Access to C(sp3)-C(sp2) and C(sp2)- C(sp2) bond formation via sequential intermolecular carbopalladation of multiple carbon-carbon bonds

Article abstract of DOI:10.1021/jo300662x

A synthetic strategy of 4-benzyl-substituted 1,3-butadiene derivatives through Pd-catalyzed three-component coupling reaction of benzyl chlorides, alkynes, and monosubstituted alkenes is described. This tandem coupling reaction forms a C(sp³)-C(sp²) bond and a C(sp²)- C(sp²) bond sequentially in a single-step operation.

Full text of DOI:10.1021/jo300662x

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Note
An Access to C(sp3)-C(sp2) and C(sp2)-C(sp2) Bond Formation via
Sequential Intermolecular Carbopalladation of Multiple Carbon-Carbon Bonds
Yanmei Wen, Liangbin Huang, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo300662x • Publication Date (Web): 30 May 2012
Downloaded from http://pubs.acs.org on June 3, 2012
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An Access to C(sp3)-C(sp2) and C(sp2)-C(sp2) Bond Formation via
Sequential Intermolecular Carbopalladation of Multiple
Carbon-Carbon Bonds
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Yanmei Wena,b, Liangbin Huanga, Huanfeng Jiang*,a
aSchool of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
jianghf@scut.edu.cn
bCollege of Science, Guangdong Ocean University, Zhanjiang 524088, China
Abstract: A synthetic strategy of 4ꢀbenzyl substituted 1,3ꢀbutadiene derivatives
through Pdꢀcatalyzed threeꢀcomponent coupling reaction of benzyl chlorides, alkynes,
and monosubstituted alkenes is described. This tandem coupling reaction forms a
C(sp3)ꢀC(sp2) bond and a C(sp2)ꢀC(sp2) bond sequentially in a singleꢀstep operation.
The transitionꢀmetalꢀcatalyzed carbonꢀcarbon bondꢀforming is regarded as in a
sense the cornerstone of organic synthesis because of the possibility to frame complex
structure from readily available components in diverse ways.1 And nucleopalladation
of carbonꢀcarbon triple bonds followed by a crossꢀcoupling with double bonds has
been extensively researched.2 Recently, the palladiumꢀcatalyzed sequential three
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component coupling reaction was developed via carbopalladation of internal alkyne
with corresponding halides or their synthetic equivalents followed by the addition of
various terminators including organometallic reagents, alkenes, and terminal alkynes.3
However, these synthetic developments were only demonstrated to provide
C(sp2)ꢀC(sp2) and C(sp)ꢀC(sp2) bonds, which have been extensively reported.4 In
contrast, researches in the field of C(sp3)ꢀC(sp2) bond forming reactions with
sp3ꢀhybridized organic fragments are much less usual,5 and remains one of the biggest
challenges in organic synthesis. Obviously, the direct utilization of benzyl halides as
coupling partners based upon two successive intermolecular carbopalladation
reactions to form a C(sp3)ꢀC(sp2) and a C(sp2)ꢀC(sp2) in one batch would be an
appealing approach.
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1,3ꢀDiene unit is often found in many natural products that have shown potential
biological activities, such as cellꢀcycle regulating properties and apoptotic, antifungal,
and antiviral activities.6 Furthermore, 1,3ꢀdiene unit is also very useful synthon in
organic synthesis.7 Although there are numerous methods for the preparation of
1,3ꢀbutadiene, development of general and efficient routes to the regioꢀ and
stereoselective synthesis of benzylated 1,3ꢀdienes is still challenging, and only an
example was reported by Ma’s group who developed 4ꢀbenzyl substituted
1,3ꢀbutadiene
through
Pd(0)ꢀcatalyzed
coupling
reactions
of
ethyl
2ꢀbenzylbutaꢀ2,3ꢀdienoate with 1ꢀalkenylboronic acid.8 Considering both the
advantages of benzyl chlorides compared with those of the aryl iodides or iodoalkenes
and a continuing interest in the coupling reactions on basis of internal alkynes
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(Scheme 1),9 we here report an efficient palladiumꢀcatalyzed sequential
threeꢀcomponent coupling of benzyl chlorides, internal alkynes, and alkenes to
selectively synthesize 4ꢀbenzyl substituted 1,3ꢀbutadienes. To the best of our
knowledge, no example of intermolecular tandem benzylation/alkenylation of a
simple alkyne has been reported. Herein, we describe our preliminary results for two
sequential C(sp3)ꢀC(sp2) and C(sp2)ꢀC(sp2) bondꢀforming processes.
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Scheme 1. Our group’s works on difunctionalization of alkynes
Our initial work was aimed at developing a set of reaction conditions that would
work well for a variety of substrates. The reaction of benzyl chloride (1a), methyl
octꢀ2ꢀynoate (2a), and methyl acrylate (3a) was chosen as the model system for
optimization of this process, and the results are summarized in Table 1. When the
reaction of benzyl chloride, methyl octꢀ2ꢀynoate (1 equiv), and methyl acrylate (1
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o
equiv) was conducted in the presence of Pd(OAc)2 in CH3CN/Et3N (1:1) at 80 C for
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h, the 1:1:1 coupling proceeded to afford (2E,4E)ꢀdimethyl
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2ꢀbenzylꢀ3ꢀpentylhexaꢀ2,4ꢀdienedioate (4aaa) in 18% yield, along with minor
amounts of normal MizorokiꢀHeckꢀtype product was also detected by GCꢀMS.
Fortunately, when 2 equiv of benzyl chloride, 1 equiv of methyl octꢀ2ꢀynoate, and 2
equiv of methyl acrylate were employed, the yield of 1:1:1 coupling products
increased dramatically to 90%. Further experiments confirmed the ratio of benzyl
chloride, methyl octꢀ2ꢀynoate and methyl acrylate played a significant role in forming
product 4aaa (Table 1, entries 1−3). Plus, the most suitable reaction temperature
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o
appears to be 80 C and lower reaction temperature was not beneficial for the
conversion (Table 1, entries 2, 4, 5). Efforts to further optimize the reaction conditions
revealed that NEt3 was the best base for this reaction (Table 1, entries 6−8). This
reaction was subsequently repeated in the presence of 5 mol % Pd(OAc)2 and the
lower product yield of 16% was obtained (Table 1, entry 9). Unfortunately, when this
reaction was conducted using benzyl bromide instead of benzyl chloride, only
afforded a mixture of products (Table 1, entry 10). Moreover, when this reaction was
conducted using aryl halide, the desired product wasn’t obtained.
Table 1. Optimization Reaction Conditions of Benzyl Chloride (1a) with Methyl
Oct-2-ynoate (2a) and Methyl Acrylate (3a) a
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Entry
Ratiob
Solvent
T/ oC
Yield(%)c
18
1
2
1:1:1
2:1:2
CH3CN/Et3N
CH3CN/Et3N
80
80
90 (82)
3
4
3:1:3
2:1:2
2:1:2
2:1:2
2:1:2
2:1:2
2:1:2
2:1:2
CH3CN/Et3N
CH3CN/Et3N
CH3CN/Et3N
CH3CN
80
60
40
80
80
80
80
80
45
n.r.
n.r.
n.d.
n.d.
n.d.
16
5
6d
7e
8f
CH3CN
CH3CN
9g
10h
CH3CN/Et3N
CH3CN/Et3N
n.d.
aAll reactions were run on a 0.5ꢀmmol scale (limiting reagent) employing Pd(OAc)2 (10 mol %) as
the catalyst in 2 mL of solvent for 2 h. bRatio of benzyl chloride:alkynoate:alkene. cDetermined by
d
e
GC. Number in parentheses is isolated yield. 2.0 equiv K2CO3 instead of Et3N. 2.0 equiv DBU
instead of Et3N. f2.0 equiv DABCO instead of Et3N. g5 mol % Pd(OAc)2. hBenzyl bromide instead
of benzyl chloride. n.r. = no reaction, n.d. = no desired product.
Under these optimized conditions (Table 1, entry 2), we examined the scope of
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threeꢀcomponent coupling process with respect to a variety of benzyl chlorides,
alkynes and alkenes(Scheme 2). As far as the scope of the substituted acrylates was
concerned, acrylates in a common use within other acetoxypalladation systems
provided the corresponding benzylated product with good activation (4aaa, 4aab,
4aac, 4aad, 4aae, 4aaf). In addition, acrylonitrile and pentꢀ1ꢀenꢀ3ꢀone were also
tolerated in this transformation to generate desired products (4aag, 4aah). Then, the
scope of the palladiumꢀcatalyzed threeꢀcomponent coupling leading to 4ꢀbenzyl
substituted 1,3ꢀbutadienes was further expanded to a range of substituted benzyl
chlorides (1a). Both electronꢀrich and electronꢀdeficient benzyl chlorides could be
smoothly transformed into the desired products. Furthermore, substituents at different
positions on the benzene ring (para, meta, and ortho positions) did not affect the
reaction efficiency (4baa, 4caa, 4daa, 4eaa). It is noteworthy that haloꢀsubstituted
benzyl chloride was tolerated well, thus leading to haloꢀsubstituted products, which
could be used for further transformations (4faa). Inspired by these results, we became
interested in further expanding the substrate scope of this methodology to alkynes. To
our delight, aliphatic alkynoates afford good yields of the desired product (4aaa,
4aba), but aromatic alkynes appears to require higher reaction temperature to achieve
the comparable yields (4aca, 4ada, 4aea). The results show that alkynes bearing
electronꢀdonating substitutents gave lower yields than those bearing
electronꢀwithdrawing substitutents. One important reason for this fact is that benzyl
chloride could react with methyl acrylate to give MizorokiꢀHeckꢀtype product very
easily at higher temperature, thus suggesting a different reaction pathway leads to the
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formation of our target product in a low yield. The stereochemistry of the double bond
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in 4aaa was confirmed by H NMR and NOESY spectra, which indicated the
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cisꢀcarbopalladation involved in this reaction.
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Scheme 2. Reaction of Benzyl Chlorides with Alkynoates and Alkenesa,b
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a Reactions were carried out using benzyl chloride (1 mmol), alkynoate (0.5 mmol), alkene (1
mmol), Pd(OAc)2 (10 mol %), acetonitrile (1.0 mL), triethylamine (1.0 mL), 80 oC, 2 h. b Isolated
yields. c Ratio of benzyl chloride alkynoate and alkene: 2:1:4. d Ratio of benzyl chloride, alkynoate
and alkene: 3:1:3. e110 oC for 2 h.
We suggest two possible mechanisms (cycles I and II) to account for the present
processes (Scheme 3). The main difference between these two mechanisms is the first
Pd(0) oxidative addition step. In cycle I, the Pd(0) complex initially undergoes
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oxidative addition with the benzyl chloride 1a to generate benzylpalladium species A
in which the metal atom is bonded to a sp3ꢀhybridized carbon. Subsequent reaction
with the alkyne 2a affords vinylpalladium intermediate B, which undergoes
crossꢀcoupling with alkene 3a to give alkylpalladium species C. Subsequent βꢀH
elimination yields the observed product 4aaa with simultaneous regeneration of the
Pd(0) catalyst. Cycle II involves initial oxidative cyclization of alkyne (2a) and
alkene (3a) to Pd(0) to generate palladacyclopentene intermediate D, which then
reacts with the benzyl chloride (1a) to afford intermediate E. Subsequent reductive
elimination yields intermediate C which regenerates the Pd(0) catalyst with the
release of the target product. The regiochemical course of the reaction seems to favor
the process described in cycle II, and other mechanistic possibilities are also under
consideration. While the majority of the reactions reported here are quite clean, in
reactions affording much lower yields of 1,3ꢀdienes, side products consistent with this
mechanism are observed. The potential side reactions are immediate crossꢀcoupling of
intermediate A with the alkene to give simple Heck products.
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Scheme 3. Mechanistic Hypothesis for the Palladium-Catalyzed Domino Process for
Synthesis of 4-Benzyl Substituted 1,3-Butadienes
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In conclusion, we have developed a novel threeꢀcomponent coupling reaction for
the synthesis of 1,3ꢀbutadiene derivatives, which allows the rapid, efficient, and
selective construction of a C(sp3)ꢀC(sp2) bond and a C(sp2)ꢀC(sp2) bond in a single
reaction. This is the first example of palladiumꢀcatalyzed oneꢀpot reaction forming
butadienes bearing benzyl groups in a chemoꢀ, regioꢀ, and stereoselective manner
from simple, readily available starting materials. Further studies for construction of
other benzylated alkene systems using this method are underway.
Experimental Section
1
General method. H and 13C NMR spectra were recorded on a 400 MHz spectrometer using
CDCl3 as solvent and TMS as an internal standard. HRMS was carried out on a MAT 95XP
(Thermo). All reagents were purchased as reagent grade and used without further purification.
Typical procedure for the synthesis of 4-benzyl substituted 1,3-butadienes. Pd(OAc)2 (11 mg,
0.05 mmol) was mixed with CH3CN (1.0 mL)/Et3N (1.0 mL) in a test tube (10 mL) equipped with
a magnetic stirring bar. Then, alkyne (0.5 mmol), benzyl chloride (1.0 mmol) and alkene (1.0
mmol) were added. The mixture was stirred at 80 oC for 2 h. The reaction mixture was taken up by
in ether (10 mL) and washed with brine (10 mL). The organic layer was dried (MgSO4),
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concentrated in vacuo and purified by flash silica gel chromatography using petroleum ether/ethyl
acetate 50:1 to give the desired products. The stereochemistry of 4aaa was further confirmed by
NOESY methods.
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(2E,4E)-dimethyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aaa, 135 mg, 82%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 16.0 Hz, 1H), 7.30–7.26 (m, 2H),
7.21–7.14 (m, 3H), 6.18 (d, J = 15.6 Hz, 1H), 3.89 (s, 2H), 3.78 (s, 3H), 3.66 (s, 3H), 2.49–2.45 (m,
2H), 1.55–1.47 (m, 2H), 1.36–1.30 (m, 4H), 0.90 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
169.3, 167.2, 141.2, 141.0, 138.3, 136.0, 128.6, 128.3, 126.5, 122.2, 51.8, 51.7, 35.5, 32.1, 30.7, 29.3,
22.4, 14.0 ppm; νmax(KBr)/cm−1 2951, 1720, 1620, 1441, 1300, 1227, 1174, 1090; HRMS EI (m/z):
calcd for C20H26O4, 330.1831; found, 330.1825.
(2E,4E)-6-butyl 1-methyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aab, 138 mg, 74%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 15.6 Hz, 1H), 7.26 (t, J = 7.2 Hz, 2H),
7.20–7.13 (m, 3H), 6.15 (d, J = 15.6 Hz, 1H), 4.17 (t, J = 6.8 Hz, 2H), 3.88 (s, 2H), 3.66 (s, 3H), 2.46 (t,
J = 8.0 Hz, 2H), 1.69–1.62 (m, 2H), 1.52–1.47 (m, 2H), 1.45–1.37 (m, 2H), 1.33–1.29 (m, 4H), 0.94 (t,
J = 7.2 Hz, 3H), 0.90 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4, 166.9, 141.2, 141.0,
138.4, 135.8, 128.5, 128.3, 126.4, 122.6, 64.6, 51.7, 35.5, 32.1, 30.7, 29.3, 22.4, 19.2, 14.0, 13.7 ppm;
νmax(KBr)/cm−1 2957, 1718, 1617, 1459, 1229, 1171; HRMS EI (m/z): calcd for C23H32O4, 372.2301;
found, 372.2296.
(2E,4E)-6-(2-ethylhexyl) 1-methyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aac, 139 mg, 65%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 15.6 Hz, 1H), 7.24 (d, J = 6.8 Hz, 2H),
7.19–7.12 (m, 3H), 6.14 (d, J = 16.0 Hz, 1H), 4.09–4.05 (m, 2H), 3.86 (s, 2H), 3.66 (s, 3H), 2.48–2.42
(m, 2H), 1.63–1.58 (m, 1H), 1.53–1.46 (m, 2H), 1.36–1.28 (m, 12H), 0.90–0.87 (m, 9H); 13C NMR
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(100 MHz, CDCl3) δ 169.4, 166.9, 141.3, 140.9, 138.4, 135.7, 128.5, 128.3, 126.4, 122.6, 67.2, 51.7,
38.8, 35.5, 32.1, 30.6, 30.5, 29.3, 28.9, 23.9, 22.9, 22.4, 14.0, 11.0 ppm; νmax(KBr)/cm−1 2930, 1719,
1459, 1227, 1170; HRMS EI (m/z): calcd for C27H40O4, 428.2927; found, 428.2922.
(2E,4E)-6-cyclohexyl 1-methyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aad, 127 mg, 64%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 16.0 Hz, 1H), 7.29–7.25 (m, 2H),
7.22–7.14 (m, 3H), 6.14 (d, J = 16.0 Hz, 1H), 4.88–4.82 (m, 1H), 3.88 (s, 2H), 3.67 (s, 3H), 2.48–2.44
(m, 2H), 1.91–1.87 (m, 2H), 1.75–1.72 (m, 2H), 1.56–1.43 (m, 6H), 1.40–1.29 (m, 6H), 0.90 (t, J = 6.8
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4, 166.2, 141.4, 140.7, 138.5, 135.6, 128.5, 128.3, 126.4,
123.1, 73.0, 51.7, 35.5, 32.1, 31.7, 30.7, 29.3, 25.4, 23.8, 22.4, 14.0 ppm; νmax(KBr)/cm−1 2938, 1716,
1455, 1228, 1175; HRMS EI (m/z): calcd for C25H34O4, 398.2457; found, 398.2453.
(2E,4E)-6-(tetrahydrofuran-3-yl)methyl 1-methyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aae, 96
mg, 48%)
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Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 15.6 Hz, 1H), 7.31–7.27 (m, 2H),
7.22–7.15 (m, 3H), 6.25 (d, J = 16.0 Hz, 1H), 4.31–4.27 (m, 1H), 4.14–4.09 (m, 1H), 3.93–3.80 (m,
4H), 3.68 (s, 3H), 2.50–2.46 (m, 2H), 2.08–2.00 (m, 1H), 1.97–1.90 (m, 2H), 1.68–1.45 (m, 4H),
1.37–1.31 (m, 4H), 0.92 (t, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4, 166.8, 141.5, 141.0,
138.3, 136.1, 128.5, 128.3, 126.4, 122.1, 76.5, 68.5, 66.8, 51.7, 35.5, 32.1, 30.7, 29.3, 28.0, 25.7, 22.4,
14.0 ppm; νmax(KBr)/cm−1 2953, 1719, 1226, 1169; HRMS EI (m/z): calcd for C24H32O5, 400.2250;
found, 400.2245.
(2E,4E)-6-(2,2,2-trifluoroethyl) 1-methyl 2-benzyl-3-pentylhexa-2,4-dienedioate (4aaf, 103 mg,
52%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 16.0 Hz, 1H), 7.20–7.17 (m, 2H),
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7.12–7.04 (m, 3H), 6.10 (d, J = 16.0 Hz, 1H), 4.46 (q, J = 8.4 Hz, 2H), 3.79 (s, 2H), 3.59 (s, 3H),
2.38–2.34 (m, 2H), 1.45–1.37 (m, 2H), 1.25–1.21 (m, 4H), 0.81 (t, J = 6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 169.2, 165.0, 143.4, 140.4, 138.1, 137.5, 128.6, 128.3, 126.6, 120.1, 77.0, 60.7, 60.3,
51.8, 35.59, 32.1, 30.6, 29.2, 22.4, 14.0 ppm; νmax(KBr)/cm−1 2956, 1728, 1279, 1228, 1157; HRMS EI
(m/z): calcd for C21H25F3O4, 398.1705; found, 398.1697.
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(2E)-methyl 2-benzyl-3-((E)-2-cyanovinyl)oct-2-enoate (4aag, 113 mg, 76%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 16.4 Hz, 1H), 7.32–7.28 (m, 2H),
7.24–7.21 (m, 1H), 7.14–7.10 (m, 2H), 5.64 (d, J = 16.4 Hz, 1H), 3.84 (s, 2H), 3.68 (s, 3H), 2.44–2.40
(m, 2H), 1.53–1.44 (m, 2H), 1.34–1.30 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 168.9, 147.0, 140.0, 137.5, 136.9, 128.7, 128.1, 126.8, 117.9, 100.8, 51.9, 35.4, 32.0, 29.8, 29.1, 22.3,
14.0 ppm; νmax(KBr)/cm−1 2954, 1722, 1458, 1300, 1230, 1197; HRMS EI (m/z): calcd for C19H23NO2,
297.1729; found, 297.1722.
(2E,4E)-methyl 2-benzyl-6-oxo-3-pentylocta-2,4-dienoate (4aah, 75 mg, 46%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 16.0 Hz, 1H), 7.31–7.27 (m, 2H),
7.22–7.15 (m, 3H), 6.44 (d, J = 16.0 Hz, 1H), 3.90 (s, 2H), 3.69 (s, 3H), 2.63–2.58 (m, 2H), 2.51–2.47
(m, 2H), 1.55–1.47 (m, 2H), 1.35–1.33 (m, 4H), 1.12 (t, J = 7.2 Hz, 3H), 0.91 (t, J = 6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 201.0, 169.4, 141.7, 138.5, 136.2, 130.9, 129.7, 128.6, 128.3, 126.5, 51.8,
35.5, 34.3, 32.1, 30.6, 29.4, 22.4, 14.0, 8.1 ppm; νmax(KBr)/cm−1 2956, 1725, 1595, 1280, 1192;
HRMS EI (m/z): calcd for C21H28O3, 328.2038; found, 328.2036.
(2E,4E)-dimethyl 2-(2-methylbenzyl)-3-pentylhexa-2,4-dienedioate (4baa, 119 mg, 69%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 15.6 Hz, 1H), 7.15–7.08 (m, 3H),
7.04–7.02 (m, 1H), 6.17 (d, J = 16.0 Hz, 1H), 3.84 (s, 2H), 3.76 (s, 3H), 3.60 (s, 3H), 2.48–2.44 (m,
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2H), 2.31 (s, 3H), 1.57–1.50 (m, 2H), 1.35–1.23 (m, 4H), 0.91 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 169.3, 167.2, 141.0, 140.3, 136.4, 136.2, 135.9, 130.2, 128.3, 126.6, 126.1, 122.0, 51.8, 51.6,
33.1, 32.1, 30.8, 29.3, 22.4, 19.6, 14.0 ppm; νmax(KBr)/cm−1 2952, 1722, 1437, 1226, 1170; HRMS EI
(m/z): calcd for C21H28O4, 344.1988; found, 344.1985.
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(2E,4E)-dimethyl 2-(3-methylbenzyl)-3-pentylhexa-2,4-dienedioate (4caa, 91 mg, 53%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 15.6 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H),
7.04–6.95 (m, 3H), 6.19 (d, J = 16.0 Hz, 1H), 3.87 (s, 2H), 3.80 (s, 3H), 3.69 (s, 3H), 2.51–2.47 (m,
2H), 2.33 (s, 3H), 1.56–1.49 (m, 2H), 1.36–1.31 (m, 4H), 0.92 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 169.4, 167.2, 141.3, 140.8, 138.1, 136.1, 129.2, 128.4, 127.2, 125.3, 122.1, 51.8, 51.7, 35.4,
32.1, 30.7, 29.3, 22.4, 21.4, 14.0 ppm; νmax(KBr)/cm−1 2952, 1722, 1224, 1169; HRMS EI (m/z): calcd
for C21H28O4, 344.1988; found, 344.1982.
(2E,4E)-dimethyl 2-(4-methylbenzyl)-3-pentylhexa-2,4-dienedioate (4daa, 115 mg, 67%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = 15.8 Hz, 1H), 7.11–7.04 (m, 4H), 6.19 (d,
J = 16.0 Hz, 1H), 3.86 (s, 2H), 3.80 (s, 3H), 3.69 (s, 3H), 2.49–2.45 (m, 2H), 2.32 (s, 3H), 1.54–1.48
(m, 2H), 1.37–1.34 (m, 4H), 0.94–0.91 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 169.4, 167.2, 146.4,
141.3, 140.6, 136.3, 135.1, 129.3, 128.2, 124.4, 122.6, 122.0, 51.8, 51.7, 35.1, 32.1, 30.7, 29.3, 22.40,
21.0, 14.0 ppm; νmax(KBr)/cm−1 2953, 1722, 1226, 1170; HRMS EI (m/z): calcd for C21H28O4,
344.1988; found, 344.1985.
(2E,4E)-dimethyl 2-(4-methoxybenzyl)-3-pentylhexa-2,4-dienedioate (4eaa, 119 mg, 66%)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 16.0 Hz, 1H), 7.06 (d, J = 8.4 Hz, 2H), 6.81 (d,
J = 8.8 Hz, 2H), 6.17 (d, J = 15.6 Hz, 1H), 3.85–3.82 (m, 3H), 3.78 (d, J = 2.0 Hz, 6H), 3.66 (s, 2H),
2.46–2.42 (m, 2H), 1.56–1.46 (m, 2H), 1.34–1.29 (m, 4H), 0.90 (t, J = 6.4 Hz, 3H); 13C NMR (100
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MHz, CDCl3) δ 169.4, 167.3, 158.2, 141.2, 140.3, 136.6, 130.2, 129.4, 122.0, 114.0, 55.2, 51.7, 34.6,
32.1, 30.7, 29.7, 29.3, 22.4, 14.0 ppm; νmax(KBr)/cm−1 2953, 1728, 1226, 1170; HRMS EI (m/z): calcd
for C21H28O5, 360.1937; found, 360.1933.
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(2E,4E)-dimethyl 2-(4-chlorobenzyl)-3-pentylhexa-2,4-dienedioate (4faa, 87 mg, 48%)
White solid, m. p.: 69ꢀ71 oC, 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 15.6 Hz, 1H), 7.23 (d, J = 7.6
Hz, 2H), 7.07 (d, J = 7.6 Hz, 2H), 6.18 (d, J = 15.6 Hz, 1H), 3.84 (s, 2H), 3.77 (s, 3H), 3.66 (s, 3H),
2.49–2.45 (m, 2H), 1.52–1.47(m, 2H), 1.31–1.26 (m, 4H), 0.90 (t, J = 5.6 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 169.1, 167.1, 141.6, 140.9, 136.8, 135.3, 132.3, 129.7, 128.7, 122.5, 51.8, 51.7, 34.8,
32.0, 30.7, 29.3, 22.4, 14.0 ppm; νmax(KBr)/cm−1 2950, 1719, 1383, 1168; HRMS EI (m/z): calcd for
C20H25ClO4, 364.1441; found, 364.1435.
(2E,4E)-1-ethyl 6-methyl 2-benzyl-3-methylhexa-2,4-dienedioate (4aba, 101 mg, 70%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 15.6 Hz, 1H), 7.25–7.23 (m, 2H),
7.19–7.13 (m, 3H), 6.16 (d, J = 15.6 Hz, 1H), 4.11 (q, J = 7.2 Hz, 2H), 3.90 (s, 2H), 3.76 (s, 3H), 2.06
(s, 3H), 1.15 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 169.0, 167.2, 142.0, 138.2, 137.1,
135.3, 128.5, 126.5, 122.3, 60.8, 51.8, 35.5, 16.5, 14.0 ppm; νmax(KBr)/cm−1 2950, 1718, 1301, 1225,
1176; HRMS EI (m/z): calcd for C17H20O4, 288.1362; found, 288.1358.
(2E,4Z)-methyl 4,5,6-triphenylhexa-2,4-dienoate (4aca, 81 mg, 46%)
White solid, m. p.: 108ꢀ110 oC, 1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 15.2 Hz, 1H), 7.44 (t, J =
7.6 Hz, 2H), 7.38–7.25 (m, 6H), 7.17–7.07 (m, 5H), 6.85 (d, J = 7.6 Hz, 2H), 5.33 (d, J = 15.2 Hz, 1H),
3.67 (s, 2H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.8, 148.9, 145.6, 139.8, 138.6, 138.4,
137.3, 129.8, 129.4, 128.9, 128.7, 128.2, 128.1, 127.7, 127.5, 126.0, 121.1, 51.4, 42.3 ppm;
νmax(KBr)/cm−1 3028, 1712, 1608, 1507, 1227; HRMS EI (m/z): calcd for C25H22O2, 354.1620; found,
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(2E,4Z)-methyl 4,5-bis(4-fluorophenyl)-6-phenylhexa-2,4-dienoate (4ada, 78 mg, 40%)
Yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J = 15.6 Hz, 1H), 7.24–7.20 (m, 2H), 7.16–7.10 (m,
7H), 7.03–7.01 (m, 2H), 6.84–6.82 (m, 2H), 5.32 (d, J = 15.6 Hz, 1H), 3.64 (s, 2H), 3.64 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.5, 163.5 (d, 10 Hz), 161.1 (d, 9 Hz), 148.2, 145.1, 138.2, 136.7, 135.6
(d, 3 Hz), 134.0 (d, 4 Hz), 131.4 (d, 8 Hz), 131.0 (d, 8 Hz), 128.7, 128.3, 126.2, 121.5, 115.6 (d, 67 Hz),
115.5 (d, 24 Hz), 51.5, 42.3 ppm; νmax(KBr)/cm−1 3031, 1716, 1606, 1507, 1227, 1166; HRMS EI (m/z):
calcd for C25H20F2O2, 390.1431; found, 390.1427.
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(2E,4Z)-methyl 6-phenyl-4,5-dip-tolylhexa-2,4-dienoate (4aea, 71 mg, 37%)
Light yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 15.6 Hz, 1H), 7.23 (d, J = 7.6 Hz, 2H),
7.13–7.03 (m, 9H), 6.88 (d, J = 7.2 Hz, 2H), 5.34 (d, J = 15.6 Hz, 1H), 3.67 (s, 2H), 3.62 (s, 3H), 2.39
(s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 167.9, 148.8, 146.1, 138.9, 137.4, 137.2, 137.0,
136.9, 135.5, 129.6, 129.3, 128.9, 128.0, 125.9, 120.7, 51.3, 42.2, 21.2 ppm; νmax(KBr)/cm−1 2921,
1711, 1268, 1166; HRMS EI (m/z): calcd for C27H26O2, 382.1933; found, 382.1926.
Acknowledgements
The authors are grateful to the National Natural Science Foundation of China (20932002,
21172076), National Basic Research Program of China (973 Program) (2011CB808600),
Guangdong Natural Science Foundation (10351064101000000), and the Fundamental Research
Funds for the Central Universities (2010ZP0003) for financial support.
Supporting Information
Spectral data for all new compounds; NOE studies on stereochemistry of 4aaa. This material is
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ACS Paragon Plus Environment