A Thorough Study on the Photoisomerization of Ferulic Acid Derivatives

Article abstract of DOI:10.1002/ejoc.202100064

A thorough study on the (E) to (Z) photoisomerization of ferulic acid derivatives (esters, amides of all types, and ketones) was carried out. At the photostationary state, only aliphatic or benzylic tertiary amides reach a nearly complete conversion of (E) isomers into the (Z) ones, whereas for esters, primary and secondary amides or aromatic tertiary amides mixtures of (Z)/(E) ranging from 7 : 93 to 72 : 28 are observed. Ketones show rather limited photoisomerization. However, (Z) ketones may be obtained by the reaction of organometal compounds with an isomerized (Z) Weinreb amide.

Full text of DOI:10.1002/ejoc.202100064

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A Thorough Study on the Photoisomerization of Ferulic
Acid Derivatives
Lisa Moni,[a] Luca Banfi,[a] Andrea Basso,[a] Alessia Mori,[a] Federica Risso,[a] Renata Riva,[a] and
Chiara Lambruschini*[a]
Dedicated to Prof. Franco Cozzi on his 70th birthday.
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A thorough study on the (E) to (Z) photoisomerization of ferulic
acid derivatives (esters, amides of all types, and ketones) was
carried out. At the photostationary state, only aliphatic or
benzylic tertiary amides reach a nearly complete conversion of
(E) isomers into the (Z) ones, whereas for esters, primary and
secondary amides or aromatic tertiary amides mixtures of (Z)/(E)
ranging from 7:93 to 72:28 are observed. Ketones show rather
limited photoisomerization. However, (Z) ketones may be
obtained by the reaction of organometal compounds with an
isomerized (Z) Weinreb amide.
Introduction
Ferulic acid 1 (Scheme 1) is a phenylpropanoid, which was first
isolated from Ferula Foetida in 1886. It is a ubiquitous natural
product, which is found in many plants, such as seed plants
(e.g., rice, wheat, and oat), vegetables (e.g., tomato and carrot),
and fruits (e.g., pineapple and orange).[1] It is also a component
of lignin,[2] and an intermediate in the biosynthesis of other
plant phenols.[3]
Ferulic acid can be conveniently extracted from many
sources,[2] including waste, and thus it represents one of the
most valuable biobased building block either for direct
applications as an ingredient for cosmetics[4] and nutraceutical
products,[1c,5] as well as for the synthesis of fine chemicals from
renewable starting materials. Ferulic acid and its esters, like
other natural phenols, are very well-known anti-oxidants,[6] but
they can also act as solar screens. During the exposure of skin
to radiation, interaction with trans-urocanic acid generates
singlet oxygen that can activate the entire oxygen free radical
cascade with oxidation of proteins, nucleic acids and lipids.
Ferulic acid is a strong UV absorber with a structure similar to
tyrosine, and thus it is believed to inhibit melanin formation
through competitive inhibition with tyrosine.[7]
Scheme 1. trans Urocanic acid, ferulic acid, and complete E to Z isomer-
ization of a complex tertiary amide derived from it.
whereas various feruloyl amides have been recently found in
nature.[3,9]
We have recently reported on the properties of several
polyphenolic feruloyl amides obtained in a diversity-oriented
manner through the Ugi multicomponent reaction, as inhibitors
of beta-amyloid aggregation,[10] or as anti-oxidant and lipid-
lowering compounds.[11] During those works, we made a
serendipitous discovery. A sample of one of our feruloyl amides,
namely 2a, left for few days in solution in a glass NMR tube
near a window, turned out to be isomerized at 94% to the (Z)
stereoisomer 2b.
Intrigued by this unexpected finding, we did a thorough
literature search and found that photoisomerization of ferulic
acid[12] or its esters[13] was already known for a long time. More
recently, photoisomerization of feruloyl amides (primary or
secondary) was also reported.[14] This is a property also
displayed by cinnamic acids, esters, and amides.[12b,15] However,
in all previous reports regarding ferulic acid derivatives, isomer-
ization was only partial and, either starting from the (E) or from
Apart from ferulic acid itself and its esters, some derivatives/
conjugated compounds have been studied as potential drugs,[8]
[a] Dr. L. Moni, Prof. L. Banfi, Prof. A. Basso, A. Mori, F. Risso, Prof. R. Riva,
Dr. C. Lambruschini
Department of Chemistry and Industrial Chemistry
University of Genova
Via Dodecaneso, 31, 16146 Genova, Italy
E-mail: chiara.lambruschini@unige.it
https://rubrica.unige.it/personale/V0RBX1lr
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202100064
Part of the “Franco Cozzi’s 70th Birthday” Special Collection.
© 2021 The Authors. European Journal of Organic Chemistry published by
Wiley-VCH GmbH. This is an open access article under the terms of the
Creative Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited.
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the (Z) isomers, a photostationary state was reached, with a
diastereomeric ratio typically not higher than 70:30.
Therefore, for preparing other amides, we preferred to use a
more stable protecting group able to survive to more harsh
conditions, such as the use of strong bases and nucleophiles,
and that could be selectively removed to allow the study of the
(E)/(Z) photoisomerization on the free phenolic group. Among
possible protections, we chose the allyl ether, which was
extensively used by us in our previous polyphenol synthesis.[10a]
Thus 1 was converted, in high yield, into O-allyl ferulic acid
4.[10a]
1
2
3
4
5
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7
8
9
Thus, the observed nearly complete (E) to (Z) photo-
isomerization of a feruloyl amide was unprecedented. Since it
was not clear whether this outcome was due to the particular
structure of polyphenol 2a, or it was a more general behavior
of tertiary amides of ferulic acid, we were prompted to start a
thorough study on the dependence of photoisomerization of
ferulic acid derivatives on their chemical structure.
For converting 4 into various amides 8b–j, the best method
turned out to be the one going through the acyl chloride 7,
generated by the reaction of 1 with oxalyl chloride in the
presence of catalytic DMF. In the reaction of 7 with aliphatic
primary and secondary amines, triethylamine performed well as
base (Table 1). However, with aromatic amines, surprisingly,
product 8 was contaminated by products of a Michael addition
to the conjugated double bond of the amide. This problem was
solved by substituting Et3N with pyridine. However, the syn-
thesis of Weinreb amide 8j gave an unsatisfactory yield both
with Et3N and with pyridine. After optimization, we found that
imidazole was the best base, allowing us to obtain excellent
yields. This method is in our opinion superior to the one
reported by Stevens for the preparation of MEM-protected
Weinreb amides of ferulic acid.[18] Apart from the better yield, it
avoids the use of expensive benzotriazole and pyrophoric
Me3Al. Other tertiary amides 8k–n were prepared by meth-
ylation of the aromatic or benzylic secondary amides 8d–g.
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Results and Discussion
Synthesis
Towards this goal, we decided to prepare a series of amides of
ferulic acid. Initially, we tried a direct synthesis starting from
unprotected 1. However, either going through
a mixed
anhydride[16] or using typical coupling agents such as dicyclo-
hexylcarbodiimide (DCC) or carbonyl diimidazole (CDI), the
yields were unsatisfactory. Details of these attempts are
reported in the S.I. Thus, to avoid side reactions caused by the
free phenol, we decided to start with a protected ferulic acid
(Scheme 2). Following a reported procedure, we converted 1
into acetate 3, and hence into known primary amide 9a via a
mixed anhydride.[17] The direct formation of unprotected 9a
proved that the acetate is unstable under the amidation
conditions.
Scheme 2. Synthesis of amides 8b–n, amides 9a–d,k, and esters 5, 6
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Table 1. Synthesis of amides 8 and 9[a]
1
2
Amide
R1
R2
Base for the synthesis of 8
Yield [%] of 8[b]
Yield [%] of 9[c]
3
4
5
6
7
8
9
8b
8c
8d
8d
8e
8f
8g
8h
8i
nBu
nBu
Ph
Ph
4À MeOC6H4
4À O2NC6H4
Bn
H
nBu
H
H
H
H
H
Bn
CH3
CH3
CH3
Et3N
Et3N
Et3N
75
83
32
89
82
92[d]
78
87
85
52
85
99
96
–
97
–
–
–
–
–
–
–
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
pyridine
imidazole
Bn
HOCH2CH2
CH3O
CH3O
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8j
8j
1
2
°
[a] Conditions for the synthesis of 8 from 7: base, R R NH, CH2Cl2, 0 C!rt. [b] Isolated yield from 4. [c] Isolated yield from 8. [d] The isolated product was
1
contaminated with some 4-nitroaniline. The yield was calculated from H NMR.
simple unprotected methyl ketone 10 was conveniently synthe-
sized from vanillin through a previously described crotonic
condensation.[23]
Other ketones (this time O-allylated) were prepared from
Weinreb amide (E) 8j, by reaction with some organometal
compounds.[18] The yields of these syntheses are not optimized.
Interestingly, with EtMgBr, but not with MeMgBr or PhMgBr, the
yield was lowered by the formation of side-products derived
from Michael addition of the organometal compound to the
double bond of the Weinreb amide and/or by demethoxylation
processes.[24] Unexpected behavior was noticed during the
synthesis of ketone (E) 11f. The needed organolithium deriva-
tive was prepared by treatment of 2-bromothiophene with n-
butyllithium. However, instead of halogen-metal exchange,
butyllithium deprotonated the thiophene ring at carbon 5, and
thus the final product contained the intact bromine atom. The
structure was demonstrated by HPLC-MS and NMR (HMBC)
experiments. Although apparently surprising to us, the selective
lithiation at position 2 (instead of lithium-halogen exchange) is
not unprecedented.[25]
As better described in the next section, it is possible to
photoisomerize Weinreb amide (E) 8j to the (Z) isomer.
Although isomerization is not complete, leading to a 77:23 (Z)/
(E) mixture, the two isomers can be conveniently separated by
column chromatography. This offers the opportunity to synthe-
size ferulic-derived (Z) ketones, which are not accessible by
photoisomerization (see below) and which can not be obtained
by olefination (Horner-Wadsworth-Emmons) or crotonic con-
densation from vanillin. As shown in Scheme 3, the reaction of
(Z) 8j with organometal compounds is indeed possible, with
yields higher than with the (E) isomer, and with no retro-
isomerization observed under these conditions.
Scheme 3. Preparation of ketones 10 and 11.
In order to compare the photochemical behavior of amides
with that of esters, we also prepared the known compound (E)
5.[19]
Finally, we removed in excellent yields the allyl protection
from some of the amides 8 (8b,c,d,k) to give feruloyl amides
9b,[20] 9c, 9d,[21] and 9k, whereas ester 5 was deprotected to
give known methyl ferulate 6.[22] We did not deprotect all the
amides, since preliminary photoisomerization experiments (see
below) pointed out that there was no difference between
compounds bearing a protected or unprotected phenol. Thus,
we preferred to carry out our photoisomerization studies
directly on the allylated feruloyl amides.
In order to have a complete overview of the dependence of
photoisomerization on the structure of the ferulic derivatives,
we also prepared several ketones of different nature: saturated,
unsaturated, aromatic, or heteroaromatic (Scheme 3). The
Photoisomerization
Photoisomerization experiments were carried out on deuterated
methanol solutions (except for 8l and 8m when we used CDCl3
for solubility problems) directly in a NMR tube, and the (Z)/(E)
1
ratios were determined by H NMR over time (see Figure 1 as
example). The full kinetic charts and 1H NMR spectra are
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Figure 3. Comparison of UV spectra at 25 μM in MeOH of (E) 8c (green) and
(Z) 8c (red).
Figure 1. 1H NMR spectrum of a 70 mM solution of 1 in CD3OD recorded
after irradiation at 350 nm for 120 min. Blue squares indicate the signals of
the (E) isomer, while purple triangles indicate the signal of the (Z) isomer.
The integration showing the (E)/(Z) ratio is reported.
lower and the ratios remain around 8:2. This nearly complete
isomerization seems pretty general for aliphatic tertiary amides
and it is not influenced by the presence of an aryl group (8h,
8n) or of an alcoholic moiety (8i). For Weinreb amide 8j,
unfortunately, the conversion is not complete, arriving only at
77:23. However, the two diastereomers can be separated by
chromatography and the (Z) isomer is quite stable towards
retro-isomerization. Thus, from a preparative point of view, this
allows the easy synthesis of (Z) ferulic derived ketones
(Scheme 3)
Aromatic amides show different behavior with respect to
other amides. As for the aliphatic ones, the tertiary amides
afford more (Z) isomer than the secondary ones upon photo-
isomerization (8d vs. 8k), but the % of (Z) compounds remains
below 50%, with a strong influence on the electronic nature of
the substituent. Isomerization is nearly absent with an electron-
donating substituent (8l), whereas it increases much more with
an electron-withdrawing one (8m). Photoisomerization also
seems slower than that of other amides (see Figure 2).
Figure 3 shows a comparison of the UV spectra of the (E)
and (Z) isomers of 8c. This striking difference in UV spectra is
also common to 8h, 8i, 8n. It is clear that the (Z) isomer does
not absorb at 350 nm, whereas the (E) counterpart has a λmax
around 325 nm, but still has a significant absorbance at 350 nm.
We think that the remarkable behavior of tertiary amides is due
to this hypsochromic shift of the wavelength of maximum
absorbance in the (Z) isomers. In fact, if (Z) isomers do not
absorb, the Z!E isomerization can not take place. On the
contrary, for ferulic acid, its esters, primary amides, and
secondary amides, the UV spectra after isomerization are quite
similar, according to the spectra of partially isomerized mixtures
(see S.I. Figure S2).
reported in the S.I., whereas we show here only some selected
diagrams in Figure 2 and Figure 5, and the final photostationary
state ratios for all compounds in Table 2 and Table 3. We used
two different wavelengths: 300 and 350 nm.
Comparison of both UV spectra and the kinetic charts of
photoisomerization between free phenols 1, 6, 9b, and 9c and
the corresponding O-allylated compounds 4, 5, 8b, and 8c
showed an identical behavior (see S.I.). Evidently, the free
phenol group has no influence on these phenomena. For this
reason, a comprehensive study was carried out only on the
allylated compounds. From the results reported in Table 2, it is
clear that the carboxylic acid 1, 4 the ester 5, 6, and the primary
amide 9a undergo, at 300 nm, only a partial isomerization close
to 6:4 at the photostationary state. Increasing the wavelength
to 350 nm has no effect on the primary amide, but lowers the
amount of (Z) isomer in the acids and in the esters.
With aliphatic secondary amides (9b, 8b, 8g) again the
wavelength has little influence, but the (Z)/(E) ratio is increased
to about 7:3. With aliphatic tertiary amides (9c, 8c, 8h, 8i, 8n)
a nearly complete isomerization to the (Z) stereoisomer is
achieved at 350 nm (>95:5), whereas at 300 nm conversion is
In (E) cinnamamides, the preferred conformation of the
enone system was previously demonstrated by crystallographic
and NMR studies to be s-cis, and the three planes of the aryl
ring, the double bond, and the amide are expected to be nearly
[15f]
°
coplanar (dihedral angles �15 ).
On the other hand, for (Z)
cinnamamides, a preference for the s-trans conformation was
suggested.[15f] In such conformations, coplanarity of the three
planes would place one of the two groups bound to nitrogen
too close to the aromatic ring. When this substituent is H, as in
primary and secondary amides, this can be tolerable, but even a
Figure 2. Photoisomerization at 350 nm for some feruloyl amides. For
compounds 8g, 8k, 8l and 8m the kinetic studies were extended up to
180 min in order to confirm that the photostationary state was reached after
120 min (see SI).
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Table 2. (Z)/(E) ratios of ferulic acid, esters, and amides at photostationary state after photoisomerization.[a]
1
2
3
Compound
Structure
λ=300 [nm]
(Z)/(E) ratio
λ=350 [nm]
(Z)/(E) ratio
Compound
Structure
λ=300 [nm]
(Z)/(E) ratio
λ=350 [nm]
(Z)/(E) ratio
4
1
59:41
56:44
65:35
70:30
82:18
59:41
45:55
45:55
60:40
68:32
96:4
8d
8g
8h
8i
7:93
14:86
71:29
95:5
5
6
7
8
6
72:28
83:17
80:20
68:32
20:80
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10
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9a
9b
9c
4
95:5
8j
77:23
27:73
47:53
8k
5
56:44
45:55
8l
8:92
7:93
8b
8c
72:28
83:17
68:32
8m
8n
46:54
84:16
45:55
96:4
96:4
[a] Experiments were carried out in MeOH-d4 (in CDCl3 in the case of 8l and 8m for solubility problems) at rt for 120 minutes. However, in most cases,
photostationary state was reached after 60–90 minutes in all cases (see S.I.).
Table 3. (Z)/(E) ratios of ferulic acid derived ketones 11a–c,e after photoisomerization at 350 nm.[a]
Compound
(Z)/(E)
ratio
Compound
(Z)/(E)
ratio
(E) 11a
(Z) 11a
19:81
24:76
2:98[b]
20:80
22:78
2:98
(E) 11b
(E) 11e
(E) 11c
(Z) 11e
[a] Experiments were carried out in MeOH-d4 at rt for 120 minutes. However, in most cases, photostationary state was reached after 60–90 minutes in all
cases (see S.I.). [b] In this case H NMR showed the appearance of signals due to [2+2] cycloaddition reaction.
1
CH3 group, as in 8i and 8n, is probably enough to induce a
deviation from planarity of the system, causing this hypsochro-
mic shift.[26] Deviation from planarity would also place the
substituents on nitrogen in the shielding cone of the benzene
ring, with a resulting decrease of chemical shift. This hypothesis
and from 4.81, 4.69 to 4.63, 4.54 for N-CH2Ph. Similar upfield
shifts are observed in 8c, 8h, 8i.
In Weinreb amide 8j, the smallest substituent is OCH3,
which has a steric bias intermediate between H and CH3, and
we can predict that the deviation from planarity will be
moderate. In fact, the UV spectrum of (Z) 8j shows a
hypsochromic shift that is less pronounced than in tertiary
amides. In this case, the NÀ CH3 and the OÀ CH3 δ change upon
1
is in accord with the H NMR spectra of (E) and (Z) 8c, 8h, 8i,
8n. For example, in 8n, on passing from (E) to (Z) (2 conformers
are visible), δ decrease from 3.14, 3.03 to 2.91, 2.87 for NÀ CH3
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isomerization from 3.31 to 3.16 ppm and from 3.77 to 3.63 ppm,
respectively.
We believe that the behavior of aromatic amides can be
addition reaction were detected.[27] In the case of heteroar-
omatic ketones 11f and 11g no isomerization occurs, and again
the increasing formation of saturated compounds (probably the
dimers derived from [2+2] cycloaddition) could be seen at H
NMR.
1
2
3
4
5
6
7
8
9
1
ascribed to the lack of three-dimensionality of phenyl ring. In
fact, this substituent can lie almost perpendicular to the rest of
the molecule and the steric hindrance and the deviation from
planarity in the (Z) isomer are minimized thanks to its planarity.
Figure 4 shows an interesting experiment, carried out on
tertiary amide 8c. After irradiating at 350 nm up to the steady-
state, the sample was irradiated again a 300 nm. The (Z)/(E) ratio
decreased reaching the same value obtained irradiating from
the beginning at 300 nm. This proves that the (Z)/(E) ratio at the
photostationary state depends on the absorbance of both
isomers at the selected wavelength.
Figure 5 shows a comparison between the ketones that
have given some degree of isomerization.
We can conclude that photoisomerization of ferulic acid
derived ketones does not represent a useful synthetic method
for the preparation of (Z) isomers, whereas the reaction of (Z)
Weinreb amide 8j is a valuable alternative.
Finally, we calculated the quantum yield of the E!Z
photoisomerization of (E) 8c, (E) 8h, and (E) 11a and of the Z!
E photoisomerization of (Z) 11a at 350 nm (see Experimental
and S.I.). The quantum yield of amides (E) 8c and (E) 8h was
42% and 85%, respectively. This remarkable difference can be
ascribed only to the presence of the additional phenyl rings in
(E) 8h, which somehow increase the efficiency of the process.
Having synthesized both isomers of ketone 11a, we were able
to compare the quantum yields of E!Z and Z!E. The
calculated values were 40% and 60%, respectively, showing
that there is a significant difference in the process.
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Then we moved on to study the photochemical behavior of
ketones. The results are reported in Table 3. With methyl ketone
10 (with a free phenol) and with allylated vinyl ketone 11d we
detected no isomerization at all, either at 300 nm or 350 nm.
With the other ones, isomerization was rather limited. Table 3
reports only the results at 350 nm, but at 300 nm the situation
was very similar (see S.I.). With aliphatic ketones, only about
20% of (Z) isomer could be obtained, whereas, with the phenyl
ketone, the (E) isomer was strongly predominant, either starting
1
from the (E) or the (Z) isomer. Furthermore, in this case, the H
NMR was rather dirty, and peaks likely due to [2+2] cyclo-
Stability of Z Isomers
We have carried out some experiments to check the configura-
tional stability of (Z) tertiary amides. These assays were done on
°
amide (Z) 8h (Scheme 4). This amide was heated at 65 C in
°
methanol for 48 hours or in DMSO at 150 C for 48 hours, but
no retro-isomerization occurred. The same happened when
exposing (Z) 8h to 10% PdÀ C in methanol at rt for 48 h.
Deblocking of the allyl group under our standard conditions
(Pd(0) homogeneous catalysis) brought about only a very small
degree of isomerization. Finally, no isomerization of free phenol
(Z) 9h took place on exposure to a strong acid (Amberlite® IR
120 H) or basic (Amberlyst® A-26 OH) resin.
These experiments, along with the retention of (Z) config-
uration during the reaction of Weinreb amide (Z) 8j with
Figure 4. Photochemical behavior of tertiary amide 8c.
Figure 5. Comparison of photochemical isomerization at 350 nm of ketones
11a,b,c,e
Scheme 4. Configurational stability of amides (Z) 8h and 9h.
Eur. J. Org. Chem. 2021, 1737–1749
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million (ppm) using as internal standard tetramethylsilane (TMS,
organometal compounds, show that the isomerized (Z) feruloyl
amides are configurationally pretty stable, paving the way to
their further synthetic elaborations.
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5
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7
8
9
0.00 ppm) or the residual solvent signal (CDCl3 at 77.16 ppm for 13C,
1
DMSO-d6 at 2.50 and 39.43 ppm for H and 13C, respectively). The
data are reported as follow: chemical shift (sorted in ascending
order), integration, multiplicity (indicated as: s, singlet; d, doublet; t,
triplet; q, quartet; m, multiplet, and combinations thereof), coupling
constants (J) in Hertz (Hz) and assignation (when possible). Peak
assignments were done with the aid of gCOSY (gradient correlation
spectroscopy), gHSQC (gradient heteronuclear single-quantum
correlation spectroscopy), and gHMBC (gradient heteronuclear
Conclusion
The results described above had clearly shown that at the
photostationary state nearly complete photoisomerization of
ferulic acid derivatives takes place only with tertiary amides
(except for the aromatic ones). On the contrary, with esters,
primary amides, or secondary amides, isomerization is not
complete at the photostationary state, whereas with ketones no
or little photoisomerization occurs. We think that the reason for
the peculiar behavior of tertiary amides is due to steric strain,
which flips the amide from coplanarity with the unsaturated
system, thus causing an hypsochromic shift of the maximum
absorbance wavelength. It is the difference in λmax that allows,
at the appropriate wavelength, to strongly shift the equilibrium
to the (Z) isomer. Although being a sort of tertiary amide,
Weinreb amide (E) 8j does not reach a high degree of
isomerization. However, the stereoisomers can be separated by
chromatography, and this unlocks a useful access to (Z) ferulic
derived ketones, which are not accessible by photoisomeriza-
tion nor are easily accessible by other traditional chemical
methodologies.
Feruloyl amides have demonstrated interesting pharmaco-
logical activities,[8c,10c,20,28] and surely the configuration of the
double bond has an important influence on biological
properties.[14,29] Thus, apart from the theoretical interest, the
here reported study opens the way to the synthesis and the
biological evaluation of (Z) feruloyl amides.
Moreover, we plan to exploit tertiary (Z) feruloyl amides for
selective functionalization of the aryl ring, in order to expand
the chemical space accessible from this very important,
biobased and renewable, building block.
1
multiple-bond correlation spectroscopy, only for 11f). Copies of H
and 13C NMR are reported in the S.I., while copies of 2D NMR data
are available on request. Fourier transform infrared (FTIR) spectra
were recorded on a Perkin Elmer Spectrum 65 (Perkin Elmer,
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Waltham, MA, USA) instrument, equipped with
a universal
attenuated total reflectance (ATR) sampling accessory. UV-Vis
spectra were performed using Varian Cary® 50 UV-Vis Spectropho-
tometer. HRMS: samples were analyzed with a Synapt G2 QToF
mass spectrometer (Waters, Milford, MA, USA). MS signals were
acquired from 50 to 1200 m/z in either ESI positive or negative
ionization mode. Photo-induced isomerizations were performed
with a Southern New England Ultraviolet Company Rayonet®
apparatus equipped with 8 Iles Optical lamps (300 or 350 nm). The
lamps used were cylindrical with a length of 26.5 cm and a power
of 8 watts. The sample was fixed at a 10 cm distance from the lamp.
General procedure A: preparation of amides. Freshly prepared
acyl chloride 7 (2.50 mmol) was dissolved in dry DCM (5 mL) under
N2 atmosphere and added to a solution of Et3N, or pyridine,
(5.50 mmol) and the selected amine (3.00 mmol) in dry DCM
°
(10 mL) at 0 C. After stirring for 18 h at rt, 0.1 N HCl solution (pH 1–
2) was added. The reaction mixture was extracted with EtOAc (3×
20 mL), and the organic layer was washed with 0.1 N NaOH solution
(3×20 mL), brine, and dried over Na2SO4. After filtration and
evaporation of the solvent, the crude was purified by chromatog-
raphy to give the desired product.
General procedure B: methylation of amides. To a solution of
amide (0.200 mmol) in dry DMF (1 mL) was added NaH (60%
°
dispersion in mineral oil, 0.300 mmol) a 0 C. The mixture was
stirred at rt for 30 min, then MeI (0.340 mmol) was added. After 1 h
30 min at rt, H2O (10 mL) was added and the pH was adjusted to
neutral with NH4Cl saturated aq. solution (5 mL) and few drops of
2 N HCl. The reaction mixture was extracted with Et2O (3×20 mL),
and the organic layer was washed with brine (5×) and dried over
Na2SO4. After filtration and evaporation of the solvent, the crude
was purified by chromatography to give the desired product.
Experimental Section
General remarks. All non-aqueous reactions were performed under
an inert atmosphere of argon or nitrogen. Inert gases were passed
over a U-tube of silica and activated 3 Å molecular sieves. Reactions
were stirred magnetically and monitored by thin-layer chromatog-
raphy (TLC). Analytical thin-layer chromatography was performed
using MERCK Silica Gel 60 F254 0.25 mm TLC glass plates and
visualized by ultraviolet light (UV, 254 nm). TLC plates were also
stained with cerium ammonium molybdate (CAM, Hanessian’s stain)
by dipping and heating. Rf values were measured after elution of 6–
7 cm Concentration under reduced pressure was performed by
General procedure C: allyl deprotection. A mixture of the amide
(0.400 mmol), ammonium formate (55 mg, 0.88 mmol) and
PdCl2(PPh3)2 (15 mg, 0.022 mmol) in dry and degassed (for 15 min)
MeCN (6 mL) was stirred in a sealed tube (N2 atmosphere) for 24 h
°
at 80 C. Then NaHCO3 saturated aq. solution (15 mL) was added
and the reaction mixture was extracted with EtOAc (3×15 mL). The
organic layer was washed with brine and dried over Na2SO4. After
filtration and evaporation of the solvent, the crude was purified by
chromatography to give the desired product.
°
rotator evaporation at 40 C. Chromatographic purification was
General procedure D: preparation of ketones. To a solution of 8j
(200 mg, 0.721 mmol) in dry THF (7 mL) was added the selected
organometal reagent (1.44 mmol) at the indicated temperature
under Ar. The mixture was reacted until completion and then
poured into NH4Cl saturated aq. solution (15 mL) and extracted
with EtOAc (3×15 mL). The organic layer was washed with brine
and dried over Na2SO4. After filtration and evaporation of the
solvent, the crude was purified by chromatography to give the
desired product.
performed as flash chromatography on MERCK Geduran® Si 60 (40–
63 μm) under positive pressure and the crude mixtures were loaded
as solid absorbed on silica. Purified compounds were dried further
under high vacuum (~10À 2 torr). All chemicals and dry or non-dry
solvents were purchased from Sigma Aldrich and used as received
°
from the vendor. Petroleum ether is 40–60 C. Nuclear Magnetic
Resonance (NMR) spectra were recorded on VARIAN MERCURY
1
(300 MHz H and 75 MHz 13C). Experiments were carried out at the
specified temperature. Chemical shifts (δ) are reported in parts per
Eur. J. Org. Chem. 2021, 1737–1749
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doi.org/10.1002/ejoc.202100064
methyl (E)-3-(4-(allyloxy)-3-methoxyphenyl)acrylate (5). To a sol-
2874, 2932, 2959. UV/Vis (25 μM in MeOH): 220 (0.2926), 236
(0.3072), 295 (0.3985), 320 (0.4781). HRMS (ESI+): calcd. for
C21H32NO3 [M+H]+346.2382, found 346.2383.
1
2
3
4
5
ution of 4 (142 mg, 0.733 mmol) in MeOH (2 mL) was added AcCl
(0.50 mL, 7.33 mmol) at rt. After stirring for 18 h, the solvent was
removed and the residue (147 mg, 81%) was used in the following
step without further purification. Rf 0.95 (DCM/MeOH 95:5).
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-phenylacrylamide
(8d).
Following the general procedure A, 7 (1.71 mmol), pyridine (270 μL,
3.42 mmol) and aniline (207 μL, 2.23 mmol) in dry DCM was reacted
for 18 h. After workup and chromatography (PE/EtOAc 6:4) the
methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate (6). Following
6
the general procedure C,
5 (147 mg, 0.734 mmol), HCO2NH4
(102 mg, 1.61 mmol) and Pd(PPh3)2Cl2 (13 mg, 0.018 mmol) in dry
desired compound was afforded as white solid (471 mg, 89%). Rf
7
8
9
1
°
°
CH3CN (5 mL) was reacted for 24 h at 80 C. After workup and
0.45 (PE/EtOAc 6:4). m.p. 124.6–125.5 C. H NMR (300 MHz, CDCl3)
chromatography (PE/EtOAc 6:4) the desired compound was
afforded as pale yellow foam (126 mg, 71%). Rf 0.23 (PE/EtOAc 6:4).
UV/Vis (25 μM in MeOH): 218 (0.3395), 236 (0.3022), 295 (0.3527),
325 (0.5026). Others data were in accordance with the literature.[30]
δ=7.69 (d, J=15.4, 1H, ArCH=CH), 7.62 (d, J=7.9, 2H, 2×o-CH Ph),
7.50 (s, 1H, NH), 7.34 (t, J=8.0, 2H, 2×m-CH Ph), 7.12 (t, J=7.4, 1H,
p-CH Ph), 7.09–7.01 (m, 2H, CHÀ 2+CHÀ 6), 6.85 (d, J=8.2, 1H,
CHÀ 5), 6.45 (d, J=15.4, 1H, ArCH=CH), 6.07 (ddt, J=17.2, 10.7, 5.4,
1H, CH2=CH), 5.41 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.31 (dq, J=
10.5, 1.3, 1H, CHcisH=CH), 4.64 (dt, J=5.4, 1.4, 2H, CH2O), 3.88 (s, 3H,
OCH3). 13C NMR (75 MHz, CDCl3) δ=165.1 (C=O), 149.5 (CÀ O), 149.2
(CÀ O), 141.7 (ArCH=CH), 138.5 (CÀ NH), 132.6 (CH2=CH), 128.9 (2×
mÀ CH Ph), 127.8 (CÀ 1), 124.1 (p-CH Ph), 121.6 (CHÀ 6), 120.2
(ArCH=CH), 119.3 (2×o-CH Ph), 118.4 (CH2=CH), 112.8 (CHÀ 5), 110.3
(CHÀ 2), 69.6 (CH2O), 55.5 (OCH3). IR (νmax): 610, 656, 687, 708, 733,
749, 760, 808, 849, 930, 969, 994, 1013, 1034, 1139, 1166, 1224,
1250, 1266, 1317, 1419, 1440, 1499, 1508, 1523, 1595, 1648, 2849,
2879, 2939, 2967, 3012, 3054, 3123, 3310. UV/Vis (25 μM in MeOH):
239 (0.3353), 299 (0.5427), 330 (0.8137). HRMS (ESI+): calcd. for
C19H20NO3 [M+H]+310.1443, found 310.1440.
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(E)-3-(4-(allyloxy)-3-methoxyphenyl)acryloyl chloride (7). To
a
suspension of 4 (508 mg, 2.61 mmol) in dry DCM (15 mL) were
added oxalyl chloride (400 μL, 4.71 mmol) and dry DMF (8 μL,
°
0.105 mmol) at 0 C under N2 atmosphere. After stirring for 4 h, the
solvent was removed from the resulting solution and the crude was
washed with dry DCM (3×5 mL, evaporation after each step) and
directly used in the following step.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-butylacrylamide (8b). Fol-
lowing the general procedure A, 7 (2.57 mmol), Et3N (715 μL,
5.14 mmol) and butylamine (330 μL, 3.34 mmol) in dry DCM was
reacted for 18 h. After workup and chromatography (PE/EtOAc 6:4)
the desired compound was afforded as pale yellow solid (464 mg,
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-(4-methoxyphenyl)
75%). Rf 0.38 (PE/EtOAc 6:4). m.p. 110.1–111.1 C. 1H NMR
°
acrylamide (8e). Following the general procedure A, 7 (1.69 mmol),
pyridine (272 μL, 3.38 mmol) and 4-methoxyaniline (271 mg,
2.20 mmol) in dry DCM was reacted for 18 h. After workup and the
crude was triturated with Et2O (8 mL) and the desired compound
(300 MHz, CDCl3) δ=7.55 (d, J=15.5, 1H, ArCH=CH), 7.09–6.97 (m,
2H, CHÀ 6+CHÀ 2), 6.83 (d, J=8.0, 1H, CHÀ 5), 6.29 (d, J=15.5, 1H,
ArCH=CH), 6.07 (ddt, J=17.2, 10.7, 5.4, 1H, CH2=CH), 5.79 (t, J=5.1,
1H, NH), 5.41 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.30 (dq, J=10.5,
1.3, 1H, CHHcis=CH), 4.63 (dt, J=5.4, 1.5, 2H, CH2O), 3.87 (s, 3H,
OCH3), 3.38 (td, J=7.1, 5.8, 2H, CH2CH2CH2CH3), 1.61–1.48 (m, 2H,
CH2CH2CH2CH3), 1.45–1.31 (m, 2H, CH2CH2CH2CH3), 0.94 (t, J=7.3,
3H, CH2CH2CH2CH3). 13C NMR (75 MHz, CDCl3) δ=166.2 (C=O), 149.6
(2×CÀ O), 140.6 (ArCH=CH), 133.0 (CH2=CH), 128.3 (CÀ 1), 121.7
(CHÀ 6), 119.0 (ArCH=CH), 118.4 (CH2=CH), 113.1 (CHÀ 5), 110.2
(CHÀ 2), 69.9 (CH2O), 56.0 (OCH3), 39.6 (CH2CH2CH2CH3), 31.9
(CH2CH2CH2CH3), 20.2 (CH2CH2CH2CH3), 13.9 (CH2CH2CH2CH3). IR
(νmax): 604, 760, 803, 849, 933, 988, 1014, 1034, 1140, 1158, 1163,
1213, 1243, 1257, 1422, 1462, 1509, 1569, 1582, 1599, 1609, 1652,
2830, 2870, 2926, 2954, 3002, 3083, 3257. UV/Vis (25 μM in MeOH):
219 (0.4064), 235 (0.4097), 291 (0.4751), 316 (0.5140). HRMS (ESI+):
calcd. for C17H24NO3 [M+H]+290.1756, found 290.1753.
was afforded as silver solid (470 mg, 82%).Rf 0.30 (PE/EtOAc 6:4).
1
°
m.p. 158–161 C. H NMR (300 MHz, DMSO-d6) δ=9.98 (s, 1H, NH),
7.66–7.56 (m, 2H, para syst.), 7.48 (d, J=15.6, 1H, ArCH=CH), 7.20 (d,
J=1.9, 1H, CHÀ 2), 7.13 (dd, J=8.4, 1.9, 1H, CHÀ 6), 6.98 (d, J=8.3,
1H, CHÀ 5), 6.93–6.84 (m, 2H, para syst), 6.66 (d, J=15.6, 1H,
ArCH=CH), 6.03 (ddt, J=17.2, 10.5, 5.3, 1H, CH2=CH), 5.38 (dq, J=
17.3, 1.6, 1H, CHtransH=CH), 5.24 (dq, J=10.5, 1.3, 1H, CHcisH=CH),
4.57 (dt, J=5.4, 1.5, 2H, CH2O), 3.81 (s, 3H, OCH3), 3.71 (s, 3H,OCH3).
13C NMR (75 MHz, DMSO-d6) δ=163.8 (C=O), 155.6 (CÀ O), 149.6
(CÀ O), 149.5 (CÀ O), 140.1 (ArCH=CH), 134.0 (CH2=CH), 133.1 (CÀ NH),
128.3 (CÀ 1), 122.0 (CHÀ 6), 121.0 (2×CH para syst.), 120.6
(ArCH=CH), 118.2 (CH2=CH), 114.4 (2×CH para syst.), 113.7 (CHÀ 5),
110.7 (CHÀ 2), 69.3 (CH2O), 55.9 (OCH3), 55.6 (OCH3). IR (νmax): 605,
685, 725, 735, 769, 803, 813, 818, 838, 844, 914, 922, 969, 991, 995,
1030, 1109, 1138, 1167, 1230, 1255, 1264, 1296, 1339, 1411, 1448,
1454, 1508, 1516, 1596, 1652, 2838, 2865, 2921, 2952, 3009, 3054,
3084, 3125, 3288. UV/Vis (25 μM in MeOH): 234 (0.4563), 294
(0.5075), 329 (0.8500). HRMS (ESI+): calcd. for C20H22NO4 [M+H]+
340.1549, found 340.1554.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N,N-dibutylacrylamide (8c).
Following the general procedure A, 7 (2.61 mmol), Et3N (730 μL,
5.22 mmol) and dibutylamine (570 μL, 3.39 mmol) in dry DCM was
reacted for 18 h. After workup and chromatography (PE/EtOAc 7:3)
the desired compound was afforded as pale yellow oil (622 mg,
1
83%). Rf 0.40 (PE/EtOAc 7:3). H NMR (300 MHz, CDCl3) δ=7.63 (d,
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-benzylacrylamide
(8g).
J=15.3, 1H, ArCH=CH), 7.08 (dd, J=8.3, 1.8, 1H, CHÀ 6), 7.02 (d, J=
1.9, 1H, CHÀ 2), 6.87 (d, J=8.3, 1H, CHÀ 5), 6.69 (d, J=15.3, 1H,
ArCH=CH), 6.08 (ddt, J=17.2, 10.7, 5.4, 1H, CH2=CH), 5.41 (dq, J=
17.3, 1.6, 1H, CHtransH=CH), 5.30 (dq, J=10.5, 1.4, 1H, CHHcis=CH),
4.64 (dt, J=5.4, 1.5, 2H, CH2O), 3.90 (s, 3H, OCH3), 3.50–3.31 (m, 4H,
2×CH2CH2CH2CH3), 1.71–1.48 (m, 4H, 2×CH2CH2CH2CH3), 1.46–1.27
(m, 4H, 2×CH2CH2CH2CH3), 0.98 (t, J=7.4, 3H, CH2CH2CH2CH3), 0.95
(t, J=7.3, 3H, CH2CH2CH2CH3). 13C NMR (75 MHz, CDCl3) δ=166.2
(C=O), 149.5 (CÀ O), 149.4 (CÀ O), 142.1 (ArCH=CH), 133.0 (CH2=CH),
128.9 (CÀ 1), 121.3 (CHÀ 6), 118.3 (CH2=CH), 115.9 (ArCH=CH), 113.2
(CHÀ 5), 110.7 (CHÀ 2), 69.8 (CH2O), 56.0 (OCH3), 47.9
(CH2CH2CH2CH3), 46.7 (CH2CH2CH2CH3), 32.0 (CH2CH2CH2CH3), 30.2
(CH2CH2CH2CH3), 20.4 (CH2CH2CH2CH3), 20.2 (CH2CH2CH2CH3), 14.0
(CH2CH2CH2CH3), 13.9 (CH2CH2CH2CH3). IR (νmax): 605, 805, 980, 993,
1002, 1137, 1170, 1209, 1231, 1261, 1417, 1509, 1589, 1642, 2863,
Following the general procedure A, 7 (0.655 mmol), pyridine
(106 μL, 1.31 mmol) and benzylamine (93 μL, 0.852 mmol) in dry
DCM was reacted for 18 h. After workup and chromatography (PE/
EtOAc 6:4) the desired compound was afforded as white solid
1
°
(165 mg, 78%). Rf 0.27 (PE/EtOAc 6:4). m.p. 120.0–120.5 C. H NMR
(300 MHz, CDCl3) δ=7.59 (d, J=15.6, 1H, ArCH=CH), 7.40–7.21 (m,
5H, Ph), 7.07–6.97 (m, 2H, CHÀ 2+CHÀ 6), 6.81 (d, J=8.1, 1H, CHÀ 5),
6.33 (d, J=15.5, 1H, ArCH=CH), 6.22 (t, J=5.8, 1H, NH), 6.06 (ddt,
J=17.2, 10.6, 5.4, 1H, CH2=CH), 5.40 (dq, J=17.2, 1.5, 1H,
CHtransH=CH), 5.29 (dq, J=10.5, 1.4, 1H, CHcisH=CH), 4.61 (dt, J=5.4,
1.5, 2H, CH2O), 4.53 (d, J=5.7, 2H, NHCH2), 3.83 (s, 3H, OCH3). 13C
NMR (75 MHz, CDCl3) δ=166.1 (C=O), 149.5 (CÀ O), 149.4 (CÀ O),
141.1 (ArCH=CH), 138.3 (CH2C), 132.8 (CH2=CH), 128.7 (2×CH Ph),
128.0 (CÀ 1), 127.8 (2×CH Ph), 127.5 (CH Ph), 121.7 (CHÀ 6), 118.5
(ArCH=CH), 118.3 (CH2=CH), 112.9 (CHÀ 5), 110.1 (CHÀ 2), 69.7
Eur. J. Org. Chem. 2021, 1737–1749
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(CH2O), 55.8 (OCH3), 43.8 (NHCH2). IR (νmax): 612, 666, 671, 697, 741,
3079, 3384. UV/Vis (25 μM in MeOH): 219 (0.3233), 235 (0.3449), 298
(0.4479), 320 (0.5375). HRMS (ESI+): calcd. for C16H22NO4 [M+H]+
292.1549, found 292.1545.
1
2
3
4
5
6
7
8
9
804, 849, 925, 968, 1008, 1028, 1135, 1171, 1211, 1240, 1254, 1332,
1513, 1546, 1599, 1614, 1652, 2585, 2843, 2868, 2920, 2939, 2962,
3030, 3059, 3276. UV/Vis (25 μM in MeOH): 336 (0.4262), 292
(0.4833), 318 (0.5439). HRMS (ESI+): calcd. for C20H22NO3 [M+H]+
324.1600, found 324.1598.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-methoxy-N-meth-
ylacrylamide ((E) 8j). Freshly prepared acyl chloride 7 (5.12 mmol)
was dissolved in dry DCM (30 mL) under N2 atmosphere and
imidazole (1045 mg, 15.36 mmol) and N,O-dimethylhydroxylamine
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N,N-dibenzylacrylamide ((E)
8h). Following the general procedure A, 7 (0.655 mmol), pyridine
(106 μL, 1.31 mmol) and dibenzylamine (164 μL, 0.852 mmol) in dry
DCM was reacted for 18 h. After workup and chromatography (PE/
°
hydrochloride (650 mg, 6.66 mmol) were added at 0 C. After
stirring for 18 h at rt, 0.1 N HCl solution (pH 1–2) was added. The
reaction mixture was extracted with EtOAc (3×20 mL), and the
organic layer was washed with 0.1 N NaOH solution (3×20 mL),
brine and dried over Na2SO4. After filtration and evaporation of the
solvent, the crude was purified by chromatography (PE/EtOAc
55:45) to give the desired product as colorless oil (1208 mg, 85%).
EtOAc 75:25) the desired compound was afforded as white solid
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1
°
(236 mg, 87%). Rf 0.64 (PE/EtOAc 6:4). m.p. 118.3–120.5 C. H NMR
(300 MHz, CDCl3) δ=7.79 (d, J=15.3, 1H, ArCH=CH), 7.42–7.20 (m,
10H, 2×Ph), 7.03 (dd, J=8.4, 2.0, 1H, CHÀ 6), 6.94 (d, J=2.0, 1H,
CHÀ 2), 6.82 (d, J=8.3, 1H, CHÀ 5), 6.75 (d, J=15.2, 1H, ArCH=CH),
6.06 (ddt, J=17.3, 10.7, 5.4, 1H, CH2=CH), 5.39 (dq, J=17.3, 1.6, 1H,
CHtransH=CH), 5.29 (dq, J=10.5, 1.4, 1H, CHcisH=CH), 4.72 (s, 2H,
NCH2), 4.66–4.56 (m, 4H, NCH2 +OCH2), 3.85 (s, 3H, OCH3). 13C NMR
(75 MHz, CDCl3) δ=167.4 (C=O), 149.6 (CÀ O), 149.4 (CÀ O), 143.7
(ArCH=CH), 137.4 (CH2C), 137.0 (CH2C), 132.8 (CH2=CH), 129.0, 128.6
(2×CH Ph), 128.4 (2×CH Ph), 128.4 (CÀ 1), 128.3 (2×CH Ph), 127.7
(CH Ph), 127.4 (CH Ph), 126.6 (2×CH Ph), 121.6 (CHÀ 6), 118.3
(CH2=CH), 115.1 (ArCH=CH), 112.9 (CHÀ 5), 110.5 (CHÀ 2), 69.7
(CH2O), 56.0 (OCH3), 50.1 (NHCH2), 48.9 (NHCH2). IR (νmax): 627, 701,
1145, 1205, 1271, 1275, 1453, 1508, 2934, 3027, 3061. UV/Vis
(25 μM in MeOH): 241 (0.3365), 297 (0.4199), 324 (0.5501). HRMS
(ESI+): calcd. for C27H28NO3 [M+H]+414.2069, found 414.2073.
1
Rf 0.40 (PE/EtOAc 1:1) and 0.20 (PE/Et2O 1:2+1% EtOH). H NMR
(300 MHz, CDCl3) δ=7.67 (d, J=15.7, 1H, ArCH=CH), 7.13 (dd, J=
8.3, 2.0, 1H, HÀ 6), 7.09 (d, J=2.0, 1H, HÀ 2), 6.89 (d, J=15.7, 1H,
ArCH=CH), 6.87 (d, J=8.3, 1H, HÀ 5), 6.08 (ddt, J=17.3, 10.6, 5.4, 1H,
CH2=CH), 5.42 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.31 (dq, J=10.5,
1.4, 1H, CHcisH=CH), 4.65 (dt, J=5.4, 1.5, 2H, OCH2), 3.92 (s, 3H,
OCH3), 3.77 (s, 3H, NOCH3), 3.31 (s, 3H, NCH3). 13C NMR (75 MHz,
CDCl3) δ=167.2 (C=O), 149.7 (CÀ O), 149.4 (CÀ O), 143.4 (ArCH=CH),
132.8 (CH2=CH), 128.4 (CÀ 1), 121.9 (C-6), 118.3 (CH2=CH), 113.6
(ArCH=CH), 112.9 (CÀ 5), 110.6 (CÀ 2), 69.7 (OCH2), 61.8 (NOCH3), 56.0
(OCH3), 32.5 (NCH3). IR (νmax): 607, 815, 851, 919, 993, 1013, 1104,
1147, 1162, 1191, 1226, 1255, 1267, 1419, 1454, 1509, 1595, 1605,
1646, 2605, 2831, 2855, 2926, 2969, 3012, 3038, 3080, 3445. UV/Vis
(25 μM in MeOH): 222 (0.2554), 236 (0.2867), 296 (0.3778), 326
(0.4862). HRMS (ESI+): calcd. for C15H20NO4 [M+H]+278.1392,
found 278.1396.
(Z)-3-(4-(allyloxy)-3-methoxyphenyl)-N,N-dibenzylacrylamide ((Z)
8h). A solution of (E) 8h (90 mg, 0.218 mmol) in MeOH (3 mL) was
irradiated at 350 nm until the photostationary state was reached as
1
judged by H NMR (4 h). The desired compound was directly used
(Z)-3-(4-(allyloxy)-3-methoxyphenyl)-N-methoxy-N-meth-
in the following experiments. Rf 0.74 (PE/EtOAc 1:1). 1H NMR
(300 MHz, CDCl3) δ=7.43–7.20 (m, 10H, CH Ph), 7.13 (d, J=2.0, 1H,
CHÀ 2), 6.93 (dd, J=8.3, 1.9, 1H, CHÀ 6), 6.71 (d, J=8.4, 1H, CHÀ 5),
6.59 (d, J=12.7, 1H, ArCH=CH), 6.17–5.98 (m, 2H, CH2=CH+
ArCH=CH), 5.42 (dq, J=17.3, 1.5, 1H, CHtransH=CH), 5.37–5.26 (m, 1H,
CHcisH=CH), 4.62 (dt, J=5.4, 1.3, 2H, OCH2), 4.59 (s, 2H, NCH2), 4.43
(s, 2H, NCH2), 3.76 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ=169.5
(C=O), 149.2 (CÀ O), 148.5 (CÀ O), 136.8 (CH2C), 136.4 (CH2C), 134.4
(ArCH=CH), 133.2 (CH2=CH), 128.95 (2×CH Ph), 128.85 (2×CH Ph),
128.7 (CÀ 1), 128.7 (2×CH Ph), 127.8 (CH Ph), 127.6 (CH Ph), 127.3
(2×CH Ph), 122.1 (CHÀ 6), 121.3 (ArCH=CH), 118.3 (CH2=CH), 112.9
(CHÀ 5), 112.2 (CHÀ 2), 69.9 (CH2O), 56.0 (OCH3), 50.8 (NCH2), 46.9
(NCH2). IR (νmax): 624, 697, 1139, 1210, 1257, 1270, 1451, 1509, 2933,
3028, 3062. UV/Vis (25 μM in MeOH): 273 (0.3030), 304 (0.2306).
ylacrylamide ((Z) 8j). A solution of (E) 8j (500 mg, 1.80 mmol) in
MeOH (18 mL) was irradiated at 350 nm until the photostationary
1
state was reached as judged by H NMR (4 h). After evaporation of
the solvent, the E/Z mixture (27:73) was purified by chromatog-
raphy (PE/Et2O 1:2+1% EtOH) to give pure Z isomer as colorless
oil (273 mg). Rf 0.27 (PE/Et2O 1:2+1% EtOH). 1H NMR (300 MHz,
DMSO-d6) δ=7.33 (d, J=2.1, 1H, CHÀ 2), 7.07 (dd, J=8.4, 2.1, 1H,
CHÀ 6), 6.92 (d, J=8.4, 1H, CHÀ 5), 6.65 (d, J=12.8, 1H, ArCH=CH),
6.14 (d, J=12.9, 1H, ArCH=CH), 6.03 (ddt, J=17.3, 10.6, 5.3, 1H,
CH2=CH), 5.38 (dq, J=17.3, 1.7, 1H, CHtransH=CH), 5.24 (dq, J=10.5,
1.5, 1H, CHcisH=CH), 4.56 (dt, J=5.3, 1.5, 2H, OCH2), 3.74 (s, 3H,
OCH3), 3.63 (s, 3H, NOCH3), 3.16 (s, 3H, NCH3). 13C NMR (75 MHz,
DMSO-d6) δ=167.5 (C=O), 149.3 (CÀ O), 148.9 (CÀ O), 136.6
(ArCH=CH), 134.2 (CH2=CH), 129.0 (CÀ 1), 123.3 (CHÀ 6), 119.8
(ArCH=CH), 117.8 (CH2=CH), 114.2 (CHÀ 2), 114.1 (CHÀ 5), 69.6
(OCH2), 61.5 (NOCH3), 56.2 (OCH3), 33.0 (NCH3). IR (νmax): 636, 806,
993, 1139, 1230, 1256, 1270, 1509, 2935, 3090. UV/Vis (25 μM in
MeOH): 275 (0.2411), 301 (0.2279).
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-(2-hydroxyethyl)-N-meth-
ylacrylamide (8i). Following the general procedure A,
7
(0.653 mmol), pyridine (93 μL, 1.31 mmol) and N-meth-
ylethanolamine (68 μL, 0.849 mmol) in dry DCM was reacted for
18 h. After workup and chromatography (EtOAc/EtOH 96:4) the
desired compound was afforded as white solid (161 mg, 85%). Rf
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-methyl-N-phenylacryla-
mide (8k). Following the general procedure B, 8d (232 mg,
0.750 mmol), NaH (60% dispersion in mineral oil, 45 mg,
1.125 mmol) and MeI (80 μL, 1.275 mmol) in dry DMF (4 mL) was
reacted and, after workup and chromatography (PE/EtOAc 1:1), the
desired compound was afforded as white solid (238 mg, 98%). Rf
0.28 (EtOAc/EtOH 96:4). m.p. 85.2–86.7 C. 1H NMR (300 MHz,
°
DMSO-d6) δ=7.40 (d, J=15.4, 1H, ArCH=CH), 7.26 (d, J=2.0, 1H,
CHÀ 2), 7.16 (dd, J=8.3, 2.1, 1H, CHÀ 6), 6.98 (d, J=8.3, 1H, CHÀ 5),
6.97 (d, J=15.4, 1H, ArCH=CH), 6.05 (ddt, J=17.4, 10.6, 5.3, 1H,
CH2=CH), 5.40 (dq, J=17.3, 1.7, 1H, CHtransH=CH), 5.25 (dq, J=10.5,
1.5, 1H, CHcisH=CH), 4.60 (dt, J=5.3, 1.6, 2H, OCH2), 4.46 (broad s,
1H, OH), 3.84 (s, 3H, OCH3), 3.60 (q, J=5.3, 2H, NCH2CH2), 3.56–3.49
(m, 2H, NCH2CH2), 3.07 (s, 3H, NCH3). 13C NMR (75 MHz, DMSO-d6)
δ=166.6 (C=O), 150.2 (CÀ O), 149.8 (CÀ O), 141.0 (ArCH=CH), 134.2
(CH2=CH), 129.5 (CÀ 1), 121.9 (C-6), 117.80 and 117.76 (CH2=CH +
ArCH=CH), 114.9 (CHÀ 5), 112.8 (CHÀ 2), 69.9 (CH2O), 59.7 (NCH2CH2),
56.7 (OCH3), 51.5 (NCH2CH2), 35.6 (NCH3). IR (νmax): 607, 815, 843,
920, 988, 1012, 1032, 1061, 1111, 1145, 1206, 1258, 1405, 1418,
1444, 1508, 1584, 1641, 2603, 2882, 2907, 2940, 2962, 2994, 3042,
0.52 (PE/EtOAc 1:1). m.p. 92.5–93.7 C. 1H NMR (300 MHz, CDCl3)
°
δ=7.61 (d, J=15.5, 1H, ArCH=CH), 7.47–7.40 (m, 2H, 2×CH Ph),
7.39–7.32 (m, 1H, CH Ph), 7.27–7.21 (m, 2H, 2×CH Ph), 6.90 (dd, J=
8.3, 2.0, 1H, CHÀ 6), 6.81 (d, J=2.0, 1H, CHÀ 2), 6.78 (d, J=8.3, 1H,
CHÀ 5), 6.23 (d, J=15.5, 1H, ArCH=CH), 6.04 (ddt, J=17.3, 10.6, 5.4,
1H, CH2=CH), 5.37 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.27 (dq, J=
10.5, 1.4, 1H, CHcisH=CH), 4.59 (dt, J=5.4, 1.5, 2H, OCH2), 3.80 (s, 3H,
OCH3), 3.41 (s, 3H, NCH3). 13C NMR (75 MHz, CDCl3) δ=166.3 (C=O),
149.3 (CÀ O), 149.3 (CÀ O), 143.7 (NÀ C), 141.5 (ArCH=CH), 132.8
(CH2=CH), 129.5 (2×CH Ph), 128.4 (CÀ 1), 127.4 (CH Ph), 127.3 (2×
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CH Ph), 121.2 (C-6), 118.2 (CH2=CH), 116.8 (ArCH=CH), 112.9 (CÀ 5),
110.9 (CÀ 2), 69.7 (OCH2), 55.9 (OCH3), 37.5 (NCH3). IR (νmax): 603, 699,
775, 800, 839, 944, 986, 1007, 1034, 1121, 1143, 1220, 1244, 1261,
1383, 1495, 1510, 1581, 1592, 1652, 2606, 2882, 2939, 2967, 3005,
3047. UV/Vis (25 μM in MeOH): 214 (0.5023), 238 (0.4837), 297
(0.4969), 328 (0.6691). HRMS (ESI+): calcd. for C20H22NO3 [M+H]+
324.1600, found 324.1608.
the desired compound was afforded as white foam (125 mg, 91%).
Rf 0.60 (PE/EtOAc 6:4). H NMR (300 MHz, DMSO-d6) δ=7.47 (d, J=
1
2
3
4
5
6
7
8
9
1
15.3, 1H, ArCH=CH), 7.39–7.19 (m, 6H, 5×CH Ph+CHÀ 2), 7.14 (dd,
J=8.3, 2.0, 1H, CHÀ 6), 7.02 (d, J=15.4, 1H, ArCH=CH), 6.95 (d, J=
8.4, 1H, CHÀ 5), 6.03 (ddt, J=17.1, 10.5, 5.3, 1H, CH2=CH), 5.37 (dq,
J=17.3, 1.6, 1H, CHtransH=CH), 5.23 (dq, J=10.5, 1.5, 1H, CHcisH=CH),
4.68 (s, 2H, NCH2), 4.57 (dt, J=5.1, 1.4, 2H, OCH2), 3.81 (d, J=1.2,
3H, OCH3), 3.02 (s, 3H, NCH3 buried by H2O). 13C NMR (75 MHz,
DMSO-d6) δ=166.7 (C=O), 150.2 (CÀ O), 150.0 (CÀ O), 141.8
(ArCH=CH), 138.5 (C quat. Ph), 134.2 (CH2=CH), 129.3 (CÀ 1), 128.9
(2×CH Ph), 127.7 (CH Ph), 127.5 (2×CH Ph), 122.2 (CHÀ 6), 117.8
(CH2=CH), 117.2 (ArCH=CH), 114.9 (CHÀ 5), 112.7 (CHÀ 2), 69.9
(OCH2), 56.7 (OCH3), 34.9 (NCH3). IR (νmax): 697, 726, 1138, 1250,
1509, 1594, 2246, 2934, 3063. UV/Vis (25 μM in MeOH): 218
(0.3188), 238 (0.3001), 295 (0.3787), 325 (0.4755). HRMS (ESI+):
calcd. for C21H24NO3 [M+H]+338.1756, found 338.1750.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-(4-methoxyphenyl)-N-
methylacrylamide (8l). Following the general procedure B, 8e
(60 mg, 0.177 mmol), NaH (60% dispersion in mineral oil, 11 mg,
0.266 mmol) and MeI (20 μL, 0.301 mmol) in dry DMF (1 mL) was
reacted and, after workup and chromatography (PE/EtOAc 1:1), the
desired compound was afforded as pale yellow solid (58 mg, 92%).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Rf 0.34 (PE/EtOAc 1:1). m.p. 115.2–116.5 C. 1H NMR
°
(300 MHz,CDCl3) δ=7.59 (d, J=15.5, 1H, ArCH=CH), 7.21–7.10 (m,
2H, para syst.), 6.99–6.88 (m, 3H, para syst.+CHÀ 6), 6.82 (d, J=2.0,
1H, CHÀ 2), 6.78 (d, J=8.3, 1H, CHÀ 5), 6.23 (d, J=15.4, 1H,
ArCH=CH), 6.04 (ddt, J=17.3, 10.6, 5.4, 1H, CH2=CH), 5.38 (dq, J=
17.2, 1.6, 1H, CHtransH=CH), 5.28 (dq, J=10.5, 1.3, 1H, CHcisH=CH),
4.60 (dt, J=5.4, 1.5, 2H, OCH2), 3.85 (s, 3H, OCH3), 3.81 (s, 3H, OCH3),
3.37 (s, 3H, NCH3). 13C NMR (75 MHz, CDCl3) δ=166.5 (C=O), 158.7
(CÀ O), 149.3 (CÀ O), 149.3 (CÀ O), 141.4 (ArCH=CH), 136.6 (CÀ N),
132.9 (CH2=CH), 128.6 (CÀ 1), 128.5 (2×CH para syst.), 121.0 (C-6),
118.2 (CH2=CH), 116.8 (ArCH=CH), 114.6 (2×CH para syst.), 113.0
(CÀ 5), 111.2 (CÀ 2), 69.7 (OCH2), 56.0 (OCH3), 55.5 (OCH3), 37.7
(NCH3). IR (νmax): 602, 800, 809, 838, 945, 988, 1007, 1019, 1039,
1107, 1123, 1142, 1222, 1249, 1423, 1509, 1599, 1651, 2598, 2847,
2882, 2940, 2963, 3011, 3049. UV/Vis (25 μM in MeOH): 237
(0.4847), 298 (0.4099), 323 (0.5540). HRMS (ESI+): calcd. for
C21H24NO4 [M+H]+354.1705, found 354.1700.
(E)-3-(4-hydroxy-3-methoxyphenyl)acrylamide (9a).[17] To a solu-
tion of ferulic acid (400 mg, 2.06 mmol) in 1 M NaOH (aq. solution,
°
5 mL) was added Ac2O (0.78 mL, 8.25 mmol) at 0 C. After stirring at
rt for 2 h, the white precipitate formed was filtered, washed with
H2O (10 mL) and purified by chromatography (PE/EtOAc 3:7+5%
MeOH) to give 3 as white solid (263 mg, 66%). To a solution of 3
(154 mg, 0.737 mmol) in dry THF (7 mL) were added Et3N (235 μL,
°
1.70 mmol) and ethyl chloroformate (162 μL, 1.70 mmol) at 0 C.
After stirring for 30 min at rt, NH4OH (28% aq., 665 μL) was added
dropwise and the mixture was reacted for 18 h. Then the volume
was reduced and the mixture was extracted with H2O (20 mL) and
EtOAc (3×20 mL). The organic layer was washed with brine and
dried over Na2SO4. After filtration and evaporation of the solvent,
the crude was purified by chromatography (PE/EtOAc 1:9+1%
EtOH) to give 8a as yellow sticky solid (76 mg, 53%). Rf 0.31 (PE/
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-methyl-N-(4-nitrophenyl)
acrylamide (8m). Following the general procedure A,
°
EtOAc 9:1+1% EtOH). m.p. 105.4–153.2 C. UV/Vis (25 μM in
7
MeOH): 220 (0.2924), 237 (0.3071), 295 (0.3985), 321 (0.4784). Others
data were in accordance with the literature.
(1.69 mmol), pyridine (273 μL, 3.38 mmol) and 4-nitroaniline
(304 mg, 2.20 mmol) in dry DCM was reacted for 18 h. After workup
and chromatography (PE/EtOAc 2:8) the desired secondary amide
co-eluted with 4-nitroaniline (80:20 respectively by 1H NMR,
corrected yield 92%) that was impossible to remove. Following the
general procedure B, the above mentioned mixture (58 mg,
corresponding to 0.150 mmol of secondary amime), NaH (60%
dispersion in mineral oil, 9 mg, 0.225 mmol) and MeI (16 μL,
0.255 mmol) in dry DMF (0.75 mL) was reacted and, after workup
and chromatography (PE/EtOAc 6:4), the desired tertiary amide
(iE)-N-butyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (9b). Fol-
lowing the general procedure C, 8a (211 mg, 0.730 mmol),
HCO2NH4 (101 mg, 1.61 mmol) and Pd(PPh3)2Cl2 (13 mg,
°
0.018 mmol) in dry CH3CN (5 mL) was reacted for 24 h at 80 C. After
workup and chromatography (DCM+4% MeOH) the desired
compound was afforded as pale yellow foam (182 mg, 99%). Rf 0.35
(DCM+4% MeOH). 1H NMR (300 MHz, CDCl3) δ=7.54 (d, J=
15.5 Hz, 1H, ArCH=CH), 7.05 (dd, J=8.2, 1.9 Hz, 1H, HÀ 6), 6.97 (d,
J=1.9 Hz, 1H, HÀ 2), 6.90 (d, J=8.2 Hz, 1H, HÀ 5), 6.26 (d, J=15.5 Hz,
1H, ArCH=CH), 6.04 (s, 1H, OH), 5.72 (t, J=5.8 Hz, 1H, NH), 3.89 (s,
3H, OCH3), 3.38 (td, J=7.1, 5.8 Hz, 2H, CH2CH2CH2CH3), 1.63–1.47 (m,
2H, CH2CH2CH2CH3), 1.46–1.29 (m, 2H, CH2CH2CH2CH3), 0.94 (t, J=
7.3 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ=166.7 (C=O), 147.6
(CÀ O), 147.0 (CÀ O), 140.9 (ArCH=CH), 127.3 (CÀ 1), 121.9 (CHÀ 6),
118.4 (ArCH=CH), 115.0 (CHÀ 5), 110.0 (CHÀ 2), 55.8 (OCH3), 39.6
(CH2CH2CH2CH3), 31.7 (CH2CH2CH2CH3), 20.2 (CH2CH2CH2CH3), 13.8
(CH3). UV/Vis (25 μM in MeOH): 219 (0.3675), 234 (0.3689), 293
(0.3895), 319 (0.4895). Others data were in accordance with the
literature.[20b]
was afforded as pale yellow solid (25 mg, 45% from 7). Rf 0.20 (PE/
1
°
EtOAc 6:4). m.p. 151.7–13.2 C. H NMR (300 MHz,CDCl3) δ=8.33–
8.27 (m, 2H, para syst.), 7.69 (d, J=15.4, 1H, ArCH=CH), 7.45–7.39
(m, 2H, para syst.), 6.96 (dd, J=8.4, 2.0, 1H, CHÀ 6), 6.86 (d, J=2.0,
1H, CHÀ 2), 6.81 (d, J=8.4, 1H, CHÀ 5), 6.26 (d, J=15.4, 1H,
ArCH=CH), 6.05 (ddt, J=17.2, 10.6, 5.4, 1H, CH2=CH), 5.39 (dq, J=
17.3, 1.6, 1H, CHtransH=CH), 5.29 (dq, J=10.2, 1.4, 1H, CHcisH=CH),
4.62 (dt, J=5.4, 1.5, 2H, OCH2), 3.83 (s, 3H, OCH3), 3.48 (s, 3H, NCH3).
13C NMR (75 MHz, CDCl3) δ=166.2 (C=O), 149.9 (CÀ O), 149.7 (CÀ O),
149.4 (CÀ O), 145.9 (CÀ N), 143.5 (ArCH=CH), 132.7 (CH2=CH), 127.8
(CÀ 1), 127.2 (2×CH para syst.), 124.9 (2×CH para syst.), 121.4
(CHÀ 6), 118.4 (CH2=CH), 115.7 (ArCH=CH), 113.0 (CHÀ 5), 111.1
(CHÀ 2), 69.7 (OCH2), 56.0 (OCH3), 37.3 (NCH3). IR (νmax): 604, 699,
796, 847, 852, 858, 868, 929, 986, 997, 1013, 1035, 1104, 1117, 1138,
1225, 1258, 1334, 1492, 1510, 1585, 1653, 2850, 2922, 2963, 3072,
3105. UV/Vis (25 μM in MeOH): 239 (0.3704), 294 (0.4506), 328
(0.4886). HRMS (ESI+): calcd. for C20H21N2O5 [M+H]+369.1450,
found 369.1457.
(E)-N,N-dibutyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide (9c).
Following the general procedure C, 8c (232 mg, 0.671 mmol),
HCO2NH4 (93 mg, 1.48 mmol) and Pd(PPh3)2Cl2 (12 mg, 0.017 mmol)
°
in dry CH3CN (5 mL) was reacted for 24 h at 80 C. After workup and
chromatography (PE/EtOAc 6:4) the desired compound was
afforded as pale yellow oil (197 mg, 96%). Rf 0.34 (PE/EtOAc 6:4).
1H NMR (300 MHz, CDCl3) δ=7.62 (d, J=15.3 Hz, 1H, ArCH=CH),
7.09 (dd, J=8.2, 2.0 Hz, 1H, CHÀ 6), 6.97 (d, J=1.9 Hz, 1H, CHÀ 2),
6.92 (d, J=8.2 Hz, 1H, CHÀ 5), 6.68 (d, J=15.3 Hz, 1H, ArCH=CH),
5.89 (s, 1H, OH), 3.92 (s, 3H, OCH3), 3.50–3.30 (m, 4H 2 x
CH2CH2CH2CH3), 1.73–1.50 (m, 4H, 2×CH2CH2CH2CH3), 1.47–1.27 (m,
4H, 2×CH2CH2CH2CH3 ), 0.98 (t, J=7.3 Hz, 3H, CH3), 0.94 (t, J=
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-N-benzyl-N-meth-
ylacrylamide (8n). Following the general procedure B, 8g (131 mg,
0.406 mmol), NaH (60% dispersion in mineral oil, 24 mg,
0.609 mmol) and MeI (43 μL, 0.690 mmol) in dry DMF (2 mL) was
reacted and, after workup and chromatography (PE/EtOAc 50:45),
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doi.org/10.1002/ejoc.202100064
7.3 Hz, 3H, CH3). 13C NMR (75 MHz, CDCl3) δ=166.5 (C=O), 147.5
4.64 (dt, J=5.4, 1.5, 2H, OCH2), 3.92 (s, 3H, OCH3), 2.23 (s, 3H,
CH3À C=O). 13C NMR (75 MHz, CDCl3) δ=200.0 (C=O), 149.4 (CÀ O),
148.7 (CÀ O), 141.2 (ArCH=CH), 132.9 (CH2=CH), 128.4 (CÀ 1), 126.2
(ArCH=CH), 124.5 (CHÀ 6), 118.3 (CH2=CH), 113.2 (CHÀ 2), 112.3
(CHÀ 5), 69.7 (OCH2), 55.9 (OCH3), 31.4 (CH3À C=O). IR (νmax): 636, 976,
994, 1135, 1174, 1231, 1255, 1509, 2936, 3004, 3097. UV/Vis (25 μM
in MeOH): 230 (0.2019), 300 (0.2002), 333 (0.2590). HRMS (ESI+):
calcd. for C14H17O3 [M+H]+233.1178, found 233.1183.
1
2
3
4
5
6
7
8
9
(CÀ O), 146.9 (CÀ O), 142.5 (ArCH=CH), 128.1(CÀ 1), 121.6 (CHÀ 6),
115.3 (ArCH=CH), 115.0 (CHÀ 5), 110.4 (CHÀ 2), 56.0 (OCH3), 48.0
(CH2CH2CH2CH3), 46.8 (CH2CH2CH2CH3), 32.0 (CH2CH2CH2CH3), 30.2
(CH2CH2CH2CH3), 20.4 (CH2CH2CH2CH3), 20.2 (CH2CH2CH2CH3), 14.0
(CH3), 13.9 (CH3). IR (νmax): 605, 798, 818, 975, 1036, 1129, 1165,
1196, 1204, 1250, 1281, 1288, 1409, 1445, 1460, 1480, 1513, 1572,
2658, 2792, 2858, 2872, 2931, 2959, 3014, 3094. UV/Vis (25 μM in
MeOH): 219 (0.4042), 236 (0.3919), 299 (0.4440), 223 (0.5882). HRMS
(ESI+): calcd. for C18H28NO3 [M+H]+306.2069, found 306.2072.
(E)-1-(4-(allyloxy)-3-methoxyphenyl)pent-1-en-3-one (11b). Fol-
lowing the general procedure D, (E) 8j (150 mg, 0.541 mmol),
EtMgBr (3.0 M in Et2O, 1.1 mL, 3.25 mmol) in dry THF (5 mL) was
(E)-3-(4-hydroxy-3-methoxyphenyl)-N-phenylacrylamide (9d). Fol-
lowing the general procedure C, 8d (96 mg, 0.310 mmol), HCO2NH4
(44 mg, 0.682 mmol) and Pd(PPh3)2Cl2 (5 mg, 7.75 μmol) in dry
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
°
reacted for 4 h at À 30 C. After workup and chromatography (PE/
EtOAc 9:1) the desired compound was afforded as pale yellow solid
CH3CN (2.5 mL) was reacted for 24 h at 80 C. After workup and
(42 mg, 31%). Rf 0.24 (PE/EtOAc 9:1). m.p. 65.1–65.8 C. 1H NMR
°
°
chromatography (PE/EtOAc 55:45) the desired compound was
afforded as pale yellow oil (81 mg, 97%). Rf 0.44 (PE/EtOAc 1:1).
UV/Vis (25 μM in MeOH): 237 (0.2763), 332 (0.6671). Others data
were in accordance with the literature.[31]
(300 MHz, CDCl3) δ=7.50 (d, J=16.2, 1H, ArCH=CH), 7.14–7.06 (m,
2H, HÀ 2+HÀ 6), 6.87 (d, J=9.3, 1H, HÀ 5), 6.63 (d, J=16.1, 1H,
ArCH=CH), 6.08 (ddt, J=17.2, 10.6, 5.4, 1H, CH2=CH), 5.42 (dq, J=
17.3, 1.6, 1H, CHtransH=CH), 5.31 (dq, J=10.5, 1.4, 1H, CHcisH=CH),
4.65 (dt, J=5.4, 1.5, 2H, OCH2), 3.91 (s, 3H, OCH3), 2.69 (q, J=7.3,
2H, CH2CH3), 1.17 (t, J=7.3, 3H, CH2CH3). 13C NMR (75 MHz, CDCl3)
δ=200.9 (C=O), 150.2 (CÀ O), 149.5 (CÀ O), 142.2 (ArCH=CH), 132.7
(CH2=CH), 127.6 (CÀ 1), 124.1 (ArCH=CH), 122.7 (CHÀ 6), 118.4
(CH2=CH), 112.8 (CHÀ 5), 110.0 (CHÀ 2), 69.7 (OCH2), 55.9 (OCH3), 33.8
(CH2CH3), 8.3 (CH2CH3). IR (νmax): 617, 781, 813, 844, 925, 930, 960,
994, 1008, 1141, 1167, 1190, 1200, 1226, 1258, 1424, 1512, 1653,
2833, 2875, 2938, 2955, 2976, 3019, 3041, 3082, 3294. UV/Vis
(25 μM in MeOH): 240 (0.2032), 298 (0.2980), 333 (0.4596). HRMS
(ESI+): calcd. for C15H19O3 [M+H]+247.1334, found 247.1330.
(Z)-N,N-dibenzyl-3-(4-hydroxy-3-methoxyphenyl)acrylamide ((Z)
9h). Following the general procedure C, (Z)-8h (45 mg,
0.109 mmol), HCO2NH4 (15 mg, 0.240 mmol) and Pd(PPh3)2Cl2 (2 mg,
°
2.72 μmol) in dry CH3CN (1 mL) was reacted for 24 h at 80 C. After
workup and chromatography (PE/EtOAc 7:3) the desired com-
pound was afforded as pale yellow foam (31 mg, 75%). Rf 0.59 (PE/
1
EtOAc 1:1). H NMR of the crude showed that almost no isomer-
ization occurs.
(E)-3-(4-hydroxy-3-methoxyphenyl)-N-methyl-N-phenylacrylamide
(9k). Following the general procedure C, 8k (101 mg, 0.312 mmol),
HCO2NH4 (44 mg, 0.684 mmol) and Pd(PPh3)2Cl2 (6 mg, 7.75 μmol)
(E)-1-(4-(allyloxy)-3-methoxyphenyl)hept-1-en-3-one (11c). Fol-
lowing the general procedure D, (E) 8j (205 mg, 0.739 mmol), nBuLi
(1.6 M in hexane, 0.9 mL, 1.48 mmol) in dry THF (7 mL) was reacted
°
in dry CH3CN (2.5 mL) was reacted for 24 h at 80 C. After workup
and chromatography (PE/EtOAc 1:1) the desired compound was
°
for 2 h at À 40 C. After workup and chromatography (PE/EtOAc
1
afforded as pale yellow oil (80 mg, 90%). Rf 0.33 (PE/EtOAc 1:1). H
10:1) the desired compound was afforded as white foam (89 mg,
44%). Rf 0.20 (PE/EtOAc 10:1). 1H NMR (300 MHz, CDCl3) δ=7.49 (d,
J=16.1, 1H, ArCH=CH), 7.15–7.05 (m, 2H, HÀ 2+HÀ 6), 6.87 (d, J=
8.5, 1H, HÀ 5), 6.62 (d, J=16.1, 1H, ArCH=CH), 6.08 (ddt, J=17.3,
10.7, 5.4, 1H, CH2=CH), 5.42 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.31
(dq, J=10.5, 1.4, 1H, CHcisH=CH), 4.65 (dt, J=5.4, 1.5, 2H, OCH2),
3.91 (s, 3H, OCH3), 2.65 (t, J=7.4, 2H, CH2C=O), 1.67 (p, J=7.4, 2H,
CH2CH2CH3), 1.38 (hex, J=7.4, 2H, CH2CH2CH3), 0.94 (t, J=7.3, 3H,
CH3). 13C NMR (75 MHz, CDCl3) δ=200.6 (C=O), 150.2 (CÀ O), 149.5
(CÀ O), 142.3 (ArCH=CH), 132.7 (CH2=CH), 127.7 (CÀ 1), 124.4
(ArCH=CH), 122.7 (CHÀ 6), 118.4 (CH2=CH), 112.8 (CHÀ 5), 110.1
(CHÀ 2), 69.7 (OCH2), 55.9 (OCH3), 40.4 (CH2C=O), 26.6 (CH2CH2CH3),
22.5 (CH2CH2CH3), 13.9 (CH3). IR (νmax): 611, 789, 810, 880, 921, 926,
979, 996, 1033, 1144, 1168, 1182, 1228, 1265, 1423, 1453, 1513,
1593, 1653, 2885, 2901, 2953, 2990, 3012, 3081, 3095, 3119, 3281.
UV/Vis (25 μM in MeOH): 239 (0.1839), 298 (0.2758), 335 (0.4362).
HRMS (ESI+): calcd. for C17H23O3 [M+H]+275.1647, found
275.1641.
NMR (300 MHz, CDCl3) δ=7.60 (d, J=15.5, 1H, ArCH=CH), 7.50–7.39
(m, 2H, 2×CH Ph), 7.39–7.32 (m, 1H, CH Ph), 7.29–7.20 (m, 2H, 2×
CH Ph), 6.89 (dd, J=8.2, 1.7, 1H. HÀ 6), 6.82 (d, J=8.2, 1H, HÀ 5), 6.79
(d, J=1.7, 1H, HÀ 2), 6.21 (d, J=15.5, 1H, ArCH=CH), 5.90 (s, 1H, OH),
3.83 (s, 3H, OCH3), 3.41 (s, 3H, NCH3). 13C NMR (75 MHz, CDCl3) δ=
166.6 (C=O), 147.3 (CÀ O), 146.6 (CÀ O), 143.9 (CÀ N), 141.9
(ArCH=CH), 129.7 (2×CH Ph), 127.9 (CÀ 1), 127.6 (CH Ph), 127.5 (2×
CH Ph), 121.7 (C-6), 116.5 (ArCH=CH), 114.8 (CÀ 5), 110.4 (CÀ 2), 56.0
(OCH3), 37.7 (NCH3). IR (νmax): 603, 667, 698, 772, 799, 812, 1033,
1121, 1168, 1226, 1263, 1286, 1377, 1429, 1518, 1563, 1635, 2587,
2836, 2937, 2965, 2995, 3061. UV/Vis (25 μM in MeOH): 216
(0.2854), 241 (0.3600), 299 (0.3420), 331 (0.5366). HRMS (ESI+):
calcd. for C17H18NO3 [M+H]+284.1287, found 284.1289.
(E)-4-(4-(allyloxy)-3-methoxyphenyl)but-3-en-2-one ((E) 11a). Fol-
lowing the general procedure D, (E) 8j (200 mg, 0.721 mmol),
MeMgBr (3.0 M in Et2O, 1.5 mL, 4.33 mmol) in dry THF (7 mL) was
°
reacted for 4 h at À 30 C. After workup and chromatography (PE/
EtOAc 75:25) the desired compound was afforded as pale yellow
(E)-1-(4-(allyloxy)-3-methoxyphenyl)penta-1,4-dien-3-one (11d).
Following the general procedure D, (E) 8j (93 mg, 0.335 mmol),
vinylMgBr (1.0 M in THF, 1.7 mL, 1.68 mmol) in dry THF (7 mL) was
°
solid (119 mg, 72%). Rf 0.27 (PE/EtOAc 75:25). m.p. 67.8–68.8 C.
UV/Vis (25 μM in MeOH): 237 (0.2097), 298 (0.3106), 332 (0.4821).
Others data were in accordance with the literature.[32]
°
reacted for 2 h at 0 C. After workup and chromatography (PE/
EtOAc 85:15) the desired compound was afforded as yellow oil
(Z)-4-(4-(allyloxy)-3-methoxyphenyl)but-3-en-2-one ((Z) 11a). Fol-
lowing the general procedure D, (Z) 8j (136 mg, 0.490 mmol),
MeMgBr (3.0 M in Et2O, 0.5 mL, 1.47 mmol) in dry THF (5 mL) was
1
(30 mg, 36%). Rf 0.71 (PE/EtOAc 6:4). H NMR (300 MHz, CDCl3) δ=
7.63 (d, J=15.9, 1H, ArCH=CH), 7.19–7.09 (m, 2H, HÀ 2+HÀ 6), 6.88
(d, J=8.0, 1H, HÀ 5), 6.87 (d, J=15.9, 1H, ArCH=CH), 6.73 (dd, J=
17.4, 10.6, 1H, CH2=CHC=O), 6.37 (dd, J=17.4, 1.4, 1H,
CHtransH=CHC=O), 6.08 (ddt, J=17.1, 10.7, 5.4, 1H, CH2=CH), 5.85
(dd, J=10.6, 1.3, 1H, CHcisH=CHC=O), 5.42 (dq, J=17.3, 1.5, 1H,
CHtransH=CH), 5.32 (dq, J=11.0, 1.3, 1H, CHcisH=CH), 4.66 (dt, J=5.4,
1.5, 2H, OCH2), 3.93 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ=
189.4 (C=O), 150.4 (CÀ O), 149.6 (CÀ O), 144.0 (ArCH=CH), 135.3
(CH2=CHC=O), 132.6 (CH2=CH), 128.2 (CH2=CHC=O), 127.7 (CÀ 1),
°
reacted for 4 h at À 30 C. After workup and chromatography (PE/
EtOAc 9:1) the desired compound was afforded as yellow oil
1
(92 mg, 83%). Rf 0.74 (PE/EtOAc 6:4). H NMR (300 MHz, CDCl3) δ=
7.64 (d, J=2.1, 1H, HÀ 2), 7.09 (dd, J=8.3, 2.1, 1H, HÀ 6), 6.84 (d, J=
8.4, 1H, HÀ 5), 6.72 (d, J=12.8, 1H, ArCH=CH), 6.13 (d, J=12.7, 1H,
ArCH=CH), 6.08 (ddt, J=17.3, 10.5, 5.4, 1H, CH2=CH), 5.41 (dq, J=
17.3, 1.6, 1H, CHtransH=CH), 5.30 (dq, J=10.5, 1.4, 1H, CHcisH=CH),
Eur. J. Org. Chem. 2021, 1737–1749
www.eurjoc.org
1747
© 2021 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202100064
122.9 (CHÀ 6), 122.4 (ArCH=CH), 118.4 (CH2=CH), 112.8 (CHÀ 5), 110.3
(dq, J=10.5, 1.3, 1H, CHcisH=CH), 4.66 (dt, J=5.4, 1.5, 2H, OCH2),
3.94 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ=180.8 (C=O), 150.6
(CÀ O), 149.6 (CÀ O), 147.2 (CÀ C=O), 144.7 (ArCH=CH), 132.6
(CH2=CH), 131.5 (CHÀ 3 thienyl), 131.3 (CH-4 thienyl), 127.7 (CÀ 1),
123.1 (CHÀ 6), 122.4 (CÀ Br), 118.5 (CH2=CH), 118.4 (ArCH=CH), 112.9
(CHÀ 5), 110.7 (CHÀ 2), 69.7 (OCH2), 56.0 (OCH3). IR (νmax): 620, 708,
718, 734, 737, 801, 812, 837, 849, 913, 925, 962, 980, 995, 1008,
1023, 1076, 1138, 1177, 1213, 1225, 1239, 1255, 1321, 1341, 1413,
1513, 1577, 1587, 1641, 2832, 2864, 2916, 2959, 2984, 3015, 3031,
3077, 3101, 3159. UV/Vis (25 μM in MeOH): 270 (0.2413), 318
(0.3797), 371 (0.6465). HRMS (ESI+): calcd. for C17H16BrO3S [M+H]+
379.0004, found 379.0006.
1
2
3
4
5
6
7
8
9
(CHÀ 2), 69.7 (OCH2), 56.0 (OCH3). IR (νmax): 607, 806, 985, 1101, 1137,
1208, 1226, 1253, 1507, 1576, 2935, 3079, 3389. UV/Vis (25 μM in
MeOH): 242 (0.1831), 351 (0.2907). HRMS (ESI+): calcd. for C15H17O3
[M+H]+245.1178, found 245.1187.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-1-phenylprop-2-en-1-one ((E)
11e). Following the general procedure D, (E) 8j (150 mg,
0.541 mmol), PhMgCl (2.0 M in THF, 1.6 mL, 3.25 mmol) in dry THF
°
(7 mL) was reacted for 2 h at À 30 C. After workup and chromatog-
raphy (PE/EtOAc 9:1) the desired compound was afforded as bright
yellow solid (130 mg, 62%). Rf 0.29 (PE/EtOAc 9:1). m.p. 78.1–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
1
°
79.4 C. H NMR (300 MHz, CDCl3) δ=8.07–7.96 (m, 2H, 2×CH Ph),
7.76 (d, J=15.6, 1H, ArCH=CH), 7.64–7.51 (m, 1H, CH Ph), 7.56–7.43
(m, 2H, 2×CH Ph), 7.39 (d, J=15.6, 1H, ArCH=CH), 7.20 (dd, J=8.3,
1.9, 1H, HÀ 6), 7.17 (d, J=2.0, 1H, HÀ 2), 6.89 (d, J=8.2, 1H, HÀ 5),
6.09 (ddt, J=17.3, 10.6, 5.4, 1H, CH2=CH), 5.43 (dq, J=17.2, 1.6, 1H,
CHtransH=CH), 5.32 (dq, J=10.5, 1.3, 1H, CHcisH=CH), 4.66 (dt, J=5.4,
1.5, 2H, OCH2), 3.94 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ=
190.6 (C=O), 150.4 (CÀ O), 149.6 (CÀ O), 145.0 (ArCH=CH), 138.5
(CÀ C=O), 132.7 (CH2=CH), 132.6 (CH Ph), 128.6 (2×CH Ph), 128.4
(2×CH Ph), 128.0 (CÀ 1), 122.9 (CHÀ 6), 120.1 (ArCH=CH), 118.4
(CH2=CH), 112.9 (CHÀ 5), 110.5 (CHÀ 2), 69.7 (OCH2), 56.0 (OCH3). IR
(νmax): 611, 659, 693, 705, 711, 728, 740, 779, 788, 801, 850, 868, 915,
978, 999, 1019, 1037, 1139, 1169, 1176, 1197, 1212, 1225, 1237,
1256, 1446, 1511, 1576, 1589, 2832, 2858, 2912, 2935, 2958, 2992,
3065. UV/Vis (25 μM in MeOH): 262 (0.3055), 356 (0.4733). HRMS
(ESI+): calcd. for C19H19O3 [M+H]+295.1334, found 295.1329.
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-1-(pyridin-2-yl)prop-2-en-1-
one (11g). To a solution of 2-bromopyridine (394 μL, 4.13 mmol) in
dry THF (18.5 mL) was added drop-wise nBuLi (1.6 M in hexane,
°
2.1 mL, 3.30 mmol) at À 78 C under Ar. After 1 h, part of the
resulting solution (~0.16 M, 7.0 mL, 1.12 mmol) was transferred into
°
an empty 2-neck flask placed at À 78 C under Ar. Then a solution of
(E) 8j (103 mg, 0.371 mmol) in dry THF (3 mL) was added drop-wise
and the mixture was reacted for 3 h allowing the temperature to
warm up. The mixture was poured into NH4Cl saturated aq. solution
(15 mL) and extracted with EtOAc (3×15 mL). The organic layer was
washed with brine and dried over Na2SO4. After filtration and
evaporation of the solvent, the crude was purified by chromatog-
raphy (PE/EtOAc 8:2) to give the desired product as green solid
1
°
(27 mg, 25%). Rf 0.52 (PE/EtOAc 75:25). m.p. 71.0–74.8 C. H NMR
(300 MHz, CDCl3) δ=8.75 (ddd, J=4.8, 1.7, 0.9, 1H, CHÀ 6 Py), 8.19
(dt, J=7.9, 1.3, 0.9, 1H, CHÀ 3 Py), 8.15 (d, J=15.9, 1H, ArCH=CH),
7.90 (d, J=16.0, 1H, ArCH=CH), 7.88 (td, J=7.7, 1.7, 1H, CH-4 Py),
7.49 (ddd, J=7.6, 4.7, 1.3, 1H, CHÀ 5 Py), 7.30–7.24 (m, 2H, CHÀ 2+
CHÀ 6), 6.90 (d, J=8.8, 1H, CHÀ 5), 6.09 (ddt, J=17.2, 10.7, 5.4, 1H,
CH2=CH), 5.43 (dq, J=17.3, 1.5, 1H, CHtransH=CH), 5.32 (dq, J=10.5,
1.3, 1H, CHcisH=CH), 4.67 (dt, J=5.4, 1.5, 2H, OCH2), 3.97 (s, 3H,
OCH3). 13C NMR (75 MHz, CDCl3) δ=189.3 (C=O), 154.4(CÀ C=O),
150.5 (CÀ O), 149.5 (CÀ O), 148.7 (CHÀ 6 Py), 145.1 (ArCH=CH), 137.0
(CH-4 Py), 132.7 (CH2=CH), 128.3 (CÀ 1), 126.8 (CHÀ 5 Py), 123.7
(CHÀ 6), 122.9 (CHÀ 3 Py), 118.6 (ArCH=CH), 118.4 (CH2=CH), 112.7
(CHÀ 5), 110.5 (CHÀ 2), 69.7 (OCH2), 56.0 (OCH3). IR (νmax): 601, 616,
679, 687, 743, 789, 811, 838, 924, 941, 993, 1013, 1024, 1035, 1050,
1095, 1141, 1155, 1209, 1237, 1250, 1257, 1265, 1323, 1418, 1510,
1571, 1591, 1661, 2831, 2883, 2962, 2984, 2998, 3010, 3052, 3078,
3310. UV/Vis (25 μM in MeOH): 254 (0.1937), 267 (0.2221), 364
(0.4201). HRMS (ESI+): calcd. for C18H18NO3 [M+H]+296.1287,
found 296.1282.
(Z)-3-(4-(allyloxy)-3-methoxyphenyl)-1-phenylprop-2-en-1-one
((Z) 11e). Following the general procedure D, (Z) 8j (136 mg,
0.490 mmol), PhMgCl (2.0 M in THF, 0.75 mL, 1.47 mmol) in dry THF
°
(5 mL) was reacted for 2 h at À 30 C. After workup and chromatog-
raphy (PE/EtOAc 10:1) the desired compound was afforded as
bright yellow oil (115 mg, 79%). Rf 0.82 (PE/EtOAc 6:4). 1H NMR
(300 MHz, CDCl3) δ=8.03–7.92 (m, 2H, 2×CH Ph), 7.57–7.47 (m, 1H,
CH Ph), 7.47–7.35 (m, 2H, 2×CH Ph), 7.25 (d, J=1.9, 1H, CHÀ 2), 7.02
(dd, J=8.4, 2.0, 1H, CHÀ 6), 6.92 (d, J=13.0, 1H, ArCH=CH), 6.76 (d,
J=8.3, 1H, CHÀ 5), 6.55 (d, J=12.9, 1H, ArCH=CH), 6.04 (ddt, J=
17.4, 10.6, 5.4, 1H, CH2=CH), 5.37 (dq, J=17.3, 1.6, 1H, CHtransH=CH),
5.27 (dq, J=10.5, 1.5, 1H, CHcisH=CH), 4.59 (dt, J=5.4, 1.5, 2H,
OCH2), 3.75 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3) δ=194.4 (C=O),
148.9 (CÀ O), 148.7 (CÀ O), 140.1 (ArCH=CH), 137.7 (CÀ C=O), 133.0
(CH Ph), 132.9 (CH2=CH), 128.8 (2×CH Ph), 128.5 (2×CH Ph), 128.3
(CÀ 1), 124.1 (ArCH=CH), 123.9 (CHÀ 6), 118.2 (CH2=CH), 113.0 (CHÀ 2),
112.4 (CHÀ 5), 69.6 (OCH2), 55.8 (OCH3). IR (νmax): 617, 689, 699, 753,
806, 996, 1004, 1016, 1137, 1221, 1256, 1507, 2934, 3004, 3059. UV/
Vis (25 μM in MeOH): 260 (0.3552), 356 (0.3369).
Photoisomerization studies. 70 mM solutions of the synthesized
compounds in CD3OD were exposed to different light sources
1
(300 nm, 350 nm) and H NMR spectra were registered over time
(E)-3-(4-(allyloxy)-3-methoxyphenyl)-1-(5-bromothiophen-2-yl)
prop-2-en-1-one (11f). To a solution of 2-bromothiophene (400 μL,
4.13 mmol) in dry THF (18.5 mL) was added drop-wise nBuLi (1.6 M
until the photostationary state was reached (15 min, 30 min,
60 min, 90 min, and 120 min). The (E)/(Z) ratio was determined by
integration.
°
in hexane, 2.1 mL, 3.30 mmol) at À 78 C under Ar. After 1 h, part of
the resulting solution (~0.16 M, 9.0 mL, 1.44 mmol) was transferred
Determination of the quantum yield. Solutions of (E) 8c, (E) 8h,
(E) 11a, and (Z) 11a in CDCl3 were precisely prepared (ca. 70 mM,
[P0]) and exposed for 60 s and 120 s at 350 nm. The (E)/(Z) ratio was
determined by integration and these values were used to
determine the concentration of the stating isomer after the given
amount of time [Pt]. Using the following equation the quantum
yield (Φ) was calculated as average of the values determined after
60 s and 120 s of irradiation.
°
into an empty 2-neck flask placed at À 78 C under Ar. Then a
solution of (E) 8j (200 mg, 0.721 mmol) in dry THF (5 mL) was
added drop-wise and the mixture was reacted for 3 h allowing the
temperature to warm up. The mixture was poured into NH4Cl
saturated aq. solution (15 mL) and extracted with EtOAc (3×15 mL).
The organic layer was washed with brine and dried over Na2SO4.
After filtration and evaporation of the solvent, the crude was
purified by chromatography (PE/EtOAc 85:15) to give the desired
product as yellow solid (163 mg, 60%). Rf 0.25 (PE/EtOAc 85:15).
V
� ¼ ð½P0� À ½Pt�Þ
qðn;pÞ � t
1
°
m.p. 103.5–104.3 C. H NMR (300 MHz, CDCl3) δ=7.78 (d, J=15.4,
1H, ArCH=CH), 7.59 (d, J=4.1, 1H, CHÀ 3 thienyl), 7.19 (dd, J=8.3,
1.7, 1H, CHÀ 6), 7.17 (d, J=15.5, 1H, ArCH=CH), 7.15–7.11 (m, 2H,
CH-4 thienyl+CHÀ 2), 6.89 (d, J=8.3, 1H, CHÀ 5), 6.08 (ddt, J=17.2,
10.6, 5.4, 1H, CH2=CH), 5.43 (dq, J=17.3, 1.6, 1H, CHtransH=CH), 5.32
Where [P0] and [Pt] are the molar concentrations of the starting
isomer at 0 s and at time t, V is the volume of the irradiated
Eur. J. Org. Chem. 2021, 1737–1749
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© 2021 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202100064
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Acknowledgements
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Conflict of Interest
The authors declare no conflict of interest.
Keywords: Amides
·
Biomass
·
Isomerization
·
Natural
products · Photochemistry
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Manuscript received: January 21, 2021
Revised manuscript received: March 1, 2021
Accepted manuscript online: March 2, 2021
Eur. J. Org. Chem. 2021, 1737–1749
www.eurjoc.org
1749
© 2021 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH