Reductive Bis-addition of Aromatic Aldehydes to α,β-Unsaturated Esters via the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans

Article abstract of DOI:10.1021/acs.joc.7b00278

The novel bis-addition of benzaldehydes to acrylates or maleates was achieved by the direct use of samarium metal with the assistance of CuI under mild conditions under dry air, and the useful 2-hydroxylalkyl-γ-butyrolactons and lignan derivatives were thus constructed with high efficiency. The key factors that influence the reaction efficiency were investigated. The use of potassium iodide and molecular sieves as additives can improve the reaction efficiency remarkably.

Full text of DOI:10.1021/acs.joc.7b00278

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Note
Reductive Bis-addition of Aromatic Aldehydes to #,#-Unsaturated Esters via
the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran Lignans
Yongjun Liu, Guang Tian, Jingjing Li, Yan Qi, Yonghong Wen, and Feng Du
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 16 May 2017
Downloaded from http://pubs.acs.org on May 16, 2017
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Reductive Bisꢀaddition of Aromatic Aldehydes to α,βꢀUnsaturated Esters
via the Use of Sm/Cu(I) in Air: A Route to the Construction of Furofuran
Lignans
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Yongjun Liu,* Guang Tian, Jingjing Li, Yan Qi, Yonghong Wen, Feng Du
State Key Laboratory Base of Ecoꢀchemical Engineering; Key Laboratory of Ecoꢀchemical Engineering,
Ministry of Education; College of Chemistry and Molecular Engineering, Qingdao University of Science
and Technology, Qingdao 266042, P. R. China.
yongjunliu@qust.edu.cn
ABSTRACT GRAPHIC
O
O
O
Sm/CuI/KI, THF, air
Ar
OR
OH
Ar
OH
O
O
O
O
Ar
O
ArCHO +
O
Ar
Sm/CuI/KI Ar
OR
OR
OR
4A MS
4-TsOH
(one-pot)
OH
O
+
Ar
OR THF, air
O
Ar
Ar
O
OR
OH
O
O
(1 step)
Sm/CuI/KI, THF, 4A MS, air
ABSTRACT: The novel bisꢀaddition of benzaldehydes to acrylates or maleates was achieved by the direct
use of samarium metal with the assistance of CuI under mild conditions under dry air, and the useful
2ꢀhydroxylalkylꢀγꢀbutyrolactons and lignan derivatives were thus constructed with high efficiency. The key
factors that influence the reaction efficiency were investigated. The use of potassium iodide and molecular
sieves as additives can improve the reaction efficiency remarkably.
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Samarium reagents in the past three decades have emerged as one of the reagents extensively exploited in a
variety of synthetic strategies.1ꢀ3 In contrast to the everꢀincreasing explorations of SmI2 owing to its
powerful reducing reactivity,1,2 however, the direct use of samarium metal draws relatively fewer attention
and in most cases acts as a moderate reductive agent in organic synthesis.3 Nevertheless, the direct use of
samarium metal as a reducing agent showed certain advantages as of being more practical and
electronꢀeconomical than the use of SmI2.3a
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The chemical skeleton I (Figure 1) is found in natural products and other widespread compounds of
biomedical relevance.4 For example, 2ꢀhydroxylbenzylꢀγꢀbutyrolacton II (also see product 3a in this paper)
is a natural product existing in smoking compositions as one of the main components of tobacco
flavorantꢀrelease.4a Dilactons IIIꢀa (also see products 7 herein)5 containing the moiety of I can readily
transform to 2,6ꢀdiarylꢀ3,7ꢀdioxabicyclo[3.3.0]octanes (IIIꢀb)6 via a facile reduction.5a Both of them are
actually the furofuran lignans7 which have exhibited diverse range of biological activities of particular
importance in antitumor, antihypertensive, antiꢀinflammatory, insecticidal, plateletꢀactivating factor
antagonist activities, as well as in treating immunopathy, in the improvement of cerebral circulation,
metabolism, and function.5ꢀ7
O
Ar
O
Ar
O
Ph
O
O
O
O
Ph
Ar'
O
Ar'
O
O
OH
(I)
OH
(II)
(IIIꢀa)
(IIIꢀb)
Figure 1. 2ꢀHydroxylbenzylꢀγꢀbutyrolactons and furofuran lignans.
So far, the efficient syntheses for such compounds were usually involved with long reaction routes
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and harsh operation conditions, such as KHMDS (ꢀ70 ºC, starting from synꢀaldols, 3 steps),4b LDA (ꢀ78 ºC,
from αꢀbenzoylsuccinic ester, 4 steps),4c,5a LDA (ꢀ78 ºC, photochemistry, from cyclic ketene silyl acetals, 2
steps),4d LHMDS (ꢀ78 ºC, from βꢀketoesters, 6 steps),5d DIBALH (ꢀ78 ºC, from TCꢀ1 and selectfluor, 2
steps),6a and so on.
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On the other hand, the incorporation of copper salts into other metals for the achievement of
specific purposes is impressive.8 These metals mainly includes lithium, palladium,8a magnesium,8b
zinc,8c,d titanium8e and so on, which exhibit particular reactivity in the presence of copper. By virtue of
copper’s strong coupling ability, samarium reagents incorporated with copper may exhibit exceptional
reactivity. Herein the Sm/Cu(I) combination was applied in the coupling of aldehydes to acrylates and
thus afforded a facile synthesis of 2ꢀhydroxylalkylꢀγꢀbutyrolactons (Scheme 1), which is
fundamentally different from the known reports which mainly involved with a reductive conjugate
addition promoted by SmI2.9aꢀe
Scheme 1. Addition between Aldehydes and Acrylates
O
O
SmI2
Reported additionRef.9a-c
Ar
Ar
conditions
Ar CHO
+
CH2 CH CO2R
O
O
Sm/CuI
THF
Bis-addition (this work)
OH
Ar
A series of conditions were screened to optimize the reaction (Table 1). First of all, the presence
of copper salts proved to be crucial to establishing the reactions (entry 1). Room temperature was
sufficient to realize the coupling reaction while higher temperature led to lower yields (entries 1ꢀ2). By
the addition of KI, the reaction can be remarkably accelerated and even proceed with better efficiency
in dry air despite the longer reaction time, while no reaction could be detected at all without the
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addition of KI in dry air (entries 3ꢀ4). Although CuCl, CuCl2 or AgNO3 alone hardly promote the
reaction, the combination of either of them with KI could facilitate the reaction (entries 5ꢀ7), instead,
no product was obtained in the presence of Cu(OAc)2, CuSO4 or NiCl2 (entries 8ꢀ10). Certain additives
such as 1,10ꢀphenanthroline or HMPA can accelerate the reaction (entries 11ꢀ12), due probably to the
efficient coordination with copper or samarium. On the other hand, TMSCl or I2 may accelerate the
reaction by activation to samarium metal (entries 13ꢀ14). In almost all these cases, the addition
efficiency was mainly influenced by the byproduct of benzoin which was formed via the selfꢀcoupling
of benzaldehyde.9f A significant improvement of the yield was observed when 4A molecular sieves
were added together with KI at the beginning of the reaction (entry 15ꢀ16). For comparison, a
complicated reaction mixture containing 3a was obtained when SmI2 was used in the same reaction
although the starting materials were consumed out very soon (entry 17), while no 3a was observed at
all when only SmI2 was used in the absence of CuI (entry 18).
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Table 1. Screening on the Conditions for the Coupling Reaction between Benzaldehyde and
Methyl Acrylate
O
O
Sm, THF Ph
Ph CHO + CH2 CH CO2CH3
OH
H
conditions
H
Ph
1a
2a
3a
Entrya
Metal salt
CuI
CuI
CuI
CuI
Additive
T (ºC) t (h)
Yield (%)b
42c
1
2
3
4
5
6
7
8
rt
5
reflux
rt
3
3
31
KI
KI
KI
KI
KI
KI
61
rt
rt
10
3
67d,e
60d
CuCl
CuCl2
AgNO3
Cu(OAc)2
reflux
reflux
reflux
10
10
10
13d
16d
ꢀꢀf
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CuSO4
NiCl2
CuI
CuI
CuI
CuI
CuI
CuI
KI
KI
reflux
reflux
10
10
3
ꢀꢀf
10
11
12
13
14
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17
18
19
ꢀꢀf
1,10ꢀphen
HMPA
TMSCl
I2
KI/4A MS
KI/4A MS
rt
rt
rt
rt
rt
rt
rt
rt
57
54
48
4
2.5
2.5
10
3
0.5
0.5
12
49g
81e,h
78h
14i
ꢀꢀf,i
57h,j
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SmI2/CuI
SmI2
CuI
KI/4A MS rt
aSm (2 mmol), 1a (2 mmol), 2a (4 mmol), metal salt (2 mmol), additive
(4 mmol), N2, unless otherwise specified. bIsolated yields. cNo reactions
occur in the absence of CuI. dNo reactions occur in the absence of KI.
eIn dry air. Product 3a was not observed. A grain of I2 was added. 4A
f
g
h
i
molecular sieves and KI were added at the beginning. Complicated
mixture observed. jOpen flask without preventing moisture.
According to the results, although moisture impeded the coupling reaction significantly (entry 19),
the reaction can be carried out with better efficiency in dry air, and the use of KI proved necessary in
establishing and improving the reactions. Although 1,10ꢀphenanthroline can also improve the reaction
efficiency to a certain extent, it was not introduced into the optimal conditions considering the
simplicity of the reagents. The reaction efficiency was remarkably improved by 4A molecular sieves
which were proposed to be able to deprive methanol10 thereby promoting the cyclization process
(Scheme 2).
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Scheme 2. Promotion of the Formation of 3 by 4A Molecular Sieves
O
O
O
Ar
OH
+ CH3OH
OCH3
Ar CHO +
R
Sm/CuI/KI in THF
in the presence of
R
Ar
4A MS
At the stage, the scope and limitation of this reaction were investigated under the optimal
conditions. A variety of benzaldehydes and acrylates were compatible with the conditions to afford
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products 3 in good yields (Table 2). The results showed the reaction efficiency decreased obviously
when the reaction was carried out in the absence of 4A MS (entries 2, 11, 19), or when bulkyꢀalkyl
acrylates were used as the bisꢀaddition acceptor (entries 3ꢀ9, 11). These results further support the
promotion effect of 4A MS in Scheme 2. Besides, the influences of the steric hindrance were observed
from the acrylates with different alkoxy groups (entries 2ꢀ9, 11, 19). The acrylates with bulky leaving
groups such as tertꢀbutyl (2c), isoꢀoctyl (2d) and octadecyl (2e) all underwent the reaction sluggishly
in moderate yields (entries 4ꢀ6), while better results were brought out when aryl acrylates (2f, 2g) were
used, probably due to the better leaving ability of phenolate than that of alkoxy (entries 6, 7, 10).
Interestingly, no obvious differences were observed from αꢀmethylacrylate (2h) and other acrylates
(2aꢀ2e). The functional group tolerance to Br and NO2 is also interesting (entries 7, 8), the resulting
tribromophenol and dinitrophenol from the cyclization can be recovered, without the debromination
and NH2 reduction products observed.
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The bisꢀaddition exhibited excellent diastereoselectivity in most cases (entries 1ꢀ11, 13ꢀ17).
However, lower diastereoselectivity of the reaction was observed for the acrylates with an αꢀmethyl
(entries 18ꢀ21). The results also showed that better yields were obtained for the benzaldehydes with
electronꢀdonating groups (entries 10ꢀ15 and 20ꢀ21) than those with electronꢀwithdrawing groups
(entries 16ꢀ17). Nevertheless, strong electronꢀwithdrawing groups led to the simple reduction of
aldehydes into benzyl alcohols rather than the bisꢀaddition (entries 22ꢀ23). Attempts to expand the
coupling reaction to ketones and aliphatic aldehydes were not successful, where only complicated
products were afforded.
Table 2. BisꢀAddition of Benzaldehydes to Acrylates
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O
O
O
Sm/CuI/KI, air
4A MS, THF
Ar
OH
OR1
Ar CHO +
H
R
R
Ar
(maior)
Yield (%)b dr Ratioc
2
3
Entrya Ar
R
H
H
H
H
R1
10
11
12
13
14
15
16
17
18
19
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1
2
3
4
Ph
Ph
Ph
Ph
Me (2a)
Me
Et (2b)
tꢀBu (2c)
81 (3a)
67d
>99:1
>99:1
>99:1
>99:1
71
56
5
6
Ph
Ph
H
H
59
61
>99:1
>99:1
(2d)
CH3
16
(2e)
Br
Br
7
8
Ph
Ph
H
H
76
73
>99:1
>99:1
Br
(2f)
O2N
NO2
(2g)
9
4ꢀMeꢀC6H4
4ꢀMeꢀC6H4
4ꢀMeꢀC6H4
4ꢀEtꢀC6H4
3,4ꢀdiMeꢀC6H3
4ꢀMeOꢀC6H4
3ꢀMeꢀC6H4
3ꢀFꢀC6H4ꢀ
3ꢀClꢀC6H4
Ph
H
H
H
H
H
H
H
H
H
Me
Me
Me
Me
H
70 (3b)
86
>99:1
>99:1
>99:1
88:12
>99:1
>99:1
>99:1
>99:1
>99:1
67:33
67:33
95:5
2f
Me
Et
Me
Me
Me
Me
Me
Me
Me (2h)
Me
Me
Me
Me
10
11
12
13
14
15
16
17
18
19
20
21
22
23
69d
80 (3c)
87 (3d)
82 (3e)
81 (3f)
73 (3g)
68 (3h)
81 (3i)
58 (3i)d
76 (3j)
82 (3k)
71e
Ph
4ꢀMeOꢀC6H4
3,4ꢀdiMeꢀC6H3
3ꢀpyridinyl
4ꢀNO2ꢀC6H4
80:20
H
Me
67e
aBenzaldehydes (2 mmol), 2 (4 mmol), Sm (2 mmol), CuI (2 mmol), KI (4
mmol) and 4A MS in THF (15 mL) at r.t. in air. Isolated yields. Determined
by 1H NMR. dIn the absence of 4A MS. eReduction products (benzyl alcohols).
b
c
Singleꢀcrystal structures of 3a and 3j show unambiguously that the products have a
hydroxybenzyl group in the αꢀposition of the carbonyl, indicating the occurrence of the bisꢀaddition.11
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The stereochemistry shows a synꢀconfiguration between αꢀR and γꢀH of the butyrolacton ring.
Probably due to the steric hindrance between αꢀCH3 and γꢀH, the diastereoselectivity decreased
(entries 18ꢀ21).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
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Maleates 4 contain the moiety of acrylates and are proved to be more reactive in the reaction
(Table 3). However, probably due to the hindrance, either products 5 or the monocyclic products 6
were obtained in different cases. No good regularity of the ratio between 5 and 6 can be observed
(entries 1ꢀ5 compared with entries 6ꢀ8). Notably, no desired product was formed from fumarate, which
may be contributed to the transꢀconfiguration that impede the bisꢀaddition and / or the cyclization
process.
Table 3. BisꢀAddition of Benzaldehydes to Maleates
OH
O
O
O
O
H
H
O
Ar
Sm/CuI/KI Ar
OR
OR
OR
+
OH
+
Ar CHO
H
Ar
OR THF, air
O
Ar
H
OR
O
OH
4
5
6
Entrya
Ar
Ph
R
Yield (5 and 6) (%)b
70 (5a)
73 (5b:6b = 43:30)
75 (5c)
68 (5d)
66 (5e)
72 (6a)
65 (6c)
68 (6d)
1
2
3
4
5
6
7
8
Et
4ꢀMeꢀC6H4
4ꢀEtꢀC6H4
4ꢀClꢀC6H4
2ꢀClꢀC6H4
Ph
Me
Me
Me
Me
Me
Et
4ꢀMeꢀC6H4
4ꢀMeOꢀC6H4
Me
aBenzaldehydes (2 mmol), 4 (4 mmol), Sm (2 mmol), CuI (2 mmol), KI
(4 mmol) at r. t. in air. bIsolated yields.
Encouraging results were also obtained when 4A MS were added right before the reaction start.
Single bicyclic products 7 were afforded in better efficiency in one step with the assistance of 4A MS
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(Table 4). It is also found that the resulting products 5 and 6 from table 3 can be transformed to 7
provided 4A MS were added together with 4ꢀTsOH to the final reaction mixture in a oneꢀpot manner
(Table 4, entries 3ꢀ4). No diastereomers observed by 1H NMR indicates the excellent
diastereoselectivity of the reaction.
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11
12
13
14
15
16
17
18
19
20
21
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Table 4. BisꢀAddition of Benzaldehydes to Maleates in the Presence of 4A MS
O
Ar
O
O
H
OR
OR
Ar CHO +
5 + 6
O
over 4A MS
one-step
O
4
H
7
O
Ar
Entry
Ar
Ph
Ph
Ph
Ph
R
Me
Me
Et
nꢀBu
Me
Me
Me
Me
Yield (5 and 6) (%)a
84 (7a)
1
2
3
4
5
6
7
8
78 (7a)b
76 (7a)c
65 (7a)c
3,4ꢀdiMeꢀC6H3
4ꢀMeOꢀC6H4
3ꢀClꢀC6H4
86 (7b)
82 (7c)
77 (7d)
80 (7e)
1ꢀNaphthaldehyde
aIsolated yields. bBenzaldehydes (2 mmol), 4 (4 mmol), Sm (2 mmol),
b
CuI (2 mmol), KI (4 mmol) at r. t. in dry air. N2 atmosphere.
c4ꢀToluenesulfonic acid was added.
The relative stereochemistry of product 7 was identified by single crystal.11 Products 5 and 6 are
the precursors of 7, so there is stereochemical similarity between compounds 5 (or 6) and 7.
The reaction mechanism is not clear yet at current stage. As it is well known, olefins can
coordinate efficiently with copper which affects the reactivity of olefins significantly,12 and various
reactions have been documented13 such as reduction,13a oxidation,13bꢀd and the CꢀH bond activation.13eꢀg
Besides, catalyzed by copper a singleꢀelectron oxidative addition13b,c often occurs during the ATRP
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process in which olefins are polymerized controllably.14 Such reactivity of copper may play important
roles during the bisꢀaddition.
7
8
9
In summary, a new application of Sm/Cu(I) was demonstrated. The bisꢀaddition between
benzaldehydes and acrylates or maleates provides an efficient method for the synthesis of
2ꢀhydroxylbenzylꢀγꢀbutyrolacton and lignans derivatives from readily available materials in a facile
and novel way in short steps.
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EXPERIMENTAL SECTION
General
All NMR spectra were measured in CDCl3 and recorded on Bruker Avanceꢀ500 spectrometer (1H NMR
13
1
500 MHz, and C NMR 125 MHz) with TMS or the residual signals of the solvent (δ 7.26 for H NMR
13
and δ 77.16 for C NMR) as the internal standard. Chemical shifts are expressed in δ values (ppm) and
Coupling Constants are given in J values (Hz). IR spectra were recorded on a Bruker Tensorꢀ27
spectrometer. High resolution mass spectra (HRMS) were measured on Thermo Scientific LTQ Orbitrap
XL mass spectrometer using Electrospray Ionization (ESI) and Electron Impact (EI) methods. Melting
points were measured on RYꢀ1 melting point apparatus, and the values are uncorrected. All chemical
reagents and solvents were purchased from commercial sources and used without further purification
unless otherwise specified. Before use, THF was refluxed and redistilled over sodium and benzophenone.
Flash column chromatography was performed over silica gel (100ꢀ200 mesh). All reaction mixtures were
stirred magnetically and were monitored by thinꢀlayer chromatography using silica gel preꢀcoated glass
plates, which were visualized with UV light and then, developed using either iodine or a solution of
anisaldehyde.
Typical procedure for the synthesis of 2ꢀhydroxylphenylmethylꢀ4ꢀphenylꢀγꢀbutyrolacton (3a):
To a mixture of samarium powder (0.3 g, 2 mmol), cuprous iodide (0.39 g, 2 mmol), potassium iodide
(0.68 g, 4 mmol) in anhydrous tetrahydrofuran (15 mL), benzaldehyde (2 mmol, 0.21 mL), methyl acrylate
(4 mmol, 0.36 mL) and 4A molecular sieves (1 g) were added at room temperature with magnetic stirring
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under dry air. Then the flask was sealed with rubber stoppers to prevent moisture, and the reaction mixture
turned dark in 2 h. After the reaction proceeded overnight, dilute hydrochloric acid (2 mol ꢁ Lꢀ1, 5 mL) was
added and the resulting mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic layer
was washed with brine and saturated sodium thiosulfate solution successively, dried over anhydrous
sodium sulfate, and concentrated under reduced pressure. The crude product was purified with flash
chromatography (over silica, hexane : ethyl acetate = 7 : 1 v/v) to afford 217 mg of 3a with 81 % yield.
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Typical procedure for the synthesis of diethyl 2,3ꢀbis(hydroxy(phenyl)methyl)succinate (5a):
To a mixture of samarium powder (0.3 g, 2 mmol), cuprous iodide (0.39 g, 2 mmol), potassium iodide
(0.68 g, 4 mmol) in anhydrous tetrahydrofuran (15 mL), benzaldehyde (2 mmol, 0.21 mL), diethyl maleate
(4 mmol, 0.63 mL) and 4A molecular sieves (1 g) were added at room temperature with magnetic stirring
under dry air. Then the flask was sealed with rubber stoppers to prevent moisture, and the reaction mixture
turned dark in 2 h. After the reaction proceeded overnight, dilute hydrochloric acid (2 mol ꢁ Lꢀ1, 5 mL) was
added and the resulting mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic layer
was washed with brine and saturated sodium thiosulfate solution successively, dried over anhydrous
sodium sulfate, and concentrated under reduced pressure. The crude product was purified with flash
chromatography (over silica, hexane : ethyl acetate = 2 : 1 v/v) to afford 270 mg of 5a with 70 % yield.
Typical
procedure
for
the
synthesis
of
methyl
4ꢀ(hydroxy(phenyl)methyl)ꢀ5ꢀoxoꢀ2ꢀphenyltetrahydrofuranꢀ3ꢀcarboxylate (6a):
To a mixture of samarium powder (0.3 g, 2 mmol), cuprous iodide (0.39 g, 2 mmol), potassium iodide
(0.68 g, 4 mmol) in anhydrous tetrahydrofuran (15 mL), benzaldehyde (2 mmol, 0.21 mL), dimethyl
maleate (4 mmol, 0.50 mL) and 4A molecular sieves (1 g) were added at room temperature with
magnetic stirring under dry air. Then the flask was sealed with rubber stoppers to prevent moisture, and the
reaction mixture turned dark in 2 h. After the reaction proceeded overnight, dilute hydrochloric acid (2 mol
ꢁ Lꢀ1, 5 mL) was added and the resulting mixture was extracted with ethyl acetate (3 × 10 mL). The
combined organic layer was washed with brine and saturated sodium thiosulfate solution successively,
dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was
purified with flash chromatography (over silica, hexane : ethyl acetate = 5 : 1 v/v) to afford 235 mg of 6a
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with 72 % yield.
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Typical procedure for the synthesis of methyl 3,6ꢀdiphenyltetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7a):
To a mixture of samarium powder (0.3 g, 2 mmol), cuprous iodide (0.39 g, 2 mmol), potassium iodide
(0.68 g, 4 mmol) in anhydrous tetrahydrofuran (15 mL), benzaldehyde (2 mmol, 0.21 mL), dimethyl
maleate (4 mmol, 0.50 mL) and 4A molecular sieves (1 g) were added at room temperature with
magnetic stirring under dry air. Then the flask was sealed with rubber stoppers to prevent moisture, and the
reaction mixture turned dark in 2 h. After the reaction proceeded overnight, dilute hydrochloric acid (2 mol
ꢁ Lꢀ1, 5 mL) was added and the resulting mixture was extracted with ethyl acetate (3 × 10 mL). The
combined organic layer was washed with brine and saturated sodium thiosulfate solution successively,
dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was
purified with flash chromatography (over silica, hexane : ethyl acetate = 7 : 1 v/v) to afford 247 mg of 7a
with 84 % yield.
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3ꢀ(Hydroxy(phenyl)methyl)ꢀ5ꢀphenyldihydrofuranꢀ2(3H)ꢀone (3a)
1
O
White solid. m.p. 217 mg (81 %). 184ꢀ186 ºC. HNMR (500 MHz, CDCl3) δppm
OH
O
7.40ꢀ7.28 (m, 10 H), 5.49 (s, 1 H), 5.35ꢀ5.31 (m, 1 H), 3.20ꢀ3.16 (m, 1 H), 2.50ꢀ2.43
(m, 2 H), 2.33ꢀ2.27 (m, 1 H); 13C NMR (125 MHz, CDCl3) δppm 177.0, 141.4, 139.1,
128.8, 128.7, 127.9, 125.9, 125.5, 125.0, 80.0, 70.3, 49.9, 30.7; IR (KBr/cmꢀ1) ν 3432, 3055, 2900, 1678,
+
1596, 1580, 1446; HRMS m/z calcd for C17H17O3 [M + H]+ 269.1178, found 269.1185.
3ꢀ(Hydroxy(pꢀtolyl)methyl)ꢀ5ꢀpꢀtolyldihydrofuranꢀ2(3H)ꢀone (3b)
White solid. 255 mg (86 %). m.p. 164ꢀ167 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
OH
O
7.26ꢀ7.15 (m, 8 H), 5.44 (m, 1 H), 5.30ꢀ5.27 (m, 1 H), 3.14 (m, 1 H), 2.46 (m, 2 H),
2.49 (s, 3H), 2.43 (s, 3H), 2.36 (m, 1 H); 13C NMR (125 MHz, CDCl3) δppm 177.0,
138.5, 137.5, 136.1, 129.4, 129.3, 126.0, 125.4, 80.0, 70.3, 49.9, 30.8, 21.3, 21.2.
+
IR (KBr/cmꢀ1) ν 3457, 3036, 2912, 1677, 1588, 1581, 1432; HRMS m/z calcd for C19H21O3 [M + H]+
297.1491, found 297.1485.
5ꢀ(4ꢀEthylphenyl)ꢀ3ꢀ((4ꢀethylphenyl)(hydroxy)methyl)dihydrofuranꢀ2(3H)ꢀone (3c)
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White solid. 259 mg (80 %). m.p. 144ꢀ146 ºC. 1HNMR (500 MHz, CDCl3)
δppm 7.28ꢀ7.17 (m, 8 H), 5.44 (s, 1 H), 5.30ꢀ5.27 (m, 1 H), 3.16ꢀ3.12 (m, 1 H),
2.66ꢀ2.63 (m, 4 H), 2.50ꢀ2.43 (m, 2 H), 2.32ꢀ2.26 (m, 1 H), 1.25ꢀ1.19(m, 6 H);
13C NMR (125 MHz, CDCl3) δppm 177.2, 145.0, 144.0, 138.8, 136.3, 128.2,
O
OH
O
128.1, 126.1, 125.5, 80.1, 70.3, 49.9, 30.7, 28.6, 15.7; IR (KBr/cmꢀ1) ν 3464, 3076, 2956, 1677, 1575, 1565,
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+
1466; HRMS m/z calcd for C21H25O3 [M + H]+ 325.1804, found 325.1810.
5ꢀ(3,4ꢀDimethylphenyl)ꢀ3ꢀ((3,4ꢀdimethylphenyl)(hydroxy)methyl)dihydrofuranꢀ2(3H)ꢀone (3d)
1
O
White solid. 282 mg (87 %). m.p. 134ꢀ136 ºC. HNMR (500 MHz, CDCl3)
OH
O
δppm 7.14ꢀ7.10 (m, 6 H), 5.39 (s, 1 H), 5.27ꢀ5.24 (m, 1 H), 3.13 (m, 1 H),
2.46ꢀ2.43 (m, 2 H), 2.30ꢀ2.29 (t, 1 H), 2.28 (s, 3 H), 2.27 (s, 3 H), 2.26 (s, 3 H),
13
2.25 (s, 3 H); C NMR (125 MHz, CDCl3) δppm 177.1, 139.0, 137.2, 137.1,
136.9, 136.5, 136.1, 129.9, 127.2, 126.7, 123.5, 122.9, 80.1, 70.4, 49.9, 30.9, 19.8, 19.4. IR (KBr/cmꢀ1) ν
3435, 3045, 2943, 1676, 1576, 1534, 1454; HRMS m/z calcd for C21H25O3 [M + H]+ 325.1804, found
+
325.1802.
3ꢀ(Hydroxy(4ꢀmethoxyphenyl)methyl)ꢀ5ꢀ(4ꢀmethoxyphenyl)dihydrofuranꢀ2(3H)ꢀone (3e)
1
O
White solid. 269 mg (82 %). m.p. 162ꢀ164 ºC. HNMR (500 MHz, CDCl3)
OH
O
δppm 7.30ꢀ7.26 (m, 4 H), 6.91ꢀ6.88 (m,4 H), 5.43ꢀ5.41 (m, 1 H), 5.29ꢀ5.26 (m,
1 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.15ꢀ3.10 (m, 1 H), 2.48ꢀ2.41 (m, 2 H),
O
13
O
2.30ꢀ2.25 (m, 1 H); C NMR (125 MHz, CDCl3) δppm 177.0, 160.0, 159.2,
133.5, 130.9, 127.6, 126.7, 114.1, 114.0, 79.9, 70.2, 55.3, 49.9, 30.7; IR (KBr/cmꢀ1) ν 3389, 3023, 2956,
1674, 1574, 1517, 1422; HRMS m/z calcd for C19H21O5 [M + H]+ 329.1389, found 329.1379.
+
3ꢀ(Hydroxy(mꢀtolyl)methyl)ꢀ5ꢀmꢀtolyldihydrofuranꢀ2(3H)ꢀone (3f)
White solid. 239 mg (81 %). m.p. 164ꢀ167 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
OH
O
7.26ꢀ7.15 (m, 8 H), 5.44 (m, 1 H), 5.30ꢀ5.27 (m, 1 H), 3.14 (m, 1 H), 2.46 (m, 2 H),
2.49 (s, 3 H), 2.43 (s, 3 H), 2.36 (m, 1 H); 13C NMR (125 MHz, CDCl3) δppm 176.4,
140.9, 138.5, 138.0, 137.8, 128.8, 128.0, 124.9, 125.5, 122.4, 122.0,79.5, 69.8, 49.3,
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30.2, 20.9, 20.8; IR (KBr/cmꢀ1) ν 3434, 3074, 2937, 1676, 1585, 1531, 1454; HRMS m/z calcd for
5
6
+
C19H21O3 [M + H]+ 297.1491, found 297.1487.
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5ꢀ(3ꢀFluorophenyl)ꢀ3ꢀ((3ꢀfluorophenyl)(hydroxy)methyl)dihydrofuranꢀ2(3H)ꢀone (3g)
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White solid. 222 mg (73 %). m.p. 156ꢀ158 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
OH
O
7.31ꢀ7.03 (m, 8 H), 5.75ꢀ5.74 (m, 1 H), 5.64ꢀ5.62 (m, 1 H), 3.36 (m, 1 H), 2.56ꢀ2.55
(m, 1 H), 2.36ꢀ2.32 (m, 2 H); 13C NMR (125 MHz, CDCl3) δppm 176.4, 160.6
F
F
(158.7, JCꢀF = 246.6 Hz), 159.9 (158.0 JCꢀF = 242.8), 129.9, 129.3, 128.4, 127.1,
126.8, 126.3, 124.6, 124.4, 115.5, 115.3, 74.1, 64.7, 47.8, 29.9; IR (KBr/cmꢀ1) ν 3461, 3045, 2924, 1681,
+
1557, 1543, 1445; ν HRMS m/z calcd for C17H15F2O3 [M + H]+ 305.0989, found 305.0992.
5ꢀ(3ꢀChlorophenyl)ꢀ3ꢀ((3ꢀchlorophenyl)(hydroxy)methyl)dihydrofuranꢀ2(3H)ꢀone (3h)
White solid. 228 mg (68 %). m.p. 166ꢀ168 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
OH
O
7.33ꢀ7.21 (m, 8 H), 5.47ꢀ5.45 (m, 1 H), 5.31ꢀ5.28 (m, 1 H), 3.18ꢀ3.13 (m, 1 H),
13
2.55ꢀ2.54 (m, 1 H), 2.41ꢀ2.28 (m, 2 H); C NMR (125 MHz, CDCl3) δppm 176.2,
Cl
Cl
143.4, 140.9, 134.8, 130.1, 130.0, 128.8, 128.0, 125.9, 125.6, 123.8, 123.6, 114.8,
78.9, 69.5, 49.6, 30.3; IR (KBr/cmꢀ1) ν 3457, 3047, 2968, 1681, 1578, 1523, 1436; HRMS m/z calcd for
C17H15Cl2O3 [M + H]+ 337.0398, found 337.0389.
+
3ꢀ(Hydroxy(phenyl)methyl)ꢀ3ꢀmethylꢀ5ꢀphenyldihydrofuranꢀ2(3H)ꢀone (3i)
O
White solid. 228 mg (68 %). Obtained together with its diastereomer (67 : 33). m.p.
OH
O
130ꢀ136 ºC. 1HNMR (500 MHz, CDCl3) δppm7.40ꢀ7.27 (m, 10 H), 5.40ꢀ5.37 (m, 1
H), 5.02ꢀ5.01 (m, 1 H), 2.87ꢀ2.82 (m, 1 H), 2.72ꢀ2.70 (m, 1 H), 1.96ꢀ1.92 (m, 1 H),
13
1.21 (s, 3 H); C NMR (125 MHz, CDCl3) δppm 180.6, 139.7, 128.7, 128.6, 128.2, 128.0, 127.1, 125.9,
78.5, 75.8, 51.3, 37.5, 20.5; IR (KBr/cmꢀ1) ν 3457, 3047, 2968, 1681, 1578, 1523, 1436; HRMS m/z calcd
for C18H19O3 [M + H]+ 283.1334, found 283.1339.
+
3ꢀ(Hydroxy(4ꢀmethoxyphenyl)methyl)ꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ3ꢀmethyldihydrofuranꢀ2(3H)ꢀone (3j)
O
White solid. 260 mg (76 %). Obtained together with its diastereomer (95 : 5).
OH
O
1
m.p. 160ꢀ162 ºC. HNMR (500 MHz, CDCl3) δppm7.32ꢀ7.24 (m, 4 H),
O
O
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6.92ꢀ6.86 (m, 4 H), 5.36ꢀ5.32 (m, 1 H), 4.98ꢀ4.95 (m, 1 H), 3.82 (s, 3 H), 3.80 (s, 3 H), 2.86ꢀ2.81 (m, 1 H),
4
5
6
13
2.60ꢀ2.59 (m, 1 H), 1.92ꢀ1.88 (m, 1 H), 1.18(s, 3 H); C NMR (125 MHz, CDCl3) δppm 180.7, 159.9,
7
8
159.6, 131.9, 131.3, 128.3, 127.6, 114.1, 113.7, 78.4, 76.0, 55.3, 51.4, 37.5, 20.6; IR (KBr/cmꢀ1) ν 3402,
9
+
3033, 2954, 1676, 1566, 1542, 1443; HRMS m/z calcd for C20H23O5 [M + H]+ 343.1545, found 343.1549.
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5ꢀ(3,4ꢀDimethylphenyl)ꢀ3ꢀ((3,4ꢀdimethylphenyl)(hydroxy)methyl)ꢀ3ꢀmethyldihydrofuranꢀ2(3H)ꢀone (3k)
O
White solid. 277 mg (82 %). Obtained together with its diastereomer (80 : 20). m.p.
OH
O
164ꢀ168 ºC. 1HNMR (500 MHz, CDCl3) δppm7.26ꢀ7.03 (m, 6 H), 5.45ꢀ5.32 (m, 1
H), 4.95ꢀ4.90 (s, 1 H), 3.09ꢀ2.82 (m, 1 H), 2.60ꢀ2.53 (d, 1 H), 2.30 (s, 3 H), 2.28 (s,
3 H), 2.26 (s, 3 H), 2.22 (s, 3 H), 1.95ꢀ1.71 (m, 1 H), 1.21ꢀ1.15 (s, 3 H); 13C NMR
(125 MHz, CDCl3) δppm 181.0, 137.3, 137.0, 136.8, 136.5, 136.4, 129.8, 129.5, 128.3, 127.3, 126.5, 124.7,
123.6, 79.0, 75.9, 51.3, 37.8, 20.6, 20.5, 19.8, 19.5; IR (KBr/cmꢀ1) ν 3412, 3045, 2945, 1676, 1578, 1532,
1412; HRMS m/z calcd for C22H27O3 [M + H]+ 339.1960, found 339.1956.
+
Diethyl 2,3ꢀbis(hydroxy(phenyl)methyl)succinate (5a)
White solid. 270 mg (70 %). m.p. 255ꢀ257 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
7.40ꢀ7.34 (m, 10 H), 5.68ꢀ5.67 (m, 2 H), 4.31ꢀ4.29 (m, 2 H), 3.76ꢀ3.70 (m, 2 H),
O
O
13
3.68ꢀ3.66 (m, 2 H), 3.65ꢀ3.56 (m, 2 H), 0.73ꢀ0.71 (m, 6 H); C NMR (125 MHz,
HO
O
CDCl3) δppm 174.8, 169.6, 134.4, 128.8, 128.4, 125.5, 81.0, 61.1, 51.2, 41.6, 31.1,
HO
29.7, 13.4; IR (KBr/cmꢀ1) ν 3501, 3302, 3045, 2934, 1761, 1739, 1567, 1487, 1455;
HRMS m/z calcd for C22H27O6 [M + H]+ 387.1808, found 387.1801.
+
Dimethyl 2,3ꢀbis(hydroxy(pꢀtolyl)methyl)succinate (5b)
White solid. 166 mg (43 %). m.p. 252ꢀ253 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
O
O
7.17ꢀ7.15 (m, 4 H), 7.08ꢀ7.06 (m,4 H), 5.79ꢀ5.77 (m, 2 H), 3.83ꢀ3.78 (m, 2 H),
HO
O
13
3.75ꢀ3.71 (m, 2 H), 3.40 (s, 6 H), 2.33 (s, 6 H); C NMR (125 MHz, CDCl3) δppm
HO
174.5, 168.9, 139.2, 131.7, 129.3, 125.8, 79.1, 52.3, 49.4, 40.1, 21.2; IR (KBr/cmꢀ1)
ν 3498, 3302, 3057, 2958, 1759, 1743, 1589, 1467, 1422; HRMS m/z calcd for
+
C22H27O6 [M + H]+ 387.1808, found 387.1807.
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Dimethyl 2,3ꢀbis((4ꢀethylphenyl)(hydroxy)methyl)succinate (5c)
5
6
White solid. 311 mg (75 %). m.p. 254ꢀ256 ºC. 1HNMR (500 MHz, CDCl3) δppm
7
8
9
O
O
7.17ꢀ7.15 (d, 4 H, J = 6.5 Hz), 7.08 (d, 4 H, J = 6.5 Hz), 5.93ꢀ5.91 (m, 2 H),
O
4.59ꢀ4.55 (m, 2 H), 3.56ꢀ3.53 (m, 2 H), 3.40 (s, 6 H), 2.62 (q, 4 H, J = 6.0 Hz),
1.20 (t, 6 H, J = 6.0 Hz); 13C NMR (125 MHz, CDCl3) δppm 175.6, 168.9, 145.4,
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HO
O
HO
132.6, 128.0, 126.0, 79.2, 52.3, 49.5, 39.5, 28.5, 15.5; IR (KBr/cmꢀ1) ν 3498, 3303,
+
3065, 2967, 1760, 1744, 1566, 1476, 1423; HRMS m/z calcd for C24H31O6 [M + H]+ 415.2121, found
415.2116.
Dimethyl 2,3ꢀbis((4ꢀchlorophenyl)(hydroxy)methyl)succinate (5d)
White solid. 290 mg (68 %). m.p. 262ꢀ263 ºC. 1HNMR (500 MHz, CDCl3) δppm
Cl
O
O
7.36 (d, 4 H, J = 6.5 Hz), 7.15 (d, 4 H, J = 6.5 Hz), 5.81ꢀ5.79 (m, 2 H), 3.88ꢀ3.78
O
13
HO
(m, 2 H), 3.70ꢀ3.66 (m, 2 H), 3.44 (s, 6 H); C NMR (125 MHz, CDCl3) δppm
O
HO
174.2, 169.5, 132.7, 132.3, 130.3, 129.7, 127.2, 127.0, 52.4, 48.3, 42.0; IR
(KBr/cmꢀ1) ν 3517, 3308, 3049, 2954, 1769,1744, 1597, 1495, 1443; HRMS m/z
Cl
calcd for C20H21Cl2O6 [M + H]+ 427.0715, found 427.0709.
+
Dimethyl 2,3ꢀbis((2ꢀchlorophenyl)(hydroxy)methyl)succinate (5e)
White solid. 281 mg (66 %). m.p. 255ꢀ257 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
O
O
7.40ꢀ7.39 (m, 2 H), 7.32ꢀ7.31 (m, 6 H), 6.26ꢀ6.24 (m, 2 H), 4.14 (m, 2 H), 3.64ꢀ3.63
Cl
HO
(m, 2 H), 3.32 (s, 6 H); 13C NMR (125 MHz, CDCl3) δppm 173.8, 170.5, 140.2, 135.4,
O
HO
Cl
135.3, 134.8, 130.7, 130.0, 129.5, 129.4, 125.8, 124.8, 123.7, 122.8, 80.1, 79.3, 50.6,
44.9; IR (KBr/cmꢀ1) ν 3522, 3313, 3045, 2946, 1770, 1746, 1597, 1498, 1445; HRMS
+
m/z calcd for C20H21Cl2O6 [M + H]+ 427.0715, found 427.0711.
Methyl 4ꢀ(hydroxy(phenyl)methyl)ꢀ5ꢀoxoꢀ2ꢀphenyltetrahydrofuranꢀ3ꢀcarboxylate (6a)
1
White solid. 235 mg (72 %). m.p. 199ꢀ201 ºC. HNMR (500 MHz, CDCl3)
δppm7.36ꢀ7.32 (m, 5 H), 7.30ꢀ7.24 (m, 5 H), 5.57 (d, 1 H, J = 6.0 Hz), 5.19 (d, 1 H, J =
O
O
O
9.0 Hz), 4.30 (s, 1 H), 3.30 (dd, 1 H, J = 7.5 Hz, J = 9.0 Hz), 3.20 (s, 3 H), 3.12 (dd, 1
O
HO
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5
13
H, J = 6.0 Hz, J = 7.5 Hz); C NMR (125 MHz, CDCl3) δppm 176.7, 168.8, 139.6, 133.8, 128.8, 128.4,
126.5, 125.2, 80.1, 71.3, 58.5, 51.8, 51.6, 50.9; IR (KBr/cmꢀ1) ν 3455, 3036, 2933, 1767, 1722, 1515, 1453;
6
7
8
+
HRMS m/z calcd for C19H19O5 [M + H]+ 327.1232, found 327.1233.
9
10
11
12
13
14
15
16
17
18
19
20
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59
60
Methyl 4ꢀ(hydroxy(pꢀtolyl)methyl)ꢀ5ꢀoxoꢀ2ꢀpꢀtolyltetrahydrofuranꢀ3ꢀcarboxylate (6b)
White solid. 98 mg (30 %). m.p. 211ꢀ213 ºC. 1HNMR (500 MHz, CDCl3) δppm
7.15ꢀ7.10 (m, 8 H), 5.54ꢀ5.53 (d, 1 H, J = 6.0 Hz), 5.13 (d, 1 H, J = 9.0 Hz), 4.28 (s,
O
O
O
1 H), 3.27 (dd, 1 H, J = 7.5 Hz, J = 9.0 Hz), 3.21 (s, 3 H), 3.09 (dd, 1 H, J = 6.0 Hz,
O
13
HO
J = 7.5 Hz), 2.33 (s, 3 H), 2.32 (s, 3 H); C NMR (125 MHz, CDCl3) δppm 177.0,
168.9, 138.7, 138.6, 136.8, 130.9, 129.9, 129.1, 126.5, 125.2, 80.4, 71.2, 51.9, 51.7,
51.0, 21.2; IR (KBr/cmꢀ1) ν 3452, 3033, 2920, 1768, 1721, 1514, 1441; HRMS m/z calcd for C21H23O5 [M
+
+ H]+ 355.1545, found 355.1541.
Ethyl 4ꢀ(hydroxy(pꢀtolyl)methyl)ꢀ5ꢀoxoꢀ2ꢀpꢀtolyltetrahydrofuranꢀ3ꢀcarboxylate (6c)
White solid. 239 mg (65 %). m.p. 209ꢀ211 ºC. 1HNMR (500 MHz, CDCl3) δppm
7.25ꢀ6.99 (m, 8 H), 5.51ꢀ5.49 (m, 1 H), 5.02ꢀ5.00 (m, 1 H), 3.73ꢀ3.72 (m, 1 H),
O
O
O
3.66ꢀ3.63 (m, 1 H), 3.55 (q, 2 H, J = 7.0 Hz), 3.46ꢀ3.43 (m, 1 H), 2.31 (s, 3 H) ,
O
13
HO
2.30 (s, 3 H), 0.79ꢀ0.77 (t, 3 H, J = 7.0 Hz); C NMR (125 MHz, CDCl3) δppm
176.7, 168.3, 136.2, 132.2, 130.9, 129.2, 129.0, 126.4, 126.2, 125.7, 79.6, 73.7,
61.2, 49.1, 48.5, 22.7, 21.1, 14.1 ; IR (KBr/cmꢀ1) ν 3447, 3027, 2944, 1767, 1719, 1532, 1435; HRMS m/z
calcd for C22H25O5 [M + H]+ 369.1702, found 369.1701.
+
Methyl 4ꢀ(hydroxy(4ꢀmethoxyphenyl)methyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀoxotetrahydrofuranꢀ3ꢀcarboxylate (6d)
White solid. 262 mg (68 %). m.p. 196ꢀ198 ºC. 1HNMR (500 MHz, CDCl3) δppm
O
7.20ꢀ7.15 (m, 4 H), 6.87ꢀ6.84 (m, 4 H), 5.53 (d, 1 H, J = 6.0 Hz), 5.12 (d, 1 H, J =
O
9.0 Hz), 4.25 (s, 1 H), 3.79 (s, 3 H) , 3.78 (s, 3 H), 3.28 (dd, 1 H, J = 7.5 Hz, J =
O
O
9.0 Hz), 3.24 (s, 3 H), 3.08 (dd, 1 H, J = 6.0 Hz, J = 7.5 Hz); 13C NMR (125 MHz,
CDCl3) δppm 176.8, 168.9, 159.9, 159.8, 131.9, 127.8, 126.7, 125.9, 114.2, 113.8,
80.2, 70.9, 55.3, 51.9, 51.6, 51.1; IR (KBr/cmꢀ1) ν 3444 3025, 2956, 1766, 1721,
O
HO
O
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+
1534, 1429; HRMS m/z calcd for C21H23O7 [M + H]+ 387.1444, found 387.1441.
5
6
7
3,6ꢀDiphenyltetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7a)
8
9
White solid. 247 mg (84 %). m.p. 184ꢀ186 ºC. 1HNMR (500 MHz, CDCl3) δppm
7.46ꢀ7.33 (m, 10 H), 5.90ꢀ5.89 (m, 1 H) , 5.84 (m, 1 H), 3.89ꢀ3.86 (m, 1 H),
3.70ꢀ3.68 (m, 1 H); 13C NMR (125 MHz, CDCl3) δppm 174.5, 171.1, 138.5,
O
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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49
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58
59
60
O
O
133.6, 129.3, 129.2, 129.1, 128.7, 125.6, 124.6, 81.1, 80.3, 50.9, 45.4; IR (KBr/cmꢀ1) ν 3046, 2922, 1775,
+
1767, 1510, 1449; HRMS m/z calcd for C18H15O4 [M + H]+ 295.0970, found 295.0966.
3,6ꢀBis(3,4ꢀdimethylphenyl)tetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7b)
White solid. 301 mg (86 %). m.p. 172ꢀ173 ºC. 1HNMR (500 MHz, CDCl3)
O
O
δppm 7.19ꢀ7.04 (m, 6 H), 5.83ꢀ5.82 (m, 1 H) , 5.77 (m, 1 H), 3.86ꢀ3.83 (m,
O
1 H), 3.67ꢀ3.64 (m, 1 H), 2.28 (s, 3 H) , 2.27 (s, 3 H) , 2.26 (s, 3 H) , 2.16 (s,
O
13
3 H); C NMR (125 MHz, CDCl3) δppm 174.8, 171.4, 137.8, 137.6, 137.0, 135.9, 130.9, 130.3, 129.9,
126.8, 125.9, 123.1, 122.1, 81.2, 80.4, 50.9, 45.6, 19.9, 19.7, 19.5; IR (KBr/cmꢀ1) ν 3040, 2952, 1774, 1768,
1506, 1450; HRMS m/z calcd for C22H23O4 [M + H]+ 351.1596, found 351.1596.
+
3,6ꢀBis(4ꢀmethoxyphenyl)tetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7c)
White solid. 290 mg (82 %). m.p. 158ꢀ160 ºC. 1HNMR (500 MHz, CDCl3)
O
O
O
δppm 7.23 (d, 4 H, J = 8.5 Hz), 6.92 (d, 4 H, J = 8.5 Hz), 5.88 (s, 2 H),
O
O
13
3.80 (s, 6 H), 3.56 (s, 2 H); C NMR (125 MHz, CDCl3) δppm 174.9,
O
160.2, 130.0, 126.2, 114.6, 81.9, 55.4, 48.3; IR (KBr/cmꢀ1) ν 3055, 2947, 1772, 1763, 1510, 1448; HRMS
m/z calcd for C20H19O6 [M + H]+ 355.1182, found 355.1178.
+
3,6ꢀBisꢀ(3ꢀchlorophenyl)tetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7d)
White solid. 279 mg (77 %). m.p. 177ꢀ178 ºC. 1HNMR (500 MHz, CDCl3)
O
Cl
O
δppm 7.39ꢀ7.21 (m, 8 H), 5.85ꢀ5.84 (m, 1 H) , 5.80 (m, 1 H), 3.87ꢀ3.84 (m, 1
O
13
Cl
H), 3.69ꢀ3.67 (m, 1 H); C NMR (125 MHz, CDCl3) δppm 173.8, 170.5,
O
140.2, 135.4, 135.3, 134.8, 130.6, 130.0, 129.5, 129.4, 125.8, 124.8, 123.7, 122.8, 80.1, 79.3, 50.6, 44.9;
+
IR (KBr/cmꢀ1) ν 3037, 2945, 1775, 1769, 1512, 1447; HRMS m/z calcd for C18H13Cl2O4 [M + H]+
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363.0191, found 363.0189.
4
5
6
7
3,6ꢀDi(naphthalenꢀ1ꢀyl)tetrahydrofuro[3,4ꢀc]furanꢀ1,4ꢀdione (7e)
8
9
White solid. 236 mg (60 %). m.p. 252ꢀ254 ºC. 1HNMR (500 MHz, CDCl3)
O
O
10
11
12
13
14
15
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60
δppm 8.28ꢀ8.26 (m, 1 H), 7.97ꢀ7.87 (m, 4 H), 7.74ꢀ7.67 (m, 2 H), 7.63ꢀ7.52
O
(m, 5 H) , 7.44ꢀ7.35 (m, 2 H), 6.63 (m, 1 H), 6.55 (m, 1 H), 4.02ꢀ3.97 (m, 2
O
13
H); C NMR (125 MHz, CDCl3) δppm 174.7, 170.9, 133.9, 129.8, 129.6, 129.3, 127.6, 126.9, 126.6,
1256.0, 125.5, 122.8, 122.2, 121.2, 121.0, 78.8, 78.1, 52.5, 46.9; IR (KBr/cmꢀ1) ν 3064, 2945, 1785, 1771,
+
1639, 1558, 1540, 1507; HRMS m/z calcd for C26H19O4 [M + H]+ 395.1283, found 395.1282.
ACKNOWLEDGMENTS
The project sponsored by the Promotive Research Fund for Excellent Young and MiddleꢀAged Scientists
of Shandong Province (BS2011CL019), and the Scientific Research Foundation for the Returned Overseas
Chinese Scholars, State Education Ministry (Project No. [2007]1108).
Supporting Information Available: CIF files of crystal data, NMR data for products. This material is
available free of charge via the Internet at http://pubs.acs.org.
REFERENCES AND NOTES
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A.; Skrydstrup T.; Procter, D. J. Organic Synthesis Using Samarium Diiodide: Synthetic Strategies and
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Overcoming synthetic challenges in target synthesis using SmI2: recent advances, Vol. 40, RSC Publishing,
Cambridge, Organomet. Chem., 2016, 1ꢀ32.
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ACS Paragon Plus Environment