Enantioselective synthesis of enol lactones from tandem Michael addition/lactonization catalyzed by a chiral squaramide catalyst

Article abstract of DOI:10.1016/j.tetasy.2014.01.005

The enantioselective tandem Michael addition reaction of dimedone and related 1,3-dicarbonyl compounds with α,β-unsaturated N-acylated succinimides catalyzed by a chiral squaramide catalyst has been investigated. This reaction provides a new approach for the synthesis of chiral enol lactones in good yields with moderate to high enantioselectivities (up to 88% ee) through the enantioselective Michael addition followed by lactonization and removal of the succinimide auxiliary.

Full text of DOI:10.1016/j.tetasy.2014.01.005

Tetrahedron: Asymmetry 25 (2014) 310–317
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantioselective synthesis of enol lactones from tandem Michael
addition/lactonization catalyzed by a chiral squaramide catalyst
⇑
Bo-Liang Zhao, Da-Ming Du
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 November 2013
Accepted 7 January 2014
The enantioselective tandem Michael addition reaction of dimedone and related 1,3-dicarbonyl com-
pounds with a,b-unsaturated N-acylated succinimides catalyzed by a chiral squaramide catalyst has been
investigated. This reaction provides a new approach for the synthesis of chiral enol lactones in good
yields with moderate to high enantioselectivities (up to 88% ee) through the enantioselective Michael
addition followed by lactonization and removal of the succinimide auxiliary.
Ó 2014 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Enol lactones, such as the derivatives of coumarin, flavonoids,
and neoflavonoids, are present in a number of biologically active
natural products and have strong biological activity.1,2 Many
compounds contain the exocyclic enol lactone substructure3 or
endocyclic enol lactone ring.4 A recent report on a tetrameric
4-hydroxycoumarin-derived inhibitor provided a lead example of
an HIV integrase inhibitor.5 Coumarin derivatives and related enol
lactones were also found to be very efficient non-peptide HIV-1
protease inhibitors.6 In addition, endocyclic enol lactones are also
useful intermediates in the synthesis of more complex natural
products. Endocyclic enol lactones with optical activity have more
potential value with bio-availability such as the alkaloid
(ꢀ)-aspidospermidine.7 However, there are few reports on the
synthesis of enol lactone derivatives.8–14 Reports on the synthesis
of optically active enol lactone compounds are even more rare;
Kanemasa et al. reported on the reaction of dimedone with
1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles catalyzed by cata-
lytic amounts of both DBFOX/Ph-nickel-(II) perchlorate trihydrate
and 2,2,6,6-tetramethylpiperidine to produce the corresponding
enol lactones with high enantioselectivities through enantioselec-
tive Michael addition followed by cyclization with removal of the
pyrazole auxiliary.8 Therefore, to find effective and convenient
methods to access optically active enol lactone compounds is of
great significance and a major challenge in synthetic organic
chemistry. Herein we report one effective synthetic approach to
enol lactone systems via Michael addition reaction of dimedone
We first evaluated the reaction between 5,5-dimethylcyclohex-
ane-1,3-dione (dimendone) 1 and 1-cinnamoylpyrrolidine-2,5-dione
2a. When 5 mol % of squaramide I15 derived from hydroquinine was
used, product 3a was obtained in 96% yield and with 66% ee in CH2Cl2
at room temperature for 48 h. For the sake of comparison, N-cinnam-
oyl pyrazole and N-cinnamoyl oxazolidinone were also examined in
this reaction under the same reaction conditions. However, we found
that N-cinnamoyl pyrazole as the reactant afforded the product 3a in
21% yield and 94% ee. N-Cinnamoyl oxazolidinone as the reactant did
not afford the target product. We found that 2a had better reactivity.
Considering the yield, enantioselectivity, and novelty of the Michael
acceptor, we chose 1-cinnamoylpyrrolidine-2,5-dione 2a as the reac-
tant. Next, we performed an optimization of the model reaction
between 5,5-dimethylcyclohexane-1,3-dione (dimendone) 1 and
1-cinnamoylpyrrolidine-2,5-dione 2a. A series of chiral squaramide
or thiourea catalysts I–VII were investigated in this reaction (Fig. 1).
When squaramide I or II derived from hydroquinine was used, prod-
uct 3awas obtainedwithsimilar yieldand enantioselectivity (Table1,
entries 1 and 2). Cinchonidine derived squaramide III16 gave a slightly
lower enantioselectivity than squaramides I and II. The C2-symmetric
squaramide IV17 was also evaluated, but no improved enantioselec-
tivity was observed (Table 1, entry 4). In contrast, the corresponding
thiourea V or squaramide VI18 derived from (1S,2S)-cyclohexane-1,2-
diamine afforded lower enantioselectivity (Table 1, entries 5 and 6).
The new squaramide VII19 derived from aminoglucopyranose and
hydroquinine was tested, the enantioselectivity was enhanced but
with a slightly lower yield (Table 1, entry 8). After screening different
catalysts, using squaramide I as a catalyst was found to be the best in
terms of enantioselectivity and yield. Therefore, further optimiza-
tions were carried out using squaramide I as the catalyst.
and related 1,3-dicarbonyl compounds with
a,b-unsaturated
N-acylated succinimides, which rarely reported as a Michael recep-
tor, by the catalysis of chiral squaramide organocatalyst.
In order to enhance the enantioselectivity of the desired prod-
uct, further screening of reaction parameters such as the solvent,
⇑
Corresponding author. Tel./fax: +86 10 68914985.
E-mail address: dudm@bit.edu.cn (D.-M. Du).
0957-4166/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2014.01.005

B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
311
O
O
OMe
N
O
O
H
CF3
H
N
N
O
H
O
N
N
NH
HN
H
Ar
N
H
N
H
OMe
N
H
MeO
N
H
F3C
N
N
N
I: Ar = 3,5-(CF3)2C6H3
II: Ar = 4-CF3C6H4
III
IV
CF3
OAc
O
O
O
O
OMe
CF3
O
H
AcO
AcO
N
H
S
HN
NH
N
N
H
N
H
F3C
OAc
N
N
H
N
H
F3C
OMe
N
N
V
VII
VI
Figure 1. Structures of chiral squaramides and thioureas.
Table 1
Table 2
Screening of different chiral catalysts
Optimization of reaction conditions
O
O
O
O
Ph
O
O
O
O
Ph
O
O
5 mol % I
5 mol % catalyst
+
N
Ph
+
N
Ph
solvent
CH2Cl2, rt, 36-48 h
O
O
O
O
O
O
1
2a
3a
3a
1
2a
Entrya
Solvent
CH3CN
Yieldb (%)
eec (%)
Entrya
Catalyst
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
88
94
89
91
91
86
94
92
97
90
42
40
86
86
78
64
66
64
76
85
78
17
1
2
3
4
5
6
7
I
II
96
94
94
91
91
92
86
66
66
59
42
11
17
69
Toluene
Xylene
a,a,a-Trifluorotoluene
CHCl3
ClCH2CH2Cl
THF
Toluene
Toluene
Toluene
Toluene
III
IV
V
VI
VII
8d
9e
10f
11g
a
Reaction conditions: 5,5-dimethylcyclohexane-1,3-dione 1 (0.3 mmol) and 1-
cinnamoylpyrrolidine-2,5-dione 2a (0.2 mmol) in CH2Cl2 (0.5 mL) with 5 mol %
catalyst for 36–48 h at room temperature.
Determined by HPLC on a Daicel Chiralpak AD-H column (n-hexane/2-propa-
nol = 90:10, 1.0 mL/min).
b
a
Reaction conditions: unless noted otherwise, reactions were carried out with
5,5-dimethylcyclohexane-1,3-dione 1 (0.3 mmol) and 1-cinnamoylpyrrolidine-2,5-
dione 2a (0.2 mmol) in 0.5 mL of solvent with 5 mol % catalyst I for 48 h at room
temperature.
c
Determined by HPLC on a Daicel Chiralpak AD-H column.
b
Isolated yields by column chromatography.
Determined by HPLC on Daicel Chiralpak AD-H column (n-hexane/2-propa-
c
catalyst loading, and temperature was investigated. When the
reaction was performed in acetonitrile, product 3a was obtained
in 88% yield but with low enantioselectivity (40% ee). When tolu-
ene was used as the solvent, a significant improvement in the
enantioselectivity was realized (Table 2, entry 2). Other solvents
such as CHCl3, THF, or ClCH2CH2Cl afforded moderate enantioselec-
tivities. After a brief screening of the solvent, toluene was found to
be the best. The enantioselectivity and yield of the product 3a de-
creased slightly when decreasing the catalyst loading to 2.5 mol %.
The yield of product 3a was improved slightly by increasing the
catalyst loading to 10 mol % (Table 2, entry 9). Increasing the reac-
tion temperature to 50 °C led to a decrease in the enantioselectiv-
ity. The enantioselectivity and yield both drastically decline when
lowering the temperature to ꢀ10 °C. Hence we selected 10 mol %
catalyst loading at room temperature for 48 h, with toluene as
the solvent, as the optimum reaction conditions.
nol = 90:10, 1.0 mL/min).
d
The reaction was conducted with 2.5 mol % catalysts loading for 72 h.
The reaction was conducted with 10 mol % catalyst loading.
The reaction was performed at 50 °C for 30 h with 10 mol % catalyst loading.
The reaction was performed at ꢀ10 °C for 144 h with 10 mol % catalyst loading.
e
f
g
explored. The reactions of dimedone 1 (1.5 equiv) with a,b-unsat-
urated N-acylated succinimide 2a–j afforded 7,7-dimethyl-4,6,7,8-
tetrahydro-3H-chromene-2,5-dione 3a–j in high yield (up to 97%)
and with moderate to high enantioselectivities (up to 88% ee) as
shown in Table 3. Electron-withdrawing and electron-rich
substituents in the benzene ring of 2 (Table 3, entries 2–6) gave
satisfactory results. As the alkyl chain increased in length at the
b-substituted position of 2 (Table 3, entries 8–10), the enantiose-
lectivity and yield decreased. The absolute configuration of enol
lactones 3a and 3c–j was assigned according to the literature.8
Other Michael donors, such as cyclohexane-1,3-dione 4,
4-hydroxycoumarin 6, 4-hydroxy-6-methyl-2H-pyran-2-one 8,
and acyclic acetoacetone 10 were also investigated in order to
After optimization of the reaction conditions, the substrate
scope for the enantioselective enol lactone synthesis from
dimedone 1 with 1-(2-alkenoyl)-pyrrolidine-2,5-dione 2a–j was

312
B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
Table 3
However, there was no improvement in the corresponding enanti-
oselectivity. Cyclopentane-1,3-dione and cycloheptane-1,3-dione
were also examined; these reactions produced a lot of by-products.
This phenomenon may be ascribed to the increased ring tension,
which means that the target products were not easy to generate.
The main products were also unstable. The main product of these
corresponding reactions cannot be obtained by column chroma-
tography, which may be due to the enol lactone ring being too easy
to open under the catalysis of silica gel. The experimental results
indicated that the two methyl groups of 5,5-dimethylcyclohex-
ane-1,3-dione play a very important role in the enantioselective
process of the reaction. As a comparison, cyclohexane-1,3-dione
4, which lacks the two methyl groups gave lower enantioselectiv-
ities (Table 4, entries 1 and 2). The reactions of 6, 8, and 10 with
Chiral squaramide-catalyzed enantioselective synthesis of a variety of enol lactones
R
O
O
O
O
10 mol % I
+
N
R
toluene, rt
O
O
O
O
3a-j
1
2a-j
Entry
R
Time (h)
Product
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
9
10
Ph
48
48
60
3a
3b
3c
3d
3e
3f
3g
3h
3i
97
88
93
95
78
83
73
96
71
63
85
54
88
85
70
80
88
77
69
72
2-ClC6H4
4-BrC6H4
4-MeOC6H4
4-O2NC6H4
4-MeC6H4
2-Furyl
Me
60
48
72
48
24
96
120
a,b-unsaturated N-acylated succinimide 2 gave the corresponding
products 7, 9, and 11 in low to moderate enantioselectivities
(Table 4, entries 3–7).
Et
n-Pr
3j
The tentative proposed reaction mechanism to explain the
enantioselective generation of the final product 3a is shown in
Figure 2. Squaramide I activates the 1-cinnamoylpyrrolidine-2,5-
dione 2a through a double hydrogen bonding interaction, while
the dimendone 1 is activated by the tertiary nitrogen of the quinu-
clidine. The enolate anion attacks the 1-cinnamoylpyrrolidine-2,5-
dione from the Si-face via transition state A to form the Michael
adduct intermediate B. Subsequent intramolecular protonation
and tautomerization of B gave enolate transition state C. The final
step involved the cyclization of C with the removal of succinimide
auxiliary to give enol lactone 3a.
a
Isolated yields by column chromatography.
Determined by HPLC using a chiral column.
b
explore the generality of this reaction. The Michael reactions of
these donors to acceptors 2 can also be performed successfully,
affording the corresponding enol lactones 5, 7, 9, and 11, respec-
tively (Table 4), although the enantioselectivities were not very
good in most reactions. As a result, we changed the reaction condi-
tions, such as the temperature, solvents and using other catalysts.
Table 4
Enantioselective synthesis of other enol lactones
10 mol % I
toluene
2
donor 4, 6, 8 or 10
+
enol lactone 5, 7, 9 or 11
Entry
1c
Donor
Reactant 2
Product
Time (h)
48
Yielda (%)
eeb (%)
O
Ph
O
O
O
2a
96
72
O
O
O
5a
5b
4
O
Me
2c
2h
2a
48
48
87
77
60
23
O
O
O
O
4
OH
Ph
O
O
3d
O
O
O
O
6
6
7a
7b
OH
Me
O
4d
2h
24
90
50
O
O
O

B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
313
Table 4 (continued)
Entry
Donor
Reactant 2
Product
Time (h)
Yielda (%)
eeb (%)
OH
O
R
O
O
5d
2f
48
76
19
Me
O
O
O
O
Me
Me
9a
R = 4-MeC6H4
8
OH
Me
O
O
6d
2h
2a
24
48
92
48
46
29
Me
O
O
O
O
O
9b
8
O
Ph
O
7d
10
O
11a
a
Isolated yields by column chromatography.
Determined by HPLC using a chiral column.
b
c
Reactions were carried out with cyclohexane-1,3-dione 4 (0.3 mmol) and 2 (0.2 mmol) in toluene (0.5 mL) with catalyst I at room temperature.
Reactions were carried out with 6, 8 or 10 (0.3 mmol), and 2 (0.2 mmol) in toluene (0.5 mL) with catalyst I at 50 °C.
d
N
CF3
O
O
OMe
H
F3C
N
H
N
H
N
N
Ph
O
O
2a
O
O
O
H
H
3a
O
OH
1
I
N
N
H
H
O
H
O
O
H
H
O
H
O
O
N
O
Ph
N
O
Ph
O
N
A
O
H
O
C
H
H
Si-face attack
O
O
H
N
O
O
Ph
B
Figure 2. Proposed reaction mechanism.
the catalysis of a chiral squaramide catalyst, and the corre-
sponding products were obtained in high yield (up to 97%)
and with moderate to good enantioselectivity (up to 88% ee).
This reaction provides a very simple and valuable method to
synthesize enol lactones using 1,3-dicarbonyl compounds as
the raw materials.
3. Conclusion
In conclusion, we have developed a convenient synthesis for
a variety of chiral enol lactones through the enantioselective
tandem Michael addition/lactonization reaction of various nucle-
ophile precursors to
a,b-unsaturated N-acylated succinimides by

314
B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
1.57–1.36 (m, 7H), 0.81 (t, J = 7.2 Hz, 1H), 0.66 (br s, 1H) ppm;
4. Experimental
4.1. General
13C NMR (100 MHz, DMSO-d6): d 184.6, 179.7, 168.4, 163.1,
157.8, 147.7, 144.3, 143.0, 142.3, 131.5, 127.4, 126.50, 126.46,
1
2
124.3 (q, JC–F = ꢀ270.2 Hz), 122.5 (q, JC–F = 32.0 Hz), 121.8,
118.0, 101.3, 57.1, 55.6, 40.2, 36.6, 27.8, 26.8, 25.7, 24.9,
Unless otherwise noted, commercially available compounds
were used without further purification. Column chromatography
was carried out with silica gel (200–300 mesh). Melting points
were measured with a melting point apparatus without correction.
1H NMR spectra were recorded with a Varian Mercury-plus
400 MHz spectrometer. Chemical shifts were reported in ppm with
the internal TMS signal at 0.0 ppm as a standard. The data are re-
ported as follows: chemical shift (ppm), and multiplicity (s = sin-
glet, d = doublet, t = triplet, q = quartet, m = multiplet or
unresolved, br s = broad singlet), coupling constant(s) in Hz, inte-
gration assignment. 13C NMR spectra were recorded at 100 MHz.
Infrared spectra were obtained with a Perkin Elmer Spectrum
One spectrometer. The high resolution MS spectra were obtained
with ESI ionization using a Bruker APEX IV FTMS spectrometer.
Optical rotations were measured with a WZZ-3 polarimeter at
the indicated concentration with units g/100 mL. The enantiomeric
excesses were determined by chiral HPLC using an Agilent 1200 LC
instrument with a Daicel Chiralpak column AD-H or IB.
11.8 ppm; IR (KBr):
m 3226, 3184, 3002, 2962, 2940, 2869, 1800,
1675, 1655, 1621, 1606, 1575, 1542, 1513, 1475, 1460, 1443,
1420, 1377, 1329, 1322, 1269, 1241, 1192, 1172, 1162, 1119,
1070, 1042, 1016, 840, 826, 767, 728, 715, 681, 637 cmꢀ1; HRMS
(ESI): m/z calcd for
565.24180.
C
31H32F3N4O3 [M+H]+ 565.24210, found
4.2.2. General procedure for the preparation of
N-acylated succinimide
a,b-unsaturated
Under argon,
a mixture of pyrrolidine-2,5-dione (2.97 g,
30 mmol) and pyridine (2.54 mL, 31.5 mmol) in anhydrous dichlo-
romethane (50 mL) was added dropwise to crotonoyl chloride
(2.55 mL, 31.5 mmol) in dichloromethane (100 mL) at 0 °C for
more than half an hour, after which the mixture was stirred for
3 h at 0 °C. Next, the reaction mixture was allowed to warm to
room temperature for 48 h. The reaction mixture was then poured
into saturated sodium hydrogen carbonate and extracted with
dichloromethane. The combined organic layers were washed with
30 mL of hydrochloric acid solution (1 M), brine, dried over magne-
sium sulfate, and concentrated in vacuo. The crude residue was
passed through a flash silica gel column by eluting with dichloro-
methane to provide analytically pure 2f (3.3 g, 66%).
4.2. Materials
Chiral squaramide catalysts I,15 III,16 IV,17 VI,18 and VII19 were
prepared according to the reported procedures. Cyclic diketones,
4-hydroxycoumarin, 4-hydroxy-6-methyl-2H-pyran-2-one, and
pyrrolidine-2,5-dione were purchased from commercial supplies.
The racemic reference compounds were synthesized by the direct
treatment of 1-(2-alkenoyl)-pyrrolidine-2,5-dione 2 with 1, 4, 6,
8, or 10 in the presence of triethylamine.
Other unsaturated imide substrates were prepared according to
a similar procedure from pyrrolidine-2,5-dione and the corre-
sponding (E)-2-alkenoyl chlorides
4.3. General procedure for the enantioselective synthesis of enol
lactones
4.2.1. Synthesis of organocatalysts II
Procedure A: To a dried small bottle were added a,b-unsaturated
N-acylated succinimide 2 (0.2 mmol) and catalyst I (12.6 mg,
0.02 mmol, 10 mol %), followed by the addition of toluene
(0.5 mL). The mixture was stirred at room temperature for
15 min, then 5,5-dimethylcyclohexane-1,3-dione 1 (0.3 mmol) or
cyclohexane-1,3-dione 4 (0.3 mmol) was added in one portion.
After stirring at room temperature for 48–120 h, the reaction mix-
ture was concentrated and purified directly by silica gel column
chromatography to afford the desired product 3 or 5.
O
O
O
O
F3C
F3C
MeOH
48 h, rt
+
NH2
OMe
MeO
OMe
N
H
H
N
H2N
N
OMe
N
OMe
Procedure B: To a dried small bottle were added a,b-unsaturated
O
O
F3C
H
N
N-acylated succinimide 2 (0.2 mmol) and catalyst I (12.6 mg,
0.02 mmol, 10 mol %), followed by the addition of toluene
(0.5 mL). The mixture was stirred at 50 °C for 15 min, then 4-
hydroxycoumarin 6 (0.3 mmol) or 4-hydroxy-6-methyl-2H-pyr-
an-2-one 8 (0.3 mmol) was added in one portion. After stirring at
50 °C for 24–48 h, the reaction mixture was concentrated and puri-
fied directly by silica gel column chromatography to afford the de-
sired products 7 or 9.
N
H
N
CH2Cl2, 48 h, rt
H
II
In a 25 mL round-bottomed flask, 4-(trifluoromethyl)aniline
(0.805 g, 5.0 mmol) was added to dimethyl squarate (0.71 g,
5.0 mmol) which was dissolved in 10 mL of methanol. The mixture
was then stirred at room temperature for 48 h, after which the pre-
cipitate was filtered to afford the mono-squaramide as a white so-
lid (1.06 g, 78% yield). To a solution of hydroquinine derivatives
(325 mg, 1.0 mmol) in CH2Cl2 (10 mL) was added mono-squara-
mide (272 mg, 1 mmol). After stirring for 48 h at room tempera-
ture, squaramide catalyst II was obtained by filtration as a white
solid (480 mg, 85% yield). Mp 203–205 °C (decomp.),
4.3.1. (R)-7,7-Dimethyl-4-phenyl-4,6,7,8-tetrahydro-3H-chro-
mene-2,5-dione 3a8
Compound 3a was obtained according to general procedure A as
a white solid (52.4 mg, 97% yield), mp 110–112 °C. ½a D25
¼ ꢀ98:8 (c
ꢁ
2.14, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 90:10, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 9.0 min, tminor = 16.2 min, 85% ee. 1H NMR (400 MHz,
CDCl3): d 7.30–7.14 (m, 5H, ArH), 4.30 (t, J = 4.0 Hz, 1H, CH), 2.93
(t, J = 2.8 Hz, 2H, CH2), 2.53 (s, 2H, CH2), 2.32 (s, 2H, CH2), 1.15 (s,
3H, CH3), 1.10 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d
196.1, 165.9, 165.7, 140.5, 129.0, 127.4, 126.4, 116.0, 50.5, 40.9,
½
a 2D8
ꢁ
¼ ꢀ72:7 (c 0.30, DMSO). 1H NMR (400 MHz, DMSO-d6): d
10.07 (br s, 1H), 8.88 (d, J = 4.4 Hz, 1H), 8.41 (br s, 1H), 8.03 (d,
J = 9.2 Hz, 1H), 7.83 (br s, 1H), 7.74 (d, J = 4.4 Hz, 1H), 7.68 (d,
J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.48 (dd, J1 = 9.2 Hz,
J2 = 2.4 Hz, 1H), 6.09 (br s, 1H), 4.01 (s, 3H), 3.53–3.35 (m, 4H),
3.21–3.16 (m, 1H), 2.66 (br s, 1H), 2.50 (d, J = 12.8 Hz, 1H),
36.3, 33.7, 32.5, 28.5, 28.1 ppm. Lit.8 ½a D25
¼ ꢀ131:18 (c 0.51, CHCl3)
ꢁ
99% ee.

B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
315
4.3.2. (S)-4-(2-Chlorophenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-
3H-chromene-2,5-dione 3b20
697, 615, 603, 584 cmꢀ1. HRMS (ESI): m/z calcd for C17H18NO5
[M+H]+ 316.11795, found: 316.11870.
Compound 3b was obtained according to general procedure A
as
a
white solid (53.6 mg, 88% yield), mp 115–116 °C.
4.3.6. (R)-7,7-Dimethyl-4-(p-tolyl)-4,6,7,8-tetrahydro-3H-chro-
mene-2,5-dione 3f
½
a 2D5
ꢁ
¼ ꢀ36:5 (c 0.48, CH2Cl2); HPLC (Daicel Chiralpak AD-H col-
umn, n-hexane/2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detec-
tion at 254 nm): tmajor = 4.9 min, tminor = 5.7 min, 54% ee. 1H NMR
(400 MHz, CDCl3): d 7.39 (dd, J1 = 7.6 Hz, J2 = 2.0 Hz, 1H, ArH),
7.20–7.13 (m, 2H, ArH), 6.91 (dd, J1 = 7.0 Hz, J2 = 2.0 Hz, 1H, ArH),
4.74 (t, J = 4.4 Hz, H, CH), 2.94 (s, 1H, CH2), 2.92 (d, J = 1.6 Hz, 1H,
CH2), 2.60 (s, 1H, CH2), 2.59 (d, J = 1.2 Hz, 1H, CH2), 1.98 (s, 2H,
CH2), 1.18 (s, 3H, CH3), 1.17 (s, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 195.5, 166.9, 165.3, 137.0, 133.4, 130.5,
128.9, 127.3, 126.7, 114.7, 50.5, 41.1, 35.2, 32.5, 31.2, 28.5,
28.4 ppm.
Compound 3f was obtained according to the general procedure
A
as a white solid (47.2 mg, 83% yield), mp 134–136 °C.
¼ ꢀ82:1 (c 1.03, CH2Cl2); HPLC (Daicel Chiralpak AD-H col-
½
a 2D5
ꢁ
umn, n-hexane/2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detec-
tion at 254 nm): tmajor = 6.6 min, tminor = 10.6 min, 80% ee. 1H NMR
(400 MHz, CDCl3): d 7.09 (d, J = 8.0 Hz, 2H, ArH), 7.03 (d, J = 8.0 Hz,
2H, ArH), 4.26 (dd, J1 = 5.6 Hz, J2 = 3.2 Hz, 1H, CH), 2.91
(t, J = 3.6 Hz, 2H, CH2), 2.53 (s, 2H, CH2), 2.31 (s, 2H, CH2), 2.29 (s,
3H, CH3), 1.15 (s, 3H, CH3), 1.10 (s, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 196.2, 166.1, 165.5, 137.5, 137.1, 129.7,
126.3, 116.2, 50.6, 41.0, 36.4, 33.4, 32.5, 28.5, 28.1, 21.0 ppm. IR
4.3.3. (R)-4-(4-Bromophenyl)-7,7-dimethyl-4,6,7,8-tetrahydro-
3H-chromene-2,5-dione 3c8
(KBr):
m 3026, 3004, 2960, 2927, 2873, 1786, 1733, 1668, 1655,
1514, 1466, 1414, 1373, 1333, 1314, 1291, 1272, 1270, 1180,
Compound 3c was obtained according to general procedure A as
1161, 1102, 1036, 1017, 969, 859, 822, 737, 600, 549, 520 cmꢀ1
.
a white solid (64.9 mg, 93% yield), mp 173–174 °C. ½a D25
ꢁ
¼ ꢀ27:7
HRMS (ESI): m/z calcd for C18H21O3 [M+H]+ 285.14852, found:
(c 1.43, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/
2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 7.5 min, tminor = 16.5 min. 88% ee. 1H NMR (400 MHz,
CDCl3): d 7.33 (d, J = 8.4 Hz, 2H, ArH), 6.96 (d, J = 8.4 Hz, 2H, ArH),
4.17 (d, J = 6.8 Hz, 1H, CH), 2.90–2.78 (m, 2H, CH2), 2.45 (s, 2H,
CH2), 2.23 (s, 2H, CH2), 1.06 (s, 3H, CH3), 1.01 (s, 3H, CH3) ppm.
13C NMR (100 MHz, CDCl3): d 196.0, 165.9, 165.5, 139.5, 132.1,
128.2, 121.3, 115.5, 50.4, 40.9, 35.9, 33.3, 32.5, 28.5, 28.0 ppm.
285.14860.
4.3.7. (S)-7,7-Dimethyl-4-(furan-2-yl)-4,6,7,8-tetrahydro-3H-
chromene-2,5-dione 3g8
Compound 3g was obtained according to the general procedure
A as a white solid (38.0 mg, 73% yield), mp 78–79 °C. ½a D25
¼ ꢀ24:8
ꢁ
(c 0.99, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 6.3 min, tminor = 9.0 min, 88% ee. 1H NMR (400 MHz, CDCl3):
d 7.28 (d, J = 1.2 Hz, 1H, ArH), 6.24 (dd, J1 = 3.0 Hz, J2 = 2.0 Hz, 1H,
ArH), 6.06 (d, J = 3.2 Hz, 1H, ArH), 4.37 (d, J = 7.2 Hz, 1H, CH),
3.06 (dd, J1 = 16.0 Hz, J2 = 1.6 Hz, 1H, CH2), 2.83 (dd, J1 = 16.0 Hz,
J2 = 7.2 Hz, 1H, CH2), 2.48 (s, 2H, CH2), 2.33 (s, 2H, CH2), 1.14 (s,
3H, CH3), 1.08 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d
195.6, 166.1, 165.4, 152.6, 142.2, 113.9, 110.2, 105.9, 50.4, 40.9,
Lit.8
½
a 2D5
ꢁ
¼ ꢀ130:8 (c 0.51, CHCl3) >99% ee.
4.3.4. (R)-4-(4-Methoxyphenyl)-7,7-dimethyl-4,6,7,8-tetrahy-
dro-3H-chromene-2,5-dione 3d
Compound 3d was obtained according to general procedure A
as
½ ꢁ
a
white solid (57.0 mg, 95% yield), mp 138–139 °C.
¼ ꢀ76:9 (c 2.04, CH2Cl2); HPLC (Daicel Chiralpak AD-H
column, n-hexane/2-propanol = 80:20, flow rate 1.0 mL minꢀ1
a 2D5
,
33.6, 32.4, 28.5, 27.8, 27.7 ppm. Lit.8
89% ee.
½
a 2D5
ꢁ
¼ ꢀ60:7 (c 0.74, CHCl3)
detection at 254 nm): tmajor = 8.6 min, tminor = 15.9 min, 85% ee.
1H NMR (400 MHz, CDCl3): d 7.07 (d, J = 8.4 Hz, 2H, ArH), 6.80
(d, J = 8.0 Hz, 2H, ArH), 4.24 (d, J = 6.0 Hz, 1H, CH), 3.75 (s, 3H,
CH3), 2.90 (d, J = 6.4 Hz, 2H, CH2), 2.52 (s, 2H, CH2), 2.31 (s, 2H,
CH2), 1.14 (s, 3H, CH3), 1.10 (s, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 196.2, 166.2, 165.5, 158.8, 132.6, 127.6,
116.4, 114.4, 109.7, 55.2, 50.6, 41.0, 36.6, 33.0, 32.6, 28.6,
4.3.8. (S)-4,7,7-Trimethyl-4,6,7,8-tetrahydro-3H-chromene-2,5-
dione 3h8
Compound 3h was obtained according to general procedure A as
a white solid (40.0 mg, 96% yield), mp 55–57 °C. ½a D25
¼ ꢀ5:0 (c 2.09,
ꢁ
CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-propa-
28.1 ppm. IR (KBr):
m
3004, 2963, 2931, 2887, 2875, 1772, 1738,
nol = 90:10, flow rate 1.0 mL minꢀ1
, detection at 254 nm):
1671, 1653, 1607, 1582, 1510, 1466, 1422, 1376, 1314, 1306,
1278, 1247, 1239, 1176, 1159, 1114, 1100, 1035, 1009, 964, 860,
840, 818, 809, 764, 750, 661, 627, 603 cmꢀ1. HRMS (ESI): m/z calcd
for C18H21O4 [M+H]+ 301.14344, found: 301.14392.
tmajor = 7.2 min, tminor = 11.2 min, 77% ee. 1H NMR (400 MHz,
CDCl3): d 3.17–3.10 (m, 1H, CH), 2.71–2.60 (m, 2H, CH2), 2.42
(ABq, J = 18.0 Hz, 2H, CH2), 2.31 (s, 2H, CH2), 1.12 (s, 3H, CH3), 1.10
(s, 3H, CH3), 1.07 (d, J = 7.2 Hz, 3H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): d 196.5, 166.7, 164.7, 118.0, 50.6, 40.8, 36.0, 32.5, 28.5,
4.3.5. (R)-7,7-Dimethyl-4-(4-nitrophenyl)-4,6,7,8-tetrahydro-
3H-chromene-2,5-dione 3e
27.9, 23.3, 19.3 ppm. Lit.8 ½a D25
¼ ꢀ8:7 (c 0.41, CHCl3) 98% ee.
ꢁ
Compound 3e was obtained according to general procedure A as
4.3.9. (S)-4-Ethyl-7,7-dimethyl-4,6,7,8-tetrahydro-2H-chromene-
2,5-dione 3i8
a white solid (49.2 mg, 78% yield), mp 139–141 °C. ½a D25
¼ ꢀ92:4
ꢁ
(c 1.50, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/
2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 14.1 min, tminor = 41.7 min, 70% ee. 1H NMR (400 MHz,
CDCl3): d 8.08 (d, J = 8.4 Hz, 2H, ArH), 7.27 (d, J = 8.8 Hz, 2H, ArH),
4.33 (d, J = 7.6 Hz, 1H, CH), 2.97 (dd, J1 = 16.2 Hz, J2 = 8.0 Hz, 1H,
CH2), 2.86 (d, J = 16.0 Hz, 1H, CH2), 2.49 (s, 2H, CH2), 2.26 (s, 2H,
CH2), 1.09 (s, 3H, CH3), 1.02 (s, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 196.0, 166.5, 165.0, 147.9, 147.1, 127.6,
124.3, 114.9, 50.3, 40.9, 35.5, 33.7, 32.5, 28.5, 28.0 ppm. IR (KBr):
Compound 3i was obtained according to general procedure A as
a white solid (31.6 mg, 71% yield), mp 67–69 °C. ½a D25
¼ þ4:6 (c
ꢁ
1.14, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 5.1 min, tminor = 7.6 min, 69% ee. 1H NMR (400 MHz, CDCl3):
d 2.91 (q, J = 6.8 Hz, 1H, CH), 2.69 (d, J = 16.0 Hz, 1H, CH2), 2.53 (dd,
J1= 16.2 Hz, J2 = 7.2 Hz, 1H, CH2), 2.36 (ABq, J = 18.0 Hz, 2H, CH2),
2.24 (ABq, J = 16.4 Hz, 2H, CH2), 1.48–1.38 (m, 1H, CH2), 1.32–
1.22 (m, 1H, CH2), 1.05 (s, 3H, CH3), 1.03 (s, 3H, CH3), 0.820 (t,
J = 7.2 Hz, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 196.6,
167.0, 165.1, 117.0, 50.6, 40.8, 33.2, 32.4, 29.3, 28.6, 27.7, 26.5,
m
3111, 3078, 2961, 2931, 2892, 2873, 1789, 1735, 1655, 1599,
1521, 1494, 1469, 1415, 1372, 1348, 1311, 1277, 1238, 1216,
1181, 1161, 1101, 1038, 1015, 969, 925, 857, 816, 783, 763, 737,
10.8 ppm. Lit.8
½
a 2D5
ꢁ
¼ þ11:2 (c 0.34, CHCl3) 93% ee.

316
B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
4.3.10. (S)-7,7-Dimethyl-4-propyl-4,6,7,8-tetrahydro-3H-chro-
mene-2,5-dione 3j8
2.02, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 10.3 min, tminor = 12.2 min, 50% ee. 1H NMR (400 MHz,
CDCl3): d 7.75 (d, J = 7.2 Hz, 1H, ArH), 7.52 (t, J = 8.4 Hz, 1H, ArH),
7.29–7.21 (m, 2H, ArH), 3.35–3.28 (m, 1H, CH), 2.89 (dd,
J1 = 15.8 Hz, J2 = 7.2 Hz, 1H, CH2), 2.76 (dd, J1 = 15.8 Hz,
J2 = 1.6 Hz, 1H, CH2), 1.22 (d, J = 7.2 Hz, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 164.8, 160.8, 156.3, 152.7, 132.5, 124.5,
122.4, 116.7, 113.5, 108.3, 35.6, 25.6, 19.1 ppm. Lit.8
Compound 3j was obtained according to general procedure A as
colorless oil (29.8 mg, 63% yield). ½a D25
¼ þ1:7 (c 1.83, CH2Cl2); HPLC
ꢁ
(Daicel Chiralpak AD-H column, n-hexane/2-propanol = 80:20, flow
rate 1.0 mL minꢀ1
,
detection at 254 nm): tmajor = 4.6 min,
tminor = 5.8 min, 72% ee. 1H NMR (400 MHz, CDCl3): d 3.05 (q,
J = 6.4 Hz, 1H, CH), 2.75 (dd, J1 = 16.0 Hz, J2 = 1.6 Hz, 1H, CH2), 2.60
(dd, J1 = 16.0 Hz, J2 = 6.8 Hz, 1H, CH2), 2.43 (ABq, J = 17.6 Hz, 2H,
CH2), 2.31 (ABq, J = 16.4 Hz, 2H, CH2), 1.42–1.35 (m, 2H, CH2),
1.29–1.22 (m, 2H, CH2), 1.12 (s, 3H, CH3), 1.10 (s, 3H, CH3), 0.89 (t,
J = 6.8 Hz, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 196.6,
167.0, 165.0, 117.4, 50.5, 40.8, 35.6, 33.5, 32.4, 28.6, 27.7, 19.6,
½
a 2D5
ꢁ
¼ ꢀ55:00 (c 0.32, CHCl3) 93% ee.
4.3.15. (R)-7-Methyl-4-(p-tolyl)-3,4-dihydropyrano[4,3-b]pyran-
2,5-dione 9a
13.9 ppm. Lit.8 ½a D25
ꢁ
¼ þ6:3 (c 0.38, CHCl3) 91% ee.
Compound 9a was obtained according to general procedure B as
a white solid (41.1 mg, 76% yield), mp 117–118 °C. ½a D25
¼ þ9:1 (c
ꢁ
4.3.11. (R)-4-Phenyl-4,6,7,8-tetrahydro-3H-chromene-2,5-dione
5a
1.77, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 10.2 min, tminor = 13.2 min, 19% ee. 1H NMR (400 MHz,
CDCl3): d 7.12–7.07 (m, 4H, ArH), 5.99 (s, 1H, CH), 4.32 (dd,
J1 = 6.8 Hz, J2 = 2.4 Hz, 1H, CH), 3.10–2.99 (m, 2H, CH2), 2.30 (s,
3H, CH3), 2.28 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d
164.8, 163.3, 162.5, 161.5, 137.5, 136.6, 129.8, 126.3, 103.5, 98.8,
Compound 5a was obtained according to general procedure A as
a white solid (46.5 mg, 96% yield), mp 112–113 °C. ½a D25
¼ þ80:8 (c
ꢁ
1.54, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 7.0 min, tminor = 9.6 min, 72% ee. 1H NMR (400 MHz, CDCl3):
d 7.30–7.20 (m, 3H, ArH), 7.15 (d, J = 7.6 Hz, 2H, ArH), 4.31 (d,
J = 2.8 Hz, 1H, CH), 2.93 (ABq, J = 15.2 Hz, 2H, CH2), 2.73–2.59 (m,
2H, CH2), 2.44 (t, J = 6.4 Hz, 2H, CH2), 2.15–2.04 (m, 2H, CH2)
ppm. 13C NMR (100 MHz, CDCl3): d 196.2, 167.3, 165.8, 140.4,
128.9, 127.3, 126.4, 117.1, 36.6, 36.1, 33.6, 27.2, 20.5 ppm. IR
36.0, 34.7, 21.0, 20.1 ppm. IR (KBr):
m 3092, 3023, 2961, 2923,
1796, 1717, 1656, 1597, 1514, 1445, 1410, 1394, 1319, 1273,
1215, 1187, 1133, 1102, 1037, 1022, 992, 956, 872, 817, 779,
740, 607, 557, 541 cmꢀ1. HRMS (ESI): m/z calcd for C16H15O4
[M+H]+ 271.09649, found: 271.09709.
(KBr):
m 3086, 3061, 3029, 2953, 2900, 2875, 1785, 1725, 1651,
1601, 1585, 1494, 1454, 1426, 1417, 1376, 1338, 1301, 1274,
1243, 1214, 1194, 1171, 1140, 1107, 1062, 1031, 1014, 961, 916,
879, 859, 841, 772, 734, 714, 700, 542, 525 cmꢀ1. HRMS (ESI): m/
z calcd for C15H15O3 [M+H]+ 243.10157, found: 243.10210.
4.3.16. (S)-4,7-Dimethyl-3,4-dihydropyrano[4,3-b]pyran-2,5-
dione 9b8
Compound 9b was obtained according to general procedure B as
a white solid (35.7 mg, 92% yield), mp 132–135 °C. ½a D25
¼ þ8:1 (c
ꢁ
0.15, CH2Cl2); HPLC (Daicel Chiralpak AD-H column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tmajor = 8.2 min, tminor = 9.9 min, 46% ee. 1H NMR (400 MHz, CDCl3):
d 5.87 (s, 1H, CH), 3.18–3.14 (m, 1H, CH), 2.77 (dd, J1 = 15.8 Hz,
J2 = 7.2 Hz, 1H, CH), 2.66 (dd, J1 = 16.0 Hz, J2 = 2.0 Hz, 1H, CH),
2.21 (s, 3H, CH3), 1.15 (d, J = 7.2 Hz, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3): d 165.2, 162.6, 160.8, 105.2, 98.8, 35.7, 24.9,
4.3.12. (S)-4-Methyl-4,6,7,8-tetrahydro-3H-chromene-2,5-dione
5b8
Compound 5b was obtained according to general procedure A
as
a
white solid (31.3 mg, 87% yield), mp 135–137 °C.
½
a 2D5
ꢁ
¼ ꢀ7:0 (c 1.36, CH2Cl2); HPLC (Daicel Chiralpak AD-H column,
n-hexane/2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at
254 nm): tmajor = 6.7 min, tminor = 9.1 min, 60% ee. 1H NMR
(400 MHz, CDCl3): d 3.18–3.11 (m, 1H, CH), 2.69 (dd, J1 = 15.8 Hz,
J2 = 6.8 Hz, 1H, CH2), 2.61 (dd, J1 = 15.6 Hz, J2 = 2.0 Hz, 1H, CH2),
2.56 (t, J = 6.4 Hz, 2H, CH2), 2.46–2.43 (m, 2H, CH2), 2.10–2.04 (m,
2H, CH2), 1.06 (d, J = 6.8 Hz, 3H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): d 196.6, 166.5, 166.4, 119.2, 109.7, 36.6, 35.9, 27.1, 23.4,
23.4, 20.6, 19.3 ppm.
20.0, 19.0 ppm. Lit.8
½
a 2D5
ꢁ
¼ þ15:60 (c 0.35, CHCl3) 98% ee.
4.3.17. (R)-5-Acetyl-3,4-dihydro-6-methyl-4-phenylpyran-2-one
11a21
Compound 11a was obtained according to general procedure B
as a white solid (22.1 mg, 48% yield), mp 102–104 °C. ½a D25
¼ ꢀ89:1
ꢁ
(c 0.18, CH2Cl2); HPLC (Daicel Chiralpak IB column, n-hexane/2-
propanol = 80:20, flow rate 1.0 mL minꢀ1, detection at 254 nm):
tminor = 6.5 min, tmajor = 7.4 min, 29% ee. 1H NMR (400 MHz, CDCl3):
d 7.35–7.29 (m, 3H, ArH), 7.15 (d, J = 6.8 Hz, 2H, ArH), 4.15 (d,
J = 7.6 Hz, 1H, CH), 2.97 (dd, J1 = 15.8 Hz, J2 = 7.2 Hz, 1H, CH2),
2.83 (dd, J1 = 15.8 Hz, J2 = 2.4 Hz, 1H, CH2), 2.43 (s, 3H, CH3), 2.12
(s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3): d 197.8, 165.6,
160.2, 139.6, 129.4, 127.9, 126.6, 117.2, 38.8, 37.1, 29.7,
4.3.13. (R)-4-Phenyl-3,4-dihydropyrano[3,2-c]chromene-2,5-
dione 7a8
Compound 7a was obtained according to the general procedure
B
½
as a white solid (45.0 mg, 77% yield), mp 143–145 °C.
¼ ꢀ23:5 (c 2.15, CH2Cl2); HPLC (Daicel Chiralpak AD-H col-
a 2D5
ꢁ
umn, n-hexane/2-propanol = 80:20, flow rate 1.0 mL minꢀ1, detec-
tion at 254 nm): tmajor = 12.7 min, tminor = 17.7 min, 23% ee. 1H
NMR (400 MHz, CDCl3): d 7.90 (d, J = 8.0 Hz, 1H, ArH), 7.61 (t,
J = 7.6 Hz, 1H, ArH), 7.39–7.24 (m, 7H, ArH), 4.53 (d, J = 7.2 Hz,
1H, CH), 3.21 (dd, J1 = 16.2 Hz, J2 = 7.6 Hz, 1H, CH2), 3.13 (d,
J = 16.0 Hz, 1H, CH2) ppm. 13C NMR (100 MHz, CDCl3): d 164.2,
160.7, 157.2, 153.0, 139.3, 132.9, 129.2, 127.9, 126.5, 124.6,
19.0 ppm. Lit.21
½
a 2D0
ꢁ
¼ ꢀ116:1 (c 1.0, CHCl3) 92% ee.
Acknowledgments
We are grateful for financial support from the National Natural
Science Foundation of China (Grant No. 21272024).
122.7, 116.8, 113.4, 106.2, 35.9, 35.8 ppm. Lit.8
0.33, CHCl3) 91% ee.
½
a 2D5
ꢁ
¼ ꢀ164:86 (c
References
4.3.14. (S)-4-Methyl-3,4-dihydropyrano[3,2-c]chromene-2,5-
dione 7b8
1. Seo, E. K.; Wani, M. C.; Wall, M. E.; Navarro, H.; Mukherjee, R.; Farnsworth, N.
R.; Kinghorn, A. D. Phytochemistry 2000, 55, 35–42.
2. Mazumder, A.; Wang, S.; Neamati, N.; Nicklaus, M.; Sunder, S.; Chen, J.; Milne, G.
W. A.; Rice, W. G.; Burke, T. R., Jr.; Pommier, Y. J. Med. Chem. 1996, 39, 2472–2481.
Compound 7b was obtained according to general procedure B as
a white solid (41.4 mg, 90% yield), mp 124–126 °C. ½a D25
¼ ꢀ19:2 (c
ꢁ

B.-L. Zhao, D.-M. Du / Tetrahedron: Asymmetry 25 (2014) 310–317
317
3. Mason, C. P.; Edwards, K. R.; Carlson, R. E.; Pignatello, J.; Gleason, F. K.; Wood, J.
M. Science 1982, 215, 400–402.
4. Tori, M.; Shiotani, Y.; Tanaka, M.; Nakashima, K.; Sono, M. Tetrahedron Lett.
2000, 41, 1797–1799.
13. Shen, H. C.; Wang, J.; Cole, K. P.; McLaughlin, M. J.; Morgan, C. D.; Douglas, C. J.;
Hsung, R. P.; Coverdale, H. A.; Gerasyuto, A. I.; Hahn, J. M.; Liu, J.; Sklenicka, H.
M.; Wei, L.-L.; Zehnder, L. R.; Zificsak, C. A. J. Org. Chem. 2003, 68, 1729–1735.
14. Zehnder, L. R.; Dahl, J. W.; Hsung, R. P. Tetrahedron Lett. 2000, 41, 1901–1905.
15. Bae, H. Y.; Some, S.; Lee, J. H.; Kim, J.-Y.; Song, M. J.; Lee, S.; Zhang, Y. J.; Song, C.
E. Adv. Synth. Catal. 2011, 353, 3196–3202.
16. Yang, W.; Du, D. M. Org. Lett. 2010, 12, 5450–5453.
17. Lee, J. W.; Ryu, T. H.; Oh, J. S.; Bae, H. Y.; Jang, H. B.; Song, C. E. Chem. Commun.
2009, 7224–7226.
18. Yang, W.; Du, D. M. Adv. Synth. Catal. 2011, 353, 1241–1246.
19. Zhao, B. L.; Du, D. M. Org. Biomol. Chem. 2014. http://dx.doi.org/10.1039/
C3OB42137F.
20. Jin, T. S.; Wang, A. Q.; Cheng, Z. L.; Zhang, J. S.; Li, T. S. J. Chem. Res. 2004, 7, 457–
459.
5. Zhao, H.; Neamati, N.; Hong, H.; Mazumder, A.; Wang, S.; Sunder, S.; Milne, G.
W. A.; Pommer, Y.; Burke, T. R., Jr. J. Med. Chem. 1997, 40, 242–249.
6. Wang, S.; Milne, G. W. A.; Yan, X.; Posey, I. J.; Nicklaus, M. C.; Graham, L.; Rice,
W. G. J. Med. Chem. 1996, 39, 2047–2054.
7. Schultz, A. G.; Pettus, L. J. Org. Chem. 1997, 62, 6855–6861.
8. Itoh, K.; Hasegawa, M.; Tanaka, J.; Kanemasa, S. Org. Lett. 2005, 7, 979–981.
9. Lee, Y. J.; Tseng, T. H.; Lee, Y. J. Synthesis 2001, 2247–2254.
10. Speranza, G.; Morelli, C. F.; Manitto, P. Synthesis 2000, 123–126.
11. de la Hoz, A.; Moreno, A.; Vázquez, E. Synlett 1999, 608–610.
12. Speranza, G.; Di Meo, A.; Zanzola, S.; Fontana, G.; Manitto, P. Synthesis 1997,
931–936.
21. Wang, G.; Chen, X.; Yao, W. J.; Ma, C. J. Org. Chem. 2013, 78, 6223–6232.