A phosphine-catalyzed regioselective [3+2] cycloaddition of ethyl 5,5-Diarylpenta-2,3,4-trienoate with aromatic aldehydes and α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1002/adsc.201301000

Tributylphosphine-catalyzed regioselective [3+2] cycloadditions between ethyl 5,5-diarylpenta- 2,3,4-trienoate 1 and various aromatic aldehydes 2 to produce a wide variety of polysubstituted 2,5-dihydrofurans 3, and between 1 and β-unsubstituted α,β-unsat

Full text of DOI:10.1002/adsc.201301000

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DOI: 10.1002/adsc.201301000
A Phosphine-Catalyzed Regioselective [3+2]Cycloaddition of
Ethyl 5,5-Diarylpenta-2,3,4-trienoate with Aromatic Aldehydes
and a,b-Unsaturated Carbonyl Compounds
Lu-Feng Wang,a Xiao-Ping Cao,a,* Zi-Fa Shi,a,* Peng An,a and Hak-Fun Chowb
a
State Key Laboratory of Applied Organic Chemistry & College of Chemistry and Chemical Engineering, Lanzhou
University, Lanzhou 730000, Peopleꢀs Republic of China
Fax : (+86)-931-8915557; e-mail: caoxplzu@163.com or shizf@lzu.edu.cn
Department of Chemistry, The Center of Novel Functional Molecules, and State Key Laboratory of Synthetic Chemistry,
b
The Chinese University of Hong Kong, Hong Kong, Peopleꢀs Republic of China
Received: November 7, 2013; Published online: May 13, 2014; Accepted: January 2, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301000.
Abstract: Tributylphosphine-catalyzed regioselective of 2, followed by the ring closure between the alde-
[3+2]cycloadditions between ethyl 5,5-diarylpenta- hydic oxygen of 2 and the g-position of butatriene,
2,3,4-trienoate 1 and various aromatic aldehydes 2 to which is the first report of a normal [3+2] cycloaddi-
produce a wide variety of polysubstituted 2,5-dihy- tion between cumulenes and aldehydes. For the for-
drofurans 3, and between 1 and b-unsubstituted a,b- mation of cyclopentenes 6, the reaction involved
unsaturated carbonyl compounds 5 to give polysub- attack of the g-position of the butatriene to the elec-
stituted cyclopentenes 6 with a quaternary carbon tron-deficient b-position of the a,b-unsaturated car-
center, are reported. In both cases the reaction part- bonyl compounds 5, followed by the ring closure be-
ners approach each other via the sterically less hin- tween the a-position of 5 and the a-position of buta-
dered orientation to afford the target products in ex- triene, which shows a different regioselectivity to the
cellent regioselectivity. The reaction mechanism in- previously reported [3+2]cycloadditions between bu-
volved first the generation of a zwitterionic inter- tatriene and olefins.
mediate between the butatriene 1 and PBu3. For the
formation of 2,5-dihydrofurans 3, the preferred cycli-
zation mode encompassed the nucleophilic attack of Keywords: butatrienes; cycloaddition; phosphine cat-
the a-position of butatriene to the aldehydic carbon alysis; regioselectivity
Introduction
thesis and reactivity of butatrienes derivatives have
already appeared in the literature.[3]
Cumulenes have attracted much attention in organic
The phosphine-catalyzed [3+2]cycloaddition, devel-
chemistry because the cumulated C=C double bonds oped by Lu in 1995,[4] is considered to be one of the
exhibited some very interesting and unique reactivi- most important reactions for cumulenes. For the reac-
ties. For example, they can serve as nucleophiles, elec- tion between allenic substrates and electron-deficient
trophiles and dienophiles in many different classes of olefins, the reaction products are five-membered car-
reactions.[1] Among the various types of cumulenes, bocycles with a quaternary stereogenic center.[5] This
allenes have been demonstrated as extremely useful motif is also an important structural skeleton found in
reaction substrates as they often showed excellent many natural products and bioactive molecules.[6] Al-
regio- and stereoselectivities when employed in many ternatively, allenes could also react with aldehydes to
reactions.[1a] Some allene derivatives have also been produce dioxanes, pyrones, dihydropyrone, 1,3-dienes,
employed in the synthesis of natural products and ma- or vinylcyclopropanes, and with ketones to construct
terials.[2] Compared with allenes, butatrienes may pos- dihydrofurans,[7] but there is only one example of g-
sess an even richer chemistry and interesting reactivi- alkyl allenates with aryl aldehydes giving tetrahydro-
ty due to the presence of an extra double bond func- furans, in which the g-methyl or methylene was di-
tionality. Indeed, several research works on the syn- rectly involved in the carbon-carbon bond-forming
steps,[7g] rather than the normal [3+2]cycloaddition.
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Lu-Feng Wang et al.
Table 1. Optimization of conditions of the [3+2]cycloaddi-
tion of 1 and 2a.
For similar reactions involving butatrienes, there is
only one report in the literature. Shi disclosed the
synthesis of five-membered carbocycles or pyrrolines
via phosphine-mediated [3+2]cycloadditions between
ethyl 5,5-diarylpenta-2,3,4-trienoates 1 and b-substi-
tuted conjugated olefins or N-tosylimines, respective-
ly.[3g] It was noted that these products were formed
from a-attack of the butatrienes to the b-position of
the electron-deficient conjugated olefins, or the a-po-
sition of N-tosylimines. Herein, we wish to report two
new reaction modes in the [3+2]cycloaddition reac-
tions involving ethyl 5,5-diphenylpenta-2,3,4-trienoate
1. First, the phosphine-catalyzed reaction between bu-
tatriene 1 and aromatic aldehydes 2 afforded furan
derivatives – the normal [3+2]cycloaddition products
resulting from the a-attack of the butatriene to the al-
dehydic carbon. Second, butatriene 1 reacted with b-
unsubstituted a,b-unsaturated carbonyl compounds 5
to produce five-membered carbocycles 6. The reac-
tion course was originated from g-attack of the buta-
triene to the b-position of the conjugated ester or
ketone as the main product. This work further high-
lights the rich chemistry of butatriene compounds and
their versatility in the construction of complex organic
structures.
Entry[a] Lewis
base
Solvent Temp.
Time
[h]
Yield
[%][b]
[8C]
1
2
3
4
5
6
7
8
PBu3
PBu3
THF
CHCl3 50
60
10
2[c]
10
10
10
10
10
10
2[c]
10
20
10
2[c]
10
66
42
36
31
NR
51
43
NR
34
PPhMe2 CHCl3 50
PPh2Me CHCl3 50
PPh3
Et3N
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
PBu3
CHCl3 50
CHCl3 50
toluene 80
CH3CN 30
DMF
DCM
CCl4
9
60
30
60
10
11
12
13
NR
46
68
CHCl3 30
CHCl3 reflux
[a]
All reactions were carried out with 1 (28 mg, 0.1 mmol)
and 2a (15 mg, 0.1 mmol) in the presence of Lewis base
(50 mol%) in solvent (2.0 mL) under an argon atmos-
phere.
Isolated yields.
The reaction time was determined by the consumption of
Results and Discussion
[b]
[c]
Initial experimentation with ethyl 5,5-diphenylpenta-
2,3,4-trienoate (1) and para-nitrobenzaldehyde (2a) in
the presence of tributylphosphine in THF at 608C led
to the formation of a normal [3+2]cycloaddition
1.
adduct 3a in very low yield (Table 1, entry 1). The re- the product 3a was obtained in 66% yield (entry 2).
action parameters were then adjusted in order to When the reaction was performed at a higher temper-
identify the optimal conditions for the [3+2]cycload- ature (refluxing CHCl3), 3a was formed in a slightly
dition reaction. Fortunately, when the reaction was improved yield of 68% (entry 13). Hence the use of
carried in CHCl3 at 508C, a furan derivative 3a was 50% mol of PBu3 in refluxing CHCl3 was determined
obtained in 66% yield (Table 1, entry 2). Thus, using to be the optimized reaction conditions.
CHCl3 as the solvent, various phosphine catalysts
Under the optimized reaction conditions, we set
(50 mol%) were employed as the promotors, it was out to examine the scope and limitations of this reac-
found that tributylphosphine (PBu3), dimethylphenyl- tion using 1 as the substrate with various aromatic al-
phosphine
(PPhMe2),
methyldiphenylphosphine dehydes in the presence of PBu3 (50 mol%) in reflux-
(PPh2Me), and triphenylphosphine (PPh3) (entries 2– ing CHCl3 (Table 2). When the aromatic aldehydes
5) could all catalyze the reaction, but the yield of the possessed an electron-withdrawing substituent at the
product was the highest with the use of PBu3. This para or meta position of the aromatic ring, the reac-
result implied that the nucleophilicity of the phos- tions were found to proceed smoothly and the prod-
phines had a significant influence on the outcome of ucts 3 were obtained in moderate to good (64–84%)
the reaction. Accordingly,
a
nitrogen-containing yields (entries 1–4). When the electron-withdrawing
Lewis base such as triethylamine (Et3N) was also groups were introduced at the ortho position of the
tried, but no reaction occurred under the same condi- aromatic ring, the reaction time was longer and the
tions (entry 6). Using PBu3 (50 mol%) as the opti- corresponding products were obtained in moderate
mized catalyst, the solvent effects were then explored (40–48%) yields (entries 5 and 6). On increasing the
(entries 1, 2, 7–11), all the reactions were carried out number of the electron-withdrawing substituents at
below the reflux temperature of the solvent. Com- the aromatic ring, there was a little improvement of
pared with THF, toluene, CH3CN, DMF, DCM, and the yield (entry 7). But using benzaldehyde as the
CCl4, CHCl3 was the best reaction solvent in which substrate resulted in a low yield (entry 8). When het-
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A Phosphine-Catalyzed Regioselective [3+2]Cycloaddition
Table 2. Scope of the PBu3-mediated [3+2] cycloaddition of 1 and 2.
Entry[a]
2
R3
Time [h]
3
Product
Yield [%][b]
1
2
3
4
5
6
7
8
2b
2c
2d
2e
2f
2g
2h
2i
X=p-Br
2[c]
2[c]
2[c]
2[c]
10
3b
3c
3d
3e
3f
3g
3h
3i
64
80
84
67
40
48
73
28
X=p-CN
X=p-CF3
X=m-Br
X=o-Br
X=o-NO2
X=2,4-dichloro
X=H
10
2[c]
10
9
2j
2k
2l
2[c]
3j
3k
3l
64
60
72
10
11
10
2[c]
12
2m
2[c]
3m
82
[a]
All reactions were carried out with 1 (28 mg, 0.1 mmol) and 2 (0.1 mmol) in the presence of PBu3 (50 mol%) in CHCl3
(2.0 mL) under an argon atmosphere.
Isolated yields.
The reaction time was determined by the consumption of 1.
[b]
[c]
eroaromatic aldehydes were employed, the reaction
The reaction was also examined with butatriene
also proceeded smoothly to afford 3 in good to excel- 1 and methyl 2-phenylacrylate (5a) in the presence of
lent (60–82%) yields (entries 9–12). Interestingly, tributylphosphine in THF at 608C, a cyclopentene de-
when the reaction solvent was switched to CH3CN at rivative 6a was obtained in 65% yield (Table 3,
608C, a polysubstituted furan 4 was formed in 74% entry 1). The reaction parameters were then adjusted
yield (Scheme 1). The structure of compound 4 was in order to identify the optimal conditions for the
1
confirmed by H and 13C NMR, HMBC, and HR-MS
analyses. When a solution of 3a in CH3CN was stirred
at 608C with or without PBu3 as catalyst, neither of
them generated 4. The furan derivative 4 was presum-
ably formed directly from starting material 1 by cyclo-
addition–isomerization, which might be more thermo-
dynamically stable compared to 3a. However, no
furan product was formed when other substrates 2b–
2m were subjected to the same reaction conditions,
and only 3b–3m were recovered unchanged.
Scheme 1. Synthesis of compound 4.
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Lu-Feng Wang et al.
Table 3. Optimization of conditions of the [3+2] cycloaddi-
tion of 1 and 5a.
After optimizing the reaction conditions, we then
examined the substrate scope of the reaction between
compound 1 and a variety of b-unsubstituted conju-
gated olefins 5 (Table 4). Similar to the case observed
with aromatic aldehydes, when a-aryl a,b-unsaturated
esters 5 (R1 =Ar, R2 =OR) with an electron-with-
drawing substituent introduced at the para or meta
position of the a-aryl ring were used as the substrates,
the reactions proceeded very fast and the products 6
were obtained in excellent (84–91%) yields (entries 1,
2, 6, and 7). For substrates 5 (R1 =Ar) bearing an
electron-donating substituent at the para position of
the a-aryl ring, the reaction time was longer and the
corresponding adducts were obtained in moderate
(52–61%) yields (entries 3–5). On the other hand,
when the substituent was located at an ortho-position
Entry[a] Lewis base
[mol%]
Solvent
Temp. Time Yield
G
[8C]
[h]
[%][b]
1
2
3
4
5
6
7
8
PBu3 (50)
PMe3 (50)
PPhMe2 (50) THF
PPh2Me (50) THF
THF
THF
60
60
60
60
60
60
60
60
60
60
60
35
3[c]
1[c]
10[c]
10[c]
20
65
55
55
36
NR
NR
NR
30
48
40
58
45
56
57
67
72
PPh3 (50)
HPPh2 (50)
Et3N (50)
PBu3 (50)
PBu3 (50)
PBu3 (50)
PBu3 (50)
PBu3 (50)
PBu3 (50)
PBu3 (30)
PBu3 (80)
PBu3 (50)
THF
THF
THF
DCE
toluene
CH3CN
DMF
DCM
Table 4. Scope of the PBu3-mediated [3+2] cycloaddition of
1 and 5.
20
20
10[c]
10[c]
2[c]
2[c]
10[c]
4[c]
20
9
10
11
12
13
14
15
16
1,4-dioxane 60
THF
THF
THF
60
60
3[c]
Entry[a] R1
R2
Time Product,
[h]
reflux 2[c]
Yield [%][b]
[a]
All reactions were carried out with 1 (28 mg, 0.1 mmol)
and 5a (16 mg, 0.1 mmol) in the presence of a Lewis base
in solvent (2.0 mL) under an argon atmosphere.
Isolated yields.
The reaction time was determined by the consumption of
1.
1
2
3
4
5
6
7
8
p-ClC6H4
OMe
OMe
OMe
OMe
2[c]
2[c]
8
6b, 85
6c, 88
6d, 61
6e, 52
6f, 53
6g, 84
6h, 91
6i, 32
6j, 55
6k, 83
6l, 55
6m, 78
6n, 75
6o, 40
6p, 88
6q, 64
6r, 34
6s, 58
6t, 72
6u, 60
6v, 64
6w, 62
6x, 64
p-BrC6H4
p-MeC6H4
p-t-BuC6H4
[b]
[c]
8
8
p-MeOC6H4 OMe
m-BrC6H4
m-CF3C6H4
o-ClC6H4
o-NO2C6H4
p-BrC6H4
C6H5
p-ClC6H4
C6H5
C6H5
OMe
OMe
OMe
OMe
OC6H5
C6H5
C6H5
2[c]
2[c]
8
[3+2]cycloaddition reaction. Using THF as the sol-
vent, other phosphine compounds such as trimethyl-
phosphine (PMe3), PPhMe2, PPh2Me were also exam-
ined, but in all cases lower yields were obtained (en-
tries 2–4). On the other hand, electron-deficient phos-
phines such as PPh3 and diphenylphosphine (HPPh2),
and a nitrogen-containing Lewis base Et3N could not
promote the reaction (entries 5, 6, and 7). With the
choice of PBu3 as the catalyst, a further survey of con-
ditions indicated that THF was the best solvent as
compared with DCE, toluene, CH3CN, DMF, DCM,
and 1,4-dioxane (entries 8–13). Meanwhile, the effects
of the amount of PBu3 and the reaction temperature
were examined. Using less PBu3 (30 mol%) resulted
in a slowing down of the reaction and a decrease of
the product yield of 6a, and increasing the amount of
the catalyst (80 mol%) resulted in little improvement
of yield (entries 14 and 15). In addition, the reaction
gave a slightly improved yield of 6a when it was car-
ried out in refluxing THF (entry 16). Thus, the cyclo-
addition was best conducted in refluxing THF in the
presence of 0.5 equiv. of PBu3.
9
8
10
11[d]
12
13
14
15
16
17
18
19
20
21
22
23
2[c]
5
2[c]
2[c]
p-BrC6H4
p-MeOC6H4 2[c]
p-ClC6H4
p-ClC6H4
p-ClC6H4
2[c]
p-MeOC6H4 2[c]
p-MeOC6H4 p-MeOC6H4 2[c]
p-ClC6H4
n-propyl
OMe
OEt
2[c]
3[c]
3[c]
3[c]
3[c]
H
H
H
H
H
O-n-Bu
O-t-Bu
Ocyclohexyl 3[c]
[a]
All reactions were carried out with 1 (28 mg, 0.1 mmol)
and 5 (0.1 mmol) in the presence of PBu3 (50 mol%) in
THF (2.0 mL) under argon atmosphere.
Isolated yields.
[b]
[c]
The reaction time was determined by the consumption of
1.
[d]
This reaction was carried out at 408C.
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A Phosphine-Catalyzed Regioselective [3+2]Cycloaddition
Figure 1. X-ray crystallographic structures of compounds 3e, 6a, and 6c.
in the a-aryl ring, the corresponding products 6 were hydic carbon of compounds 2, followed by the ring
obtained in lower (32% and 55%) yields (entries 8 closure between the aldehydic oxygen of compounds
and 9). This may presumably be due to the steric 2 with the g-position of butatriene. On the other
blocking effect of the ortho substituent. Switching the hand, the corresponding [3+2]cycloaddition reactions
ester functionality of 5 from methyl ester to phenyl between butatriene 1 and a,b-unsaturated carbonyl
ester showed little influence on the reaction (entries 2 compounds 5 involved the attack of the g-position of
vs. 10).
butatriene to the b-position of 5, followed by the ring
Ethyl 5,5-diphenylpenta-2,3,4-trienoate 1 could also closure between the a-position of compounds 5 and
react with b-unsubstituted a,b-unsaturated ketones 5 the a-position of butatriene.
(R1 =Ar, R2 =R) to give the corresponding polysub-
Based on other similar phosphine-catalyzed
stituted cyclopentenes 6 in moderate to good yields [3+2]cycloaddition reactions,[2d,3g] a plausible reaction
under the same conditions (Table 4, entries 11–18). mechanism is proposed (Scheme 2). The reaction is
Similarly, when the a-aryl ring had an electron-with- believed to first involve a Michael-type addition reac-
drawing group at the para position, good (75–88%) tion between PBu3 to the b-position of butatriene 1 to
yields of 6 could be obtained (entries 12, 13, and 15), generate a zwitterionic intermediate A. Subsequently,
while lower (34–64%) yields were found with elec- nucleophilic attack of the intermediate A to alde-
tron-donating substituents at the para position (en- hydes 2 or the conjugated carbonyl compounds 5 give
tries 14, 16, and 17). The reaction also worked when intermediates B or D, respectively. After proton
R2 was changed to an n-propyl group, and the yield of transfer and elimination of PBu3, the catalytic cycle is
the cyclopentene 6 was 58% (entry 18). Alkyl acryl- completed to give products 3 or 6 along with the re-
ates (R1 =H, R2 =OR) could also serve as substrates generation of PBu3.
to perform the cycloaddition reaction. The reactions
We reasoned that the different regioselectivities ex-
proceeded smoothly to give 6 in similar (60–72%) hibited in the cycloaddition reactions of aromatic al-
yields, irrespective of the nature of the ester moiety dehydes 2 and a,b-unsaturated carbonyl compounds 5
(entries 19–23). This suggested that the steric size of with butatriene 1 could be attributed to the difference
the ester group in the acrylate had little influence on in the steric environment of the substrates
the reactivity.
(Scheme 2). From the computational results of the
The structures of all the reaction products were stable conformation of the zwitterionic intermediate
1
characterized by H and 13C NMR spectroscopy and A (for computational details see the Supporting Infor-
HR-MS. The regioselectivity of the [3+2]cycloaddi- mation), it is noted that the plane defined by carbon
tion reactions between the butatriene and aromatic atoms 5, 6 and 7 is nearly orthogonal to the one de-
aldehydes was confirmed by determination of the fined by carbon atoms 2, 3 and phosphorus atom (the
structure of 3e by the X-ray crystallography dihedral angle is 90.68). For the aromatic aldehydes 2,
(Figure 1). Similarly, the reaction regioselectivity be- the aldehydic carbon atom is sterically more hindered
tween butatriene 1 and a,b-unsaturated carbonyl than the aldehydic oxygen atom. As a result, the pre-
compounds could also be confirmed by the X-ray ferred mode of regiochemistry would involve the
crystallographic analysis of compounds 6a and 6c. attack of the a-position of the butatriene to the car-
Hence, it was unambiguously confirmed that the re- bonyl carbon, followed by ring closure between the
gioselectivity of the [3+2]cycloaddition reactions be- carbonyl oxygen and the g-position of 1 to give the
tween butatriene 1 and aromatic aldehydes 2 involved cycloaddition adduct B. On the other hand, for the
the attack of the a-position of butatriene to the alde- a,b-unsaturated carbonyl substrates 5, in order to
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Lu-Feng Wang et al.
Scheme 2. Proposed reaction mechanisms.
avoid unfavorable steric repulsion in the transition drofurans 3 were formed by the a-attack of the buta-
state, the benzene ring of zwitterionic intermediate A triene 1 to the aldehydic carbon, followed by ring clo-
and the substituents R1 and R2 in compounds 5 would sure between the aldehydic oxygen and the g-position
be distant from each other during cycloaddition. As of 1. For a,b-unsaturated carbonyl compounds 5, g-
a result, g-attack of the butatriene 1 to the b-position attack of 1 to the b-position of 5, followed by ring clo-
of compounds 5, followed by ring closure between the sure between the a-position of 5 and the a-position of
a-atom of 5 and the a-position of 1 is the preferred 1 is the preferred mode of cyclization to give the
mode of cyclization.
polysubstituted cyclopentenes 6. Further mechanistic
investigations and studies on the synthesis of differ-
ently substituted butatrienes and the asymmetric
[3+2]cycloaddition reaction are currently ongoing in
our laboratory.
Conclusions
In summary, a series of polysubstituted 2,5-dihydro-
furans and polysubstituted cyclopentenes with a qua-
ternary carbon center were synthesized by using
PBu3-catalyzed [3+2]cycloaddition reactions involv-
ing butatriene derivative 1. In both reactions the re-
gioselectivity was dictated by the steric environment
of the substrate molecules. For aromatic aldehydes 2
Experimental Section
General Information
PBu3, PPhMe2, PPh2Me, PPh3, and PMe3 were purchased
as the reaction partners, the polysubstituted 2,5-dihy- from Alfa Chemical Co. and were used as received. All re-
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A Phosphine-Catalyzed Regioselective [3+2]Cycloaddition
actions which required anhydrous conditions were run
under argon atmospheres. Other commercially available re-
agents were used as received. THF was distilled from
sodium benzophenone, while other solvents were dried by
distillation over the appropriate drying reagents. Reactions
were monitored by TLC on silica gel (GF-254) plates.
Column chromatography was performed through silica gel
(200–300 mesh). The petroleum ether (PE) used had a boil-
tion of PBu3 (10 mg, 0.05 mmol). The reaction mixture was
stirred at 608C for 2 h. The solvent was removed under re-
duced pressure and the residue was purified by flash column
chromatography (SiO2, eluent: EtOAc/petroleum ether=1/
20) to yield compound 4 as a brown solid; yield: 32 mg
(74%); mp 110–1128C; 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=8.23–8.15 (m, 4H), 7.36–7.30 (m, 4H), 7.28–7.25
(m, 2H), 7.23–7.21 (m, 4H), 6.43 (d, 3JH,H =0.8 Hz, 1H),
1
3
ing range of 60–908C. H and 13C NMR spectra were record-
5.52 (s, 1H), 4.30 (q, 3JH,H =7.2 Hz, 2H), 1.32 (t, JH,H
=
ed on a Bruker AM 400 MHz spectrometer (1H at 400 MHz
and 13C at 100 MHz) using tetramethylsilane or residual sol-
vent signals as the internal reference (CDCl3: dH =7.26, dC =
77.0 ppm; acetone-d6: dH =2.04, dC =29.8 ppm). Chemical
shifts (d) were reported in parts per million (ppm). Multi-
plicity was indicated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet), dd (doublet of doublet).
Coupling constants were reported in Hertz (Hz). Melting
points were determined by use of a Reichert Microscope ap-
paratus and are uncorrected. Single crystal X-ray diffraction
measurements were made on a Bruker X8 APEX diffrac-
tometer working with graphite monochromated Mo-Ka radi-
ation. Accurate mass measurements were obtained on
a Bruker Daltonics APEX II 47e FT-ICR mass spectrometer
or on a Fisons VG Autospec double focusing sector-field in-
strument.
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=
163.2 (C), 157.4 (C), 153.7 (C), 147.5 (C), 140.6 (C), 135.5
(C), 128.70 (CH), 128.67 (CH), 127.2 (CH), 123.3 (CH),
117.3 (C), 112.3 (CH), 61.0 (CH2), 50.7 (CH), 14.2 (CH3),
one tertiary carbon signal missing due to signal overlapping;
HR-MS (ESI): m/z=428.1497, calcd for C26H21NO5 +H+
[M+H+]: 428.1492.
Synthesis of Compounds 6
b-Unsubstituted a,b-unsaturated esters and ketones 5[8]
(0.1 mmol) was added to a stirred solution of ethyl 5,5-di-
phenylpenta-2,3,4-trienoate 1 (28 mg, 0.1 mmol) in THF
(2 mL) under argon, followed by addition of PBu3 (10 mg,
0.05 mmol). The reaction mixture was stirred at reflux for
the given period of time. The solvent was removed under re-
duced pressure and the residue was purified by flash column
chromatography (SiO2, eluent: EtOAc/petroleum ether=1/
20) to yield compounds 6.
CCDC 910662 (3e), CCDC 910664 (6a), and CCDC
910661 (6c) contain the supplementary crystallographic data
for the paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
2-Ethyl 1-methyl 4-(diphenylmethylene)-1-phenylcyclo-
pent-2-ene-1,2-dicarboxylate (6a): White solid; yield: 72%;
mp 133–1358C; 1H NMR (400 MHz, CDCl3, 258C, TMS):
3
d=7.35–7.28 (m, 10H), 7.24–7.16 (m, 6H), 4.11 (q, JH,H
=
Synthesis of Compounds 3
3
7.2 Hz, 2H), 3.78 (s, 3H), 3.73 (d, JH,H =16.8 Hz, 1H), 3.28
(d, 3JH,H =16.8 Hz, 1H), 1.15 (t, 3JH,H =7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=174.3 (C),
164.5 (C), 143.7 (CH), 142.1 (C), 141.9 (C), 141.4 (C), 141.2
(C), 141.0 (C), 139.4 (C), 130.1 (CH), 129.3 (CH), 128.2
(CH), 128.1 (CH), 127.9 (CH), 127.7 (CH), 127.6 (CH),
127.3 (CH), 126.8 (CH), 62.4 (C), 60.4 (CH2), 52.5 (CH3),
48.3 (CH2), 14.0 (CH3); HR-MS (ESI): m/z=439.1910,
calcd. for C29H26O4 +H+ [M+H+]: 439.1904.
Aromatic aldehydes 2 (0.1 mmol) was added to a stirred so-
lution of ethyl 5,5-diphenylpenta-2,3,4-trienoate 1 (28 mg,
0.1 mmol) in CHCl3 (2 mL) under argon, followed by addi-
tion of PBu3 (10 mg, 0.05 mmol). The reaction mixture was
stirred at reflux for the given period of time. The solvent
was removed under reduced pressure and the residue was
purified by flash column chromatography (SiO2, eluent:
EtOAc/petroleum ether=1/30) to yield compounds 3.
Ethyl 5-(diphenylmethylene)-2-(4-nitrophenyl)-2,5-dihy-
drofuran-3-carboxylate (3a): Yellow solid; yield: 68%; mp
140–1428C; 1H NMR (400 MHz, CDCl3, 258C, TMS): d=
8.24 (d, 3JH,H =8.8 Hz, 2H), 7.61 (d, 3JH,H =8.8 Hz, 2H),
7.47–7.38 (m, 5H), 7.31–7.24 (m, 4H), 7.21–7.17 (m, 1H),
7.09 (d, 3JH,H =2.0 Hz, 1H), 6.45 (d, 3JH,H =1.6 Hz, 1H),
4.17–4.05 (m, 2H), 1.17 (t, 3JH,H =7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=162.0 (C), 156.1 (C),
148.1 (C), 145.4 (C), 139.6 (C), 138.0 (C), 136.9 (C), 134.8
(CH), 131.0 (CH), 129.7 (CH), 128.5 (CH), 128.1 (CH),
128.0 (CH), 127.6 (CH), 127.2 (CH), 123.7 (CH), 119.8 (C),
87.5 (CH), 61.1 (CH2), 14.0 (CH3); HR-MS (ESI): m/z=
428.1497, calcd. for C26H21NO5 +H+ [M+H+]: 428.1492.
The spectroscopic data of compounds 3b–3m can be
found in the Supporting Information.
The spectroscopic data of compounds 6b–6x can be found
in the Supporting Information.
Acknowledgements
The authors are grateful to the National Basic Research Pro-
gram of China (973 program, Grant No. 2010CB833203), the
National Natural Science Foundation of China (Grant Nos.
21272098, 21190034, J1103307), the Program for Changjiang
Scholars and Innovative Research Team in University
(PCSIRT: IRT1138), the Fundamental Research Funds for
the Central University (FRFCU: lzujbky-2013-ct02), the 111
Project, and the RAC of CUHK for the financial support. We
are grateful to Prof. Hao-Li Zhang, Lanzhou University, for
his helpful guidance in the preparation of the manuscript. We
gratefully also acknowledge Ms. Yong-Liang Shao, Lanzhou
University, for conducting X-ray crystallographic analyses.
Synthesis of Ethyl 5-Benzhydryl-2-(4-nitrophenyl)-
furan-3-carboxylate (4)
Aldehyde 2a (15 mg, 0.1 mmol) was added to a stirred solu-
tion of ethyl 5,5-diphenylpenta-2,3,4-trienoate 1 (28 mg,
0.1 mmol) in CH3CN (2 mL) under argon, followed by addi-
Adv. Synth. Catal. 2014, 356, 3383 – 3390
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3389

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3390
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Adv. Synth. Catal. 2014, 356, 3383 – 3390