Tunable Synthesis of 2-Ene-1,4-diones, 4-Hydroxycyclopent-2-en-1-ones, and 2-(Furan-3-yl)acetamides via Palladium-Catalyzed Cascade Reactions of Allenols

Article abstract of DOI:10.1021/acs.joc.8b01753

An efficient and regioselective synthesis of 2-ene-1,4-diones, 4-hydroxycyclopent-2-en-1-ones, or 2-(furan-3-yl)acetamides is successfully realized through palladium-catalyzed one-pot multicomponent reactions of allenols with aryl iodides and carbon monoxide in the presence of tertiary amines. Interestingly, the selectivity depends on the substitution patterns of the allenol substrates. To be specific, from the reaction of allenols with no substituent attached on the internal position of the allenic moiety, 2-ene-1,4-diones or 4-hydroxycyclopent-2-en-1-ones were formed selectively through carbonylation of aryl iodide followed by acylation of allenol with the in situ formed acyl palladium species, β-hydride elimination of the in situ formed allyl palladium complex, and further tautomerization or intramolecular aldol reaction. From the reaction of allenols bearing a substituent at the internal position of the allenic unit, on the other hand, diversely substituted 2-(furan-3-yl)acetamides were formed through a cascade process combining carbonylation of aryl iodide, acylation, and carbonylation of allenol followed by intramolecular condensation and amination by tertiary amine featuring an oxidant-free C-N bond cleavage.

Full text of DOI:10.1021/acs.joc.8b01753

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Article
Tunable Synthesis of 2-Ene-1,4-diones, 4-Hydroxycyclopent-2-
en-1-ones and 2-(Furan-3-yl)acetamides via
Palladium-Catalyzed Cascade Reactions of Allenols
Yan He, Zhi Zheng, Qimeng Liu, Guixian Song, Nan Sun, and Xinyuan Chai
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01753 • Publication Date (Web): 21 Sep 2018
Downloaded from http://pubs.acs.org on September 21, 2018
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Tunable Synthesis of 2-Ene-1,4-diones, 4-Hydroxycyclopent-2-en-1-ones and
2-(Furan-3-yl)acetamides via Palladium-Catalyzed Cascade Reactions of Allenols
Yan He,* Zhi Zheng, Qimeng Liu, Guixian Song, Nan Sun, and Xinyuan Chai
School of Environment, Henan Key Laboratory for Environmental Pollution Control, Collaborative
Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Henan Key
Laboratory of Organic Functional Molecules and Drug Innovation, Henan Normal University,
Xinxiang, Henan 453007, P. R. China.
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E-mail: heyan@htu.cn
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Abstract: An efficient and regio-selective synthesis of 2-ene-1,4-diones, 4-hydroxycyclopent-
2-en-1-ones or 2-(furan-3-yl)acetamides is successfully realized through palladium-catalyzed one-pot
multi-component reactions of allenols with aryl iodides and carbon monoxide in the presence of tertiary
amines. Interestingly, the selectivity is depended on the substitution patterns of the allenol substrates. To
be specific, from the reaction of allenols with no substituent attached on the internal position of the
allenic moiety, 2-ene-1,4-diones or 4-hydroxycyclopent-2-en-1-ones were formed selectively through
carbonylation of aryl iodide followed by acylation of allenol with the in situ formed acyl palladium
species, β-hydride elimination of the in situ formed allyl palladium complex, and further tautomerization
or intramolecular Aldol reaction. From the reaction of allenols bearing a substituent at the internal
position of the allenic unit, on the other hand, diversely substituted 2-(furan-3-yl)acetamides were
formed through a cascade process combining carbonylation of aryl iodide, acylation and cabonylation of
allenol followed by intramolecular condensation and amination by tertiary amine featureing with an
oxidant-free C–N bond cleavage.
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INTRODUCTION
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Cascade carbonylation by using CO as a readily available C1 source has become an attractive
tool in organic chemistry since it allows rapid generation of structurally diverse carbonyl
containing products in a one-pot manner by using simple substrates.1 Meanwhile, allene
derivatives are indispensable intermediates frequently utilized in cascade reactions leading to the
formation of advanced organic compounds.2 In this regard, we have recently reported a novel
synthesis of 2-(furan-3-yl)acetate derivatives through palladium-catalyzed and K2CO3 promoted
one-pot multi-component cascade reactions of allenols with aryl iodides, alcohols and CO
(Scheme 1a).3 As a continuation of our interests in this aspect, we have been trying to prepare
2-(furan-3-yl)acetamide via palladium-catalyzed cascade dicarbonylaion of allenols with aryl
iodides, tertiary amines, and carbon monoxide. Surprisingly, we found that products
2-ene-1,4-diones, 4-hydroxycyclopent-2-en-1-ones and 2-(furan-3-yl)acetamides can be
selectively obtained by controlling the structures of allenols: (i) when allenols without
substituents attached on the internal and terminal positions of the allenic moiety were used as
substrates, but-2-ene-1,4-diones were afforded as the main products (Scheme 1b). Notably, when
phenethyl substituted allenol was used as substrate, 4-hydroxycyclopent-2-en-1-ones were
obtained (Scheme 1c). Instead, for allenols with a substituent on the terminal position of allenic
moiety, 2-enebutane-1,4-diones were formed selectively (Scheme 1d); (ii) when allenols bearing
a substituent attached at the internal position of allenic moiety were used as substrates,
dicarbonylation products 2-(furan-3-yl)acetamides could be formed through carbonylation of
aryl iodide, acylation and carbonylation of allenols, intramolecular condensation of the
α-hydroxylenone intermediate, and amination of the in situ formed 2-(furan-3-yl)acetyl
palladium complex with tertiary amines via oxidant-free C–N bond cleavage (Scheme 1e). In
this cascade dicarbonylative reaction, we deduced tertiary amine was not only used as base to
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promote the construction of furan structure but also as amine source to participate in
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aminocarbonylative process via C–N bond cleavage without oxidant.
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Scheme 1. Diverse Transformations of Allenols
As far as we know, carbonylation between amines and carbon nucleophiles is challenging. The
main problem of this transformation is the higher binding affinity of primary or secondary
amines to the transition metal.4 Thus, tertiary amines could be utilized as an alternative amine
source to avoid the above mentioned problem.5 Although, activation of C–N bond of inert
tertiary amines as well as utilization of this strategy in cascade process still remains a scientific
challenge due to the difficulty of the cleavage of C(sp3)–N bond6 and the requirement of
oxidants.5c,7
In addition, it is well known that furan-carboxamide unit constitutes the core of numerous natural and
pharmaceutical compounds.8 While several efficient and reliable protocols for the preparation of
furan-carboxamide derivatives have been developed,9 most of them usually start from substrates that
already have a furan scaffold or suffer from difficult-to-obtain raw materials. On the other hand,
2-ene-1,4-dione and 4-hydroxycyclopent-2-en-1-one derivatives have attracted intensive interest from
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scientists as they are highly valuable intermediates for the synthesis of numerous fine chemicals and
pharmaceuticals.10,11 Therefore, the development of novel and straightforward methods for efficient
preparation of 2-ene-1,4-dione, 4-hydroxycyclopent-2-en-1-one and furan-carboxamide scaffolds is an
important task in both synthetic and medicinal arena. Based on the above facts, we were interested in a
detailed study on the reaction of allenols with aryl iodides, tertiary amines, and carbon monoxide with
the aim to develop it into a practical and general protocol for the preparation of 2-ene-1,4-diones,
4-hydroxycyclopent-2-en-1-ones and 2-(furan-3-yl)acetamides.
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RESULTS AND DISCUSSION
We started our experiments by using 1-phenylbuta-2,3-dien-1-ol (1a), iodobenzene (2a) and
triethylamine (3a) as substrates in a ratio of 1:2:5, in the presence of PdCl2 (10 mol%), and
o
PivOH (40 mol%) under an atmosphere of CO at 80 C in CH3CN for 8 h. From this reaction,
product 2-methyl-1,4-diphenylbut-2-ene-1,4-dione (4a) was obtained in 51% yield (Table 1,
entry 1). In order to improve the yield of 4a, different palladium salts were tried and Pd(OAc)2
(entry 2) was found to be more effective than PdCl2, Pd(PPh3)2Cl2 , and Pd2(dba)3 (entry 1 and
entries 3-4). Next, the effect of ligands such as PPh3, 2-dicyclohexylphosphino
-2',4',6'-triisopropylbiphenyl (XPhos), 2-dicyclohexylphosphino-2',4',6'-dimethoxybiphenyl
(SPhos),
studied (entries 5-9). It turned out that P(2-furyl)3 is more effective than the other ligands (entry
vs entry 2 and entries 5-8). In further exploration steps, we tried to decrease or increase the
L-proline, and P(2-furyl)3 frequently used in palladium catalyzed carbonylation were
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amounts of ligand and catalyst. However, both resulted in lower efficiencies (entries 10-13). We
next optimized conditions by using different solvents such as toluene, DCE, 1,4-dioxane, and
DMF and found all these attempts did not improve the product yield (entries 14-17). Further
changing the reaction temperature to 120 or 40 °C, the reaction gave a relatively lower
conversion (entries 18-19). Finally, decreased loading of NEt3 (3 eq.) (entry 20) and different
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bases were tried (entries 21-22). The results showed that NEt3 (5 eq.) led to the highest yield of
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4a (entry 9 vs entries 20-22).
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Table 1. Optimization Studies for the Formation of 4aa
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Entry
Catalyst (mol %)
Ligand (mol %)
Solvent
Yield (%) b
T (°C)
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2
PdCl2 (10)
Pd(OAc)2 (10)
Pd(PPh3)2Cl2 (10)
Pd2(dba)3 (5)
PivOH (40)
PivOH (40)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Toluene
DCE
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80
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80
80
120
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80
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80
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PivOH (40)
Trace
Trace
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PivOH (40)
5
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (20)
Pd(OAc)2 (5)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
PPh3 (40)
6
XPhos(40)
40
7
SPhos (40)
30
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L-Proline (40)
P(2-furyl)3 (40)
P(2-furyl)3 (20)
P(2-furyl)3 (80)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
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71
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20c
21d
22e
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1,4-Dioxane
DMF
50
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CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
65
31
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32
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a Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), NEt3 (1.5 mmol), catalyst (0.03 mmol), ligand (0.12 mmol),
solvent (2 mL), CO (1 atm), 8 h. b Isolated yields. c NEt3 (0.9 mmol). d K2CO3 (1.5 mmol). e Cs2CO3 (1.5 mmol).
Having established the optimum conditions, a series of allenols (
1) and iodoaryls (2) were
tried as substrates and the results are listed in Table 2. Initially, aryl iodides with different
substituents attached on the phenyl ring were tested (4a-4f). Among them, a sterically
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encumbered o-methyl iodobenzene seemed reluctant to undergo this reaction, in which 4b was
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obtained in 62% yield. Meanwhile, aryl iodide with electron-donating group (EDG) gave the
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corresponding product (4d) in higher yield than that with electron-withdrawing group (EWG)
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(
4e). Futhermore, iodothiophene survived the reaction conditions, affording 4g in moderate yield.
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Then, we were pleased to find that 1-phenyl substituted allenols with either EDG or EWG on the
phenyl ring underwent this cascade process smoothly to give 4h-4j in moderate to good yields.
Notably, thienyl substituted allenol was successfully engaged into this reaction, providing
but-2-ene-1,4-dione 4k with 72% yield.
Table 2. Substrate Scope for the Synthesis of 4a-4la,b,c
4a, 71%, 5:1
4d, 78%, 4:1
4b, 62%, 2:1
4c, 72%, 6:1
4e, 58%, 7:1
4i, 74%, 8:1
4f, 69%, 5:1
4k, 72%, 6:1
4g, 65%, 6:1
4l, 0%
4h, 66%, > 20:1
4j, 67%, >20:1
a Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), Pd(OAc)2 (0.03 mmol), P(2-furyl)3 (0.12 mmol), Et3N (1.5 mmol),
o
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CH3CN (2 mL), 80 C, 8 h, under CO (1 atm). Isolated yield (as a mixture of Z/E isomer). The configuration of
double bond in 4 was established based on the corresponding NOE experiments.
When phenethyl-allenol was subjected to this reaction, the desired product 4l was not obtained.
11d
Instead, a cyclic product 5-benzyl-4-hydroxy-3-methyl-4-phenylcyclopent-2-en-1-one (5a
)
was observed in 75% yield. Considering 4-hydroxycyclopent-2-en-1-one is a key structural unit
in numerous compounds displaying significant medicinal activities.11 Some other aryl iodides
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were also tried to explore the generality of this cascade reaction for the formation of
4-hydroxycyclopent-2-en-1-ones. It showed that all of them were suitable substrates to give the
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corresponding products 5b-5f with good efficiency (Scheme 2).
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Scheme 2. Synthesis of 4-Hydroxycyclopent-2-en-1-ones (5)
Interestingly, when allenols bearing a phenyl or propyl group instead of hydrogen atom at the
terminal
position
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allenic
moiety
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2-benzylidene-1,4-diphenylbutane-1,4-dione 6a (82%) and 2-butylidene-1,4-diphenylbutane-
1,4-dione 6b (71%) were obtained in high regioselectivity (Table 3). Next, different aryl iodides
(2) were tested and it showed that the steric hindrance effect of these substituents had little
influence on this reaction (6c vs 6d). Aryl iodide with EDG (6e) was more favourable than that
with EWG (6f). Importantly, iodothiophene, thienyl-allenol and alkyl-allenol were also
compatible to the reaction conditions, furnishing the corresponding products 6g, 6h and 6i in
65%, 63% and 66% yields, respectively.
Then, allenol substrate (1a') with substituent attached on the internal position of the allenic
moiety was subjected to the standard conditions as shown in Scheme 3. To our surprise, the
results showed that dicarbonylation product
N,N-diethyl-2-(4-methyl-2,5-diphenylfuran-3-yl)
acetamide (7a, 52%) was composed without the formation of 2-ene-1,4-diones (Scheme 3A).
After a careful screening of conditions, 7a was obtained in a maximum yield of 70% by
changing Pd(OAc)2 and P(furyl)3 into PdCl2 and PivOH (Scheme 3B).
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Table 3. Substrate Scope for the Synthesis of 6 a,b,c
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6e, 78%, 8:1
6a, 82%, > 20:1
6f, 60%, 6:1
6b, 71%, > 20:1
6g, 65%, 9:1
6c, 65%, 4:1
6d, 73%, 2:1
6i, 66%, 2:1
6h, 63%, 10:1
a Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), Pd(OAc)2 (0.03 mmol), P(2-furyl)3 (0.12 mmol), Et3N (1.5 mmol),
o
b
c
CH3CN (2 mL), 80 C, 8 h, under CO (1 atm). Isolated yield (as a mixture of E/Z isomer). The configuration of
double bond in 6 was established based on the corresponding NOE experiments.
Scheme 3. Formation of 2-(Furan-3-yl)acetamide (7a)
Moreover, we were delighted to find that the fourfold scaled-up reaction afforded a
comparable result, wherein the product 7a was obtained in 68% yield (Table 4). Encouraged by
this result, a variety of allenols were used to investigate the scope of this palladium-catalyzed
cascade dicarbonylation method leading to the formation of 2-(furan-3-yl)acetamides (7). Firstly,
various substituents attached on the aromatic ring, including methyl, methoxy, fluoro and even
bromo or chloro, which might participate in palladium-catalyzed coupling reactions, survived the
reaction conditions, allowing possible subsequent elaboration of the products (7b
-7h), and the
electronic nature of these substituents had little influence on this reaction. However, it showed
that the obstacle effect with the allenols lead to relatively low yields of
7 (7f and 7g). A
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heteroaryl-allenol was also suitable substrate. Thienyl furan (7i) could be obtained in a yield as
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high as 77%.
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Table 4. Substrate Scope for the Synthesis of 7 a,b
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7a, 70% (68%)c
7f, 40%
7b, 75%
7g, 47%
7l, 75%
7c, 65%
7h, 55%
7m, 77%
7r, 35%
7d, 60%
7i, 77%
7e, 62%
7j, 83%
7o, 68%
7t, 73%
7y, 30% e,f
7k, 78%
7n, 73%
7s, 45%
7x, 85% d
7p, 70%
7q, 67%
7v, 71%
7aa, 69% h
7u, 55%
7w, 53%
7bb, 65% h
7z, 43% e,g
a Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), 3a (Et3N, 1.5 mmol), PdCl2 (0.03 mmol), PivOH (0.12 mmol),
i
o
b
c
CH3CN (2 mL), 80 C, 8 h, under CO (1 atm). Isolated yield. The yield within parentheses was obtained on a 1.2
mmol scale. d nBu3N instead of 3a. e Et2NMe instead of 3a. f 7a was also obtained in 28% yield at the same time. g 7b was
also obtained in 31% yield at the same time. h iPr2NEt instead of 3a.
Apart from aryl-substituted allenols, a cinnamenyl-substituted allenol, a geraniyl-allenol and
even alkyl-allenols were well compatible to this reaction affording the differently substituted
furyl rings in 73-83% yields (7j-7n). Moreover, in addition to methyl group, allenols bearing
ethyl or phenyl group on the internal position of the allene moiety could also be converted into
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the desired products under the optimized reaction conditions (7o-7r). Secondly, the effect of
iodoaryls ( ) was tested by treating different iodoaryls ( ) with and 3a. The results showed that
the electronic nature of the aryl unit of affected the yield of dramatically (7s-7v). In general,
with EWG (7t) was more favourable than that with EDG (7s), and the obstacle of showed
some effect on the yield of product (7u). Interestingly, starting from 2-iodothiophene,
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N,N-diethyl-2-(4-methyl-2,5-di(thiophen-2-yl)furan-3-yl)acetamide
(
7w)
with fluorescence
property could be conveniently obtained.12 Thirdly, to further explore the substrate generality of
this reaction, diverse amines (3) were treated with different allenols (1) and iodobenzene (2a).
The results showed that symmetric tributylamine with a longer alkyl chain was also compatible
with this process and afford the according product (7x) in 85% yield. Interestingly, when
unsymmetric tertiary amine
acetamides (7a and 7b vs 7y and 7z) were obtained respectively. While, another unsymmetric
amine -ethyl- -isobutyl-2-methylpropan-1-amine furnished products 7aa and 7bb resulting
N-ethyl-N-methylethanamine was used as substrate, different
N
N
from the selectively cleaved CH2–N bonds.
Based on the above observations and previous reports, 3,6c,13,14 plausible pathways accounting
for the formation of
4
,
5
,
6
and 7a are proposed in Scheme 4 and Scheme 5, respectively.
forms intermediate , which then undergoes
. In the presence of , alkene coordination and
Initially, oxidative addition of Pd(0) into
2
A
carbonylation to afford an acylpalladium species
insertion into the Pd–C(O)Ar bond gives an allyl palladium intermediate C.3 Subsequently,
forms intermediate D,13 which then undergoes β-hydride elimination to
B
1
1,3-palladium shift of
C
afford 4-hydroxy-2-methylene-1,4-diphenylbut-3-en-1-ones
E and regenerates Pd(0). Then, E
with hydrogen atoms or substituents on the terminal position of the olefinic moiety, undergoes
, respectively. Instead, when R1 is phenethyl group and R is a
tautomerization to form
4 or 6
hydrogen atom, tautomerization of
E occurs to generate intermediate F, which undergoes
intramolecular Aldol reaction to give cycle product
5.
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Scheme 4. Plausible Mechanism for the Formation of 4, 5 and 6
On the other hand, alkene of 1a' coordinates and inserts into the Pd–C(O)Ph bond of B' which
is formed through the carbonylaion of phenylpalladium(II)iodide (A') to give the allyl palladium
intermediate C'. Due to the steric hindrance influence of methyl group, C' is hard to undergo
1,3-palladium shift to form intermediate D'' and E'' 13
The corresponding product
.
2-ene-1,4-dione will be failed to be obtained. Thus, C' undergoes carbonylation to give an
acylpalladium complex D'.3 By the action of base, an intramolecular nucleophilic addition
occurs with D' to afford intermediate E', which undergoes tautomerization and dehydration to
form the 2-(furan-3-yl)acetyl palladium complex F' and releases water. Then, the palladium of
F' coordinates with the lone pair of 3a to form intermediate G'. Subsequently, intermediate H' is
given through the elimination of HI from G'. Facilitated by the in situ formed water, H' was
transformed into I' via C–N bond cleavage and eliminate acetaldehyde and H2 as by-products.6c,
14 Finally, reductive elimination of I' affords product 7a and regenerates Pd(0) (Scheme 5).
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Scheme 5. Plausible Mechanism for the Formation of 7a
To shed some light on the mechanism, control experiments were carried out. At first, the
reaction of 1a' with 2a and Et2NH ( ) was carried out under standard reaction conditions for the
8
formation of 2-(furan-3-yl)acetamides. Under this circumstance, the yield of 7a decreased to
36% (Scheme 6A), showing that tertiary amine is a more efficient amino source than secondary
amine for this reaction. Then, to verify the effect of water in the aminocarbonylative process via
C–N bond cleavage, 4Å molecule sieves were used to trap the in situ formed water. As a result,
7a was obtained only in 15% yield (Scheme 6B). In addition, when 30 equiv of H2O was added
in the reaction of 1a' with 2a, 3a and CO, 7a was afforded in 67% yield (Scheme 6C). These
results told that water is crucial for aminocarbonylation of allenol 1a', and the amount of water
which was released from the dehydration of 2,5-dihydrofuran-2-ol intermediate is enough to
promote the C–N bond cleavage of tertiary amine 3a
.
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Scheme 6. Control Experiments
CONCLUSION
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In conclusion, we have established an efficient and regio-selective strategy for the preparation of
diversely substituted 2-ene-1,4-diones, 4-hydroxycyclopent-2-en-1-ones and 2-(furan-3-yl)acetamides
from palladium-catalyzed and tertiary amines promoted/participated one-pot multi-component reactions
of allenols with aryl iodides and carbon monoxide. Notably, in the formation of 2-(furan-3-yl)acetamides,
tertiary amine was not only utilized as a base to promote the construction of furan skeleton but also as an
amine source to participate in aminocarbonylative process via C–N bond cleavage. Compared with
previous reports, reactions reported herein have advantages such as high regioselectivity, easily
obtainable substrates, good functional group tolerance and step-efficiency. Further exploitation on the
detailed mechanism is currently underway in our laboratory.
EXPERIMENTAL SECTION
I. General Experimental Information
Commercial reagents were used without further purification, and the solvents were dried before using.
Allenols, with no substituent attached on the internal position of the allenic moiety, were synthesized via
CuI and diisopropylamine promoted one-pot reactions of 1-substituted prop-2-yn-1-ols with
corresponding aldehydes.15 Allenols, bearing a substituent at the internal position of the allenic unit,
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were synthesized through zinc promoted reactions of 1-bromobut-2-yne/1-bromopent-2-yne/
(3-bromoprop-1-yn-1-yl) benzene with the corresponding aldehydes.3,16 Melting points were recorded
with a micro melting point apparatus and uncorrected. The 1H NMR spectra were recorded at 400 MHz
or 600 MHz. The 13C NMR spectra were recorded at 100 MHz or 150 MHz. The 19F NMR spectra were
recorded at 376 and 565 MHz. Chemical shifts were expressed in parts per million (δ) downfield from
the internal standard tetramethylsilane, and were reported as s (singlet), d (doublet), t (triplet), q
(quadruplet), dd (doublet of doublet), td (doublet of triplet), m (multiplet), br s (broad singlet), etc. The
coupling constants J were given in Hz. High resolution mass spectra (HRMS) were obtained via ESI
mode by using a MicrOTOF mass spectrometer. The conversion of starting materials was monitored by
thin layer chromatography (TLC) using silica gel plates (silica gel 60 F254 0.25 mm), and components
were visualized by observation under UV light (254 and 365 nm).
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II. Experimental Procedures and Spectroscopic Data
1. Typical procedure for the preparation of 2-methyl-1,4-diphenylbut-2-ene-1,4-dione (4a)
To a flask containing 1-phenylbuta-2,3-dien-1-ol (1a, 44 mg, 0.3 mmol) and iodobenzene (2a, 67 µL,
0.6 mmol) in CH3CN (2 mL) was added Pd(OAc)2 (7 mg, 0.03 mmol), P(2-furyl)3 (28 mg, 0.12 mmol)
and Et3N (3a, 208 µL, 1.5 mmol). The mixture was then stirred at 80 ºC under CO atmosphere (1 atm)
for 8 h. Upon completion, the reaction was quenched with aqueous NH4Cl and extracted with ethyl
acetate (10 mL × 3). The combined organic layers were washed with water and brine, and dried over
anhydrous Na2SO4. The solvent was evaporated under vacuum and the crude product was purified by
column chromatography on silica-gel to afford 4a-(Z) and 4a-(E) in 59% and 12% yields, respectively.
Other 1,4-dione derivatives 4b-4k, 5a-5f, and 6a-6i were prepared in a similar manner.
(Z)-2-Methyl-1,4-diphenylbut-2-ene-1,4-dione (4a)17
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (44 mg, 59%); 1H NMR (600 MHz, CDCl3) δ:
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2.17 (d, J = 1.8 Hz, 3H), 7.077-7.082 (m, 1H), 7.34-7.38 (m, 4H), 7.46 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 2H),
7.82-7.85 (m, 4H). 13C NMR (150 MHz, CDCl3) δ: 22.2, 122.9, 128.4, 128.6, 128.7, 128.8, 133.3, 133.4,
134.5, 136.9, 156.4, 188.1, 199.4. HRMS calcd for C17H14O2Na: 273.0886 [M+Na]+, found: 273.0886.
(E)-2-Methyl-1,4-diphenylbut-2-ene-1,4-dione (4a)17
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (9 mg, 12%); 1H NMR (600 MHz, CDCl3) δ:
2.28 (d, J = 1.8 Hz, 3H), 7.04 (d, J = 1.2 Hz, 1H), 7.38-7.44 (m, 4H), 7.49-7.54 (m, 2H), 7.80-7.84 (m,
4H). 13C NMR (150 MHz, CDCl3) δ: 16.0, 128.5, 128.7, 128.8, 129.8, 130.5, 133.2, 133.5, 136.2, 137.6,
149.4, 192.1, 198.3. HRMS calcd for C17H14O2Na: 273.0886 [M+Na]+, found: 273.0890.
(Z)-2-Methyl-4-phenyl-1-(o-tolyl)but-2-ene-1,4-dione (4b)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (33 mg, 41%); 1H NMR (400 MHz, CDCl3) δ:
2.28 (d, J = 1.2 Hz, 3H), 2.73 (s, 3H), 7.06 (q, J = 1.6 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 8.0
Hz, 1H), 7.35 (td, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 7.40-7.44 (m, 2H), 7.51-7.58 (m, 2H), 7.85-7.88 (m,
2H). 13C NMR (150 MHz, CDCl3) δ: 21.8, 22.5, 123.2, 123.52, 123.53, 128.5, 128.6, 130.7, 132.1,
132.3, 133.1, 133.8, 137.1, 140.7, 157.1, 188.7, 200.9. HRMS calcd for C18H16O2Na: 287.1043 [M+Na]+,
found: 287.1044.
(E)-2-Methyl-4-phenyl-1-(o-tolyl)but-2-ene-1,4-dione (4b)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (17 mg, 21%); 1H NMR (400 MHz, CDCl3) δ:
2.26 (d, J = 1.2 Hz, 3H), 2.41 (s, 3H), 7.08 (q, J = 1.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.38-7.48 (m, 4H),
7.56-7.58 (m, 1H), 7.82-7.84 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 14.3, 20.1, 125.4, 128.49, 128.53,
128.9, 130.7, 131.3, 133.7, 134.4, 137.0, 137.3, 137.7, 148.7, 192.7, 200.6. HRMS calcd for
C18H16O2Na: 287.1043 [M+Na]+, found: 287.1046.
(Z)-2-Methyl-4-phenyl-1-(m-tolyl)but-2-ene-1,4-dione (4c)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (49 mg, 62%); 1H NMR (600 MHz, CDCl3) δ:
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2.16 (d, J = 1.2 Hz, 3H), 2.29 (s, 3H), 7.07 (d, J = 1.2 Hz, 1H), 7.23 (t, J = 7.8 Hz, 1H), 7.27 (d, J = 7.2
Hz, 1H), 7.35 (t, J = 7.8 Hz, 2H), 7.46 (t, J = 7.8 Hz, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.69 (s, 1H), 7.83
(dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 21.4, 22.3, 122.8, 125.8, 128.6, 128.7,
128.8, 133.2, 134.2, 134.5, 137.0, 138.7, 156.5, 188.1, 199.6. HRMS calcd for C18H17O2: 265.1223
[M+H]+, found: 265.1224.
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(E)-2-Methyl-4-phenyl-1-(m-tolyl)but-2-ene-1,4-dione (4c)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (8 mg, 10%); 1H NMR (400 MHz, CDCl3) δ:
2.28 (d, J = 1.6 Hz, 3H), 2.36 (s, 3H), 7.03 (d, J = 1.6 Hz, 1H), 7.31-7.34 (m, 2H), 7.40 (t, J = 7.2 Hz,
2H), 7.51 (t, J = 7.6 Hz, 1H), 7.58-7.62 (m, 2H), 7.84 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 2H 1H). 13C NMR
(100 MHz, CDCl3) δ: 16.0, 21.4, 127.1, 128.46, 128.53, 128.8, 130.2, 130.3, 133.5, 134.0, 136.2, 137.7,
138.6, 149.7, 192.1, 198.5. HRMS calcd for C18H17O2: 265.1223 [M+H]+, found: 265.1220.
(Z)-1-(4-Methoxyphenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4d)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (52 mg, 62%); 1H NMR (600 MHz, CDCl3) δ:
2.15 (d, J = 1.8 Hz, 3H), 3.74 (s, 3H), 6.83 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H), 7.03-7.04 (m, 1H),
7.33-7.35 (m, 2H), 7.44-7.46 (m, 1H), 7.79-7.84 (m, 4H). 13C NMR (150 MHz, CDCl3) δ: 22.4, 55.5,
114.1, 122.6, 127.7, 128.6, 128.7, 130.8, 133.2, 137.1, 156.4, 163.8, 188.2, 198.1. HRMS calcd for
C18H16O3Na: 303.0992 [M+Na]+, found: 303.0997.
(E)-1-(4-Methoxyphenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4d)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (13 mg, 16%); 1H NMR (600 MHz, CDCl3) δ:
2.30 (d, J = 1.8 Hz, 3H), 3.81 (s, 3H), 6.90 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H), 6.98 (d, J = 1.8 Hz, 1H),
7.39 (t, J = 7.8 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.82-7.85 (m, 4H). 13C NMR (150 MHz, CDCl3) δ:
16.5, 55.6, 114.0, 128.3, 128.51, 128.53, 128.8, 132.3, 133.4, 137.9, 150.7, 163.9, 191.9, 196.9. HRMS
calcd for C18H16O3Na: 303.0992 [M+Na]+, found: 303.0994.
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(Z)-1-(4-Fluorophenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4e)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (41 mg, 51%); 1H NMR (600 MHz, CDCl3) δ:
2.16 (d, J = 1.2 Hz, 3H), 7.04 (td, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H), 7.08 (d, J = 1.2 Hz, 1H), 7.35-7.38 (m,
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2H), 7.46-7.49 (m, 1H), 7.83-7.87 (m, 4H). 13C NMR (150 MHz, CDCl3) δ: 22.1, 116.0 (d, JC-F = 21.9
3
1
Hz), 123.0, 128.6, 128.7, 131.0 (d, JC-F = 9.8 Hz), 131.1, 133.4, 136.8, 155.9, 165.9 (d, JC-F = 252.8
Hz), 188.1, 197.9. 19F NMR (565 MHz, CDCl3) δ: -104.8. HRMS calcd for C17H13FO2Na: 291.0792
[M+Na]+, found: 291.0796.
(E)-1-(4-Fluorophenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4e)
1
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (6 mg, 7%); H NMR (600 MHz, CDCl3) δ:
2.28 (d, J = 1.2 Hz, 3H), 7.00 (d, J = 1.8 Hz, 1H), 7.11 (t, J = 8.4 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H), 7.51
(t, J = 7.8 Hz, 1H), 7.82-7.86 (m, 4H). 13C NMR (150 MHz, CDCl3) δ: 16.1, 115.9 (d, 2JC-F = 21.9 Hz),
3
1
128.5, 128.9, 130.0, 132.4 (d, JC-F = 8.7 Hz), 132.5, 133.6, 137.6, 149.4, 165.9 (d, JC-F = 239.6 Hz),
191.9, 196.7. 19F NMR (565 MHz, CDCl3) δ: -104.4. HRMS calcd for C17H13FO2Na: 291.0792 [M+Na]+,
found: 291.0802.
(Z)-1-(4-Chlorophenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4f)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (49 mg, 58%); 1H NMR (600 MHz, CDCl3) δ:
2.16 (d, J = 1.8 Hz, 3H), 7.09 (q, J = 1.8 Hz, 1H), 7.33-7.38 (m, 4H), 7.48 (t, J = 7.2 Hz, 1H), 7.76-7.78
(m, 2H), 7.82-7.84 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 22.0, 123.1, 128.6, 128.7, 129.2, 129.7,
132.9, 133.4, 136.7, 139.7, 155.8, 188.1, 198.2. HRMS calcd for C17H13ClO2Na: 307.0496 [M+Na]+,
found: 307.0494.
(E)-1-(4-Chlorophenyl)-2-methyl-4-phenylbut-2-ene-1,4-dione (4f)
o
1
Eluent: ethyl acetate/petroleum ether (1:20); yellow solid (9 mg, 11%), mp 94-95 C; H NMR (600
MHz, CDCl3) δ: 2.27 (d, J = 1.2 Hz, 3H), 7.01 (d, J = 1.2 Hz, 1H), 7.39-7.42 (m, 4H), 7.51 (t, J = 7.2 Hz,
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1H), 7.75 (d, J = 8.4 Hz, 2H), 7.82 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ:
16.0, 128.5, 128.9, 129.0, 130.6, 131.2, 133.7, 134.5, 137.5, 139.7, 149.0, 191.9, 197.0. HRMS calcd for
C17H13ClO2Na: 307.0496 [M+Na]+, found: 307.0510.
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(Z)-2-Methyl-4-phenyl-1-(thiophen-2-yl)but-2-ene-1,4-dione (4g)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (43 mg, 56%); 1H NMR (400 MHz, CDCl3) δ:
2.20 (d, J = 1.6 Hz, 3H), 6.98-6.99 (m, 1H), 7.02 (d, J = 1.2 Hz, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.47-7.48
(m, 2H), 7.55 (dd, J1 = 4.8 Hz, J2 = 1.2 Hz, 1H), 7.83 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 2H). 13C NMR (150
MHz, CDCl3) δ: 22.3, 123.4, 128.2, 128.6, 128.7, 132.7, 133.3, 134.1, 137.1, 142.1, 154.7, 188.3, 191.5.
HRMS calcd for C15H12O2SNa: 279.0450 [M+Na]+, found: 279.0462.
(E)-2-Methyl-4-phenyl-1-(thiophen-2-yl)but-2-ene-1,4-dione (4g)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (7 mg, 9%); H NMR (400 MHz, CDCl3) δ:
2.37 (d, J = 1.2 Hz, 3H), 7.17-7.20 (m, 1H), 7.26-7.28 (m, 1H), 7.49 (t, J = 8.0 Hz, 2H), 7.60 (t, J = 7.6
13
Hz, 1H), 7.76-7.77 (m, 2H), 7.95 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 2H). C NMR (150 MHz, CDCl3) δ:
16.2, 128.3, 128.5, 128.6, 128.9, 133.6, 134.7, 135.3, 137.7, 142.4, 149.8, 189.9, 191.8. HRMS calcd for
C15H12O2SNa: 279.0450 [M+Na]+, found: 279.0450.
(Z)-4-(2-Methoxyphenyl)-2-methyl-1-phenylbut-2-ene-1,4-dione (4h)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (55 mg, 66%); 1H NMR (400 MHz, CDCl3) δ:
2.02 (s, 3H), 3.94 (s, 3H), 6.94-6.96 (m, 2H), 7.12 (s, 1H), 7.45 (t, J = 7.6 Hz, 3H), 7.53 (d, J = 7.6 Hz,
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2H), 7.96 (d, J = 7.6 Hz, 2H). C NMR (150 MHz, CDCl3) δ: 22.0, 55.7, 111.5, 120.8, 127.9, 128.0,
128.5, 128.7, 131.2, 133.2, 133.9, 134.6, 153.0, 158.7, 190.0, 199.7. HRMS calcd for C18H16O3Na:
303.0992 [M+Na]+, found: 303.0992.
(Z)-4-(4-Methoxyphenyl)-2-methyl-1-phenylbut-2-ene-1,4-dione (4i)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (55 mg, 66%); 1H NMR (400 MHz, CDCl3) δ:
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2.23 (d, J = 1.2 Hz, 3H), 3.84 (s, 3H), 6.90 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 1.2 Hz, 1H), 7.44 (t, J = 7.2
Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.90-7.93 (m, 4H). 13C NMR (100 MHz, CDCl3) δ: 22.1, 55.5, 113.9,
122.9, 128.4, 128.7, 129.9, 131.0, 133.2, 134.6, 155.4, 163.7, 186.5, 199.6. HRMS calcd for
C18H16O3Na: 303.0992 [M+Na]+, found: 303.0992.
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(E)-4-(4-Methoxyphenyl)-2-methyl-1-phenylbut-2-ene-1,4-dione (4i)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (7 mg, 8%); H NMR (400 MHz, CDCl3) δ:
2.24 (d, J = 1.6 Hz, 3H), 3.80 (s, 3H), 6.86 (dd, J1 = 6.8 Hz, J2 = 2.0 Hz, 2H), 7.00 (d, J = 1.6 Hz, 1H),
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7.43 (t, J = 7.2 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.79-7.83 (m, 4H). C NMR (150 MHz, CDCl3) δ:
15.8, 55.6, 114.0, 128.6, 129.8, 130.6, 131.0, 131.5, 133.0, 136.4, 148.0, 164.0, 190.7, 198.4. HRMS
calcd for C18H16O3Na: 303.0992 [M+Na]+, found: 303.0993.
(Z)-4-(4-Fluorophenyl)-2-methyl-1-phenylbut-2-ene-1,4-dione (4j)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (54 mg, 67%); 1H NMR (400 MHz, CDCl3) δ:
2.17 (d, J = 1.2 Hz, 3H), 7.01-7.05 (m, 3H), 7.36-7.39 (m, 2H), 7.46-7.50 (m, 1H), 7.82-7.88 (m, 4H).
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13C NMR (150 MHz, CDCl3) δ: 22.3, 115.9 (d, JC-F = 21.8 Hz), 122.5, 128.4, 128.9, 131.3 (d, JC-F
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8.7 Hz), 133.3 (d, JC-F = 2.3 Hz), 133.5, 134.4, 156.8, 165.9 (d, JC-F = 253.8 Hz), 186.6, 199.4. F
NMR (565 MHz, CDCl3) δ: -104.6. HRMS calcd for C17H13FO2Na: 291.0792 [M+Na]+, found:
291.0799.
(Z)-2-Methyl-1-phenyl-4-(thiophen-2-yl)but-2-ene-1,4-dione (4k)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (48 mg, 62%); 1H NMR (400 MHz, CDCl3) δ:
2.23 (d, J = 1.6 Hz, 3H), 6.98 (q, J = 1.6 Hz, 1H), 7.12-7.14 (m, 1H), 7.43-7.47 (m, 2H), 7.52-7.56 (m,
1H), 7.63 (dd, J1 = 5.2 Hz, J2 = 1.2 Hz, 1H), 7.77 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.90-7.93 (m, 2H).
13C NMR (150 MHz, CDCl3) δ: 22.1, 122.9, 128.4, 128.5, 128.8, 132.5, 133.4, 134.5, 134.6, 144.3,
156.1, 180.4, 199.1. HRMS calcd for C15H12O2SNa: 279.0450 [M+Na]+, found: 279.0459.
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(E)-2-Methyl-1-phenyl-4-(thiophen-2-yl)but-2-ene-1,4-dione (4k)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (8 mg, 10%); 1H NMR (400 MHz, CDCl3) δ:
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2.44 (d, J = 1.6 Hz, 3H), 7.04 (q, J = 1.6 Hz, 1H), 7.11-7.13 (m, 1H), 7.49-7.53 (m, 2H), 7.61-7.64 (m,
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2H), 7.68 (dd, J1 = 5.2 Hz, J2 = 1.2 Hz, 1H), 7.86-7.88 (m, 2H). C NMR (150 MHz, CDCl3) δ: 16.1,
128.4, 128.67, 128.72, 129.8, 132.4, 133.3, 134.7, 136.0, 145.7, 150.6, 183.6, 198.2. HRMS calcd for
C15H12O2SNa: 279.0450 [M+Na]+, found: 279.0461.
(4R*, 5R*)-5-Benzyl-4-hydroxy-3-methyl-4-phenylcyclopent-2-en-1-one (5a)11d
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (63 mg, 75%); 1H NMR (600 MHz, CDCl3) δ:
1.86 (s, 3H), 2.20-2.23 (m, 2H), 3.12-3.17 (m, 2H), 6.14 (s, 1H), 6.76 (d, J = 7.2 Hz, 2H), 7.12-7.15 (m,
5H), 7.30-7.34 (m, 3H). 13C NMR (150 MHz, CDCl3) δ: 13.6, 31.4, 62.9, 85.2, 125.8, 126.2, 127.7,
128.30, 128.34, 128.7, 129.3, 139.3, 139.4, 176.7, 204.9. HRMS calcd for C19H17O2: 277.1234 [M-H]-,
found: 277.1234.
(4R*, 5R*)-5-Benzyl-4-hydroxy-3-methyl-4-(m-tolyl)cyclopent-2-en-1-one (5b)
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (61 mg, 70%);1H NMR (400 MHz, CDCl3) δ:
1.87 (d, J = 1.2 Hz, 3H), 2.14-2.24 (m, 2H), 2.30 (s, 3H), 3.10-3.16 (m, 2H), 6.14 (d, J = 1.6 Hz, 1H),
6.16-6.85 (m, 3H), 7.10-7.26 (m, 6H). 13C NMR (150 MHz, CDCl3) δ: 13.7, 21.6, 31.5, 62.7, 85.3, 122.9,
126.1, 128.2, 128.4, 128.8, 129.4, 139.2, 139.3, 176.7, 205.1. HRMS calcd for C20H19O2: 291.1391
[M-H]-, found: 291.1393.
(4R*, 5R*)-5-Benzyl-4-hydroxy-3-methyl-4-(p-tolyl)cyclopent-2-en-1-one (5c)
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (62 mg, 71%); 1H NMR (400 MHz, CDCl3) δ:
1.85 (d, J = 1.2 Hz, 3H), 2.18-2.24 (m, 1H), 2.36 (s, 3H), 2.46 (br s, 1H), 3.05-3.13 (m, 2H), 6.10 (d, J =
13
1.2 Hz, 1H), 6.80-6.95 (m, 3H), 7.11-7.25 (m, 6H). C NMR (150 MHz, CDCl3) δ: 13.6, 21.1, 31.4,
62.9, 85.2, 125.7, 126.1, 128.2, 128.8, 129.0, 129.1, 136.4, 137.4, 139.6, 177.0, 205.2. HRMS calcd for
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C20H19O2: 291.1391 [M-H]-, found: 291.1393.
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(4R*, 5R*)-5-Benzyl-4-(4-chlorophenyl)-4-hydroxy-3-methylcyclopent-2-en-1-one (5d)
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Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (73 mg, 78%); 1H NMR (600 MHz, CDCl3) δ:
1.86 (s, 3H), 2.15-2.20 (m, 1H), 2.33 (br s, 1H), 3.13-3.16 (m, 2H), 6.14 (s, 1H), 6.79 (d, J = 7.2 Hz, 2H),
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7.03-7.17 (m, 5H), 7.29 (d, J = 7.8 Hz, 2H). C NMR (150 MHz, CDCl3) δ: 13.6, 31.4, 62.7, 84.9,
126.3, 127.4, 128.4, 128.5, 128.6, 129.5, 133.7, 138.1, 139.0, 176.4, 204.6. HRMS calcd for C19H16ClO2:
311.0844 [M-H]-, found: 311.0849.
(4R*, 5R*)-4-(5-Benzyl-1-hydroxy-2-methyl-4-oxocyclopent-2-en-1-yl)benzonitrile (5e)
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (75 mg, 82%); 1H NMR (400 MHz, CDCl3) δ:
1.85 (q, J = 1.2 Hz, 3H), 2.03 (br s, 1H), 2.07-2.14 (m, 1H), 3.13-3.23 (m, 2H), 6.20 (d, J = 1.2 Hz, 1H),
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6.74-6.76 (m, 2H), 7.13-7.16 (m, 5H), 7.59 (dd, J1 = 7.8 Hz, J2 = 1.6 Hz, 2H). C NMR (150 MHz,
CDCl3) δ: 13.7, 31.5, 62.4, 85.0, 111.6, 118.5, 126.4, 128.4, 128.5, 130.2, 138.5, 145.1, 176.1, 204.4.
HRMS calcd for C20H16NO2: 302.1187 [M-H]-, found: 302.1188.
(4R*, 5R*)-5-Benzyl-4-hydroxy-3-methyl-4-(thiophen-2-yl)cyclopent-2-en-1-one (5f)
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (52 mg, 61%); 1H NMR (400 MHz, CDCl3) δ:
1.91 (d, J = 1.2 Hz, 3H), 2.29-2.35 (m, 1H), 2.69 (br s, 1H), 3.04-3.12 (m, 2H), 5.97 (d, J = 1.2 Hz, 1H),
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6.55 (dd, J1 = 3.6 Hz, J2 = 1.2 Hz, 1H), 6.88-6.93 (m, 3H), 7.07-7.18 (m, 4H). C NMR (150 MHz,
CDCl3) δ: 12.5, 30.3, 61.5, 83.4, 123.5, 124.2, 125.2, 126.4, 127.4, 127.6, 127.7, 138.5, 144.2, 175.4,
203.0. HRMS calcd for C17H15O2S: 283.0798 [M-H]-, found: 283.0787.
2-Benzylidene-1,4-diphenylbutane-1,4-dione (6a)18
Eluent: ethyl acetate/petroleum ether (1:20); yellow solid (80 mg, 82%), mp 87-89 C (lit.17 89-90
o
oC);1H NMR (400 MHz, CDCl3) δ: 4.49 (s, 2H), 7.28-7.38 (m, 5H), 7.44 (s, 1H), 7.51 (t, J = 7.6 Hz, 4H),
7.59 (t, J = 8.4 Hz, 2H), 7.97 (d, J = 7.2 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3)
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δ: 38.6, 128.2, 128.3, 128.7, 128.8, 130.0, 132.0, 133.3, 135.3, 136.1, 136.7, 138.2, 143.9, 197.7, 198.6.
HRMS calcd for C23H18O2Na: 349.1199 [M+Na]+, found: 349.1198.
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2-Butylidene-1,4-diphenylbutane-1,4-dione (6b)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (62 mg, 71%); 1H NMR (600 MHz, CDCl3) δ:
0.86 (t, J = 7.2 Hz, 3H), 1.39-1.43 (m, 2H), 2.15-2.19 (m, 2H), 4.16 (s, 2H), 6.43 (t, J = 7.2 Hz, 1H),
7.36 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H), 7.45 (t, J = 7.8 Hz, 1H), 7.50 (t, J = 7.8 Hz, 1H), 7.70
(d, J = 7.2 Hz, 2H), 7.96 (d, J = 7.8 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.9, 22.0, 31.4, 36.9,
128.1, 128.3, 128.7, 129.7, 131.6, 133.2, 135.3, 136.8, 138.5, 148.5, 197.0, 198.2. HRMS calcd for
C20H20O2Na: 315.1356 [M+Na]+, found: 315.1356.
(E)-2-Butylidene-4-phenyl-1-(o-tolyl)butane-1,4-dione (6c)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (48 mg, 52%); 1H NMR (400 MHz, CDCl3) δ:
0.88 (t, J = 7.2 Hz, 3H), 1.39-1.45 (m, 2H), 2.17-2.22 (m, 2H), 2.33 (s, 3H), 4.19 (s, 2H), 6.49 (t, J = 7.6
Hz, 1H), 7.21 (d, J = 7.6 Hz, 2H), 7.29-7.33 (m, 2H), 7.49 (t, J = 8.0 Hz, 2H), 7.56-7.60 (m, 1H),
8.05-8.07 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.9, 19.6, 21.7, 31.7, 35.7, 125.0, 128.1, 128.3,
128.6, 129.5, 130.6, 133.2, 136.1, 136.7, 136.9, 139.2, 151.9, 196.9, 199.8. HRMS calcd for
C21H22O2Na: 329.1512 [M+Na]+, found: 329.1508.
(Z)-2-Butylidene-4-phenyl-1-(o-tolyl)butane-1,4-dione (6c)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (12 mg, 13%); 1H NMR (600 MHz, CDCl3) δ:
0.72 (t, J = 7.2 Hz, 3H), 1.26-1.29 (m, 2H), 1.76-1.80 (m, 2H), 2.45 (s, 3H), 4.13 (s, 2H), 6.02 (t, J = 7.8
Hz, 1H), 7.23-7.26 (m, 2H), 7.35 (t, J = 7.2 Hz, 1H), 7.45 (t, J = 7.2 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H),
7.82 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.6, 20.3, 22.3, 31.8,
45.1, 125.7, 128.3, 128.6, 130.1, 130.9, 131.3, 133.2, 135.1, 136.6, 137.3, 139.6, 142.6, 198.0, 199.8.
HRMS calcd for C21H22O2Na: 329.1512 [M+Na]+, found: 329.1509.
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2-Butylidene-4-phenyl-1-(m-tolyl)butane-1,4-dione (6d)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (67 mg, 73%); 1H NMR (400 MHz, CDCl3) δ:
(major) 0.93 (t, J = 7.2 Hz, 3H), 1.45-1.51 (m, 2H), 2.21-2.27 (m, 2H), 2.41 (s, 3H), 4.16 (s, 2H), 6.50 (t,
J = 7.6 Hz, 1H), 7.31-7.36 (m, 2H), 7.42-7.50 (m, 2H), 7.53-7.59 (m, 2H), 7.81-7.83 (m, 1H), 8.03 (dd,
J1 = 7.6 Hz, J2 = 1.6 Hz, 2H). (minor) 0.75 (t, J = 7.2 Hz, 3H), 1.28-1.34 (m, 2H), 1.80-1.86 (m, 2H),
2.40 (s, 3H), 4.15 (s, 2H), 5.90 (t, J = 7.6 Hz, 1H), 7.31-7.36 (m, 2H), 7.42-7.50 (m, 2H), 7.53-7.59 (m,
3H), 7.95-7.97 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: (mixture) 13.6, 13.9, 21.36, 21.37, 22.0, 22.3,
31.4, 32.3, 36.9, 45.8, 126.9, 127.0, 127.9, 128.29, 128.35, 128.36, 128.62, 128.64, 129.8, 130.1, 132.4,
133.2, 133.3, 133.5, 133.7, 135.3, 136.4, 136.8, 137.9, 138.2, 138.37, 138.42, 138.5, 148.6, 197.1, 197.7,
198.4, 199.1. HRMS calcd for C21H22O2Na: (mixture) 329.1512 [M+Na]+, found: 329.1513.
2-Butylidene-1-(4-methoxyphenyl)-4-phenylbutane-1,4-dione (6e)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (75 mg, 78%); 1H NMR (600 MHz, CDCl3) δ:
0.86 (t, J = 7.2 Hz, 3H), 1.39-1.43 (m, 2H), 2.14-2.17 (m, 2H), 3.78 (s, 3H), 4.15 (s, 2H), 6.35 (t, J = 7.2
Hz, 1H), 6.85 (d, J = 7.8 Hz, 2H), 7.38 (t, J = 7.8 Hz, 2H), 7.48 (t, J = 7.8 Hz, 1H), 7.74 (d, J = 7.8 Hz,
2H), 7.94 (d, J = 7.2 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.9, 22.0, 31.3, 37.4, 55.4, 113.4, 128.3,
128.6, 130.8, 132.1, 133.2, 135.1, 136.8, 146.5, 162.7, 197.1, 197.2. HRMS calcd for C21H22O3Na:
345.1461 [M+Na]+, found: 345.1461.
2-Butylidene-1-(4-fluorophenyl)-4-phenylbutane-1,4-dione (6f)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (56 mg, 60%); 1H NMR (600 MHz, CDCl3) δ:
0.86 (t, J = 7.2 Hz, 3H), 1.39-1.43 (m, 2H), 2.15-2.19 (m, 2H), 4.16 (s, 2H), 6.36 (t, J = 7.2 Hz, 1H),
7.05 (t, J = 7.8 Hz, 2H), 7.41 (t, J = 7.2 Hz, 2H), 7.51 (t, J = 7.2 Hz, 1H), 7.76 (d, J = 6.6 Hz, 2H), 7.95
2
(d, J = 7.8 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.9, 22.0, 31.3, 37.1, 115.2 (d, JC-F = 21.9 Hz),
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128.3, 128.7, 132.3 (d, JC-F = 8.9 Hz), 133.3, 135.3, 136.7, 147.6, 165.1 (d, JC-F = 269.1 Hz), 196.9,
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197.0. F NMR (376 MHz, CDCl3) δ: (major) -107.5; (minor) -105.7. HRMS calcd for C20H19FO2Na:
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333.1261 [M+Na]+, found: 333.1237.
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2-Butylidene-4-phenyl-1-(thiophen-2-yl)butane-1,4-dione (6g)
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Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (58 mg, 65%); 1H NMR (400 MHz, CDCl3) δ:
0.92-0.99 (m, 3H), 1.51-1.57 (m, 2H), 2.24-2.29 (m, 2H), 4.21 (s, 2H), 6.75 (t, J = 7.2 Hz, 1H),
7.12-7.14 (m, 1H), 7.45-7.48 (m, 2H), 7.57 (t, J = 7.2 Hz, 1H), 7.63 (dd, J1 = 4.8 Hz, J2 = 1.2 Hz, 1H),
7.72 (dd, J1 = 3.6 Hz, J2 = 1.2 Hz, 1H), 8.00-8.02 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: 13.9, 22.1,
31.3, 37.5, 127.6, 128.3, 128.6, 133.1, 133.2, 133.8, 135.2, 136.7, 143.2, 145.5, 189.4, 196.7. HRMS
calcd for C18H18O2SNa: 321.0920 [M+Na]+, found: 321.0928.
2-Butylidene-1-phenyl-4-(thiophen-2-yl)butane-1,4-dione (6h)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (56 mg, 63%); 1H NMR (400 MHz, CDCl3) δ:
(major) 0.94 (t, J = 7.6 Hz, 3H), 1.46-1.52 (m, 2H), 2.26-2.31 (m, 2H), 4.17 (s, 2H), 6.51 (t, J = 7.6 Hz,
1H), 7.14-7.16 (m, 1H), 7.43 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 2H), 7.50 (t, J = 5.2 Hz, 1H), 7.64 (dd, J1 =
5.2 Hz, J2 = 1.2 Hz, 1H), 7.74-7.76 (m, 2H), 7.86 (dd, J1 = 4.0 Hz, J2 = 1.2 Hz, 1H). 13C NMR (150 MHz,
CDCl3) δ: (mixture) 13.6, 13.9, 21.9, 22.3, 31.5, 32.3, 37.4, 46.2, 128.1, 128.2, 128.5, 129.5, 129.7,
131.7, 132.4, 132.5, 132.9, 133.7, 134.7, 138.4, 138.8, 143.8, 149.1, 189.8, 198.1. HRMS calcd for
C18H18O2SNa: (mixture) 321.0920 [M+Na]+, found: 321.0933.
2-Butylidene-1,6-diphenylhexane-1,4-dione (6i)
Eluent: ethyl acetate/petroleum ether (1:20); yellow liquid (63 mg, 66%); 1H NMR (400 MHz, CDCl3) δ:
(major) 0.91 (t, J = 7.2 Hz, 3H), 1.41-1.46 (m, 2H), 2.12-2.17 (m, 2H), 2.77-2.94 (m, 4H), 3.58 (s, 2H),
6.45 (t, J = 7.6 Hz, 1H), 7.13-7.20 (m, 2H), 7.23-7.29 (m, 2H), 7.39-7.55 (m, 4H), 7.67-7.69 (m, 1H),
7.93 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H). (minor) 0.74 (t, J = 7.2 Hz, 3H), 1.27-1.32 (m, 2H), 1.76-1.80
(m, 2H), 2.77-2.94 (m, 4H), 3.51 (s, 2H), 5.82 (t, J = 7.6 Hz, 1H), 7.13-7.20 (m, 2H), 7.23-7.29 (m, 4H),
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7.39-7.55 (m, 2H), 7.67-7.69 (m, 2H). 13C NMR (150 MHz, CDCl3) δ: (mixture) 13.6, 13.9, 21.9, 22.3,
29.5, 29.7, 29.8, 31.4, 32.2, 41.1, 43.9, 44.2, 49.7, 126.1, 128.1, 128.3, 128.4, 128.52, 128.54, 129.4,
129.5, 131.7, 133.0, 133.1, 134.9, 138.2, 138.3, 138.7, 141.0, 141.1, 149.1, 198.1, 198.9, 206.7, 207.3.
HRMS calcd for C22H25O2: (mixture) 321.1849 [M+H]+, found: 321.1829.
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2. Typical procedure for the preparation of N,N-diethyl-2-(4-methyl-2,5-diphenyl-furan-3-yl)-
acetamide (7a)
To a flask containing 2-methyl-1-phenylbuta-2,3-dien-1-ol (1a', 48 mg, 0.3 mmol) and iodobenzene
(2a, 67 µL, 0.6 mmol) in CH3CN (2 mL) was added PdCl2 (5 mg, 0.03 mmol), PivOH (12 mg, 0.12
mmol) and NEt3 (3a, 208 µL, 1.5 mmol). The mixture was then stirred at 80 ºC under CO atmosphere (1
atm). Upon completion, the reaction was quenched with aqueous NaCl and extracted with ethyl acetate
(10 mL × 3). The combined organic layers were washed with water and brine, and dried over anhydrous
Na2SO4. The solvent was evaporated under vacuum and the crude product was purified by column
chromatography on silica-gel to afford 7a in 70% yield. Other furan derivatives 7b-7bb were prepared in
a similar manner.
N,N-Diethyl-2-(4-methyl-2,5-diphenyl-furan-3-yl)-acetamide (7a)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (73 mg, 70%); 1H NMR (400 MHz, CDCl3) δ:
1.17 (t, J = 7.2 Hz, 6H), 2.27 (s, 3H), 3.37 (q, J = 7.2 Hz, 2H), 3.45 (q, J = 7.2 Hz, 2H), 3.69 (s, 2H),
7.28-7.34 (m, 2H), 7.43 (t, J = 7.6 Hz, 4H), 7.62 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ: 10.2, 13.1, 14.2, 29.9, 40.7, 42.3, 118.0, 119.1, 125.7, 126.5, 126.7, 127.4, 128.5,
128.6, 131.3, 131.8, 148.0, 149.2, 169.2. HRMS calcd for C23H25NO2Na: 370.1777 [M+Na]+, found:
370.1778.
N,N-Diethyl-2-(5-(4-methoxyphenyl)-4-methyl-2-phenylfuran-3-yl)acetamide (7b)
Eluent: ethyl acetate/petroleum ether (1:5); yellow liquid (85 mg, 75%); 1H NMR (600 MHz, CDCl3) δ:
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1.08 (t, J = 7.2 Hz, 6H), 2.14 (s, 3H), 3.28 (q, J = 7.2 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 3.59 (s, 2H),
3.78 (s, 3H), 6.89 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H), 7.23 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.8 Hz, 2H),
7.51 (d, J = 7.2 Hz, 2H), 7.55 (dd, J1 = 7.2 Hz, J2 = 1.8 Hz, 2H). 13C NMR (150 MHz, CDCl3) δ: 10.1,
13.1, 14.2, 30.0, 40.7, 42.3, 55.3, 114.0, 117.5, 117.9, 124.8, 126.4, 127.22, 127.24, 128.6, 131.4, 148.1,
148.6, 158.6, 169.2. HRMS calcd for C24H28NO3: 378.2064 [M+H]+, found: 378.2063.
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N,N-Diethyl-2-(4-methyl-2-phenyl-5-p-tolylfuran-3-yl)acetamide (7c)
Eluent: ethyl acetate/petroleum ether (1:10); yellow solid (70 mg, 65%), mp 120-121 oC; 1H NMR (400
MHz, CDCl3) δ: 1.11-1.17 (m, 6H), 2.23 (s, 3H), 2.38 (s, 3H), 3.36 (q, J = 7.2 Hz, 2H), 3.45 (q, J = 7.2
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Hz, 2H), 3.66 (s, 2H), 7.22-7.31 (m, 2H), 7.38-7.43 (m, 3H), 7.57-7.60 (m, 4H). C NMR (100 MHz,
CDCl3) δ: 10.1, 13.1, 14.2, 21.2, 29.9, 40.6, 42.2, 117.9, 118.4, 125.7, 126.4, 127.3, 128.4, 128.5, 129.1,
131.3, 136.5, 148.2, 148.8, 169.2. HRMS calcd for C24H28NO2: 362.2115 [M+H]+, found: 362.2112.
N,N-Diethyl-2-(5-(4-fluorophenyl)-4-methyl-2-phenylfuran-3-yl)acetamide (7d)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (66 mg, 60%); 1H NMR (600 MHz, CDCl3) δ:
1.09 (t, J = 7.2 Hz, 6H), 2.14 (s, 3H), 3.29 (q, J = 7.2 Hz, 2H), 3.36 (q, J = 7.2 Hz, 2H), 3.58 (s, 2H),
7.03 (t, J = 7.8 Hz, 2H), 7.23 (t, J = 7.8 Hz, 1H), 7.34 (t, J = 7.8 Hz, 2H), 7.50 (d, J = 7.8 Hz, 2H), 7.57
13
2
(t, J = 6.6 Hz, 2H). C NMR (150 MHz, CDCl3) δ: 10.1, 13.1, 14.3, 29.8, 40.7, 42.3, 115.5 (d, JC-F
=
21.9 Hz), 118.0, 118.7, 126.5, 127.45 (d, 3JC-F = 7.7 Hz), 127.50, 128.1 (d, 4JC-F = 3.2 Hz), 128.6, 131.2,
147.2, 149.2, 161.7 (d, 1JC-F = 245.1 Hz), 169.1. 19F NMR (565 MHz, CDCl3) δ: -115.0. HRMS calcd for
C23H24FNO2Na: 388.1683 [M+Na]+, found: 388.1689.
2-(5-(3-Bromophenyl)-4-methyl-2-phenylfuran-3-yl)-N,N-diethylacetamide (7e)
Eluent: ethyl acetate/petroleum ether (1:10); yellow solid (79 mg, 62%), mp 113-114 oC; 1H NMR (400
MHz, CDCl3) δ: 1.16 (t, J = 7.2 Hz, 6H), 2.04 (s, 3H), 3.35 (q, J = 7.2 Hz, 2H), 3.45 (q, J = 7.2 Hz, 2H),
3.70 (s, 2H), 7.24-7.49 (m, 6H), 7.62 (d, J = 7.6 Hz, 2H), 7.69 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz,
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CDCl3) δ: 9.9, 13.1, 14.2, 30.3, 40.7, 42.3, 116.7, 120.8, 123.6, 126.5, 127.1, 127.5, 128.6, 129.7, 131.2,
132.2, 132.4, 133.3, 147.4, 150.0, 169.2. HRMS calcd for C23H24BrNO2Na: 448.0883 [M+Na]+, found:
448.0881.
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N,N-Diethyl-2-(4-methyl-2-phenyl-5-o-tolylfuran-3-yl)acetamide (7f)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (43 mg, 40%); 1H NMR (400 MHz, CDCl3) δ:
1.15-1.19 (m, 6H), 2.05 (s, 3H), 2.44 (s, 3H), 3.36 (q, J = 7.2 Hz, 2H), 3.45 (q, J = 7.2 Hz, 2H), 3.71 (s,
2H), 7.27-7.32 (m, 4H), 7.42 (t, J = 7.6 Hz, 3H), 7.59 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ: 9.6, 13.1, 14.2, 20.7, 30.3, 40.7, 42.3, 116.8, 119.7, 125.4, 126.3, 127.3, 128.1, 128.6, 130.1, 130.6,
130.7, 131.4, 137.6, 149.0, 149.3, 169.3. HRMS calcd for C24H28NO2: 362.2115 [M+H]+, found:
362.2119.
2-(5-(2-Chlorophenyl)-4-methyl-2-phenylfuran-3-yl)-N,N-diethylacetamide (7g)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (54 mg, 47%); 1H NMR (400 MHz, CDCl3) δ:
1.11-1.20 (m, 6H), 2.05 (s, 3H), 3.35 (q, J = 7.2 Hz, 2H), 3.44 (q, J = 7.2 Hz, 2H), 3.70 (s, 2H),
7.28-7.32 (m, 2H), 7.40-7.43 (m, 3H), 7.48-7.52 (m, 2H), 7.62 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ: 9.9, 13.1, 14.2, 30.2, 40.7, 42.3, 116.9, 121.2, 126.48, 126.50, 127.5, 128.58, 128.62, 129.4,
130.1, 131.2, 131.9, 133.6, 146.1, 150.2, 169.2. HRMS calcd for C23H25ClNO2: 382.1568 [M+H]+,
found: 382.1567.
2-(5-(3,4-Dimethoxyphenyl)-4-methyl-2-phenylfuran-3-yl)-N,N-diethylacetamide (7h)
o
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Eluent: ethyl acetate/petroleum ether (1:5); yellow solid (67 mg, 55%), mp 136-137 C; H NMR (400
MHz, CDCl3) δ: 1.13-1.17 (m, 6H), 2.22 (s, 3H), 3.35 (q, J = 7.6 Hz, 2H), 3.43 (q, J = 7.2 Hz, 2H), 3.65
(s, 2H), 3.91 (s, 3H), 3.93 (s, 3H), 6.92 (d, J = 7.6 Hz, 1H), 7.20-7.31 (m, 3H), 7.41 (t, J = 7.6 Hz, 2H),
7.58 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ: 10.1, 13.1, 14.2, 29.9, 40.6, 42.2, 55.9, 109.3,
111.1, 117.8, 117.9, 118.6, 124.9, 126.4, 127.3, 128.5, 131.3, 148.0, 148.1, 148.6, 148.9, 169.2. HRMS
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calcd for C25H30NO4: 408.2169 [M+H]+, found: 408.2172.
N,N-Diethyl-2-(4-methyl-2-phenyl-5-(thiophen-2-yl)furan-3-yl)acetamide (7i)
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Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (82 mg, 77%); 1H NMR (400 MHz, CDCl3) δ:
1.16 (t, J = 6.8 Hz, 6H), 2.23 (s, 3H), 3.35 (q, J = 7.2 Hz, 2H), 3.44 (q, J = 7.2 Hz, 2H), 3.66 (s, 2H),
7.10 (t, J = 4.0 Hz, 1H), 7.27-7.34 (m, 3H), 7.42 (dd, J1 = 7.6 Hz, J2 = 4.0 Hz, 2H), 7.59 (d, J = 8.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ: 9.9, 13.1, 14.3, 29.8, 40.6, 42.3, 117.9, 118.7, 122.8, 123.8, 126.4,
127.5, 128.6, 129.1, 131.1, 134.0, 144.4, 148.9, 169.1. HRMS calcd for C21H24NO2S: 354.1522 [M+H]+,
found: 354.1524.
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(E)-N,N-Diethyl-2-(4-methyl-2-phenyl-5-styrylfuran-3-yl)acetamide (7j)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (93 mg, 83%); 1H NMR (400 MHz, CDCl3) δ:
1.14-1.19 (m, 6H), 2.13 (s, 3H), 3.34 (q, J = 6.8 Hz, 2H), 3.44 (q, J = 7.2 Hz, 2H), 3.65 (s, 2H), 6.96 (d,
J = 16.4 Hz, 1H), 7.09 (d, J = 16.4 Hz, 1H), 7.25 (t, J = 7.6 Hz, 1H), 7.34-7.39 (m, 3H), 7.45 (t, J = 7.6
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Hz, 2H), 7.52 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H). C NMR (100 MHz, CDCl3) δ: 8.9, 13.1,
14.2, 29.9, 40.7, 42.3, 114.7, 117.7, 121.8, 125.6, 126.2, 126.5, 127.2, 127.6, 128.6, 128.7, 131.1, 137.6,
148.1, 149.6, 169.1. HRMS calcd for C25H27NO2Na: 396.1934 [M+Na]+, found: 396.1934.
(Z)-2-(5-(2,6-Dimethylhepta-1,5-dienyl)-4-methyl-2-phenylfuran-3-yl)-N,N-diethylacetamide (7k)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (92 mg, 78%); 1H NMR (400 MHz, CDCl3) δ:
1.11-1.14 (m, 6H), 1.59-1.65 (m, 4H), 1.70 (s, 3H), 1.98 (s, 3H), 2.12 (s, 3H), 2.19 (s, 3H), 3.32 (q, J =
7.2 Hz, 2H), 3.40 (q, J = 7.2 Hz, 2H), 3.62 (s, 2H), 5.14-5.15 (m, 1H), 6.00 (s, 1H), 7.25-7.26 (m, 1H),
13
7.36-7.40 (m, 2H), 7.54 (dd, J1 = 8.4 Hz, J2 = 0.8 Hz, 2H). C NMR (100 MHz, CDCl3) δ: 8.8, 13.1,
14.1, 17.7, 18.6, 25.7, 26.8, 30.0, 40.5, 41.2, 42.2, 111.7, 116.7, 119.4, 123.9, 125.9, 126.9, 128.5, 137.5,
148.2, 148.6, 169.1. HRMS calcd for C26H36NO2: 394.2741 [M+H]+, found: 394.2743.
2-(5-Benzyl-4-methyl-2-phenylfuran-3-yl)-N,N-diethylacetamide (7l)
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Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (81 mg, 75%); 1H NMR (400 MHz, CDCl3) δ:
1.11-1.18 (m, 6H), 2.00 (s, 3H), 3.32 (q, J = 7.2 Hz, 2H), 3.43 (q, J = 7.2 Hz, 2H), 3.63 (s, 2H), 4.02 (s,
2H), 7.22-7.33 (m, 6H), 7.38 (t, J = 7.6 Hz, 2H), 7.51 (d, J = 7.6 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ: 8.7, 13.1, 14.2, 30.1, 32.5, 40.6, 42.2, 116.3, 118.0, 126.2, 127.1, 128.47, 128.49, 131.5, 138.8, 148.5,
148.6, 169.3. HRMS calcd for C24H28NO2: 362.2115 [M+H]+, found: 362.2109.
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N,N-Diethyl-2-(4-methyl-5-phenethyl-2-phenylfuran-3-yl)acetamide (7m)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (87 mg, 77%); 1H NMR (400 MHz, CDCl3) δ:
1.07-1.14 (m, 6H), 1.81 (s, 3H), 2.91-2.98 (m, 4H), 3.26-3.40 (m, 4H), 3.58 (s, 2H), 7.19-7.21 (m, 3H),
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7.25-7.30 (m, 2H), 7.37-7.40 (m, 3H), 7.50 (d, J = 7.6 Hz, 2H). C NMR (100 MHz, CDCl3) δ: 8.3,
13.0, 14.1, 28.4, 30.1, 34.8, 40.5, 42.2, 116.1, 117.2, 125.9, 126.1, 126.3, 126.9, 128.3, 128.4, 128.5,
141.5, 148.1, 149.6, 169.3. HRMS calcd for C25H29NO2Na: 398.2090 [M+Na]+, found: 398.2086.
N,N-Diethyl-2-(4-methyl-2-phenyl-5-propylfuran-3-yl)acetamide (7n)
Eluent: ethyl acetate/petroleum ether (1:10); yellow liquid (69 mg, 73%); 1H NMR (400 MHz, CDCl3) δ:
0.95 (t, J = 7.2 Hz, 3H), 1.06-1.14 (m, 6H), 1.67 (q, J = 7.2 Hz, 2H), 1.93 (s, 3H), 2.58 (t, J = 7.2 Hz,
2H), 3.28 (q, J = 7.2 Hz, 2H), 3.39 (q, J = 7.6 Hz, 2H), 3.60 (s, 2H), 7.24 (t, J = 7.2 Hz, 1H), 7.35-7.39
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(m, 2H), 7.49 (dd, J1 = 8.4 Hz, J2 = 0.8 Hz, 2H). C NMR (100 MHz, CDCl3) δ: 8.5, 13.0, 13.8, 14.0,
21.9, 28.2, 30.2, 40.6, 42.2, 116.0, 116.7, 126.0, 126.8, 128.4, 131.8, 147.8, 150.7, 169.5. HRMS calcd
for C20H27NO2Na: 336.1934 [M+Na]+, found: 336.1926.
N,N-Diethyl-2-(4-ethyl-2-phenyl-5-p-tolylfuran-3-yl)acetamide (7o)
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Eluent: ethyl acetate/petroleum ether (1:10); yellow solid (77 mg, 68%), mp 90-91 C; H NMR (400
MHz, CDCl3) δ: 1.16-1.20 (m, 6H), 1.27 (t, J = 7.6 Hz, 3H), 2.40 (s, 3H), 2.69 (q, J = 7.6 Hz, 2H), 3.38
(q, J = 7.6 Hz, 2H), 3.46 (q, J = 7.2 Hz, 2H), 3.68 (s, 2H), 7.25 (d, J = 8.0 Hz, 2H), 7.32 (t, J = 7.6 Hz,
1H), 7.43 (t, J = 7.6 Hz, 2H), 7.63 (t, J = 8.4 Hz, 4H). 13C NMR (100 MHz, CDCl3) δ: 13.1, 14.3, 14.5,
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