110 C, 80% yield. [a]2D3 +1.88 (c 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.10 (d, J =
7.6 Hz, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.2 Hz, 1H),
7.51 (t, J = 7.2 Hz, 1H), 7.48–7.38 (m, 3H), 7.27–7.26 (m, 1H), 6.90
(t, J = 7.6 Hz, 1H), 6.6–6.65 (m, 1H), 5.87 (d, J = 7.2 Hz, 1H), 5.78
(m, 1H), 4.55–4.54 (m, 1H), 3.78–3.71 (m, 1H), 3.53 (s, 3H), 2.79
(dd, J = 7.2, 10.4 Hz, 1H), 2.67 (dd, J = 7.6, 9.6 Hz, 1H), 2.07
(s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) 206.60, 183.93,
158.86, 143.00, 141.44, 139.67, 134.06, 133.31, 132.17, 131.92,
128.66, 128.64, 128.53, 127.43, 127.19, 126.88, 126.48, 120.99,
114.30, 113.00, 55.00, 50.34, 48.25, 44.79, 30.58. HRMS: exact
mass calculated for [M+NH4]+ (C25H22O3) require m/z 388.1913,
found m/z 388.1895. 91% ee, determined by Chiral HPLC. [Regis
(R, R)-Whelk O1 column, l = 254 nm, n-Hexane: EtOH = 15 : 1,
flow rate = 0.8 mL min-1]: 51.5 min (major), 58.9 min (minor).
(S)-9-(3-Oxo-1-p-tolylbutyl)anthracen-10(9H)-one
(4ap).
1
White foamy solid, 83% yield. [a]2D3 -2.00 (c 1.0, CH2Cl2). H
NMR (400 MHz, CDCl3): d (ppm) 8.09 (d, J = 7.6 Hz, 1H),
8.03 (d, J = 8.0 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.51–7.43 (m,
3H), 7.41–7.37 (m, 1H), 7.22–7.20 (m, 1H), 6.81–6.79 (m, 2H),
6.18–6.16 (m, 2H), 4.53–4.52 (m, 1H), 3.78–3.73 (m, 1H), 2.75
(dd, J = 6.8, 17.2 Hz, 1H), 2.64 (dd, J = 8.0, 17.2 Hz, 1H), 2.23 (s,
3H), 2.04 (s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) 206.827,
184.101, 142.987, 141.725, 136.713, 135.156, 133.986, 133.271,
132.121, 131.967, 128.718, 128.572, 128.494, 128.457, 127.410,
127.170, 126.933, 126.551, 50.135, 48.490, 44.805, 30.581, 21.037.
HRMS: exact mass calculated for [M+NH4]+ (C25H22O2) require
m/z 372.1964, found m/z 372.1953. 84% ee, determined by Chiral
HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-Hexane:
EtOH = 15 : 1, flow rate = 0.8 mL min-1]: 12.0 min (major),
13.2 min (minor).
(S)-9-(1-(4-Methoxyphenyl)-3-oxobutyl)anthracen-10(9H)-one
◦
(4am). White solid, 78–80 C, 85% yield. [a]2D3 -3.2 (c 1.0,
1
CH2Cl2). H NMR (400 MHz, CDCl3): d (ppm) 8.10 (d, J =
7.6 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.590 (t, J = 7.6 Hz, 1H),
7.50 (t, J = 7.6 Hz, 1H), 7.47–7.42 (m, 2H), 7.39 (t, J = 7.6 Hz,
1H), 7.23 (d, J = 7.6 Hz, 1H), 6.54–6.52 (m, 2H), 6.18–6.16 (m,
2H), 4.52–4.51 (m, 1H), 3.76–3.73 (m, 1H), 3.71 (s, 3H), 2.76 (dd,
J = 6.8, 16.8 Hz, 1H), 2.63 (dd, J = 8.0, 17.2 Hz, 1H), 2.04
(s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) 206.93, 183.89,
158.64, 143.11, 141.58, 134.00, 133.25, 132.14, 131.90, 130.05,
(S)-10-(3-Oxo-1-phenylpentyl)anthracen-9(10H)-one (4aq).
Colourless oil, 81% yield. [a]2D2 -17.12 (c 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3): d (ppm) 8.09 (d, J = 6.0 Hz, 1H), 8.03
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(d, J = 8.0 Hz, 1H), 7.62–7.60 (m, 1H), 7.56–7.41 (m, 4H), 7.31
(d, J = 7.6 Hz, 1H), 7.15–7.12 (m, 1H), 6.99 (t, J = 7.6 Hz, 2H),
6.24 (d, J = 7.2 Hz, 2H), 4.59–4.58 (m, 1H), 3.87–3.82 (m, 1H),
2.85 (dd, J = 10.0, 17.2 Hz, 1H), 2.70 (dd, J = 10.0, 17.2 Hz, 1H),
2.41–2.35 (m, 2H), 1.00 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3): d (ppm) 209.43, 184.04, 143.17, 141.48, 138.16, 134.14,
133.33, 132.23, 131.89, 128.72, 128.63, 128.56, 127.70, 127.46,
127.20, 127.11, 126.92, 126.48, 50.33, 48.34, 43.70, 36.60, 7.64.
HRMS: exact mass calculated for [M+NH4]+ (C25H26NO2) require
m/z 372.1964, found m/z 372.1954. 70% ee, determined by Chiral
HPLC. [Regis (R, R)-Whelk O1 column, l = 254 nm, n-Hexane:
EtOH = 15 : 1, flow rate = 0.8 mL min-1]: 21.2 min (major),
23.4 min (minor).
(S)-10-(3-Oxocyc◦loheptyl)anthracen-9(10H)-one (6ab). White
solid, Mp: 227–228 C, 91% yield. [a]2D3 -32.88 (c 1.0, CH2Cl2). 1H
NMR (400 MHz, CDCl3): d (ppm) 8.30–8.26 (m, 2H), 7.60–7.58
(m, 2H), 7.52–7.44 (m, 4H), 4.32–4.31 (m, 1H), 2.59–2.56 (m, 1H),
2.45–2.30 (m, 3H), 2.21–2.15 (m, 1H), 1.84–1.75 (m, 2H), 1.68–
1.64 (m, 1H), 1.37–1.32 (m, 1H), 1.14–1.07 (m, 1H), 0.90–0.82 (m,
1H). 13C NMR (100 MHz, CDCl3): d (ppm) 213.94, 185.74, 143.78,
142.41, 134.16, 133.89, 133.37, 133.09, 129.11, 128.99, 128.21,
128.10, 127.98, 127.70, 50.38, 49.12, 46.78, 44.27, 32.96, 29.01,
24.28. HRMS: exact mass calculated for [M+NH4]+ (C21H24NO2)
require m/z 322.1807, found m/z 322.1804. 44% ee, determined
by Chiral HPLC. [Daicel Chiralpak AS-H column, l = 254 nm,
n-Hexane: EtOH = 15 : 1, flow rate = 0.8 mL min-1]: 32.5 min
(major), 36.9 min (minor).
(S)-4,5-Dichloro-9-(3-oxo-1-phe◦nylbutyl)anthracen-10(9H)-one
(4ba). White solid, Mp: 139–140 C, 92% yield. [a]2D4 23.66 (c 1.0,
CH2Cl2). 1H NMR (400 MHz, CDCl3): d (ppm) 7.40–7.38 (m, 2H),
7.35–7.32 (m, 1H), 7.31–7.28 (m, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.10
(s, J = 7.6 Hz, 1H), 7.04 (d, J = 7.6 Hz, 1H), 6.48–6.46(m, 2H), 4.36
(d, J = 5.2 Hz, 1H), 3.63–3.58 (m, 1H), 2.77–2.76 (m, 2H), 2.04
(s, 3H). 13C NMR (100 MHz, CDCl3): d (ppm) 206.27, 181.74,
143.30, 142.31, 138.08, 132.82, 132.67, 132.49, 131.55, 131.27,
131.45, 130.41, 128.23, 127.65, 127.07, 126.93, 50.65, 50.09, 45.21,
30.54. HRMS: exact mass calculated for [M+NH4]+ (C24H18Cl2O2)
require m/z 426.1028, found m/z 426.1010. 90% ee, determined
by Chiral HPLC. [Daicel Chiralpak AS-H column, l = 254 nm,
n-Hexane: EtOH = 8 : 1, flow rate = 0.8 mL min-1]: 12.2 min
(major), 17.1 min (minor).
Acknowledgements
This work was supported by East China University of Science and
Technology, Shanghai Pujiang Program (08PJ1403300), National
Natural Science Foundation of China (20902018) and 111 Project
(B07023).
Notes and references
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Dixon and P. S. Hynes, Chem. Commun., 2005, 4481–4483; (h) B. Li,
L. Jiang, M. Liu, Y. Chen, L. Ding and Y. Wu, Synlett, 2005,603-606;
(i) T. Inokuma, Y. Hoashi and Y. Takemoto, J. Am. Chem. Soc., 2006,
128, 9413–9419; (j) J. Lubkoll and H. Wennemers, Angew. Chem., Int.
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(S)-10-(1-(3-Bromophenyl)-3-oxobutyl)-1,8-dihydroxyanthra-
cen-9(10H)-one (4ci). Yellow solid, 152 ◦C decomposed, 83%
yield. [a]2D3 +5.52 (c 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): d
(ppm) 11.82 (s, 1H), 11.68 (s, 1H), 7.52–7.47 (m, 2H), 7.27–7.26
(m, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.90–6.85 (m, 3H), 6.78 (d, J =
7.2 Hz, 1H), 6.30 (m, 1H), 6.14 (d, J = 7.6 Hz, 1H), 4.46–4.45 (m,
1H), 3.64–3.59 (m, 1H), 2.95 (dd, J = 8.0, 17.6 Hz, 1H), 2.69 (dd,
J = 6.8, 18.0 Hz, 1H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3):
d (ppm) 206.08, 192.57, 162.38, 161.96, 144.84, 142.18, 140.15,
136.10, 135.33, 131.72, 130.29, 128.99, 127.27, 121.67, 119.39,
119.20, 117.12, 116.80, 116.49, 116.29, 51.12, 48.28, 44.74, 30.64.
HRMS: exact mass calculated for [M+NH4]+ (C24H19BrO4) require
m/z 468.0810, found m/z 468.0807. 57% ee, determined by Chiral
HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-Hexane:
EtOH = 8 : 1, flow rate = 0.8 mL min-1]: 10.7 min (major), 13.4 min
(minor).
ˇ
´
(S)-9-(3-Oxocyclohexyl)anthracen-10(9H)-one (6aa). White
solid. Mp: 118–120 ◦C, 85% yield. [a]D23 +4.90 (c 1.0, CH2Cl2). 1H
NMR (400 MHz, CDCl3): d (ppm) 8.27–8.24 (m, 2H), 7.62–7.56
(m, 2H), 7.50–7.44 (m, 3H), 7.38–7.36 (m, 1H), 4.20–4.19 (m,
1H), 2.27–2.20 (m, 3H), 2.02–1.97 (m, 1H), 1.94–1.89 (m, 2H),
1.67–1.64 (m, 1H), 1.48–1.36 (m, 1H), 1.11–1.01 (m, 1H). 13C
NMR (100 MHz, CDCl3): d (ppm) 210.39, 184.97, 142.17,
141.82, 133.38, 133.34, 132.52, 132.49, 128.70, 128.53, 127.51,
127.49, 127.23, 127.07, 48.58, 48.28, 45.08, 40.86, 27.65, 24.75.
HRMS: exact mass calculated for [M+NH4]+(C20H18O2) require
m/z 308.1651, found m/z 308.1644. 78% ee, determined by Chiral
HPLC. [Daicel Chiralpak AS-H column, l = 254 nm, n-Hexane:
EtOH = 15 : 1, flow rate = 0.8 mL min-1]: 33.3 min (major),
36.7 min (minor).
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3250 | Org. Biomol. Chem., 2010, 8, 3244–3250
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