Modular synthesis of (E)-cinnamaldehydes directly from allylarenes via a metal-free DDQ-mediated oxidative process

Article abstract of DOI:10.1039/c8ob01469h

An efficient synthesis of (E)-cinnamaldehydes by a metal-free DDQ-mediated oxidative transformation of allylarenes was developed. The protocol provides a practical method to prepare diverse (E)-cinnamaldehydes with broad functional group tolerance in good to excellent yields, including easy access to natural products randainal and geranyloxy sinapyl aldehyde from plant extracts. Finally, the mechanism of a single-electron transfer process was proposed.

Full text of DOI:10.1039/c8ob01469h

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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DOI: 10.1039/C8OB01469H
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Modular Synthesis of (E)-Cinnamaldehydes Directly from
Allylarenes under Metal-free DDQ-mediated Oxidative Process †
TingrTing Xu a , TaorShan Jiang*, b,XiaorLan Han a, YuanrHong Xu c, JinrPing Qiao *, c
Received 00th January 20xx,
Accepted 00th January 20xx
An efficient synthesis of (E)rcinnamaldehydes by metalrfree DDQrmediated oxidative transformation of allylarenes was
developed. The protocol provides a practical method of diverse (E)rcinnamaldehydes with broad functional group
tolerance in good to excellent yields, including easily access to natural products Randainal and Geranyloxy sinapyl
aldehyde from plant extracts. Finally, the mechanism of a singlerelectron transfer process was proposed.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
Over the past decades, oxidative functionalization of
alkenes has emerged as a powerful method to obtain many
(E)rCinnamaldehyde analogues have attracted intense interest
for their diverse applications in
agrochemical,1
useful chemicals in organic synthesis.10,11 Among them,
oxidative conversion of allylarenes into cinnamaldehydes
represented an effective way (Scheme 1a).12r13 However, two
major drawbacks must be overcome for the existing methods:
(i) the involvement of transition metal catalysts which resulted
in the metal residue,12 (ii) the need of high electronrdonating
substituents on substrates that limited its wide applications
and no followrup systematic studies were reported in organic
and pharmaceutical synthesis.13 Nevertheless, an efficient
metalrfree synthesis of cinnamaldehydes from allylarenes
under mild conditions is highly desired. Herein we report an
efficient oxidative transformation of allylarenes to (E)r
cinnamaldehydes mediated by DDQ under metalrfree
conditions systematically. This reaction tolerates a variety of
substrates including heterotoms, some activated groups and
exhibits very practical synthesis of some natural product
derivatives (Scheme 1b).
pharmaceutical,2 and flavor3 industries. They are also widely
distributed throughout the plant species which have
demonstrated important biological functions.4 Several
representative molecules such as 2rHCA derivatives, Randainal
and Geranyloxy sinapyl aldehyde that have important
medicinal or bioactive values were shown in Figure 1.2, 4 On
the other hand, cinnamaldehydes are highly useful synthetic
building blocks in organic synthesis.5 So the synthesis
(especially medicinal synthesis) of cinnamaldehydes has
received much attention in synthetic and medicinal chemists.
With respect to the conventional approaches6r8 or transition
metalrcatalyzed reactions to cinnamaldehydes,9 harsh reaction
conditions, inaccessible starting substrates, unsatisfactory
selectivity or limited substrates scope, which restricted their
wide applications. In terms of pharmaceutical synthesis of
cinnamaldehydes, there should be some other requirements
to be considered: (i) transitionrmetalrfree condition to avoid
the heavy metal residues; (ii) selectivityrcontrollable and
functional group tolerable to enable the practicality.
Scheme 1. Transformations of allylarenes to cinnamaldehydes.
Fig 1. Representative bioactive compounds containing cinnamaldehyde motifs.
a.
Department of Stomatology, The First Affiliated Hospital of Anhui Medical
University, Hefei, 230022, Anhui, China.
School of Life Sciences, Anhui Agricultural University, Hefei, 230036, Anhui, China.
b.
Results and discussion
jts2015@ahau.edu.cn;
c. Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei,
230022, Anhui, China. jpqiao@ahmu.edu.cn
†Electronic Supplementary Information (ESI) available. See
DOI: 10.1039/x0xx00000x
Based on previous studies,12r13 we performed the reaction
using 2rallylphenyl acetate (1a) and water as the model
substrates to screen the optimal experiment parameters under
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Journal Name
metalrfree condition (Table 1). To our delight, the reaction to high yields (48r90%). It was noteworthy that for the
could proceed smoothly in the presence of H2O (2.0 equiv.), substrates with the electronrwithdrawing group (except for
DDQ (2.0 equiv.), DCE (2.0 mL) at 50 ºC for 10 h and the nitro group) afforded the desired products 2m–r in moderate
desired product 2a was isolated in 53% yield (Table 1, entry 1). yields (48r74%), while increasing temperature based on
However, the product was obtained only in 12% yield at room standard conditions was required. In addition, various
temperature (Table 1, entry 2).The yield was improved to 68% functional groups, such as vinyl (1m), halogen (1n
, 1o), ketone
when increasing the reaction temperature to 60 ºC (Table 1, (1p), nitrile (1q, 1r) moieties which may not compatible under
entry 3). Further raising the temperature to 80 ºC did not give metalrcatalyzed condition, were tolerated on the aryl ring
any improvement (Table 1, entry 4). Gratifyingly, the yield of under this condition. Aside from allyl benzene derivatives, allyl
2a could be further improved to 76% when 2.2 equiv. of DDQ indole and thiophene were also suitable substrates to give
was used (Table 1, entry 5). Optimization of the solvent desired products 2t and 2u in moderate yields (70 and 73%).
showed that the best result was given when DCE was used as Finally, to test the applicability of this methodology, molecules
the solvent (Table 1, entry 5 vs entries 6r12). Increasing the with functional group diversity were also evaluated. For
amount of H2O to 10 equiv. in the reaction afforded the example, substrates bearing TBS protecting group (1w), a free
product in similar yield compared to 2 equiv. of H2O (Table 1, alkyl alcohol (1x), and aldehyde group (1y), which provide
entry 5 vs entry 13).
opportunities for further transformations, were compatible
and gave products 2w in moderate to good yields (68r81%)
–
y
Table 1. Optimization of reaction conditions a.
in this oxidation conditions. However, aliphatic olefins (1z) did
not react in this process. Moreover, this reaction could be
performed on a gramrscale, clearly showing its potential
applications in organic synthesis (Scheme 2). For example,
substrate 1y could easily be converted to compound 2y (76%,
1.29 g) under standard conditions.
Entry
1
Oxidant(equiv.)
DDQ(2.0)
Solvent
DCE
Temp(ºC)
50
Yield
53
Table 2. Substrates Scope a.
2
3
DDQ(2.0)
DDQ(2.0)
DCE
DCE
r.t.
60
12
68
4
5
6
7
8
9
DDQ(2.0)
DDQ(2.2)
DDQ(2.2)
DDQ(2.2)
DDQ(2.2)
DDQ(2.2)
DCE
80
60
60
60
60
60
65
DCE
76
DMSO
CH3CN
toluene
Dioxane
N.D.
57
31
46
10
11
12
DDQ(2.2)
DDQ(2.2)
DDQ(2.2)
CH3NO2
EA
60
60
60
60
64
40
H2O
13b
DDQ(2.2)
DCE
60
74
a
Reaction conditions: All reactions were performed with 1a (0.3 mmol), H2O (2.0
b
equiv.), and oxidant (2.2 equiv.) in 2.0 mL of solvent for 10 h. H2O (10.0 equiv.) was
used.
With the optimized conditions of this oxidative reaction
without metal catalyst in hand, we next examined the
generality of this protocol to synthesize a number of
hydroxycinnamaldehyde derivatives (Table 2, 2arg). Protected
hydroxyallylarenes bearing different substituents on the aryl
ring afforded the corresponding cinnamaldehyde products in
good yields (55r86%). It was interesting that the reaction had
better selectivity when two ally groups in one benzene ring (2g
was isolatied in 55% yield with a small amount of diroxidative
product). In this oxidative system, freerphenolic hydroxyl was
not tolerated. Besides hydroxycinnamaldehydes, the scope of
this method to cinnamaldehydes from allylbenzenes was
further investigated (Table 2, 2hry). Generally, various
substituted allylbenzenes were subjected to the standard
conditions to afford corresponding cinnamaldehydes in good
2 | J. Name., 2012, 00, 1r3
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CHO
DDQ (2.2 equiv.)
selective oxidative process may serve as attractive routes in
organic synthesis for further transformations and easily
synthesis of some bioactive molecules.
Ar
Ar
H2O
DCE, 60 o
C
1
2
CHO
t-Bu
CHO
CHO
CHO
Scheme 3. Selective oxidative transformations of allylarenes.
OAc
2a, 76%
OAc
2b, 77%
OCOPh
2c, 75%
OHC
CHO
CHO
OAc
OBn
OMe
2d, 71%b
OH
2f, trace
2e, 86%
OAc
OAc
CHO
OHC
CHO
2g, 55%
2g', 13%
CHO
CHO
CHO
Condition A: DDQ (2.2 equiv.), H2O (2.0 equiv.), DCE (2.0 mL), 60 oC, 5 h;
Condition B: DDQ (4.4 equiv.), H2O (4.0 equiv.), DCE (4.0 mL), 60 oC, 10 h.
MeO
2h, 76%
2i, 80%
2j, 62%
CHO
Then substrate
6 was used for the comparison
CHO
CHO
CHO
experiments under this protocol and the previous report
(Scheme 4). To our delight, the allyl ether group was tolerated
under this metalrfree condition and the desired product was
isolated in 76% yield. However, the deally product eugenol was
detected by TLC analysis using Pd(OAc)2/O2 conditons and only
Ph
Cl
2k, 79%
2m, 59%
2p, 68%b
2s. trace
2l, 90%
CHO
CHO
CHO
Ac
8
(coniferaldehyde) was isolated in 14% yield.12a
Br
product
2n, 74%b
2q,65%b
2o, 65%b
Based on these results, the plant extract geranyloxy sinapyl
aldehyde could be easily synthesized. As shown in Scheme 5,
substituted allylbenzens 12 could be obtained in three steps,
then direct oxidation of allyl group under very mild condition
gave the geranyloxy sinapyl aldehyde 13 in 61% isolated yield.
Obviously, other similar compounds extracted from plants
could also be easily synthesized by this strategy.14
CHO
CHO
CN
NC
O2N
2r. 48%b
CHO
CHO
CHO
S
2u,73%
CHO
N
Ms
2t, 70%
2v, 75%
Scheme 4. Comparative experiment.
MeO
MeO
CHO
HO
TBSO
OHC
O
2x, 68%
2w, 76%
O
CHO
MeO
CHO
N
N
O
O
2y, 81%
2z, n.d.
a Reaction conditions: All reactions were performed with 1 (0.3 mmol), H2O (2.0 equiv.)
and DDQ (2.2 equiv.) in 2.0 mL of DCE at 60 ºC under air atmosphere for 10 h. b at 80 ºC.
Scheme 5. Synthesis of geranyloxy sinapyl aldehyde.
Scheme 2. Gramrscale reaction.
To demonstrate some applications of this metalrfree
oxidative process, Randainal shown in Figure
synthesized firstly. Diacetylated magnolol was designed to
explore the selective oxidative transformations (Scheme 3).
1 was
3
Reaction conditions: (a) allyl bromide, K2CO3, acetone, reflux, 12 h; (b) 170 ºC, 4 h; (c)
geranyl alcohol, PPh3, DEAD, THF, 24 h; (d) DDQ, DCE, r.t., 5 h.
Under standard condition, monoroxidative product
isolated in 53% yield with a minor diroxidative product
4
was
5. Thus,
The possible reaction mechanisms path
a and path b were
when the quantity of reaction parameters were double, the
main diroxidative product was obtained in 45% yield. Such
shown in Scheme 6. During the course of our studies using TLC
5
or LCrMS analysis, we observed that trace of cinnamyl alcohol
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14 but compounds 15 and 16 were not detected. The reaction
Journal Name
The starting materials 1ar1h, 1j, 1l, 1vr1z, 3, 6, 12 were
has very high selectivity. When DDQ was added to the solution commercial available reagents or precursors with simple
of allylbenzene (especially with electronrdonating group), we modifications.
observed the immediate formation of a deep green color that
15
The starting materials 1i, 1k, 1m, 1n, 1s, 1u were synthesized
is likely a chargertransfer complex B,
which maybe from a through Grignard reaction.17 The starting materials 1pr1r were
singlerelectron transfer process between the arylallylic double synthesized through Stille reaction from aryl halide.17 The starting
bond and DDQ.15, 16 Actually, Lundquist has discussed relevant materials 1o,18 1t17 were synthesized according to the literatures.
mechanism in previous work.13 It was suggested that quinol General procedure for the synthesis of 2.
monoethers and quinol diethers
this oxidative process which were analyzed through HNMR13a mmol), H2O (10.8 mg, 0.6 mmol) in DCE (1 mL), then starting
and they have high reactivity toward hydrolysis.16a We totally material
(0.3 mmol) dissolved in DCE (1.0 mL) was added.
agree with this mechanism. Based on the above results and The reaction was stirred at 60 °C (or 80 °C) for 10 h under air
C are the key intermediates in An ovenrdried tube was charged with DDQ (149.8 mg, 0.66
1
literatures, path
a
is the most possible mechanism..
conditions. After the reaction was completed, the mixture was
cooled to room temperature and neutralized with saturated
Na2CO3 (5 mL), then diluted with saturated brine (10.0 mL) and
Scheme 6. Proposed reaction mechanism.
extracted with EtOAc (15 mL
ì 3). The organic extract was
dried and concentrated under reduced pressure. The residue
was purified by flash column chromatography on a silica gel
using petroleum ether/EtOAc as the eluent to give the desired
product 2.
(E)r2r(3rOxopropr1renr1ryl)phenyl acetate (2a) 19
By following the general procedure, 2rallylphenyl acetate (52.9
mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h
under air conditions. After the work up, the crude product was
purified by flash column chromatography to afford the title
compound (43.4 mg, 76%). Rf = 0.29 (petroleum ether/EtOAc =
1
3:1); H NMR (600 MHz, CDCl3) w 9.69 (d, J = 7.8 Hz, 1H), 7.65
(d, J = 7.2 Hz, 1H), 7.54 (d, J = 16.2 Hz, 1H), 7.45 (t, J = 7.2 Hz,
1H), 7.30 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 6.72 (dd, J =
7.8, 16.2 Hz, 1H), 2.39 (s, 3H); 13CNMR (150MHz, CDCl3) w
193.5, 168.9, 149.3, 145.7, 132.1, 130.3, 128.0, 126.6, 126.5,
123.3, 21.0.
Conclusions
(E)r4r(tertrButyl)r2r(3roxopropr1renr1ryl)phenyl acetate (2b)
By following the general procedure, 2rallylr4r(tertrbutyl)phenyl
acetate (70.0 mg, 0.3 mmol) dissolved in DCE (1 mL) was
added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O
(10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
60 °C for 10 h under air conditions. After the work up, the
crude product was purified by flash column chromatography
to afford the title compound (56.8 mg, 77%). Light yellow oil,
IR (KBr) 1712, 1690, 1665, 952 cmr1, Rf = 0.30 (petroleum
ether/EtOAc = 3:1); 1H NMR (600 MHz, CDCl3) w 9.69 (d, J = 7.8
Hz, 1H), 7.63 (d, J = 2.4 Hz, 1H), 7.54 (d, J = 16.2 Hz, 1H), 7.49
(dd, J = 8.4, 2.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.74 (dd, J =
16.2, 7.8 Hz, 1H), 2.38 (s, 3H), 1.33 (s, 9H); 13CNMR (150MHz,
CDCl3) w 193.7, 169.1, 149.4, 147.1, 146.5, 130.0, 129.6, 125.7,
124.8, 122.7, 34.6, 31.2, 21.0. HRMS (ESIrTOF) m/z [M+H+]
calcd for C15H19O3 247.1334, found 247.1336.
In summary, we have developed an efficient synthesis of
various (E)rcinnamaldehydes between allyl arenes and water
using DDQ as an oxidant without any metal catalyst. The
reaction was clean and practical in mild conditions and showed
excellent functional group compatibility. This process also
provides an easy synthetic protocol for constructing
synthetically and bioactive important cinnamaldehydes motif.
Further studies on the synthetic applications of this
methodology are ongoing in our group.
Experimental section
General Information.
Unless otherwise noted, all reactions were carried out
under air atmosphere, commercial materials and solvents
1
were used without further purification. H NMR and 13C NMR
(E)r2r(3rOxopropr1renr1ryl)phenyl benzoate (2c) 20
spectra were measured on a 600 MHz spectrometer (1H: 600
MHz, 13C: 150 MHz) using CDCl3 as the solvent at room
temperature. Highrresolution mass spectra (HRMS) were
recorded on a BRUKER VPEXII spectrometer with ESI mode.
Synthesis of the Starting Materials.
By following the general procedure, 2rallylphenyl benzoate
(71.5 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h
under air conditions. After the work up, the crude product was
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1
purified by flash column chromatography to afford the title 2g’: Rf = 0.23 (petroleum ether/EtOAc = 3:1), H NMR (600
compound (56.7 mg, 75%). Rf = 0.24 (petroleum ether/EtOAc = MHz, CDCl3) w 9.72 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 7.8 Hz, 2H),
1
3:1); H NMR (600 MHz, CDCl3) w 9.62 (d, J = 7.8 Hz, 1H), 8.25 7.47 (d, J = 16.2 Hz, 2H), 7.42 (t, J = 7.8 Hz, 1H), 6.75 (dd, J = 7.8,
(d, J = 7.2 Hz, 2H), 7.73 (d, J = 7.8 Hz, 1H), 7.70 (t, J = 7.8 Hz, 16.2 Hz, 2H), 2.49 (s, 3H); 13CNMR (150MHz, CDCl3) w 193.1,
1H), 7.61 (d, J = 15.6 Hz, 1H), 7.57 (t, J = 7.8 Hz, 2H), 7.52 (t, J = 168.5, 147.8, 144.5, 131.3, 130.3, 128.5, 127.2, 20.7. HRMS
7.2 Hz, 1H), 7.36 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 6.74 (ESIrTOF) m/z [M+H+] calcd for C14H13O4 245.0814, found
(dd, J = 15.6, 7.8, Hz, 1H); 13CNMR (150 MHz, CDCl3) w 193.6, 245.0810.
164.8, 149.6, 145.6, 134.2, 132.2, 130.30, 130.25, 128.9, 128.7, (E)rCinnamaldehyde (2h) 12b
127.9, 127.0, 126.6, 123.4.
By following the general procedure, allylbenzene (36.0 mg, 0.3
mmol) dissolved in DCE (1 mL) was added to the solution of
DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE
(E)r4rFormylr2rmethoxyr6r(3roxopropr1renr1ryl)phenyl
acetate (2d)
By following the general procedure, 2rallylr4rformylr6r (1 mL). The reaction was stirred at 60 °C for 10 h under air
methoxyphenyl acetate (70.3 mg, 0.3 mmol) dissolved in DCE conditions. After the work up, the crude product was purified
(1 mL) was added to the solution of DDQ (136.2 mg, 0.60 by flash column chromatography to afford the title compound
1
mmol), H2O (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction (30.1 mg, 76%). Rf = 0.28 (petroleum ether/EtOAc = 20:1); H
was stirred at 80 °C for 10 h under air conditions. After the NMR (600 MHz, CDCl3) w 9.70 (d, J = 7.8 Hz, 1H), 7.57r7.56 (m,
work up, the crude product was purified by flash column 2H), 7.47 (d, J = 16.2 Hz, 1H), 7.43r7.42 (m, 3H), 6.72 (dd, J =
chromatography to afford the title compound (52.9 mg, 71%). 7.8, 16.2 Hz, 1H); 13CNMR (150MHz, CDCl3) w 193.6, 152.7,
Yellow solid, Mp 1325134 °C, IR (KBr) 1695, 1682, 1670, 980 134.0, 131.2, 129.1, 128.6, 128.5.
1
cmr1, Rf = 0.21 (petroleum ether/EtOAc = 3:1); H NMR (600 (E)r3r(prTolyl)acrylaldehyde (2i) 12b
MHz, CDCl3) w 9.98 (s, 1H), 9.74 (d, J = 7.8 Hz, 1H), 7.74 (d, J = By following the general procedure, 4rallyltoluene (40.0 mg,
1.2 Hz, 1H), 7.57 (d, J = 16.2 Hz, 1H), 7.54 (d, J = 1.2 Hz, 1H), 0.3 mmol) dissolved in DCE (1 mL) was added to the solution of
6.81 (dd, J = 7.8, 16.2 Hz, 1H), 3.93 (s, 3H), 2.43 (s, 3H); 13CNMR DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE
(150 MHz, CDCl3) w 193.0, 190.4, 167.7, 152.5, 143.9, 143.6, (1 mL). The reaction was stirred at 60 °C for 10 h under air
134.8, 131.6, 128.7, 122.8, 112.0, 56.5, 20.5; HRMS (ESIrTOF) conditions. After the work up, the crude product was purified
m/z [M+H+] calcd for C13H13O5 249.0763, found 249.0766.
by flash column chromatography to afford the title compound
(35.1 mg, 80%). Rf = 0.29 (petroleum ether/EtOAc = 20:1); 1
1rallylr2r NMR (600 MHz, CDCl3) w: 9.67 (d, J = 7.8 Hz, 1H), 7.46r7.43 (m,
(E)r3r(2r(Benzyloxy)phenyl)acrylaldehyde (2e) 20
H
By
following
the
general
procedure,
(benzyloxy)benzene (67.3 mg, 0.3 mmol) dissolved in DCE (1 3H), 7.23 (d, J = 7.8 Hz, 2H), 6.67 (dd, J = 7.8 Hz, J = 16.2 Hz, 1H),
mL) was added to the solution of DDQ (149.8 mg, 0.66 mmol), 2.39 (s, 3H); 13CNMR (150MHz, CDCl3) w 193.7, 152.8, 141.9,
H2O (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was 131.3, 129.8, 128.5, 127.7, 21.5.
stirred at 60 °C for 10 h under air conditions. After the work up, (E)r3r(4rMethoxyphenyl)acrylaldehyde (2j) 12b
the crude product was purified by flash column By following the general procedure, 4rallylanisole (44.5 mg, 0.3
chromatography to afford the title compound (61.5 mg, 86%). mmol) dissolved in DCE (1 mL) was added to the solution of
1
Rf = 0.39 (petroleum ether/EtOAc = 3:1); H NMR (600 MHz, DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE
CDCl3) w 9.67 (d, J = 7.8 Hz, 1H), 7.91 (d, J = 16.2 Hz, 1H), 7.59 (1 mL). The reaction was stirred at 60 °C for 10 h under air
(d, J = 7.8 Hz, 1H), 7.45r7.37 (m, 6H), 7.03r7.00 (m, 2H), 6.78 conditions. After the work up, the crude product was purified
(dd, J = 7.8, 16.2 Hz, 1H), 5.17 (s, 2H); 13CNMR (150MHz, CDCl3) by flash column chromatography to afford the title compound
w 194.5, 157.3, 147.9, 136.2, 132.6, 129.0, 128.7, 128.6, 128.2, (30.2 mg, 62%). Rf = 0.23 (petroleum ether/EtOAc = 10:1); 1
H
127.4, 123.3, 121.1, 112.7, 70.5.
NMR (600 MHz, CDCl3) w: 9.64 (d, J = 7.8 Hz, 1H), 7.52 (d, J =
(E)r2rAllylr6r(3roxopropr1renr1ryl)phenyl acetate (2g)
8.4 Hz, 2H), 7.42 (d, J = 15.6 Hz, 1H), 6.94 (d, J = 8.4 Hz, 2H),
By following the general procedure, 2,6rdiallylphenyl acetate 6.60 (dd, J = 7.8, 15.6 Hz, 1H), 3.85 (s, 3H); 13CNMR (150MHz,
(64.9 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the CDCl3) w 193.6, 162.2, 152.6, 130.3, 126.8, 126.5, 114.6, 55.4.
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 (E)r3r([1,1'rBiphenyl]r4ryl)acrylaldehyde (2k) 9b
mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h By following the general procedure, 4rallylr1,1'rbiphenyl (58.3
under air conditions. After the work up, the crude product was mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
purified by flash column chromatography to afford the title solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
compound (2g: 38.1 mg, 55%; 2g’: 9.5 mg, 13% ). 2g: Yellow mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h
solid, Mp 85587 °C, IR (KBr) 2988, 1699, 1680, 1666, 974 cmr1, under air condition. After the work up, the crude product was
1
Rf = 0.28 (petroleum ether/EtOAc = 3:1); H NMR (600 MHz, purified by flash column chromatography to afford the title
CDCl3) w 9.67 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.45 (d, compound (49.4 mg, 79%). Rf = 0.18 (petroleum ether/EtOAc =
J = 16.2 Hz, 1H), 7.35 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 20:1); 1H NMR (600 MHz, CDCl3) w 9.72 (d, J = 7.8 Hz, 1H), 7.67r
6.70 (dd, J = 7.8, 16.2 Hz, 1H), 5.91r5.84 (m, 1H), 5.13r5.09 (m, 7.62 (m, 6H), 7.51 (d, J = 16.2 Hz, 1H), 7.47 (t, J = 7.2 Hz, 2H),
2H), 3.30 (d, J = 6.6 Hz, 2H), 2.39 (s, 3H); 13CNMR (150MHz, 7.40 (t, J = 7.2 Hz, 1H), 6.76 (dd, J = 7.8, 16.2 Hz, 1H); 13CNMR
CDCl3) w 193.5, 168.8, 147.8, 146.0, 135.1, 133.5, 133.2, 130.3, (150MHz, CDCl3) w 193.6, 152.2, 144.0, 139.9, 130.0, 129.0,
127.4, 126.7, 126.1, 116.9, 34.7, 20.7. HRMS (ESIrTOF) m/z 128.9, 128.4, 128.1, 127.7, 127.1.
[M+H+] calcd for C14H15O3 231.1021, found 231.1025.
(E)r3r(Naphthalenr1ryl)acrylaldehyde (2l) 9b
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By following the general procedure, 1rallylnaphthalene (50.5 mmol) in DCE (1 mL). The reaction was stirred at 80 °C for 10 h
mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the under air conditions. After the work up, the crude product was
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 purified by flash column chromatography to afford the title
mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h compound (35.5 mg, 68%). Rf = 0.20 (petroleum ether/EtOAc =
1
under air conditions. After the work up, the crude product was 5:1); H NMR (600 MHz, CDCl3) w 9.74 (d, J = 7.2 Hz, 1H), 8.00
purified by flash column chromatography to afford the title (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 16.2 Hz,
compound (49.2 mg, 90%). Rf = 0.22 (petroleum ether/EtOAc = 1H), 6.78 (dd, J = 7.2, 16.2 Hz, 1H), 2.62 (s, 3H); 13CNMR
20:1); 1H NMR (600 MHz, CDCl3) w 9.85 (d, J = 7.8 Hz, 1H), 8.32 (150MHz, CDCl3) w 197.2, 193.3, 150.7, 138.6, 138.1, 130.4,
(d, J = 16.2 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.95 (d, J = 8.4 Hz, 129.0, 128.5, 26.8.
1H), 7.90 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.62 (t, J = (E)r4r(3rOxopropr1renr1ryl)benzonitrile (2q) 9d
7.2 Hz, 1H), 7.57r7.51 (m, 2H), 6.84 (dd, J = 7.8, 16.2 Hz, 1H); By following the general procedure, 4rallylbenzonitrile (43.0
13CNMR (150MHz, CDCl3) w 193.5, 149.2, 133.7, 131.5, 131.1, mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
130.9, 130.8, 128.9, 127.2, 126.4, 125.7, 125.4, 122.7.
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
mmol) in DCE (1 mL). The reaction was stirred at 80 °C for 10 h
(E)r3r(4rVinylphenyl)acrylaldehyde (2m)
By following the general procedure, 1rallylr4rvinylbenzene under air conditions. After the work up, the crude product was
(43.3 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the purified by flash column chromatography to afford the title
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 compound (30.6 mg, 65%). Rf = 0.20 (petroleum ether/EtOAc =
1
mmol) in DCE (1 mL). The reaction was stirred at 60 °C for 10 h 5:1); H NMR (600 MHz, CDCl3) w 9.75 (d, J = 7.2 Hz, 1H), 7.72
under air conditions. After the work up, the crude product was (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 16.2 Hz,
purified by flash column chromatography to afford the title 1H), 6.76 (dd, J = 7.2, 16.2 Hz, 1H); 13CNMR (150MHz, CDCl3) w
compound (28.0 mg, 59%). colorless oil, IR (KBr) 3025, 1670, 192.9, 149.4, 138.2, 132.9, 131.3, 128.8, 118.2, 114.4.
1
1475, 970 cmr1, Rf = 0.20 (petroleum ether/EtOAc = 20:1); H (E)r2r(3rOxopropr1renr1ryl)benzonitrile (2r)
NMR (600 MHz, CDCl3) w 9.69 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 8.4 By following the general procedure, 2rallylbenzonitrile (43.0
Hz, 2H), 7.47r7.44 (m, 3H), 6.75r6.69 (m, 2H), 5.85 (d, J = 17.4 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
Hz, 1H), 5.36 (d, J = 10.8Hz, 1H); 13CNMR (150MHz, CDCl3) w solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
193.7, 152.3, 140.5, 135.9, 133.4, 128.8, 128.3, 126.9, 116.0; mmol) in DCE (1 mL). The reaction was stirred at 80 °C for 10 h
HRMS (ESIrTOF) m/z [M+H+] calcd for C11H11O 159.0810, found under air conditions. After the work up, the crude product was
159.0806.
(E)r3r(4rChlorophenyl)acrylaldehyde (2n) 9d
purified by flash column chromatography to afford the title
compound (22.6 mg, 48%). Yellow solid, Mp 1025104 °C, IR
By following the general procedure, 1rallylr4rchlorobenzene (KBr) 2221, 1680, 1445, 980 cmr1, Rf = 0.19 (petroleum
1
(45.8 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the ether/EtOAc = 5:1); H NMR (600 MHz, CDCl3) w: 9.82 (d, J =
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 7.8 Hz, 1H), 7.84 (d, J = 16.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H),
mmol) in DCE (1 mL). The reaction was stirred at 80 °C for 10 h 7.77 (d, J = 7.2 Hz, 1H), 7.69 (t, J = 7.2 Hz, 1H), 7.55 (t, J = 7.2 Hz,
under air conditions. After the work up, the crude product was 1H), 6.84 (dd, J = 7.8, 16.2 Hz, 1H); 13CNMR (150MHz,CDCl3) w
purified by flash column chromatography to afford the title 193.0, 146.6, 136.7, 133.6, 133.2, 131.9, 131.0, 126.9, 116.8,
compound (37.0 mg, 74%). Rf = 0.22 (petroleum ether/EtOAc = 113.1; HRMS (ESIrTOF) m/z [M+H+] calcd for C10H8NO 158.0606,
20:1); 1H NMR (600 MHz, CDCl3) w 9.69 (d, J = 7.8 Hz, 1H), 7.49 found 158.0609.
(d, J = 8.4 Hz, 2H), 7.43r7.39 (m, 3H), 6.68 (dd, J = 7.8, 16.2 Hz, (E)r3r(1r(Methylsulfonyl)r1Hrindolr3ryl)acrylaldehyde (2t)
1H); 13CNMR (150MHz, CDCl3) w 193.4, 151.1, 137.3, 132.4, By following the general procedure, 3rallylr1r(methylsulfonyl)r
129.6, 129.4, 128.9.
(E)r3r(2rBromophenyl)acrylaldehyde (2o) 9d
1Hrindole (70.6 mg, 0.3 mmol) dissolved in DCE (1 mL) was
added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O
By following the general procedure, 1rallylr2rbromobenzene (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
(59.0 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the 60 °C for 10 h under air conditions. After the work up, the
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 crude product was purified by flash column chromatography
mmol) in DCE (1 mL). The reaction was stirred at 80 °C for 10 h to afford the title compound (52.3 mg, 70%). Yellow solid, Mp
under air conditions. After the work up, the crude product was 1085110 °C, IR (KBr) 1730, 1602, 1310, 1125 cmr1, Rf = 0.28
1
purified by flash column chromatography to afford the title (petroleum ether/EtOAc = 2:1); H NMR (600 MHz, CDCl3) w
compound (40.9 mg, 65%). Rf = 0.24 (petroleum ether/EtOAc = 9.67 (d, J = 7.8 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 7.8
20:1); 1 H NMR (600 MHz, CDCl3) w: 9.77 (d, J = 7.8 Hz,1H), 7.90 Hz, 1H), 7.81 (s, 1H), 7.59 (d, J = 16.2 Hz, 1H), 7.48r7.43 (m, 2H),
(d, J = 16.2 Hz, 1H), 7.66r7.64 (m, 2H), 7.37 (t, J = 7.8 Hz, 1H), 6.83 (dd, J = 7.8, 16.2 Hz, 1H), 3.22 (s, 3H); 13CNMR (150MHz,
7.28 (td, J = 1.2, 7.8 Hz, 1H), 6.67 (dd, J = 7.8, 16.2 Hz, 1H); CDCl3) w 193.7, 143.3, 135.6, 129.1, 128.9, 127.6, 126.1, 124.7,
13CNMR (150MHz, CDCl3) w 193.4, 150.6, 133.9, 133.7, 132.1, 120.9, 117.8, 113.3, 41.5; HRMS (ESIrTOF) m/z [M+H+] calcd for
130.8, 128.0, 127.9, 125.7.
(E)r3r(4rAcetylphenyl)acrylaldehyde (2p) 9d
C12H12NO3S 250.0538, found 250.0536.
(E)r3r(Thiophenr2ryl)acrylaldehyde (2u) 9d
By following the general procedure, 1r(4rallylphenyl)ethanone By following the general procedure, 2rallylthiophene (37.3 mg,
(48.0 mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the 0.3 mmol) dissolved in DCE (1 mL) was added to the solution of
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE
6 | J. Name., 2012, 00, 1r3
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(1 mL). The reaction was stirred at 60 °C for 10 h under air By following the general procedure, 6r(4rallylr2r
conditions. After the work up, the crude product was purified methoxyphenoxy)nicotinaldehyde (1.62 g, 6.0 mmol) dissolved
by flash column chromatography to afford the title compound in DCE (10 mL) was added to the solution of DDQ (3.0 g, 13.2
(30.3 mg, 73%). Rf = 0.29 (petroleum ether/EtOAc = 10:1); 1
H
mmol), H2O (216.0 mg, 12 mmol) in DCE (10 mL). The reaction
NMR (600 MHz, CDCl3) w: 9.63 (d, J = 7.8 Hz, 1H), 7.58 (d, J = was stirred at 60 °C for 10 h under air conditions. After the
15.6 Hz, 1H), 7.50 (d, J = 4.8 Hz, 1H), 7.36 (d, J = 3.6 Hz, 1H), work up, the crude product was purified by flash column
7.11 (dd, J = 3.6, 4.8 Hz, 1H), 6.52 (dd, J = 7.8, 15.6 Hz, 1H); chromatography to afford the title compound (1.29 g, 76%).
13CNMR (150MHz, CDCl3) w 192.8, 144.3, 139.3, 132.0, 130.3, Yellow solid, Mp 1605162 °C, IR (KBr) 1710, 1685, 1560, 1440
1
128.5, 127.4.
(E)r2rmethylr3rphenylacrylaldehyde (2v) 12b
cmr1, Rf = 0.24 (petroleum ether/EtOAc = 1:1); H NMR (600
MHz, CDCl3) w 9.99 (s , 1H), 9.73 (d, J = 7.8 Hz, 1H), 8.58 (d, J =
By following the general procedure, 2rmethylr3rphenylr1r 1.8 Hz, 1H), 8.22 (dd, J = 1.8, 8.4 Hz, 1H), 7.50 (d, J = 15.6 Hz,
propene (40.0 mg, 0.3 mmol) dissolved in DCE (1.0 mL) was 1H), 7.27r7.22 (m, 3H), 7.13 (d, J = 8.4 Hz, 1H), 6.71 (dd, J = 7.8,
added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O 15.6 Hz, 1H), 3.81 (s, 3H); 13CNMR (150 MHz, CDCl3) w 193.5,
(10.8 mg, 0.6 mmol) in DCE (1.0 mL). The reaction was stirred 189.3, 166.6, 152.5, 151.94, 151.88, 144.2, 138.8, 132.7, 128.7,
at 60 °C for 10 h under air conditions. After the work up, the 127.8, 123.5, 122.3, 111.8, 111.7, 55.9; HRMS (ESIrTOF) m/z
crude product was purified by flash column chromatography [M+H+] calcd for C16H14NO4 284.0923, found 284.0920.
to afford the title compound (32.9 mg, 75%). Rf = 0.27 (E)r5rAllylr5'r(3roxopropr1renr1ryl)r[1,1'rbiphenyl]r2,2'rdiyl
(petroleum ether/EtOAc = 20:1); 1 H NMR (600 MHz, CDCl3) w: diacetate (4)
9.58 (s, 1H), 7.53r7.37 (m, 5H), 7.26 (s, 1H), 2.07 (d, J = 1.2 Hz, By following the general procedure, 5,5'rdiallylr[1,1'rbiphenyl]r
3H); 13CNMR (150MHz, CDCl3) w 195.4, 149.7, 138.3, 135.1, 2,2'rdiyl diacetate (105.0 mg, 0.3 mmol) dissolved in DCE (1 mL)
129.9, 129.5, 128.6, 10.9.
was added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O
(10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
60 °C for 5 h under air conditions. After the work up, the crude
(4rallylr2r product was purified by flash column chromatography to
(E)r3r(4r((tertrButyldimethylsilyl)oxy)r3r
methoxyphenyl)acrylaldehyde (2w) 21
By
following
the
general
procedure,
methoxyphenoxy)(tertrbutyl)dimethylsilane (83.6 mg, 0.3 afford the title compound
4 (58.0 mg, 53%) and 5 (22.7 mg,
mmol) dissolved in DCE (1 mL) was added to the solution of 20%). Compound : Yellow oil, IR (KBr) 3330, 1680, 1550, 920
4
1
DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6 mmol) in DCE cmr1, Rf = 0.21 (petroleum ether/EtOAc = 3:1); H NMR (600
(1 mL). The reaction was stirred at 60 °C for 10 h under air MHz, CDCl3) w 9.69 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H),
condition. After the work up, the crude product was purified 7.50 (s, 1H), 7.47 (d, J = 16.2 Hz, 1H), 7.25r7.23 (m, 2H), 7.12 (s,
by flash column chromatography to afford the title compound 1H), 7.09 (d, J = 7.8 Hz, 1H), 6.69 (dd, J = 7.2, 16.2 Hz, 1H),
1
(66.7 mg, 76%). Rf = 0.33 (petroleum ether/EtOAc = 10:1); H 6.00r5.94 (m, 1H), 5.12r5.09 (m, 2H), 3.42 (d, J = 6.6 Hz, 2H),
NMR (600 MHz, CDCl3) w 9.64 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 2.08 (s, 3H), 2.03 (s, 3H); 13CNMR (150MHz, CDCl3) w 193.5,
16.2 Hz, 1H), 7.07r7.04 (m, 2H), 6.87 (d, J = 7.8 Hz, 1H), 6.59 169.4, 169.0, 151.3, 150.2, 146.3, 138.1, 136.7, 131.9, 131.7,
(dd, J = 7.8, 16.2 Hz, 1H), 3.83 (s, 3H), 0.99 (s, 9H), 0.17 (s, 6H); 131.5, 131.0, 129.6, 129.3, 128.9, 128.7, 123.6, 122.5, 116.5,
13CNMR (150MHz, CDCl3) w 193.7, 153.1, 151.3, 148.5, 127.9, 39.5, 20.8, 20.7; HRMS (ESIrTOF) m/z [M+H+] calcd for C22H21O5
126.7, 123.1, 121.2, 111.0, 55.4, 25.6, 18.5, r4.59.
(E)r3r(4r(2rHydroxyethoxy)r3rmethoxyphenyl)acrylaldehyde
(2x)
365.1389, found 365.1393.
5,5'rBis((E)r3roxopropr1renr1ryl)r[1,1'rbiphenyl]r2,2'rdiyl
diacetate (5)
By following the general procedure, 2r(4rallylr2r By following the general procedure, 5,5'rdiallylr[1,1'rbiphenyl]r
methoxyphenoxy)ethanol (62.5 mg, 0.3 mmol) dissolved in 2,2'rdiyl diacetate (105.0 mg, 0.3 mmol) dissolved in DCE (1 mL)
DCE (1 mL) was added to the solution of DDQ (149.8 mg, 0.66 was added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O
mmol), H2O (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction (10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
was stirred at 60 °C for 10 h under air conditions. After the 60 °C for 10 h under air condition. After the work up, the crude
work up, the crude product was purified by flash column product was purified by flash column chromatography to
chromatography to afford the title compound (45.3 mg, 68%). afford the title compound
4 (31.7 mg, 29%) and 5 (51.0 mg,
Yellow solid, Mp 1145116 °C, IR (KBr) 3526, 3050, 1670, 1445 45%). Compound : Yellow solid, Mp 95597 °C, IR (KBr) 1782,
5
1
cmr1, Rf = 0.25 (petroleum ether/EtOAc = 1:1); H NMR (600 1680, 1595, 910 cmr1, Rf = 0.36 (petroleum ether/EtOAc = 1:1);
MHz, CDCl3) w 9.64 (d, J = 7.8 Hz, 1H), 7.39 (d, J = 15.6 Hz, 1H), 1H NMR (600 MHz, CDCl3) w 9.70 (d, J = 7.2 Hz, 2H), 7.65 (dd, J
7.13 (dd, J = 1.2, 8.2 Hz, 1H), 7.06 (d, J = 1.2 Hz, 1H), 6.91 (d, J = = 1.8, 8.4 Hz, 2H), 7.51 (d, J = 1.8 Hz, 2H), 7.48 (d, J = 16.2 Hz,
8.2 Hz, 1H), 6.59 (dd, J = 7.8, 15.6 Hz, 1H), 4.15 (t, J = 4.8 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 6.70 (dd, J = 7.2, 16.2 Hz, 2H), 2.07
2H), 3.98 (t, J = 4.8 Hz, 2H), 3.89 (s, 3H), 2.92 (br, 1H); 13CNMR (s, 6H); 13CNMR (150MHz, CDCl3) w 193.4, 168.8, 150.9, 150.1,
(150MHz, CDCl3) w 193.5, 152.6, 151.1, 149.7, 127.6, 126.9, 132.1, 131.4, 130.6, 129.22, 129.16, 123.7, 20.7 ; HRMS (ESIr
123.3, 113.3, 110.3, 70.8, 61.0, 55.9; HRMS (ESIrTOF) m/z TOF) m/z [M+H+] calcd for C22H19O6 379.1182, found 379.1184.
[M+H+] calcd for C12H15O4 223.0970, found 223.0965.
(E)r6r(2rMethoxyr4r(3roxopropr1renr1r
yl)phenoxy)nicotinaldehyde (2y)
(E)r3r(4r(Allyloxy)r3rmethoxyphenyl)acrylaldehyde (7)
By following the general procedure, 4rallylr1r(allyloxy)r2r
methoxybenzene (61.3 mg, 0.3 mmol) dissolved in DCE (1 mL)
was added to the solution of DDQ (149.8 mg, 0.66 mmol), H2O
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R. Ma, F. Yin, D. Song, C. Zhao and S. Ma, Eur. J. Med. Chem.,
2015, 97, 32541; (c) Y. Zhang, S. Li and X. Kong, Bioorg. Med.
Chem. Lett., 2013, 23, 135851364.
(10.8 mg, 0.6 mmol) in DCE (1 mL). The reaction was stirred at
60 °C for 10 h under air conditions. After the work up, the
crude product was purified by flash column chromatography
to afford the title compound (49.8 mg, 76%). Yellow oil, IR (KBr)
3060, 1672, 1418, 960 cmr1, Rf = 0.23 (petroleum ether/EtOAc
= 5:1); 1H NMR (600 MHz, CDCl3) w 9.63 (d, J = 7.8 Hz, 1H), 7.38
(d, J = 16.2 Hz, 1H), 7.10 (dd, J = 1.8, 8.4 Hz, 1H), 7.06 (d, J = 1.8
Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 6.59 (dd, J = 7.8, 16.2 Hz, 1H),
6.09r6.02 (m, 1H), 5.41 (dd, J = 1.2, 17.4 Hz, 1H), 5.30 (dd, J =
0.6, 10.2 Hz, 1H), 4.64 (d, J = 5.4 Hz, 2H), 3.89 (s, 3H); 13CNMR
(150MHz, CDCl3) w 193.6, 152.9, 150.9, 149.6, 132.5, 127.1,
126.7, 123.2, 118.6, 112.7, 110.2, 69.7, 55.9; HRMS (ESIrTOF)
m/z [M+H+] calcd for C13H15O3 219.1021, found 219.1023.
(E)r3r(4r(((E)r3,7rDimethyloctar2,6rdienr1ryl)oxy)r3,5r
3
4
(a) H. rF. Yeh, C.rY. Luo, C. rY. Lin, S. rS. Cheng, Y. rR. Hsu
and S. rT. Chang, J. Agric. Food Chem., 2013, 61, 629356298;
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5
6
I. Escher and F. Glorius. Science of Synthesis 2007, 25
7335777.
,
dimethoxyphenyl)acrylaldehyde (13) 14
G. Tojo and M. Fernandes, in Oxidation of Alcohols to
Aldehydes and Ketones: A Guide to Current Common Practice,
ed. G. Tojo, Springer, Berlin, 2006, p. 15115;
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Neumann, A. Sergeev and M. Beller, Angew. Chem., Int. Ed.,
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(a) P. R. Mackie and C. E. Foster, in Comprehensive Organic
Group Transformations II, ed. A. R. Katritzky, R. J. K. Taylor
and K. Jones, Elsevier, Dordrecht, 2004, vol. 3, pp. 59–97; (b)
R. C. Larock, Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, WileyrVCH,
Weinheim, 1999, pp. 317–340.
By following the general procedure, (E)r5rallylr2r((3,7r
dimethyloctar2,6rdienr1ryl)oxy)r1,3rdimethoxybenzene (99.2
mg, 0.3 mmol) dissolved in DCE (1 mL) was added to the
solution of DDQ (149.8 mg, 0.66 mmol), H2O (10.8 mg, 0.6
mmol) in DCE (1 mL). The reaction was stirred at room
temperature for 5 h under air condition. After the work up, the
crude product was purified by flash column chromatography
to afford the title compound (63.1 mg, 61%). Rf = 0.21
7
8
1
(petroleum ether/EtOAc = 3:1); H NMR (600 MHz, CDCl3) w
9.67 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 15.6 Hz, 1H), 6.78 (s, 2H),
6.63 (dd, J = 7.8, 15.6 Hz, 1H), 5.54 (t, J = 7.2 Hz, 1H), 5.07r5.04
(m, 1H), 4.62r4.59 (m, 2H), 3.89 (s, 6H), 2.05r1.98 (m, 4H), 1.66
(s, 3H), 1.65 (s, 3H) 1.58 (s, 3H); 13CNMR (150 MHz, CDCl3) w
193.5, 154.0, 153.0, 142.0, 131.7, 129.3, 127.8, 123.9, 119.8,
109.8, 105.5, 69.6, 56.1, 39.6, 26.4, 25.7, 17.7, 16.4; HRMS
(ESIrTOF) m/z [M+H+] calcd for C21H29O4 345.2066, found
345.2064.
9
For some selected examples, see: (a) G. Battistuzzi, S. Cacchi
and G. Fabrizi, Org. Lett., 2003, 5, 7775780; (b) J. Liu, J. Zhu,
H. Jiang, W. Wang and J. Li. Chem. Commun., 2010, 46
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Sigman, Org. Biomol. Chem. 2008, , 408354088; (b)R. I.
McDonald, G. Liu and S. S. Stahl, Chem. Rev. 2011, 111
3,
3
6
,
Conflicts of interest
298153019; (c) W. Wu and H. Jiang, Acc. Chem. Res. 2012,
45, 173651748; (d) R. M. Romero, T. H. Wçste and K. MuÇiz,
Chem. Asian J. 2014, 9, 9725983; (e) S. Tang, K. Liu, C. Liu and
There are no conflicts to declare.
A. Lei, Chem. Soc. Rev. 2015, 44, 107051082.
11 For some recent examples, see: (a)Y. Yang, R.rJ. Song, X.rH.
Ouyang, C.rY. Wang, J.rH. Li and S Luo. Angew. Chem. Int. Ed.
2017, 56, 7916r7919; (b) Q. Qin, Y.rY. Han, Y.rY. Jiao, Y. He
and S. Yu. Org. Lett., 2017, 19, 290952912; (c) Y.rY. Liu, X.rH.
Acknowledgements
We are grateful for financial support from National Natural
Science Foundation of China (No. 21702002, 81501187) and
Anhui Provincial Natural Science Foundation (No.
1508085QH173, 1808085QC79).
Yang, R.rJ. Song, S. Luo and J.rH. Li. Nature Commun. 2017, 8,
14720; (d) M. Hu, L.rY. Guo, Y. Han, F.rL. Tan, R.rJ. Song and
J.rH. Li. Chem. Commun. 2017, 53, 6081r6084; (e) W.L. Yu, J.r
Q. Chen, Y.rL. Wei, Z.rY. Wang and P.rF. Xu. Chem. Commun.,
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Synth. Catal. 2018, 360, 160051604; (b)H. Chen, H. Jiang, C.
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52, 1177r1182; (b) T. IIiefski, S. Li and K. Lundquist,
Tetrahedron Lett. 1998, 39, 2413r2416.
14 Y. Zhao, X. Hao, W. Lu, J. Cai, H. Yu, T. Sevꢀnet and F.
Guꢀritte, J. Nat. Prod. 2002, 65, 9025908.
15 The same phenomenon was observed in the work about C5H
activation between allylic and active methylenic compounds
Notes and references
1
For recent selected examples, see: (a) M. P. Balaguer, M.
Borne, P. Chalier, N. Gontard, M. rH. Morel, S. Peyron, R.
Gavara and P. HernandezrMunoz, Biomacromolecules, 2013,
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2
For recent selected examples, see: (a) B. rJ. Chen, C. rS. Fu, G.
rH. Li, X. rN. Wang, H.rX. Lou, D. rM. Ren and T. Shen. Mini
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8 | J. Name., 2012, 00, 1r3
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Journal Name
ARTICLE
promoted by DDQ. see: D. Cheng and W. Bao. Adv. Synth.
Catal. 2008, 350, 126351266.
16 For some selected examples about DDQ participated single-
electron transfer process, see: (a) E. F. Kiefer and F. E. Lutz, J.
Org. Chem. 1972, 37, 151951522; (b) P. C. Montevecchi and
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This journal is © The Royal Society of Chemistry 20xx
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DOI: 10.1039/C8OB01469H
Modular Synthesis of (E)-Cinnamaldehydes Directly from Allylarenes under
Metal-free DDQ-mediated Oxidative Process
Ting-Ting Xu a, Tao-Shan Jiang *, b, Xiao-Lan Han a, Yuan-Hong Xu c, Jin-Ping Qiao *, c
A practical route to prepare (E)-cinnamaldehydes and natural products Randainal, Geranyloxy
sinapyl aldehyde has been achieved via metal-free DDQ-mediated oxidative transformation of
allylarenes.