Cis -2,3-disubstituted cyclopropane 1,1-diesters in [3 + 2] annulations with aldehydes: Highly diastereoselective construction of densely substituted tetrahydrofurans

Article abstract of DOI:10.1021/jo400554a

A series of cis-2,3-disubstituted cyclopropane 1,1-diesters were examined in the AlCl₃-promoted [3 + 2]-annulations with aldehydes. In this reaction, these cis-cyclopropanes displayed reactivities starkly different from their trans counterparts in terms of the high chemical yields (up to 98%) and provided the desired annulation products with excellent diastereomeric purity. This protocol provides a facile and highly stereoselective way to construct synthetically useful pentasubstituted tetrahydrofurans not easily accessible using other methods.

Full text of DOI:10.1021/jo400554a

Article
pubs.acs.org/joc
cis-2,3-Disubstituted Cyclopropane 1,1-Diesters in [3 + 2]
Annulations with Aldehydes: Highly Diastereoselective Construction
of Densely Substituted Tetrahydrofurans
Gaosheng Yang,* Yongxian Sun, Yue Shen, Zhuo Chai,* Shuangliu Zhou, Jiang Chu, and Jun Chai
Key Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Key Laboratory of Molecule-Based Materials,
Institute of Organic Chemistry, College of Chemistry and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, China
S
* Supporting Information
ABSTRACT: A series of cis-2,3-disubstituted cyclopropane
1,1-diesters were examined in the AlCl3-promoted [3 + 2]-
annulations with aldehydes. In this reaction, these cis-
cyclopropanes displayed reactivities starkly different from
their trans counterparts in terms of the high chemical yields
(up to 98%) and provided the desired annulation products
with excellent diastereomeric purity. This protocol provides a
facile and highly stereoselective way to construct synthetically useful pentasubstituted tetrahydrofurans not easily accessible using
other methods.
investigation on the reactivity of cis-1a in the annulation with
aldehydes.
INTRODUCTION
■
Known as donor−acceptor (D−A) cyclopropanes, cyclo-
propane 1,1-diesters have been extensively utilized as three-
carbon synthons in a number of annulations, providing various
heterocyclic compounds.1−3 In particular, the elegant work
from Johnson’s group on the annulations of these cyclo-
propanes with aldehydes demonstrated the simplicity and high
efficiency of this type of chemistry in the stereoselective
construction of valuable densely substituted tetrahydrofuran-
s.2a−g In addition to aldehydes, many other substrates such as
ketones, imines, and nitrones have also been successfully used
as reaction partner to provide various useful heterocyclic
compounds.3
Despite extensive studies on the use of diverse reaction
partners, the variation on the structures of cyclopropane 1,1-
diesters themselves has been less studied as compared to
aldehydes. Inspired by Johnson’s works, our group has
examined the reactivity of 2,3-disubstituted cyclopropane 1,1-
diesters trans-1a in this type of reaction (Scheme 1).4
Compared to the commonly used 2-substituted cyclopropane
1,1-diesters, we found that trans-1a displayed a unique product-
forming dependence on the substrate aldehydes and reaction
temperature. In addition, the use of this type of cyclopropanes
allowed for the stereoselective synthesis of otherwise difficult to
obtain pentasubstituted tetrahydrofurans. Intrigued by these
results, we became interested in the utilization of cis-1a5 in this
type of annulations. We assumed that the cis-1a was less stable
thermodynamically and might be more reactive in the
annulation process to give higher yields than the trans-1a.
Furthermore, it would be more interesting to compare the
stereochemical results obtained with the cis-1a and trans-1a,
which might be instrumental in the understanding of the
mechanism of the annulation process. Herein, we described our
RESULTS AND DISCUSSION
■
Our study commenced with the model reaction between cis-1a
and benzaldehyde 2a (Table 1). To our surprise, under the
promotion of AlCl3, the best conditions are identical for trans-
1a in the otherwise same transformation (Table 1, entry 1).4
Notably, the stereochemical results obtained with cis-1a were
compelling: only one stereoisomer of the desired annulation
product 5aa was obtained. This is in sharp contrast to the
results with trans-1a, in which three stereoisomers were usually
present and the major products were 3 or 4 (Scheme 1). In
addition, besides the known open-chained byproduct 6a, a new
byproduct 7a was also identified in this reaction. Reducing the
amount of the aldehyde 2a, varying the loading amount of
AlCl3 or raising the reaction temperature all led to inferior
results (Table 1, entries 2−8). Moreover, several other Lewis
acids were also tested for their efficiency as promoter in this
reaction and similar results were generally obtained compared
to those obtained with trans-1a (Table 1, entries 9−13): while
the use of Sn(OTf)2 and Cu(OTf)2 could lead to better
product ratios with significantly decreased yields, the use of
Mg(OTf)2 or Yb(OTf)3 led to no reaction. To summarize, the
optimal reaction conditions were selected as 5 equiv of
aldehydes, 50 mol % of AlCl3 in CH2Cl2 at 0 °C.
Subsequently, the scope of this reaction with regard to
different aldehydes was examined with cis-1a under the optimal
reaction conditions (Table 2). For most substituted benzalde-
hydes, the desired products 5 were obtained in good to
Received: March 16, 2013
Published: May 1, 2013
© 2013 American Chemical Society
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Scheme 1. Diastereoselective Annulations of 2,3-Disubstituted Cyclopropane 1,1-Diesters with Aromatic Aldehydes Promoted
by AlCl3
a
Table 1. Optimization of Reaction Conditions for the Annulation of cis-1a and Benzaldehyde
b
c
entry
2a (equiv)
Lewis acid (equiv)
temp (°C)
time (h)
product/yield (%)
product ratio 5aa:6a:7a
1
2
3
4
5
5.0
5.0
3.0
5.0
1.2
AlCl3/0.5
AlCl3/0.3
AlCl3/0.5
AlCl3/1.0
AlCl3/1.0
0
0
0
0
0
19
40
42
6
5aa/91
5aa/87
5aa/75
5aa/84
5aa/67
7a/20
94:4:2
99:0:1
99:0:1
95:0:5
76:0:24
7
6
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
AlCl3/0.5
0
30
30
30
30
30
30
30
6
2
5aa/72
5aa/77
5aa/88
5aa/40
5aa/7
92:8:0
90:5:5
7
AlCl3/0.5
8
AlCl3/0.5
15
27
27
27
27
27
90:5:5
9
Sn(OTf)2/0.5
Cu(OTf)2/0.5
Mg(OTf)2/0.5
Al(OTf)3/0.5
Yb(OTf)3/0.5
100:0:0
100:0:0
10
11
12
13
NR
5aa/19
100:0:0
NR
a
b
c
1
The reaction was conducted with 0.3 mmol of cis-1a. Isolated yield of the pure product. Determined by H NMR analysis.
excellent yields as a single diastereomer, regardless of the
electron nature or positions of the substituents on the benzene
ring. Notably, in most cases, the chemical yields of this type of
annulation products were significantly higher than those of the
reactions of trans-1a.4 Aldehydes 2c and 2e bearing strongly
electron-withdrawing substituents were not suitable for the
reaction, giving the open-chained chlorinated byproduct 6a as
the major product (Table 2, entries 3 and 5). Similar to
previous observations, aldehydes having strongly electron-
donating substituents required a higher reaction temperature
(Table 2, entries 8−11 and 14), probably due to the
competitive coordination of AlCl3 between these aldehydes
and the D−A cyclopropanes.4 In addition, the α,β-unsaturated
cinnamaldehyde 2o participated in the reaction as well,
providing the desired product in excellent yield (Table 2,
entry 15). Moreover, alkyl aldehyde 2p also underwent the
reaction smoothly, albeit with a longer reaction time and a
moderate yield (Table 2, entry 16). The relative configurations
of product 5 were determined by NOESY analysis and the
structure of 5ac was further confirmed by X-ray crystallographic
analysis.6
The scope of this annulation was further examined by varying
the substituents on the Ar1 group in the cyclopropanes cis-1
(Table 3). The use of these cis cyclopropanes demonstrated a
great advantage over their trans counterparts in terms of the
chemical yields of the desired annulation products. Except for
an extreme case, where both Ar1 (cis-1c) and Ar2 (aldehyde 2b)
are electron-deficient (Table 3, entry 6), the desired
pentasubstituted tetrahydrofurans 5 were obtained in good to
excellent yields as single diastereomers. It is worth mentioning
that while reactions of cis-1e proceeded well to deliver the
desired annulation products (Table 3, entries 13−16), the
reactions of trans-1e have been found to give a γ-lactone
byproduct, which was formed by an intramolecular attack of
one of the oxygen atom in the ester group.7
The stereochemical outcome of this reaction could be
explained by a mechanistic model similar to that originally
proposed by Johnson and co-workers2d (Scheme 2). The
catalyst AlCl3 activated cyclopropane 1a via coordination with
the diester groups to form an intermediate (I). The ensuing
nucleophilic attack of the aldehydes 2 would form a zwitterion
(II). After a bond rotation, an intramolecular nucleophilic
attack of the carbanion would close the ring to form the desired
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a
Table 2. Aldehyde Scope in AlCl3-Promoted Annulation of cis-1a.
b
entry
R
temp (°C)
time (h)
product/yield (%)
1
2
3
C6H5 (2a)
0
0
0
19
20
20
5aa/91
5ab/87
5ac/25
6a/51
4-ClC6H4 (2b)
2,4-Cl2C6H3 (2c)
4
4-BrC6H4 (2d)
0
0
22
38
18
21
19
21
20
20
22
23
18
28
42
5ad/81
6a/71
5
4-NO2C6H4 (2e)
6
4-MeC6H4 (2f)
0
5af/91
5ag/93
5ah/91
5ai/90
5aj/91
5ak/85
5al/89
5am/77
5an/89
5ao/94
5ap/63
7
4-MeOC6H4 (2g)
30
30
30
30
30
0
8
3,4-(MeO)2C6H3 (2h)
4-BnOC6H4 (2i)
9
10
11
12
13
14
15
16
3-MeO-4-BnOC6H3 (2j)
3-MeO-4-AcOC6H3 (2k)
4-TsOC6H4 (2l)
3-MeO-4-TsOC6H3 (2m)
3,4,5-(MeO)3C6H2 (2n)
(E)-PhCHCH (2o)
CH3CH2CH2 (2p)
0
30
0
0
a
b
The reaction was conducted with 0.3 mmol of cis-1a. Isolated yield.
a
Table 3. Cyclopropane Scope in the AlCl3-Promoted Annulations
b
entry
Ar1
Ar2
C6H5 (2a)
temp (°C)
time (h)
product/yield (%)
1
4-ClC6H4 (cis-1b)
0
0
18
19
40
18
96
110
93
110
16
70
38
14
46
40
47
40
5ba/96
5bb/91
5bg/98
5bh/85
5ca/81
5cb/27
5cg/82
5ch/82
5da/87
5db/82
5dg/81
5dh/90
5ea/86
5eb/87
5eg/83
2
4-ClC6H4 (cis-1b)
4-ClC6H4 (2b)
3
4-ClC6H4 (cis-1b)
4-MeOC6H4 (2g)
3,4-(MeO)2C6H3 (2h)
C6H5 (2a)
30
30
0
4
4-ClC6H4 (cis-1b)
5
4-NO2C6H4 (cis-1c)
4-NO2C6H4 (cis-1c)
4-NO2C6H4 (cis-1c)
4-NO2C6H4 (cis-1c)
4-MeOC6H4 (cis-1d)
4-MeOC6H4 (cis-1d)
4-MeOC6H4 (cis-1d)
4-MeOC6H4 (cis-1d)
3,4-(MeO)2C6H3 (cis-1e)
3,4-(MeO)2C6H3 (cis-1e)
3,4-(MeO)2C6H3 (cis-1e)
3,4-(MeO)2C6H3 (cis-1e)
6
4-ClC6H4 (2b)
0
7
4-MeOC6H4 (2g)
3,4-(MeO)2C6H3 (2h)
C6H5 (2a)
30
30
0
8
9
10
11
12
13
14
15
16
4-ClC6H4 (2b)
0
4-MeOC6H4 (2g)
3,4-(MeO)2C6H3 (2h)
C6H5 (2a)
30
30
0
4-ClC6H4 (2b)
0
4-MeOC6H4 (2g)
3,4-(MeO)2C6H3 (2h)
30
30
5eh/91
a
b
The reaction was conducted with 0.3 mmol of cis-1; the relative configuration of 5 was determined by NOESY analysis. Isolated yield.
product 5. On the other hand, the intermediate (I) may also
receive the nucleophilic attack by chloride ion to give the
byproduct 6a, or undergo proton transfer processes to give the
other byproduct 7a, which might also be derived from the
decholorination of 6a.
counterparts previously studied, the use of these cis cyclo-
propanes in the annulation led to drastically different results:
the desired polysubstituted tetrahydrofuran products were
obtained in higher yields, and more importantly, as single
diastereomers different from those obtained with the
corresponding trans cyclopropanes. Such results highlighted
the significant impact of the substitution type of the D−A
cyclopropanes on the efficiency and stereoselectivity of the [3 +
2]-annulation.
CONCLUSION
■
In conclusion, we have applied cis-2,3-disubstituted cyclo-
propane 1,1-diesters to the [3 + 2]-annulations with aldehydes
under the promotion of AlCl3. Compared to their trans
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Scheme 2. Possible Mechanism for the [3 + 2] Annulation
1
1678, 1597, 1580, 1491, 1448, 1090, 1070, 1016, 856, 760, 698. H
EXPERIMENTAL SECTION
■
NMR (CDCl3, 300 MHz): δ 7.85−7.76 (m, 2H), 7.64−7.46 (m, 5H),
7.42−7.28 (m, 7H), 5.96 (s, 1H), 5.29 (d, J = 8.7 Hz, 1H), 5.22 (d, J =
8.8 Hz, 1H), 4.10−3.97 (m, 1H), 3.93−3.76 (m, 2H), 3.50−3.36 (m,
1H), 0.85−0.72 (m, 6H). 13C NMR (CDCl3, 75 MHz): δ 199.3, 168.7,
167.9, 138.5, 137.4, 135.4, 134.1, 133.6, 128.7, 128.6, 128.1, 126.7,
85.3, 84.7, 70.6, 62.1, 61.6, 59.5, 13.3, 13.2. HRMS (ESI-TOF): calcd
for C29H28O6Cl ([M + H]+) 507.1574, found 507.1569.
General Information. All the annulations of cyclopropane-1,1-
diesters with aromatic aldehydes were carried out with flame-dried
Schlenk-type glassware using a Schlenk line. All of the cis-2,3-
disubstituted cyclopropane 1,1-diesters used were synthesized
according to a reference.5 Aluminum trichloride was purified by
sublimation of the commercial product under vacuum (residual gas
N2) at 170 °C.8 All other reagents were purchased from commercial
suppliers and purified by standard techniques. Flash column
chromatography was performed using silica gel (200−400 mesh).
For thin-layer chromatography (TLC), silica gel plates (HSGF 254)
were used and compounds were visualized by irradiation with UV
Diethyl r-4-Benzoyl-t-2-(2,4-dichlorophenyl)-t-5-phenylte-
trahydrofuran-3,3-dicarboxylate (5ac). Purified by column
chromatography (petroleum ether/ethyl acetate = 20/1) to afford a
white solid in 25% yield (41 mg). Mp: 128−129 °C. IR (KBr, cm−1): ν
1757, 1726, 1670, 1595, 1580, 1474, 1448, 1098, 1072, 1040, 891, 864,
light. H NMR (300 MHz) and 13C NMR (75 MHz) spectra were
1
1
843, 766, 698. H NMR (CDCl3, 300 MHz): δ 7.99−7.93 (m, 2H),
recorded at 300 MHz NMR spectrometer in CDCl3. All chemical
shifts (δ) are given in ppm relative to TMS (δ = 0 ppm) as internal
standard. Data are reported as follows: chemical shift, multiplicity,
coupling constants and integration. Melting points were uncorrected.
IR spectra were reported in frequency of absorption (cm−1). High-
resolution mass spectral (HRMS) data were obtained with an
ionization mode of ESI and a TOF analyzer.
General Procedure for the Annulation Reaction. To a solution
of cis-2,3-disubstituted cyclopropane-1,1-diesters (cis-1) (0.3 mmol)
and aldehydes (1.5 mmol) in 10.0 mL of dichloromethane was added
AlCl3 (0.15 mmol) at 0 or 30 °C. The reaction mixture was stirred at 0
or 30 °C and monitored by TLC. Upon completion, the reaction
mixture was passed through a small plug of silica, eluting with 20 mL
7.62 (d, J = 8.5 Hz, 1H), 7.54−7.22 (m, 10H), 6.55 (s, 1H), 5.45 (d, J
= 10.3 Hz, 1H), 5.12 (d, J = 10.3 Hz, 1H), 4.15 (dq, J = 7.1, 3.6 Hz,
1H), 3.91 (dq, J = 7.2, 3.5 Hz, 1H), 3.82 (dq, J = 7.1, 3.5 Hz, 1H), 3.36
(dq, J = 7.2, 3.5 Hz, 1H), 0.93 (t, J = 7.1 Hz, 3H), 0.86 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 75 MHz): δ 197.6, 168.5, 167.3, 137.5, 137.4,
135.0, 134.8, 134.7, 133.6, 130.2, 129.0, 128.8, 128.7, 128.6, 128.5,
126.9, 126.5, 83.8, 81.2, 70.4, 62.0, 59.4, 13.4, 13.3. HRMS (ESI-
TOF): calcd for C29H27O6Cl2 ([M + H]+) 541.1184, found 541.1181.
Diethyl r-4-Benzoyl-t-2-(4-bromophenyl)-t-5-phenyltetrahy-
drofuran-3,3-dicarboxylate (5ad). Purified by column chromatog-
raphy (petroleum ether/ethyl acetate = 10/1) to afford a white solid in
81% yield (134 mg). Mp: 113−114 °C. IR (KBr, cm−1): ν 1753, 1730,
1
1
of CH2Cl2, and the solvent was removed under vacuum. H NMR
1666, 1595, 1489, 1448, 1097, 1068, 1032, 860, 767, 702. H NMR
analyses of the unpurified products gave the diastereomeric ratios. The
crude products were purified by flash chromatography to give the pure
products.
(CDCl3, 300 MHz): δ 7.84−7.77 (m, 2H), 7.57−7.45 (m, 7H), 7.40−
7.27 (m, 5H), 5.94 (s, 1H), 5.28 (d, J = 8.8 Hz, 1H), 5.22 (d, J = 8.8
Hz, 1H), 4.03 (dq, J = 7.2, 3.6 Hz, 1H), 3.92−3.77 (m, 2H), 3.44 (dq,
J = 7.1, 3.5 Hz, 1H), 0.82 (t, J = 7.2 Hz, 3H), 0.77 (t, J = 7.1 Hz, 3H).
13C NMR (CDCl3, 75 MHz): δ 199.3, 168.7, 167.9, 138.5, 137.4,
136.0, 133.6, 131.0, 129.0, 128.7, 128.6, 126.8, 122.3, 85.3, 84.8, 70.6,
62.1, 61.6, 59.5, 13.3, 13.2. HRMS (ESI-TOF): calcd for C29H28O6Br
([M + H]+) 551.1069, found 551.1066.
Diethyl r-4-Benzoyl-t-2,t-5-diphenyltetrahydrofuran-3,3-di-
carboxylate (5aa).4 Purified by column chromatography (petroleum
ether/ethyl acetate = 10/1) to afford a white solid in 91% yield (129
mg). Mp: 106−107 °C. IR (KBr, cm−1): ν 1751, 1720, 1678, 1597,
1
1582, 1495, 1472, 1450, 1082, 1055, 1030, 770, 750, 696. H NMR
(CDCl3, 300 MHz): δ 7.85−7.79 (m, 2H), 7.65−7.60 (m, 2H), 7.54−
7.47 (m, 3H), 7.40−7.24 (m, 8H), 6.01 (s, 1H), 5.31 (d, J = 8.9 Hz,
1H), 5.23 (d, J = 8.9 Hz, 1H), 4.04 (dq, J = 7.2, 3.5 Hz, 1H), 3.86 (dq,
J = 7.2, 3.6 Hz, 1H), 3.79 (dq, J = 7.2, 3.5 Hz, 1H), 3.32 (dq, J = 7.2,
3.5 Hz, 1H), 0.82 (t, J = 7.2 Hz, 3H), 0.70 (t, J = 7.2 Hz, 3H). 13C
NMR (CDCl3, 75 MHz): δ 199.4, 168.9, 168.0, 138.7, 137.5, 136.9,
133.6, 128.7, 128.62, 128.59, 128.5, 128.3, 127.9, 127.3, 126.7, 85.5,
85.1, 70.8, 62.0, 61.5, 59.6, 13.2. HRMS (ESI-TOF): calcd for
C29H29O6 ([M + H]+) 473.1964, found 473.1961.
Diethyl r-4-Benzoyl-t-2-(4-chlorophenyl)-t-5-phenyltetrahy-
drofuran-3,3-dicarboxylate (5ab). Purified by column chromatog-
raphy (petroleum ether/ethyl acetate =10/1) to afford a white solid in
87% yield (133 mg). Mp: 112−113 °C. IR (KBr, cm−1): ν 1755, 1732,
Diethyl r-4-Benzoyl-t-5-phenyl-t-2-(4-tolyl)tetrahydrofuran-
3,3-dicarboxylate (5af). Purified by column chromatography
(petroleum ether/ethyl acetate = 10/1) to afford a white solid in
91% yield (133 mg). Mp: 125−126 °C. IR (KBr, cm−1): ν 1753, 1719,
1
1670, 1595, 1516, 1448, 1061, 766, 702, 687, 654. H NMR (CDCl3,
300 MHz): δ 7.82 (d, J = 7.5 Hz, 2H), 7.59−7.43 (m, 5H), 7.41−7.22
(m, 5H), 7.15 (d, J = 8.1 Hz, 2H), 5.97 (s, 1H), 5.29 (d, J = 9.0 Hz,
1H), 5.20 (d, J = 8.7 Hz, 1H), 4.11−3.95 (m, 1H), 3.93−3.71 (m,
2H), 3.45−3.29 (m, 1H), 2.34 (s, 3H), 0.82 (t, J = 7.2 Hz, 3H), 0.72
(t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.4, 168.9,
168.1, 138.8, 138.0, 137.6, 133.9, 133.5, 128.7, 128.6, 128.5, 128.4,
127.1, 126.7, 85.5, 85.0, 70.7, 61.9, 61.4, 59.6, 21.2, 13.24, 13.17.
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HRMS (ESI-TOF): calcd for C30H31O6 ([M + H]+) 487.2120, found
487.2110.
3.5 Hz, 1H), 2.30 (s, 1H), 0.82 (t, J = 7.2 Hz, 3H), 0.81 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 75 MHz): δ 199.4, 169.0, 168.9, 168.0, 150.7,
139.8, 138.6, 137.5, 135.7, 133.6, 128.70, 128.68, 128.63, 128.58,
126.8, 122.3, 119.5, 111.4, 85.2, 85.1, 70.7, 62.4, 61.5, 59.5, 56.0, 20.7,
13.4, 13.2. HRMS (ESI-TOF): calcd for C32H36O9N ([M + NH4]+)
578.2390, found 578.2382.
Diethyl r-4-Benzoyl-t-2-(4-anisyl)-t-5-phenyltetrahydrofur-
an-3,3-dicarboxylate (5ag). Purified by column chromatography
(petroleum ether/ethyl acetate = 8/1) to afford a white solid in 93%
yield (140 mg). Mp: 105−106 °C. IR (KBr, cm−1): ν 1748, 1720,
1
1672, 1614, 1595, 1580, 1518, 1462, 1450, 1070, 820, 770, 702. H
Diethyl r-4-Benzoyl-t-2-(4-tosyloxyphenyl)-t-5-phenyltetra-
hydrofuran-3,3-dicarboxylate (5al). Purified by column chroma-
tography (petroleum ether/ethyl acetate = 10/1) to afford a white
solid in 81% yield (156 mg). Mp: 128−129 °C. IR (KBr, cm−1): ν
NMR (CDCl3, 300 MHz): δ 7.85−7.78 (m, 2H), 7.58−7.46 (m, 5H),
7.41−7.26 (m, 5H), 6.91−6.85 (m, 2H), 5.96 (s, 1H), 5.28 (d, J = 8.9
Hz, 1H), 5.20 (d, J = 8.9 Hz, 1H), 4.03 (dq, J = 7.1, 3.6 Hz, 1H),
3.94−3.74 (m, 5H), 3.41 (dq, J = 7.2, 3.5 Hz, 1H), 0.82 (t, J = 7.2 Hz,
3H), 0.76 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.4,
169.0, 168.1, 159.7, 138.8, 137.6, 133.5, 129.1, 128.7, 128.60, 128.5,
126.7, 113.3, 85.3, 84.9, 70.6, 61.9, 61.4, 59.6, 13.3, 13.2. HRMS (ESI-
TOF): calcd for C30H30O7Na ([M + Na]+) 525.1889, found 525.1884.
Diethyl r-4-Benzoyl-t-2-(3,4-dimethoxyphenyl)-t-5-phenyl-
tetrahydrofuran-3,3-dicarboxylate (5ah). Purified by column
chromatography (petroleum ether/ethyl acetate = 5/1) to afford a
white solid in 91% yield (146 mg). Mp: 150−151 °C. IR (KBr, cm−1):
ν 1755, 1720, 1676, 1595, 1516, 1452, 1092, 1045, 1028, 862, 806,
1
1730, 1682, 1595, 1500, 1446, 1090, 1070, 1016, 837, 762, 700. H
NMR (CDCl3, 300 MHz): δ 7.83−7.75 (m, 2H), 7.74−7.67 (m, 2H),
7.61−7.44 (m, 5H), 7.41−7.27 (m, 7H), 7.02−6.94 (m, 2H), 5.94 (s,
1H), 5.26 (d, J = 8.8 Hz, 1H), 5.19 (d, J = 8.8 Hz, 1H), 4.02 (dq, J =
7.2, 3.5 Hz, 1H), 3.91−3.74 (m, 2H), 3.31 (dq, J = 7.2, 3.5 Hz, 1H),
2.45 (s, 3H), 0.81 (t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.2 Hz, 3H). 13C
NMR (CDCl3, 75 MHz): δ 199.3, 168.6, 167.9, 149.6, 145.4, 138.4,
137.4, 135.9, 133.6, 132.6, 129.8, 128.7, 128.63, 128.6, 128.5, 126.8,
121.8, 85.3, 84.7, 70.6, 62.1, 61.6, 59.5, 21.7, 13.4, 13.2. HRMS (ESI-
TOF): calcd for C36H38O9NS ([M + NH4]+) 660.2267, found
660.2263.
1
760, 702. H NMR (CDCl3, 300 MHz): δ 7.86−7.78 (m, 2H), 7.55−
7.46 (m, 3H), 7.42−7.25 (m, 5H), 7.23−7.14 (m, 2H), 6.86 (d, J = 8.3
Hz, 1H), 5.95 (s, 1H), 5.29 (d, J = 8.9 Hz, 1H), 5.21 (d, J = 8.9 Hz,
1H), 4.03 (dq, J = 7.2, 3.6 Hz, 1H), 3.92 (s, 3H), 3.91−3.79 (m, 5H),
3.42 (dq, J = 7.2, 3.5 Hz, 1H), 0.82 (t, J = 7.1 Hz, 3H), 0.78 (t, J = 7.2
Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.4, 169.0, 168.1, 149.0,
148.4, 138.7, 137.5, 133.5, 129.4, 128.7, 128.60, 128.56, 128.5, 126.7,
119.7, 110.6, 110.5, 110.4, 110.3, 85.3, 84.9, 70.6, 62.0, 61.5, 59.5,
55.95, 55.93, 13.4, 13.2. HRMS (ESI-TOF): calcd for C31H32O8Na
([M + Na]+) 555.1995, found 555.1994.
Diethyl r-4-Benzoyl-t-2-(3-methoxy-4-tosyloxyphenyl)-t-5-
phenyltetrahydrofuran-3,3-dicarboxylate (5am). Purified by
column chromatography (petroleum ether/ethyl acetate = 8/1) to
afford a white solid in 77% yield (156 mg). Mp: 155−156 °C. IR (KBr,
cm−1): ν 1747, 1724, 1674, 1595, 1506, 1458, 1088, 1032, 841, 820,
752, 721. 1H NMR (CDCl3, 300 MHz): δ 7.83−7.73 (m, 4H), 7.55−
7.44 (m, 3H), 7.40−7.27 (m, 7H), 7.20−7.15 (m, 2H), 7.08 (d, J = 8.8
Hz, 1H), 5.92 (s, 1H), 5.27 (d, J = 8.8 Hz, 1H), 5.20 (d, J = 8.8 Hz,
1H), 4.02 (dq, J = 7.2, 3.6 Hz, 1H), 3.91−3.78 (m, 2H), 3.64 (s, 3H),
3.37 (dq, J = 7.2, 3.6 Hz, 1H), 2.45 (s, 3H), 0.85−0.77 (m, 6H). 13C
NMR (CDCl3, 75 MHz): δ 199.3, 168.7, 167.9, 151.4, 145.0, 138.4,
137.4, 137.0, 133.6, 133.5, 129.5, 128.7, 128.6, 128.5, 126.8, 123.3,
119.4, 111.9, 85.3, 84.8, 70.6, 62.2, 61.6, 59.4, 55.8, 21.7, 13.5, 13.2.
HRMS (ESI-TOF): calcd for C37H40O10NS ([M + NH4]+) 690.2372,
found 690.2371.
Diethyl r-4-Benzoyl-t-2-(4-benzyloxyphenyl)-t-5-phenylte-
trahydrofuran-3,3-dicarboxylate (5ai). Purified by column
chromatography (petroleum ether/ethyl acetate = 10/1) to afford a
white solid in 90% yield (157 mg). Mp: 128−129 °C. IR (KBr, cm−1):
ν 1749, 1726, 1680, 1612, 1580, 1512, 1466, 1454, 1072, 1063, 1018,
1
864, 810, 762, 700. H NMR (CDCl3, 300 MHz): δ 7.85−7.78 (m,
2H), 7.58−7.46 (m, 5H), 7.45−7.26 (m, 10H), 6.95 (d, J = 8.8 Hz,
2H), 5.95 (s, 1H), 5.28 (d, J = 8.9 Hz, 1H), 5.19 (d, J = 8.9 Hz, 1H),
5.08 (s, 2H), 4.03 (dq, J = 7.1, 3.6 Hz, 1H), 3.92−3.73 (m, 2H), 3.34
(dq, J = 7.2, 3.4 Hz, 1H), 0.81 (t, J = 7.2 Hz, 3H), 0.72 (t, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 75 MHz): δ 199.4, 169.0, 168.1, 158.7, 138.8,
137.6, 137.0, 133.5, 129.4, 128.7, 128.60, 128.5, 127.9, 127.4, 126.7,
114.4, 85.2, 85.0, 70.6, 69.9, 61.9, 61.4, 59.6, 13.3, 13.2. HRMS (ESI-
TOF): calcd for C36H38O7N ([M + NH4]+) 596.2648, found
596.2646.
Diethyl r-4-Benzoyl-t-2-(3,4,5-trimethoxyphenyl)-t-5-phe-
nyltetrahydrofuran-3,3-dicarboxylate (5an). Purified by column
chromatography (petroleum ether/ethyl acetate = 7/1) to afford a
white solid in 89% yield (150 mg). Mp: 116−117 °C. IR (KBr, cm−1):
ν 1757, 1728, 1670, 1595, 1508, 1464, 1448, 1078, 1036, 1009, 826,
758, 702. 1H NMR (CDCl3, 300 MHz): δ 7.85−7.78 (m, 2H), 7.55−
7.45 (m, 3H), 7.40−7.27 (m, 5H), 6.88 (s, 2H), 5.92 (s, 1H), 5.29 (d,
J = 8.9 Hz, 1H), 5.22 (d, J = 8.9 Hz, 1H), 4.09−3.98 (m, 1H), 3.94−
3.79 (m, 11H), 3.54−3.42 (m, 1H), 0.87−0.76 (m, 6H). 13C NMR
(CDCl3, 75 MHz): δ 199.3, 168.9, 168.0, 152.9, 138.6, 138.0, 137.5,
133.6, 132.4, 128.7, 128.6, 128.5, 126.7, 104.43, 104.36, 85.4, 85.0,
70.6, 62.1, 61.5, 60.8, 59.5, 56.2, 13.4, 13.2. HRMS (ESI-TOF): calcd
for C32H38O9N ([M + NH4]+) 580.2546, found 580.2537.
Diethyl r-4-Benzoyl-t-5-phenyl-t-2-((E)-styryl)tetrahydro-
furan-3,3-dicarboxylate (5ao). Purified by column chromatography
(petroleum ether/ethyl acetate = 9/1) to afford a white solid in 94%
yield (141 mg). Mp: 104−105 °C. IR (KBr, cm−1): ν 1732, 1670,
1595, 1448, 1092, 970, 764, 702, 665. 1H NMR (CDCl3, 300 MHz): δ
7.79 (d, J = 7.2 Hz, 2H), 7.57−7.18 (m, 13H), 6.90 (d, J = 16.1 Hz,
1H), 6.37 (dd, J = 16.0, 5.6 Hz, 1H), 5.50 (d, J = 4.8 Hz, 1H), 5.22 (d,
J = 8.2 Hz, 1H), 5.11 (d, J = 8.3 Hz, 1H), 4.23−4.00 (m, 3H), 3.99−
3.85 (m, 1H), 1.09 (t, J = 7.1 Hz, 3H), 0.90 (t, J = 7.1 Hz, 3H). 13C
NMR (CDCl3, 75 MHz): δ 199.5, 168.9, 167.8, 138.7, 137.4, 136.5,
133.6, 132.0, 128.7, 128.6, 128.5, 127.8, 126.8, 126.6, 124.0, 85.4, 83.9,
69.4, 62.2, 61.5, 59.2, 14.0, 13.4. HRMS (ESI-TOF): calcd for
C31H31O6 ([M + H]+) 499.2120, found 499.2117.
Diethyl r-4-Benzoyl-t-2-(4-benzyloxy-3-methoxyphenyl)-t-5-
phenyltetrahydrofuran-3,3-dicarboxylate (5aj). Purified by col-
umn chromatography (petroleum ether/ethyl acetate = 8/1) to afford
a white solid in 91% yield (166 mg). Mp: 134−135 °C. IR (KBr,
cm−1): ν 1759, 1728, 1670, 1593, 1518, 1466, 1448, 1061, 1036, 1009,
1
848, 746, 700. H NMR (CDCl3, 300 MHz): δ 7.83−7.77 (m, 2H),
7.53−7.22 (m, 13H), 7.17 (d, J = 1.9 Hz, 1H), 7.09 (dd, J = 8.3, 1.9
Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 5.91 (s, 1H), 5.26 (d, J = 8.9 Hz,
1H), 5.18 (d, J = 8.9 Hz, 1H), 5.16 (s, 2H), 4.06−3.95 (m, 1H), 3.92
(s, 3H), 3.89−3.72 (m, 2H), 3.30 (dq, J = 7.2, 3.5 Hz, 1H), 0.80 (t, J =
7.2 Hz, 3H), 0.70 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ
199.4, 169.0, 168.1, 149.2, 148.0, 138.7, 137.6, 137.2, 133.5, 130.0,
128.7, 128.62, 128.59, 128.53, 128.49, 127.8, 127.2, 126.7, 119.6,
113.7, 111.1, 85.3, 85.0, 71.0, 70.6, 62.0, 61.5, 59.6, 56.1, 13.4, 13.2.
HRMS (ESI-TOF): calcd for C37H40O8N ([M + NH4]+) 626.2753,
found 626.2751.
Diethyl r-4-Benzoyl-t-2-(4-acetoxy-3-methoxyphenyl)-t-5-
phenyltetrahydrofuran-3,3-dicarboxylate (5ak). Purified by
column chromatography (petroleum ether/ethyl acetate = 10/1) to
afford a white solid in 85% yield (143 mg). Mp: 161−162 °C. IR (KBr,
cm−1): ν 1767, 1728, 1678, 1607, 1597, 1580, 1512, 1462, 1448, 1072,
Diethyl r-4-Benzoyl-t-5-phenyl-t-2-propyltetrahydrofuran-
3,3-dicarboxylate (5ap). Purified by column chromatography
(petroleum ether/ethyl acetate = 15/1) to afford a white solid in
63% yield (83 mg). Mp: 93−94 °C. IR (KBr, cm−1): ν 1751, 1734,
1672, 1597, 1579, 1496, 1477, 1446, 1093, 1066, 1047, 763, 704, 653.
1H NMR (CDCl3, 300 MHz): δ 7.79−7.68 (m, 2H), 7.56−7.46 (m,
1
1034, 860, 823, 762, 698. H NMR (CDCl3, 300 MHz): δ 7.84−7.78
(m, 2H), 7.55−7.45 (m, 3H), 7.40−7.19 (m, 7H), 7.00 (d, J = 8.1 Hz,
1H), 5.97 (s, 1H), 5.29 (d, J = 8.9 Hz, 1H), 5.23 (d, J = 8.9 Hz, 1H),
4.03 (dq, J = 7.2, 3.5 Hz, 1H), 3.93−3.78 (m, 5H), 3.40 (dq, J = 7.2,
1H), 7.44−7.22 (m, 7H), 5.10−4.96 (m, 2H), 4.78−4.67 (m, 1H),
4.37−4.21 (m, 2H), 4.10−3.96 (m, 1H), 3.94−3.80 (m, 1H), 1.96−
5397
dx.doi.org/10.1021/jo400554a | J. Org. Chem. 2013, 78, 5393−5400

The Journal of Organic Chemistry
Article
1.84 (m, 1H), 1.76−1.39 (m, 3H), 1.29 (t, J = 7.1 Hz, 3H), 0.99 (t, J =
7.1 Hz, 3H), 0.87 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ
199.8, 169.4, 167.9, 138.8, 137.2, 133.2, 128.4, 128.3, 128.1, 126.6,
85.2, 84.2, 67.9, 61.9, 61.1, 59.5, 33.3, 20.1, 13.9, 13.8, 13.1. HRMS
(ESI-TOF): calcd for C26H30O6Na ([M + Na]+) 461.1940, found
461.1940.
167.5, 147.9, 146.2, 137.2, 136.3, 134.0, 128.8, 128.7, 128.6, 128.1,
127.3, 127.2, 123.9, 85.7, 83.5, 70.6, 62.2, 61.7, 59.3, 13.2. HRMS
(ESI-TOF): calcd for C29H28NO8 ([M + H]+) 518.1815, found
518.1815.
Diethyl r-4-Benzoyl-t-2-(4-chlorophenyl)-t-5-(4-nitro-
phenyl)tetrahydrofuran-3,3-dicarboxylate (5cb). Purified by
column chromatography (petroleum ether/ethyl acetate = 5/1) to
afford a white solid in 27% yield (45 mg). Mp: 89−90 °C. IR (KBr,
cm−1): ν 1751, 1728, 1678, 1597, 1581, 1521, 1490, 1473, 1448, 1087,
Diethyl r-4-Benzoyl-t-5-(4-chlorophenyl)-t-2-phenyltetrahy-
drofuran-3,3-dicarboxylate (5ba). Purified by column chromatog-
raphy (petroleum ether/ethyl acetate = 10/1) to afford a white solid in
96% yield (146 mg). Mp: 118−119 °C. IR (KBr, cm−1): ν 1751, 1724,
1674, 1595, 1581, 1492, 1473, 1448, 1085, 1064, 1016, 862, 833, 758,
1
1035, 1014, 856, 813, 752, 705, 665. H NMR (CDCl3, 300 MHz): δ
8.19 (d, J = 8.7 Hz, 2H), 7.83 (d, J = 7.2 Hz, 2H), 7.68−7.51 (m, 5H),
7.47−7.31 (m, 4H), 5.98 (s, 1H), 5.41 (d, J = 8.7 Hz, 1H), 5.11 (d, J =
8.7 Hz, 1H), 4.09−3.95 (m, 1H), 3.92−3.76 (m, 2H), 3.52−3.37 (m,
1H), 0.88−0.70 (m, 6H). 13C NMR (CDCl3, 75 MHz): δ 198.7, 168.4,
167.3, 147.9, 145.8, 137.0, 134.7, 134.4, 134.0, 128.8, 128.6, 128.5,
128.1, 127.2, 123.8, 84.9, 83.6, 70.4, 62.2, 61.7, 59.1, 13.2, 13.1. HRMS
(ESI-TOF): calcd for C29H26NO8ClK ([M + K]+) 590.0984, found
590.0979.
Diethyl r-4-Benzoyl-t-2-(4-anisyl)-t-5-(4-nitrophenyl)tetra-
hydrofuran-3,3-dicarboxylate (5cg). Purified by column chroma-
tography (petroleum ether/ethyl acetate = 5/1) to afford a white solid
in 82% yield (135 mg). Mp: 112−113 °C. IR (KBr, cm−1): ν 1751,
1728, 1672, 1595, 1521, 1473, 1448, 1083, 1028, 854, 831, 732, 702,
665. 1H NMR (CDCl3, 300 MHz): δ 8.18 (d, J = 8.7 Hz, 2H), 7.85 (d,
J = 7.5 Hz, 2H), 7.71−7.50 (m, 5H), 7.47−7.36 (m, 2H), 6.91 (d, J =
8.8 Hz, 2H), 5.99 (s, 1H), 5.41 (d, J = 8.7 Hz, 1H), 5.10 (d, J = 8.8 Hz,
1H), 4.10−3.95 (m, 1H), 3.93−3.78 (m, 4H), 3.51−3.36 (m, 1H),
0.87−0.71 (m, 6H). 13C NMR (CDCl3, 75 MHz): δ 198.9, 168.8,
167.6, 159.9, 147.9, 146.2, 137.2, 134.0, 128.8, 128.7, 128.4, 127.3,
123.9, 113.4, 85.5, 83.4, 70.5, 62.2, 61.6, 59.3, 55.4, 13.3, 13.2. HRMS
(ESI-TOF): calcd for C30H29NO9Na ([M + Na]+) 570.1740, found
570.1742.
1
705, 686. H NMR (CDCl3, 300 MHz): δ 7.92−7.78 (m, 2H), 7.67−
7.50 (m, 3H), 7.49−7.27 (m, 9H), 5.98 (s, 1H), 5.28 (d, J = 8.7 Hz,
1H), 5.15 (d, J = 9.0 Hz, 1H), 4.10−3.96 (m, 1H), 3.92−3.72 (m,
2H), 3.40−3.25 (m, 1H), 0.81 (d, J = 7.2 Hz, 3H), 0.69 (d, J = 7.2 Hz,
3H). 13C NMR (CDCl3, 75 MHz): δ 199.2, 168.8, 167.8, 137.4, 137.3,
136.7, 134.2, 133.7, 128.8, 128.7, 128.4, 128.1, 128.0, 127.2, 85.5, 84.3,
70.7, 62.0, 61.6, 59.5, 13.2. HRMS (ESI-TOF): calcd for
C29H27O6ClNa ([M + Na]+) 529.1394, found 529.1394.
Diethyl r-4-Benzoyl-t-2,t-5-bis(4-chlorophenyl)tetrahydro-
furan-3,3-dicarboxylate (5bb). Purified by column chromatography
(petroleum ether/ethyl acetate = 10/1) to afford a white solid in 91%
yield (148 mg). Mp: 110−111 °C. IR (KBr, cm−1): ν 1755, 1728,
1678, 1597, 1580, 1493, 1448, 1088, 1043, 1014, 858, 822, 814, 737,
1
702. H NMR (CDCl3, 300 MHz): δ 7.84−7.78 (m, 2H), 7.60−7.50
(m, 3H), 7.46−7.27 (m, 8H), 5.94 (s, 1H), 5.26 (d, J = 8.7 Hz, 1H),
5.14 (d, J = 8.7 Hz, 1H), 4.02 (dq, J = 7.2, 3.5 Hz, 1H), 3.91−3.77 (m,
2H), 3.43 (dq, J = 7.2, 3.5 Hz, 1H), 0.80 (t, J = 7.2 Hz, 3H), 0.76 (t, J
= 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.2, 168.6, 167.8,
137.3, 137.1, 135.2, 134.4, 134.3, 133.8, 128.9, 128.8, 128.7, 128.6,
128.1, 84.8, 84.5, 70.5, 62.2, 61.7, 59.4, 13.3, 13.2. HRMS (ESI-TOF):
calcd for C29H27O6Cl2 ([M + H]+) 541.1184, found 541.1180.
Diethyl r-4-Benzoyl-t-2-(4-anisyl)-t-5-(4-chlorophenyl)-
tetrahydrofuran-3,3-dicarboxylate (5bg). Purified by column
chromatography (petroleum ether/ethyl acetate = 7/1) to afford a
white solid in 98% yield (158 mg). Mp: 132−133 °C. IR (KBr, cm−1):
ν 1749, 1722, 1672, 1612, 1597, 1517, 1494, 1448, 1078, 1045, 1014,
Diethyl r-4-Benzoyl-t-2-(3,4-dimethoxyphenyl)-t-5-(4-
nitrophenyl)tetrahydrofuran-3,3-dicarboxylate (5ch). Purified
by column chromatography (petroleum ether/ethyl acetate = 4/1)
to afford a white solid in 82% yield (142 mg). Mp: 142−143 °C. IR
(KBr, cm−1): ν 1747, 1720, 1674, 1606, 1597, 1527, 1517, 1465, 1450,
1
1
1047, 1031, 1014, 856, 810, 768, 698, 655. H NMR (CDCl3, 300
829, 817, 705, 684. H NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 7.5
MHz): δ 8.19 (d, J = 8.6 Hz, 2H), 7.85 (d, J = 7.6 Hz, 2H), 7.70−7.52
(m, 3H), 7.49−7.36 (m, 2H), 7.23−7.11 (m, 2H), 6.88 (d, J = 8.2 Hz,
1H), 5.97 (s, 1H), 5.41 (d, J = 8.5 Hz, 1H), 5.12 (d, J = 8.6 Hz, 1H),
4.09−3.77 (m, 9H), 3.53−3.37 (m, 1H), 0.87−0.71 (m, 6H). 13C
NMR (CDCl3, 75 MHz): δ 198.8, 168.8, 167.6, 149.2, 148.5, 147.9,
146.1, 137.1, 134.0, 128.8, 128.7, 127.3, 123.9, 119.6, 110.6, 110.4,
85.6, 83.4, 70.4, 62.2, 61.7, 59.3, 56.0, 13.4, 13.2. HRMS (ESI-TOF):
calcd for C31H31NO10Na ([M + Na]+) 600.1846, found 600.1846.
Diethyl r-4-Benzoyl-t-5-(4-anisyl)-t-2-phenyltetrahydrofur-
an-3,3-dicarboxylate (5da). Purified by column chromatography
(petroleum ether/ethyl acetate = 15/1) to afford a white solid in 87%
yield (131 mg). Mp: 109−110 °C. IR (KBr, cm−1): ν 1753, 1728,
1674, 1614, 1598, 1583, 1446, 1085, 1064, 1033, 839, 758, 700, 671.
1H NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 7.5 Hz, 2H), 7.61 (d, J =
6.6 Hz, 2H), 7.55−7.27 (m, 8H), 6.85 (d, J = 8.7 Hz, 2H), 5.97 (s,
1H), 5.23 (s, 2H), 4.11−3.97 (m, 1H), 3.94−3.72 (m, 5H), 3.39−3.25
(m, 1H), 0.83 (t, J = 7.2 Hz, 3H), 0.70 (t, J = 7.2 Hz, 3H). 13C NMR
(CDCl3, 75 MHz): δ 199.5, 168.9, 168.1, 159.7, 137.6, 137.0, 133.5,
130.8, 128.7, 128.6, 128.3, 128.2, 127.9, 127.3, 114.0, 85.3, 84.9, 70.7,
61.9, 61.4, 59.6, 55.2, 13.3, 13.2. HRMS (ESI-TOF): calcd for
C30H30O7Na ([M + Na]+) 525.1889, found 525.1888.
Hz, 2H), 7.60−7.27 (m, 9H), 6.89 (d, J = 7.8 Hz, 2H), 5.94 (s, 1H),
5.25 (d, J = 8.7 Hz, 1H), 5.13 (d, J = 8.7 Hz, 1H), 4.10−3.95 (m, 1H),
3.93−3.75 (m, 5H), 3.49−3.32 (m, 1H), 0.91−0.70 (m, 6H). 13C
NMR (CDCl3, 75 MHz): δ 199.2, 168.9, 167.9, 159.7, 137.4, 137.3,
134.2, 133.7, 128.81, 128.76, 128.7, 128.4, 128.1, 113.3, 85.3, 84.1,
70.5, 62.0, 61.5, 59.5, 55.3, 13.3, 13.2. HRMS (ESI-TOF): calcd for
C30H29O7ClNa ([M + Na]+) 559.1500, found 559.1500.
Diethyl r-4-Benzoyl-t-5-(4-chlorophenyl)-t-2-(3,4-dimeth-
oxyphenyl)tetrahydrofuran-3,3-dicarboxylate (5bh). Purified
by column chromatography (petroleum ether/ethyl acetate = 7/1)
to afford a white solid in 85% yield (145 mg). Mp: 145−146 °C. IR
(KBr, cm−1): ν 1748, 1720, 1672, 1595, 1518, 1466, 1448, 1086, 1058,
1
1047, 1032, 864, 822, 810, 770, 706. H NMR (CDCl3, 300 MHz): δ
7.85−7.80 (m, 2H), 7.57−7.50 (m, 1H), 7.45−7.35 (m, 4H), 7.32−
7.27 (m, 2H), 7.20−7.13 (m, 2H), 6.86 (d, J = 8.2 Hz, 1H), 5.92 (s,
1H), 5.26 (d, J = 8.8 Hz, 1H), 5.14 (d, J = 8.8 Hz, 1H), 4.01 (dq, J =
7.2, 3.6 Hz, 1H), 3.97−3.79 (m, 8H), 3.42 (dq, J = 7.2, 3.5 Hz, 1H),
0.81 (t, J = 7.2 Hz, 3H), 0.77 (t, J = 7.2 Hz, 3H). 13C NMR (CDCl3,
75 MHz): δ 199.2, 169.0, 167.9, 149.1, 148.6, 137.42, 137.37, 134.3,
133.7, 129.2, 128.9, 128.70, 128.68, 128.1, 119.7, 110.7, 110.5, 85.4,
84.2, 70.5, 62.1, 61.5, 59.5, 56.0, 13.4, 13.2. HRMS (ESI-TOF): calcd
for C31H35O8NCl ([M + NH4]+) 584.2051, found 584.2043.
Diethyl r-4-Benzoyl-t-5-(4-nitrophenyl)-t-2-phenyltetrahy-
drofuran-3,3-dicarboxylate (5ca). Purified by column chromatog-
raphy (petroleum ether/ethyl acetate = 5/1) to afford a white solid in
81% yield (126 mg). Mp: 165−166 °C. IR (KBr, cm−1): ν 1751, 1726,
1672, 1595, 1521, 1494, 1473, 1450, 1091, 1074, 1037, 854, 748, 705,
671. 1H NMR (CDCl3, 300 MHz): δ 8.18 (d, J = 7.8 Hz, 2H), 7.85 (d,
J = 7.8 Hz, 2H), 7.69−7.51 (m, 5H), 7.46−7.30 (m, 5H), 6.03 (s, 1H),
5.43 (d, J = 8.7 Hz, 1H), 5.13 (d, J = 9.0 Hz, 1H), 4.10−3.94 (m, 1H),
3.91−3.73 (m, 2H), 3.42−3.26 (m, 1H), 0.80 (t, J = 7.2 Hz, 3H), 0.70
(t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 198.8, 168.6,
Diethyl r-4-Benzoyl-t-5-(4-anisyl)-t-2-(4-chlorophenyl)-
tetrahydrofuran-3,3-dicarboxylate (5db). Purified by column
chromatography (petroleum ether/ethyl acetate = 10/1) to afford a
white solid in 82% yield (132 mg). Mp: 107−108 °C. IR (KBr, cm−1):
ν 1749, 1724, 1678, 1614, 1595, 1516, 1448, 1056, 1031, 844, 815,
1
765, 692, 650. H NMR (CDCl3, 300 MHz): δ 7.86−7.75 (m, 2H),
7.63−7.27 (m, 9H), 6.86 (d, J = 8.6 Hz, 2H), 5.92 (s, 1H), 5.21 (s,
2H), 4.11−3.96 (m, 1H), 3.93−3.81 (m, 2H), 3.78 (s, 3H), 3.49−3.35
(m, 1H), 0.82 (t, J = 7.1 Hz, 3H), 0.77 (t, J = 7.2 Hz, 3H). 13C NMR
(CDCl3, 75 MHz): δ 199.4, 168.8, 168.0, 159.8, 137.4, 135.5, 134.1,
133.6, 130.5, 128.7, 128.6, 128.3, 128.0, 114.0, 85.1, 84.6, 70.5, 62.1,
5398
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61.5, 59.5, 55.2, 13.2. HRMS (ESI-TOF): calcd for C30H29O7ClNa
([M + Na]+) 559.1500, found 559.1500.
70.4, 61.9, 61.4, 59.5, 55.83, 55.81, 55.3, 13.33, 13.28. HRMS (ESI-
TOF): calcd for C32H34O9Na ([M + Na]+) 585.2100, found 585.2100.
Diethyl r-4-Benzoyl-t-2,t-5-bis(3,4-dimethoxyphenyl)tetra-
hydrofuran-3,3-dicarboxylate (5eh).4 Purified by column chro-
matography (petroleum ether/ethyl acetate = 4/1) to afford a white
solid in 91% yield (162 mg). Mp: 159−160 °C. IR (KBr, cm−1): ν
1753, 1720, 1678, 1593, 1518, 1466, 1450, 1051, 1026, 870, 851, 813,
Diethyl r-4-Benzoyl-t-2,t-5-bis(4-anisyl)tetrahydrofuran-3,3-
dicarboxylate (5dg). Purified by column chromatography (petro-
leum ether/ethyl acetate = 10/1) to afford a white solid in 81% yield
(130 mg). Mp: 21−22 °C. IR (KBr, cm−1): ν 1751, 1726, 1676, 1614,
1
1514, 1463, 1448, 1074, 1033, 852, 831, 812, 758, 690, 665. H NMR
1
764, 715, 696. H NMR (300 MHz, CDCl3): δ 7.82 (d, J = 7.9 Hz,
(CDCl3, 300 MHz): δ 7.81 (d, J = 7.2 Hz, 2H), 7.61−7.32 (m, 7H),
6.94−6.80 (m, 4H), 5.92 (s, 1H), 5.21 (s, 2H), 4.10−3.96 (m, 1H),
3.93−3.72 (m, 8H), 3.47−3.34 (m, 1H), 0.82 (t, J = 7.0 Hz, 3H), 0.76
(t, J = 7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.4, 169.0,
168.1, 159.6, 159.5, 137.4, 133.4, 130.7, 129.0, 128.6, 128.5, 128.3,
128.1, 113.9, 113.2, 85.0, 84.7, 70.5, 61.8, 61.3, 59.5, 55.2, 55.1, 13.24,
13.16. HRMS (ESI-TOF): calcd for C31H32O8K ([M + K]+) 571.1733,
found 571.1729.
2H), 7.58−7.48 (m, 1H), 7.45−7.33 (m, 2H), 7.24−6.97 (m, 4H),
6.86 (d, J = 8.1 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 5.92 (s, 1H), 5.21
(s, 2H), 4.11−3.97 (m, 1H), 3.96−3.77 (m, 14H), 3.49−3.35 (m, 1H),
0.84 (t, J = 7.1 Hz, 3H), 0.77 (t, J = 7.1 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 199.6, 169.1, 168.1, 149.04, 148.99, 148.95, 148.4, 137.5,
133.6, 131.2, 129.4, 128.65, 128.62, 119.7, 119.2, 110.9, 110.6, 110.3,
109.8, 85.2, 84.9, 70.4, 61.9, 61.4, 59.5, 55.9, 55.8, 55.7, 13.4, 13.3.
HRMS (ESI-TOF): calcd for C33H36O10Na ([M + Na]+) 615.2206,
found 615.2205.
Diethyl r-4-Benzoyl-t-5-(4-anisyl)-t-2-(3,4-dimethoxy-
phenyl)tetrahydrofuran-3,3-dicarboxylate (5dh). Purified by
column chromatography (petroleum ether/ethyl acetate = 6/1) to
afford a white solid in 90% yield (152 mg). Mp: 139−140 °C. IR (KBr,
cm−1): ν 1747, 1718, 1674, 1612, 1595, 1514, 1465, 1450, 1047, 1029,
Diethyl 2-(1-Benzoyl-2-chloro-2-phenylethyl)malonate
(6a).4 White solid. Mp: 104−105 °C. IR (KBr, cm−1): ν 1740,
1
1719, 1678, 1597, 1495, 1452, 1022, 758, 696. H NMR (300 MHz,
CDCl3): δ 7.94 (d, J = 7.5 Hz, 2H), 7.56−7.22 (m, 8H), 5.33 (d, J =
8.1 Hz, 1H), 4.989 (t, J = 8.1 Hz, 1H), 4.15−3.82 (m, 5H), 1.20−1.10
(m, 6H). 13C NMR (75 MHz, CDCl3): δ 198.7, 167.6, 167.4, 138.0,
133.0, 128.9, 128.7, 128.6, 128.5, 128.3, 128.1, 62.1, 61.9, 53.9, 51.4,
13.8. HRMS (ESI-TOF): calcd for C22H24ClO5 ([M + H]+) 403.1312,
found 403.1314. Anal. Calcd for C22H23ClO5 (402.87): C, 65.59; H,
5.75. Found: C, 65.44; H, 5.78.
Diethyl 2-(1-Benzoyl-2-phenylvinyl)malonate (7a). Colorless
oil. IR (neat, cm−1): 1747, 1732, 1661, 1597, 1447, 1038, 945, 700. ν .
1H NMR (CDCl3, 300 MHz): δ 7.85 (d, J = 7.8 Hz, 2H), 7.61−7.34
(m, 9H), 4.89 (s, 1H), 4.33−4.12(m, 4H), 1.25 (t, J = 6.7 Hz, 6H).
13C NMR (CDCl3, 75 MHz): δ 196.7, 167.8, 144.1, 137.6, 134.4,
134.3, 132.2, 129.9, 129.3, 129.0, 128.8, 128.3, 61.9, 51.5, 14.0. HRMS
(ESI-TOF): calcd for C22H23O5 ([M + H]+) 367.1545, found
367.1550.
1
864, 850, 812, 709, 692. H NMR (CDCl3, 300 MHz): δ 7.88−7.78
(m, 2H), 7.57−7.33 (m, 5H), 7.23−7.12 (m, 2H), 6.92−6.81 (m, 3H),
5.91 (s, 1H), 5.21 (s, 2H), 4.09−3.97 (m, 1H), 3.96−3.80 (m, 8H),
3.78 (s, 3H), 3.49−3.36 (m, 1H), 0.82 (t, J = 7.2 Hz, 3H), 0.77 (t, J =
7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 199.5, 169.1, 168.2,
159.7, 149.0, 148.5, 137.6, 133.5, 130.8, 129.5, 128.7, 128.6, 128.2,
119.8, 114.0, 110.6, 110.5, 85.2, 84.8, 70.6, 61.9, 61.4, 59.6, 55.98,
55.96, 55.2, 13.4, 13.2. HRMS (ESI-TOF): calcd for C32H34O9Na ([M
+ Na]+) 585.2100, found 585.2100.
Diethyl r-4-Benzoyl-t-5-(3,4-dimethoxyphenyl)-t-2-phenyl-
tetrahydrofuran-3,3-dicarboxylate (5ea). Purified by column
chromatography (petroleum ether/ethyl acetate = 5/1) to afford a
white solid in 86% yield (138 mg). Mp: 106−107 °C. IR (KBr, cm−1):
ν 1749, 1722, 1680, 1595, 1516, 1496, 1463, 1448, 1062, 1026, 862,
1
817, 756, 727, 702, 646. H NMR (CDCl3, 300 MHz): δ 7.83 (d, J =
7.3 Hz, 2H), 7.62 (d, J = 6.6 Hz, 2H), 7.56−7.48 (m, 1H), 7.44−7.28
(m, 5H), 7.13−6.99 (m, 2H), 6.80 (d, J = 8.2 Hz, 1H), 5.97 (s, 1H),
5.23 (s, 2H), 4.11−3.98 (m, 1H), 3.95−3.72 (m, 8H), 3.41−3.25 (m,
1H), 0.84 (t, J = 7.0 Hz, 3H), 0.69 (t, J = 7.0 Hz, 3H). 13C NMR
(CDCl3, 75 MHz): δ 199.6, 168.9, 168.1, 149.1, 149.0, 137.6, 136.9,
133.6, 131.2, 128.7, 128.6, 128.3, 127.9, 127.2, 119.3, 111.0, 109.9,
85.4, 85.1, 70.6, 61.9, 91.4, 59.6, 55.85, 55.83, 13.3, 13.2. HRMS (ESI-
TOF): calcd for C31H33O8 ([M + H]+) 533.2175, found 533.2173.
Diethyl r-4-Benzoyl-t-2-(4-chlorophenyl)-t-5-(3,4-dimeth-
oxyphenyl)tetrahydrofuran-3,3-dicarboxylate (5eb). Purified
by column chromatography (petroleum ether/ethyl acetate = 5/1)
to afford a white solid in 87% yield (148 mg). Mp: 134−135 °C. IR
(KBr, cm−1): ν 1753, 1728, 1683, 1597, 1579, 1516, 1489, 1463, 1448,
1076, 1029, 869, 856, 812, 767, 752, 694, 669. 1H NMR (CDCl3, 300
MHz): δ 7.87−7.77 (m, 2H), 7.64−7.49 (m, 3H), 7.44−7.30 (m, 4H),
7.13−7.01 (m, 2H), 6.81 (d, J = 8.2 Hz, 1H), 5.92 (s, 1H), 5.27−5.16
(m, 2H), 4.11−3.98 (m, 1H), 3.94−3.77 (m, 8H), 3.49−3.36 (m, 1H),
0.84 (t, J = 7.2 Hz, 3H), 0.76 (t, J = 7.1 Hz, 3H). 13C NMR (CDCl3,
75 MHz): δ 199.6, 168.7, 167.9, 149.2, 149.0, 137.4, 135.4, 134.1,
133.6, 130.9, 128.65, 128.62, 128.0, 119.3, 111.0, 109.9, 85.3, 84.6,
70.4, 62.0, 61.5, 59.5, 55.85, 55.83, 13.3. HRMS (ESI-TOF) calcd for
C31H31O8ClNa ([M + Na]+) 589.1605, found 589.1600.
ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray structure of 5ac; copies of H and 13C NMR spectra for
1
5aa−5eh, 6a and 7a; copies of COSY and NOESY NMR
spectra for 5aa−5eh and 7a; and crystal data of 5ac in CIF
format. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: 0086-553-3883517. E-mail: gshyang@mail.ahnu.edu.cn,
chaizhuo@mail.ahnu.edu.cn.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully appreciate the National Natural Science
Foundation of China (NSFC Nos. 21172002, 20972001, and
21202001) for financial support.
Diethyl r-4-Benzoyl-t-2-(4-anisyl)-t-5-(3,4-dimethoxy-
phenyl)tetrahydrofuran-3,3-dicarboxylate (5eg). Purified by
column chromatography (petroleum ether/ethyl acetate = 5/1) to
afford a white solid in 83% yield (140 mg). Mp: 105−106 °C. IR (KBr,
cm−1): ν 1751, 1722, 1685, 1614, 1595, 1463, 1074, 1028, 862, 815,
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765, 698, 671. H NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 8.2 Hz,
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