E, Z -Selectivity in the reductive cross-coupling of two benzaldehydes to stilbenes under substrate control

Article abstract of DOI:10.1039/d0ob01139h

Unsymmetrical E- and Z-stilbenes can be synthesized from two differently substituted benzaldehydes in a MesP(TMS)Li-promoted reductive coupling sequence. Depending on the order of addition of the two coupling partners, the same olefin can be produced in either E- or Z-enriched form under identical reaction conditions. A systematic study of the correlation between the stereochemical outcome of the reaction and the substitution pattern at the two aldehydes is presented. The results can be used as guidelines to predict the product stereochemistry. This journal is

Full text of DOI:10.1039/d0ob01139h

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E, Z - Selectivity in the reductive cross-coupling of two
benzaldehydes to stilbenes under substrate control
Nicolas D´Imperio, Anna I. Arkhypchuk and Sascha Ott *
Received 00th January 20xx,
Accepted 00th January 20xx
Unsymmetrical E- and Z-stilbenes can be synthetized from two differently substituted benzaldehydes in a MesP(TMS)Li-
promoted reductive coupling sequence. Depending on the order of addition of the two coupling partners, the same olefin
can be produced in either E- or Z-enriched form under identical reaction conditions. A systematic study of the correlation
between the stereochemical outcome of the reaction and the substitution pattern at the two aldehydes is presented. The
results can be used as guidelines to predict product stereochemistry.
DOI: 10.1039/x0xx00000x
Introduction
The stereochemistry of carbon-carbon double bonds is of
crucial importance for the chemical properties of alkenes1-4 and
their function in nature5 and commodity chemicals.6, 7 Thus,
developing methods to selectively access either the E- or Z-
isomer has been, and still is, at the heart of organic chemistry.
A plethora of protocols for synthetizing olefins is available,8, 9
among which the most widely used are Wittig,10, 11 Horner-
Wadsworth-Emmons (HWE),12 Peterson,13 olefin metathesis14,
15
17
and cross-coupling reactions.16,
In classical carbonyl
Scheme 1: E- and Z-stereoselective Wittig reactions of ortho-substituted
benzaldehydes and phosphonium ylides. X = OMe, Br.
olefinations mediated by phosphorus compounds,9 namely
Wittig,18 Horner-Wittig19 and HWE20 reactions, the factors that
influence the E- and Z-stereoselectivity are well understood and
can be controlled, for example, by the nature of the phosphorus
reagent, the base or the solvent.21-26 It should be pointed out
that in almost all cases the stereochemical outcome of the
reaction is determined by the reaction conditions or type of
olefinating reagent, and is usually not influenced by the nature
of the aldehyde substrates. To the best of our knowledge, the
only example in which a substituent at the aldehyde has been
reported to influence the E-Z ratio of a Wittig olefination is in
case of benzaldehydes with heteroatoms such as halides or
ethers in ortho-position. This so-called “ortho-effect”27, 28 can be
exploited to synthetize enriched Z-stilbenes, as shown by
Gilheany and co-workers.29-31 As shown in Scheme 1a, the
reaction gives rise to higher proportions of Z-alkene when the
aldehyde has an ortho-substituent. In contrast, an ortho-
substituent on the phosphonium salt has no such effect, and the
thermodynamically more stable E-stilbene is formed (Scheme
1b). From a mechanistic viewpoint, the Z-directing effect of the
ortho-substituent arises from a secondary bonding interaction
between the phosphorus and the ortho-heteroatom during the
transition state.29, 31
In recent years, we have been interested in developing new
phosphorus mediated cross-coupling reactions of carbonyl
compounds to olefins.32-35 In one of our latest work, we have
been able to couple two different benzaldehydes selectively to
unsymmetrical 1,2-disubstituted stilbenes via phosphaalkene
(
2
) and phosphinate (
pot reaction, a first benzaldehyde
phosphaalkene which proceeds under Umpolung of the
carbonyl-carbon. Subsequent activation of the phosphaalkene
provides phosphinates which react with the second aldehyde
to form the unsymmetrical stilbene. In contrast to McMurry
3
) intermediates (Scheme 2).34 In this one-
is converted to a
A
2
3
B
chemistry that is traditionally used for the reductive coupling of
carbonyl compounds to alkene, the reaction proceeds by an
ionic mechanism, and allows the controlled preparation of
unsymmetrical alkenes owing to the successive addition of the
two aldehydes to the reaction. While developing this method,
an interesting trend in the E-Z ratio of the formed products
attracted our attention. Herein, we report on a systematic study
of how the stereochemical outcome of the cross-coupling
reaction can be altered simply by choosing the order of addition
of the two benzaldehyde substrates. As will be shown by various
examples, the reactions proceed to a large extent under
substrate control, with electronic effects as well as the presence
of ortho-substituents determining the product stereochemistry.
Department of Chemistry, Ångstrꢀm Laboratory, Uppsala University, Box 523, 75120
Uppsala, Sweden
*sascha.ott@kemi.uu.se
Electronic Supplementary Information (ESI) available: 1H NMR spectra of all isolated
olefinic products. See DOI: 10.1039/x0xx00000x
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DOI: 10.1039/D0OB01139H
Scheme 2: One-pot phosphorus mediated cross-coupling of two different benzaldehydes to E- and Z-olefins.34
emerges from a comparison between entries 4-6. With an
electron deficient aldehyde (entry 4, X = Br), the reaction
forms exclusively the E-isomer. This selectivity is however
Results and Discussion
A
The influence of the aldehydes’ substituents on the
stereochemical outcome of the reaction was tested and the
existence of two separate effects in the coupling procedure was
noticed. A first effect is of electronic nature, and best studied
when the aldehydes are substituted in the para position; a
second one can be observed in the reaction of ortho-substituted
benzaldehydes. Both effects will be discussed separately first,
and then in combination. To understand the role that the
electronic nature of the two benzaldehyde substrates have on
the E-Z ratio of the newly formed double bond, a series of
reactions between para-substituted benzaldehydes was
investigated. The results of the study are summarized in Table
1.
compromised by moving to more and more electron-rich
aldehydes
A. Changing the X group from the electron-
withdrawing (EWG) bromide to the electron-donating (EDG)
methyl moiety (entry 5) leads to a 1:1 mixture of E- and Z-
stilbenes, and in case of the most electron-rich para-methoxy-
substituted aldehyde
A (entry 6), the Z-isomer is observed in a
roughly 2:1 ratio. Entries 7-10 describe the results of homo-
coupling experiments which in essence further corroborate the
trends observed in entries 1-6. When X = Y = Br (entry 7), the
reaction is, as expected, E-selective as a result of the EWG in
aldehyde A. Alternative EWGs on aldehyde A such as a nitro-
group have previously been shown to also give exclusively the
E-isomer.34 However, with increasing electron-donating
character of the para-substituent in aldehyde
percentages of Z-isomers are formed.
A, higher
Table 1: E- and Z-stilbenes from the coupling of two para-substituted
benzaldehydes.
. Reaction conditions as in Scheme 2. E/Z ratios are determined from isolated
stilbenes.
X = H, Br, Me, OMe on aldehyde A. Y = H, Br, Me, OMe on aldehyde
B
Entries 11-14 illustrate the significance of the effects that are
described herein, and ways to exploit them for the preferential
preparation of E- or Z-isomers. Reactions 11-12 and 13-14
employ the same starting materials under identical conditions,
but exhibit a dramatic difference in E-Z selectivity. When
aldehyde
A carries an EWG (X = Br, entries 11 and 13), only the
E-olefins are formed. Changing the order of addition turns the
Entry
Aldehyde A
Aldehyde B
Isolated yield, %
E-Z ratio
substrates with an EDG (X = Me (entry 12) and X = OMe (entry
1
2
3
H
H
H
Br
Me
OMe
46
52
75
70/30
75/25
87/13
14)) into aldehyde
A, leading to the opposite preferential
stereoselectivity with the Z-isomers becoming the predominant
forms.
Summarizing the results from Table 1, it is clear that the
4
5
6
Br
Me
OMe
H
H
H
45
39
57
100/0
52/48
38/62
electronic nature of aldehyde
alkene stereochemistry, while that of aldehyde
E-alkenes are exclusively formed when aldehyde
deficient, while Z-alkenes become the major product for
electron-rich aldehydes . This trend can be observed in a study
where aldehyde is kept constant (for this study a para-Br) and
aldehyde varied. In entry 7, only the E-isomer is formed due
to the use of an EWG substituent on aldehyde . With electron-
A
has a great influence on the
is negligible.
is electron-
B
A
7
8
9
Br
H
Me
OMe
Br
H
Me
OMe
58
52
44
40
100/0
75/25
69/31
50/50
A
10
B
11
12
13
14
Br
Me
Br
Me
Br
OMe
Br
32
74
35
48
100/0
49/51
100/0
30/70
A
A
neutral benzaldehyde as first coupling partner (entry 1), 30% of
Z-isomer is generated. When a fairly good EDG like p-CH3 (entry
12) is used, the reaction forms E- and Z-isomers in an almost 1:1
ratio. Ultimately, with the stronger EDG p-OMe (entry 14), the
E/Z ratio is 30/70. Plotting the proportion of Z-selectivity versus
OMe
As shown in Table 1, entries 1-3, the electronic nature of the
para-substituent on aldehyde does not influence the outcome
B
of the reaction to a great extent, as all three reactions
the Hammett parameter of the substituents on aldehyde
A
predominantly form E-enriched products. A different picture
yields a straight line (see SI, Fig. S33), suggesting that it may be
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possible to predict product stereochemistry for new Consequently, both reactions give rise to predVoiemwiAnraticnletlOynlinZe-
DOI: 10.1039/D0OB01139H
combinations of reactants in the future.
isomer.
The results presented in Table 1 nicely illustrate the strength of The above data show that the ortho-effect29 is an important
this procedure: the same olefin can be synthetized in higher E- aspect to consider when coupling two benzaldehydes. ortho-
or Z- form only depending on the order of addition of the two Substituents on aldehyde
aldehydes during the sequence. The opportunities that the those on aldehyde are largely of electronic nature, and thus
method offers are greater the higher the electronic difference follow the trends from Table 1. As a result, it is possible to also
between the two benzaldehydes. direct the synthesis of specific stilbene with ortho-
B exhibit a Z-directing effect, while
A
a
Following the study on electronic effects, and inspired by the Z- substituents towards one or the other isomer by choosing the
directing ortho-effect described by Gilheany and co-workers,29, right order of addition of the two aldehydes. For example, when
31
a series of experiments with different ortho-substituted comparing entries
intentionally be produced either with 100 % E-selectivity, or in
Entries 1-3 describe reactions where the ortho-substitution is the Z-enriched form as 1:2 isomeric mixture.
on aldehyde . In all such cases, the Z-olefins are formed as the Summarizing the findings above, it is the electronic nature of
major products. No influence from the electronic nature of the aldehyde and the ortho-effect of aldehyde that determine
Y group on aldehyde is noticeable, and the E-Z ratio is similar the isomeric preference of the reaction. Depending on the exact
in all three cases. Entries 4-6 show examples in which the ortho- structure of the starting aldehydes, the two effects can oppose
substitution is on aldehyde . The stereochemical outcome is or support each other, and can be used to control and predict
1 and 4, ortho-bromo-stilbene can
benzaldehydes was performed (Table 2).
B
A
B
B
A
opposite compared to that in entries 1-3, and the E-isomer is product stereochemistry. In certain combinations, changing the
the predominant form. When X = Br (entry 4), the reaction is order of addition can have striking effects. One such example is
100% E-selective while with EDG moieties (entries 5 and 6), a illustrated in the coupling of p-methoxybenzaldehyde with o-
certain percentage of Z-isomer is formed. These trends thus bromobenzaldehyde (Scheme 3). If the former is used as
mirror the findings from Table 1, and no ortho-effect can be aldehyde
established for aldehydes predominantly due to the ortho-effect of aldehyde
, both of which are Z-directing (Scheme 3a).
A
and the latter as aldehyde
B, the Z-alkene is formed
A
.
B
and the
Entries 7-9 show examples of homocoupling reactions between EDG on aldehyde
ortho-substituted benzaldehydes. When X = Y = Br (entry 7), the
reaction forms preferentially the E-isomer. This result has to be
viewed in context of entry 1 and 4, in which the ortho-bromide
A
is Z-directing for aldehyde
B and E-directing for aldehyde A,
respectively. The two effects are thus working in opposite
Table 2: E- and Z-stilbenes by the coupling of two ortho-substituted
benzaldehydes. = H, Br, Me, OMe on aldehyde = H, Br, Me, OMe on aldehyde
. Reaction conditions as in Scheme 2. E/Z ratios are determined from isolated
stilbenes.
X
A. Y
B
Entry
Aaldehyde A Aldehyde B Isolated yield, %
E-Z ratio
1
2
3
H
H
H
Br
Me
OMe
51
38
67
33/67
34/66
41/59
4
5
6
Br
Me
OMe
H
H
H
43
76
57
100/0
71/29
75/25
7
8
9
Br
Me
OMe
Br
Me
OMe
36
33
57
62/38
37/63
36/64
Scheme 3: Example of how the electronic nature of aldehyde A and the ortho-
effect on aldehyde B can be used to direct product isomer distribution.
directions, explaining the observed reaction outcome. With
EDGs (entries 8 and 9), the situation changes, and the ortho-
By reversing the order of addition, the ortho-bromide
substituent now only exerts its electronic EWG effect and is E-
directing, while the methoxy group in para-position in aldehyde
substituent in aldehyde
EDG substituent in aldehyde
B
as well as the electronic effect of the
are both Z-directing.
A
B
has no effect. Consequently, the reaction is 100% E-selective
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(Scheme 3b). The examples in Scheme 3c and 3d follow the same
rational. In the coupling of electron-rich aldehyde with a
morpholino group in the para-position and o-
bromobenzaldehyde as aldehyde , both substituents are Z-
directing. Conversely, with a reversed order of addition of the
two coupling partners, the opposite isomer is predominately
formed (Scheme 3d).
Experimental section
Materials and methods:
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DOI: 10.1039/D0OB01139H
A
The first half of the reaction up to the addition of MeOH was
carried out in a glove box while the second part can be
conducted using regular Schlenk techniques. Glassware was
flame-dried, and aldehydes dried/distilled prior to use. THF and
Et2O were freshly distilled over Na/benzophenone under
nitrogen. MesP(TMS)2 was synthetized according to literature
procedures.38 tBuOOH was dried with an azeotrope distillation
of water and benzene from a commercial water solution of the
B
Conclusions
E- and Z-enriched stilbenes can be synthesized by the coupling
of two differently substituted benzaldehydes. Owing to the
sequential addition of the two coupling partners at different
stages of the sequence, different E- and Z-directing effects on
the two aldehydes can be exploited. Chart 1 represents a
practical tool to predict which combination of substituents can
be used to direct the synthesis towards E- or Z-enriched
stilbenes. In the left column, substrate combinations that give
rise to Z-enriched stilbenes are depicted. These contain
t
peroxide. LiOEt and BuOK were both used as a commercially
available 1M solution in THF. All the carbonyl compounds are
commercially available. NMR spectra were recorded on a JEOL
(400YH magnet) Resonance 400 MHz spectrometer. Chemical
shifts (δ) are reported in ppm and coupling constants J in Hz. 1H
NMR and 13C NMR chemical shifts are referenced to the residual
protic solvent signal and 31P NMR spectra externally to 85%
H3PO4(aq). High-resolution mass spectra (HR-MS) were
recorded on a Bruker QTOF spectrometer.
examples where aldehyde
A has an EDG, or where aldehyde B
Preparation of MesP(Li)TMS
features an ortho-substituent. Conversely, as summarized in the
right column, E-stilbenes are formed from electron-deficient To a solution of MesP(TMS)2 (1eq, 1.60 g, 5.4 mmol) in 40 mL of
aldehydes , irrespective of the structure of aldehyde . None dry THF was added a 1M THF solution of LiOEt (1eq) at room
A
B
of these opportunities are available with related carbonyl- temperature. The reaction mixture was stirred at ambient
carbonyl cross couplings such as the McMurry reaction, or also temperature for 4 hours until full conversion of the starting
more recent reports on the topic including transition-metal material to MesP(Li)TMS
catalyzed variants.36 One limitation of the procedure, though, is typical P NMR shift (-187 ppm). The solvent was removed under
the incompatibility of the procedure for the coupling of reduced pressure to afford MesP(Li)TMS as an orange oil
aldehydes with acidic protons due to acid-base chemistry with without further purification. Dry Et2O was added and the yellow
phosphorus based reagents and . The isolated yields solution was stored in the Glove box until further use for up to
1 was achieved, as judged from its
1
1
3
presented herein range from 32 to 75%, depending on the exact one month without visible changes.
nature of the substituents and the reactivity they impose. While Detailed general procedure for the coupling of two aldehydes to
being admittedly modest, it is important to remember that stilbenes (Scheme 2)
these yields are isolated yields of one-pot coupling reactions. As
To a yellow solution of 1 (1 eq, 351 mg, 1.52 mmol) in 15 mL dry
such, they compare favorably with the overall yields of 2-3 step
synthetic procedures that are typical in Wittig-type
olefinations.9, 37 We therefore believe that the results presented
herein can be useful in the preparation of pharmaceutically
relevant compounds, which is subject of on-going efforts in our
group.
Et2O was added 0.9 eq of a first aldehyde (RCHO, R = Ph, table 1
entry 8; 0.9 eq, 145 mg, 1.37 mmol) at ambient temperature;
upon this addition, reaction mixture changes immediately from
bright yellow to a pale limpid yellow solution. The formation of
the phosphaalkene
2
was monitored by 31P NMR using an
external C6D6 standard. After complete formation, achieved
within a few minutes, 0.2 mL of MeOH was added at room
temperature with stirring. Upon addition of MeOH, the reaction
mixture becomes immediately turbid. After 5 minutes, 1.2 eq of
tBuOOH were added to the reaction mixture at room
temperature; no changes are visible after addition of the
oxidant. The reaction was monitored by 31P NMR. Complete
conversion to the desired phosphinate intermediate 3 is usually
achieved within 5 minutes. The solvent was removed under
vacuum and freshly distilled THF (15 mL) was added under an
Argon flow; the color of the reaction mixture at this stage is pale
yellow. 0.9 eq of a second aldehyde (RCHO, R = Ph, table 1 entry
8; 0.9 eq, 145 mg, 1.37 mmol) were added to the reaction
mixture, followed by 1.5 eq of a 1M THF solution of tBuOK; upon
addition of the base, the mixture changes to a deep and limpid
orange color. The reaction mixture was stirred at room
Chart 1: X = EDG, EWG, H; substitution on the first aldehyde. Y = EDG, EWG,
H; substitution on the second coupling partner.
temperature until phosphinate
3
is fully consumed. After
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completion of the reaction, water was added to the mixture. reported literature values.41 The E/Z ratio was determined
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DOI: 10.1039/D0OB01139H
The aqueous phase was extracted with Et2O. The organic phase based on the characteristic signals of the pCH3 of the two
was dried over MgSO4, and the solvent removed under reduced isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ = 2.36 (s, CH3 for the
pressure to afford the crude product. The olefinic product was E-product), 2.30 (s, CH3 for the Z-product). Signals of the E-
purified via silica gel column chromatography with a mixture of isomer: 7.51-7.49 (m, 2H), 7.42-7.40 (m, 2H), 7.38-7.33 (m, 2H),
5% of EtOAc in heptane. Isolated yield: 130 mg, 52%.
7.27-7.22 (m, 2H), 7.13-7.07 (m, 3H), 2.36 (s, 3H). Signals of the
Z-isomer: 7.17-7.11 (m, 7H), 7.02 (d, J = 7.9 Hz, 2H), 6.55 (s, 2H),
2.30 (s, 3H).
Upscaling the reaction to gram scale (Scheme 2)
(E-Z) 1-methoxy-4-styrylbenzene (table 1, entry 3)
To a yellow solution of 1 (1 eq, 932 mg, 4.05 mmol) in 25 mL dry
Et2O was added 0.9 eq of a first aldehyde (RCHO, R = p-CH3-Ph,
Table 1, entry 12; 0.9 eq, 437 mg, 3.64 mmol) at ambient
temperature; upon this addition, the reaction mixture changes
immediately from bright yellow to a pale limpid yellow solution.
After stirring at ambient temperature for 5 minutes, 1 mL of
MeOH was added, upon which the reaction mixture turns turbid
immediately. After 5 minutes, 1.2 eq of tBuOOH were added at
room temperature, resulting in an exothermic reaction. The
reaction was monitored by 31P NMR. Complete conversion to
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 75%, 96 mg, pale yellow solid.
Analytical data of the compounds are in agreement with the
reported literature values.41 The E/Z ratio was determined
based on the characteristic olefinic signals of the two isomers.
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.06 (d, 3J = 16.3 Hz, CH for
the E-product), 6.97 (d, 3J = 16.3 Hz, CH for the E-product), 6.53
3
(d, J = 12.2 Hz, CH for the Z-product), 6.49 (d, J = 12.2 Hz, CH
the desired phosphinate intermediate
3 is achieved within 5
for the Z-product). Signals of the E-isomer: 7.49-7.44 (m, 4H),
7.35-7.32 (m, 2H), 7.27-7.23 (m, 1H), 7.06 (d, J = 16.3 Hz, 1H),
6.97 (d, 3J = 16.3 Hz, 1H), 6.95-6.87 (m, 2H), 3.82 (s, 3H). Signals
of the Z-isomer: 7.27-7.16 (m, 7H), 6.76-6.73 (m, 2H), 6.53 (d, 3J
= 12.2 Hz, 1H), 6.49 (d, 3J = 12.2 Hz, 1H), 3.78 (s, 3H).
(E)-1-bromo-4-styrylbenzene (table 1, entry 4)
3
minutes. The solvent was removed under vacuum and freshly
distilled THF (25 mL) was added under an Argon flow; the color
of the reaction mixture at this stage is pale yellow. 0.9 eq of a
second aldehyde (RCHO, R = p-Br-Ph, Table 1, entry 12; 0.9 eq,
637 mg, 3.63 mmol) were added to the reaction mixture,
followed by 1.5 eq of a 1M THF solution of tBuOK; upon addition
of the base, the mixture changes to a deep and limpid orange
color. Also in this case, the reaction is slightly exothermic. The
reaction mixture was stirred at room temperature until full
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as pure E-olefin,
yield 45%, 87 mg, colorless solid. Analytical data of the
compound are in agreement with the reported literature
values.39 1H NMR (CDCl3, 400 MHz, 300K) δ = 7.53 – 7.44 (m, 4H),
consumption of phosphinate
3. After completion of the
3
reaction, water was added to the mixture. The aqueous phase
was extracted with Et2O. The organic phase was dried over
MgSO4, and the solvent removed under reduced pressure to
afford the crude product. The olefinic product was purified via
silica gel column chromatography with a mixture of 5% of EtOAc
in heptane. Isolated yield: 558 mg, 56%. E/Z ratio: 60/40.
7.40 – 7.32 (m, 4H), 7.32 – 7.23 (m, 1H), 7.09 (d, J = 16.3 Hz,
1H), 7.02 (d, 3J = 16.3 Hz, 1H).
(E-Z) 1-methyl-4-styrylbenzene (table 1, entry 5)
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 39%, 47 mg, white solid.
Analytical data of the compounds are in agreement with the
reported literature values.41 The E/Z ratio was determined
based on the characteristic signals of the pCH3 of the two
isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ = 2.36 (s, CH3 for the
E-product), 2.30 (s, CH3 for the Z-product). Signals of the E-
isomer: 7.51-7.49 (m, 2H), 7.42-7.40 (m, 2H), 7.38-7.33 (m, 2H),
7.27-7.22 (m, 2H), 7.13-7.07 (m, 3H), 2.36 (s, 3H). Signals of the
Z-isomer: 7.17-7.11 (m, 7H), 7.02 (d, J = 7.9 Hz, 2H), 6.55 (s, 2H),
2.30 (s, 3H).
NMR Spectroscopic data and list of olefins
(E-Z) 1-bromo-4-styrylbenzene (table 1, entry 1)
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E -
and Z-olefins with a total yield of 46%, 72 mg, colorless solid.
Analytical data of the compounds are in agreement with the
reported literature values.39, 40 The E/Z ratio was determined
based on the characteristic olefinic signals of the two isomers.
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.02 (d, 3J = 16.3 Hz, CH for
the E-product), 6.63 (d, 3J = 12.2 Hz, CH for the Z product), 6.50
(E-Z) 1-methoxy-4-styrylbenzene (table 1, entry 6)
The product was purified via silica gel column chromatography
with a mixture of 6% of EtOAc in heptane and it was isolated as
a mixture of E- and Z-olefins with a total yield of 57%, 73 mg,
pale yellow solid. Analytical data of the compounds are in
agreement with the reported literature values.41 The E/Z ratio
was determined based on the characteristic olefinic signals of
the two isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.06 (d, 3J
= 16.3 Hz, CH for the E-product), 6.97 (d, 3J = 16.3 Hz, CH for the
E-product), 6.53 (d, 3J = 12.2 Hz, CH for the Z-product), 6.49 (d,
3J = 12.2 Hz, CH for the Z-product). Signals of the E-isomer: 7.49-
3
(d, J = 12.2 Hz, CH for the Z-product). Signals of the E-isomer:
7.53 – 7.44 (m, 4H), 7.40 – 7.32 (m, 4H), 7.32 – 7.23 (m, 1H),
7.09 (d, 3J = 16.3 Hz, 1H), 7.02 (d, 3J = 16.3 Hz, 1H). Signals of the
Z-isomer: 7.38-7.33 (m, 2H), 7.29-7.20 (m, 7H), 6.63 (d, 3J = 12.2
Hz, 1H), 6.50 (d, 3J = 12.2 Hz, 1H).
(E-Z) 1-methyl-4-styrylbenzene (table 1, entry 2)
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 52%, 61 mg, white solid.
Analytical data of the compounds are in agreement with the
3
7.44 (m, 4H), 7.35-7.32 (m, 2H), 7.27-7.23 (m, 1H), 7.06 (d, J =
3
16.3 Hz, 1H), 6.97 (d, J = 16.3 Hz, 1H), 6.95-6.87 (m, 2H), 3.82
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(s, 3H). Signals of the Z-isomer: 7.27-7.16 (m, 7H), 6.76-6.73 (m, 2H), 7.36 – 7.34 (m, 2H), 7.17 – 7.15 (m, 2H), 7.06 (d, J = 16.3
View Article Online
2H), 6.53 (d, 3J = 12.2 Hz, 1H), 6.49 (d, 3J = 12.2 Hz, 1H), 3.78 (s, Hz, 1H), 6.97 (d, 3J = 16.3 Hz, 1H), 2.35 (s,D3OHI:)1.0.1039/D0OB01139H
(E)-1-bromo-4-(4-methylstyryl)benzene (table 1, entry 12)
3H).
(E)-1,2-bis(4-bromophenyl)ethene (table 1, entry 7)
The product was purified via silica gel column chromatography
The product was purified via silica gel column chromatography with 5% EtOAc in heptane and it was isolated as pure E-olefin,
with 5% EtOAc in heptane and it was isolated as pure E-olefin, yield 36 %, 38 mg, white solid. Analytical data of the compound
yield 58%, 56 mg, colorless solid. Analytical data of the are in agreement with the reported literature values.47 1H NMR
compound are in agreement with the reported literature (CDCl3, 400 MHz, 300K) δ = δ 7.46 – 7.44 (m, 2H), 7.40 – 7.38 (m,
3
values.42 1H NMR (CDCl3, 400 MHz, 300K) δ = 7.49 – 7.45 (m, 4H), 2H), 7.36 – 7.34 (m, 2H), 7.17 – 7.15 (m, 2H), 7.06 (d, J = 16.3
7.38 – 7.33 (m, 4H), 7.01 (s, 2H).
(E)-(Z)1,2-diphenylethene (table 1, entry 8)
Hz, 1H), 6.97 (d, 3J = 16.3 Hz, 1H), 2.35 (s, 3H).
(Z)-1-bromo-4-(4-methylstyryl)benzene (table 1, entry 12)
The product was purified via silica gel column chromatography The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E- with 5% EtOAc in heptane and it was isolated as pure Z-olefin,
and Z-olefins with a total yield of 52%, 130 mg, colorless solid. yield 38%, 40 mg, colorless oil. Analytical data of the compound
Analytical data of the compound are in agreement with the are in agreement with the reported literature values.47 1H NMR
reported literature values.41 The E/Z ratio was determined (CDCl3, 400 MHz, 300K) δ = δ 7.34 – 7.31 (m, 2H), 7.12 – 7.09 (m,
3
3
based on the characteristic olefinic signals of the two isomers. 4H), 7.04 – 7.02 (m, 2H), 6.57 (d, J = 12.1 Hz, 1H), 6.45 (d, J =
1H NMR (CDCl3, 400 MHz, 300K) δ = 7.11 (s, CH for the E- 12.1 Hz, 1H), 2.31 (s, 3H).
(E)-1-bromo-4-(4-methoxystyryl)benzene (table 1, entry 13)
product), 6.60 (s, CH for the Z-product). Signals of the E-isomer:
1H NMR (CDCl3, 400 MHz, 300K) δ = 7.53-7.50 (m, 4H), 7.38-7.34
(m, 4H), 7.28-7.18 (m, 2H), 7.11 (s, 2H). Signals of the Z-isomer:
1H NMR (CDCl3, 400 MHz, 300K) δ = 7.28-7.18 (m, 10H), 6.60 (s,
2H).
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure E-olefin,
yield 35%, 62 mg, white solid. Analytical data of the compound
are in agreement with the reported literature values.45 1H NMR
(CDCl3, 400 MHz, 300K) δ = 7.47 – 7.41 (m, 4H), 7.36 – 7.31 (m,
(E-Z) 1,2-di-p-tolylethene (table 1, entry 9)
The product was purified via silica gel column chromatography 2H), 7.04 (d, 3J = 16.3 Hz, 1H), 6.93 – 6.85 (m, 3H), 3.82 (s, 3H).
(E)-1-bromo-4-(4-methoxystyryl)benzene (table 1, entry 14)
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 44%, 55 mg, white solid.
Analytical data of the compounds are in agreement with the
reported literature values.43, 44 The E/Z ratio was determined
based on the characteristic signals of the pCH3 of the two
isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ = 2.35 (s, CH3 for the
E-product), 2.30 (s, CH3 for the Z-product). Signals of the E-
isomer: 7.40-7.38 (m, 4H), 7.18-7.14 (m, 4H), 7.03 (s, 2H), 2.35
(s, 6H). Signals of the Z-isomer: 7.16-7.14 (m, 4H), 7.03-7.01 (m,
4H), 6.50 (s, 2H), 2.30 (s, 6H).
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure E-olefin,
yield 14%, 26 mg, white solid. Analytical data of the compound
are in agreement with the reported literature values.45 1H NMR
(CDCl3, 400 MHz, 300K) δ = 7.47 – 7.41 (m, 4H), 7.36 – 7.31 (m,
2H), 7.04 (d, 3J = 16.3 Hz, 1H), 6.93 – 6.85 (m, 3H), 3.82 (s, 3H).
(Z)-1-bromo-4-(4-methoxystyryl)benzene (table 1, entry 14)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure Z-olefin,
yield 34%, 60 mg, white solid. Analytical data of the compound
are in agreement with the reported literature values.48 1H NMR
(CDCl3, 400 MHz, 300K) δ = 7.36 – 7.32 (m, 2H), 7.17 – 7.10 (m,
(E)-1,2-bis(4-methoxyphenyl)ethene (table 1, entry 10)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure E-olefin,
yield 20%, 40 mg, colorless solid. Analytical data of the
compound are in agreement with the reported literature
values.45 1H NMR (CDCl3, 400 MHz, 300K) δ = 7.44 – 7.39 (m, 4H),
6.92 (s, 2H), 6.90 – 6.85 (m, 4H), 3.82 (s, 6H).
3
3
4H), 6.78 – 6.73 (m, 2H), 6.55 (d, J = 12.2 Hz, 1H), 6.40 (d, J =
12.2 Hz, 1H), 3.78 (s, 3H).
(E-Z) 1-bromo-2-styrylbenzene (table 2, entry 1)
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 51%, 60 mg, pale yellow oil.
Analytical data of the compounds are in agreement with the
reported literature values.49 The E/Z ratio was determined
based on the characteristic olefinic signals of the two isomers.
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.48 (d, 3J = 16.2 Hz, CH for
the E-product), 7.05 (d, 3J = 16.2 Hz, CH for the E-product), 6.70
(Z)-1,2-bis(4-methoxyphenyl)ethene (table 1, entry 10)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure Z-olefin,
yield 20%, 40 mg, colorless solid. Analytical data of the
compound are in agreement with the reported literature
values.46 1H NMR (CDCl3, 400 MHz, 300K) δ = 7.23 – 7.16 (m, 4H),
6.80 – 6.74 (m, 4H), 6.45 (s, 2H), 3.79 (s, 6H).
3
(d, 3J = 12.1 Hz, CH for the Z-product), 6.63 (d, J = 12.1 Hz, CH
(E)-1-bromo-4-(4-methylstyryl)benzene (table 1, entry 11)
The product was purified via silica gel column chromatography for the Z-product). Signals of the E-isomer: δ = 7.67 (dd, J = 7.8,
with 5% EtOAc in heptane and it was isolated as pure E-olefin, 1.6 Hz, 1H), 7.62 – 7.53 (m, 3H), 7.48 (d, 3J = 16.2 Hz, 1H), 7.42 –
yield 32%, 31 mg, white solid. Analytical data of the compound 7.36 (m, 2H), 7.34 – 7.27 (m, 2H), 7.16 – 7.09 (m, 1H), 7.05 (d, 3J
are in agreement with the reported literature values.47 1H NMR = 16.2 Hz, 1H). Signals of the Z-isomer: 7.61-7.55 (m, 1H), 7.20-
3
(CDCl3, 400 MHz, 300K) δ = δ 7.46 – 7.44 (m, 2H), 7.40 – 7.38 (m, 7.13 (m, 6H), 7.10-7.07 (m, 2H), 6.70 (d, J = 12.1 Hz, 1H), 6.63
(d, 3J = 12.1 Hz, 1H).
(E-Z) 1-methyl-2-styrylbenzene (table 2, entry 2)
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The product was purified via silica gel column chromatography 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.52 (d, 3J = 16.5 Hz, CH for
View Article Online
3
DOI: 10.1039/D0OB01139H
with 5% EtOAc in heptane and it was isolated as a mixture of E- the E-product), 7.13 (d, J = 16.5 Hz, CH for the E-product), 6.72
and Z-olefins with a total yield of 38%, 45 mg, colorless oil. (d, 3J = 12.3 Hz, CH for the Z-product), 6.65 (d, J = 12.3 Hz, CH
3
Analytical data of the compounds are in agreement with the for the Z-product). Signals of the E-isomer: 7.63-7.61 (m, 1H),
3
reported literature values.41 The E/Z ratio was determined 7.57-7.55 (m, 2H), 7.52 (d, J = 16.5 Hz, 1H), 7.39-7.35 (m, 2H),
3
based on the characteristic olefinic signals of the two isomers. 7.28-7.25 (m, 2H), 7.13 (d, J = 16.5 Hz, 1H), 7.01-6.97 (m, 1H),
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.01 (d, 3J = 16.3 Hz, CH for 6.93-6.89 (m, 1H), 3.90 (s, 3H). Signals of the Z-isomer: 7.23-7.18
3
3
the E-product), 6.62 (d, J = 12.3 Hz, CH for the Z-product). (m, 7H), 6.91-6.89 (m, 1H), 6.79-6.76 (m, 1H), 6.72 (d, J = 12.3
Signals of the E-isomer: 7.66-7.64 (m, 1H), 7.58-7.56 (m, 2H), Hz, 1H), 6.65 (d, 3J = 12.3 Hz, 1H), 3.83 (s, 3H).
3
(E-Z) 1,2-bis(2-bromophenyl)ethene (table 2, entry 7)
7.43-7.37 (m, 3H), 7.33-7.19 (m, 4H), 7.01 (d, J = 16.3 Hz, 1H),
2.48 (s, 3H). Signals of the Z-isomer: 7.33-7.19 (m, 9H), 6.64 (d,
3J = 12.3 Hz, 1H), 6.62 (d, 3J = 12.3 Hz, 1H), 2.32 (s, 3H).
(E-Z) 1-methoxy-2-styrylbenzene (table 2, entry 3)
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 36%, 55 mg, white solid.
The product was purified via silica gel column chromatography Analytical data of the compounds are in agreement with the
with 6% EtOAc in heptane and it was isolated as a mixture of E- reported literature values.37, 51 The E/Z ratio was determined
and Z-olefins with a total yield of 67%, 65 mg, yellow oil. based on the characteristic olefinic signals of the two isomers.
Analytical data of the compounds are in agreement with the 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.40 (s, CH for the E-
reported literature values.50 The E/Z ratio was determined product), 6.78 (s, CH for the Z-product). Signals of the E-isomer:
based on the characteristic olefinic signals of the two isomers. 7.72 (dd, J = 7.6, 1.6 Hz, 2H), 7.59 (dd, J = 8.1, 1.2 Hz, 2H), 7.40
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.52 (d, 3J = 16.5 Hz, CH for (s, 2H), 7.33 (td, J = 7.6, 1.2 Hz, 2H), 7.17 – 7.12 (m, 2H). Signals
the E-product), 7.13 (d, 3J = 16.5 Hz, CH for the E-product), 6.72 of the Z-isomer: 7.57 – 7.55 (m, 2H), 7.07 – 6.95 (m, 6H), 6.78 (s,
3
3
(d, J = 12.3 Hz, CH for the Z-product), 6.65 (d, J = 12.3 Hz, CH 2H).
(E-Z) 1,2-di-o-tolylethene (table 2, entry 8)
for the Z-product). Signals of the E-isomer: 7.63-7.61 (m, 1H),
3
7.57-7.55 (m, 2H), 7.52 (d, J = 16.5 Hz, 1H), 7.39-7.35 (m, 2H),
The product was purified via silica gel column chromatography
with 5% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 33%, 37 mg, white solid.
Analytical data of the compounds are in agreement with the
reported literature values.52, 53 The E/Z ratio was determined
based on the characteristic signals of the oCH3 of the two
3
7.28-7.25 (m, 2H), 7.13 (d, J = 16.5 Hz, 1H), 7.01-6.97 (m, 1H),
6.93-6.89 (m, 1H), 3.90 (s, 3H). Signals of the Z-isomer: 7.23-7.18
3
(m, 7H), 6.91-6.89 (m, 1H), 6.79-6.76 (m, 1H), 6.72 (d, J = 12.3
Hz, 1H), 6.65 (d, 3J = 12.3 Hz, 1H), 3.83 (s, 3H).
(E) 1-bromo-2-styrylbenzene (table 2, entry 4)
The product was purified via silica gel column chromatography isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ = 2.44 (s, CH3 for the
with 5% EtOAc in heptane and it was isolated as pure E-olefin, E-product), 2.30 (s, CH3 for the Z-product). Signals of the E-
yield 43%, 50 mg, 43%, pale yellow oil. Analytical data of the isomer: 7.62-7.60 (m, 2H), 7.28-7.20 (m, 8H), 2.44 (s, 6H).
compounds are in agreement with the reported literature Signals of the Z-isomer: 7.16-7.14 (m, 2H), 7.11-7.07 (m, 2H),
values.49 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.67 (dd, J = 7.8, 6.96-6.91 (m, 4H), 6.73 (s, 2H), 2.30 (s, 6H).
1.6 Hz, 1H), 7.62 – 7.53 (m, 3H), 7.48 (d, 3J = 16.2 Hz, 1H), 7.42 –
7.36 (m, 2H), 7.34 – 7.27 (m, 2H), 7.16 – 7.09 (m, 1H), 7.05 (d, 3J
= 16.2 Hz, 1H).
(E-Z) 1,2-bis(2-methoxyphenyl)ethene (table 2, entry 9)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 57%, 63 mg, yellow solid.
(E-Z) 1-methyl-2-styrylbenzene (table 2, entry 5)
The product was purified via silica gel column chromatography Analytical data of the compounds are in agreement with the
with 5% EtOAc in heptane and it was isolated as a mixture of E- reported literature values.54 The E/Z ratio was determined
and Z-olefins with a total yield of 76%, 81 mg, colorless oil. based on the characteristic olefinic signals of the two isomers.
Analytical data of the compounds are in agreement with the 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.49 (s, CH for the E-
reported literature values.41 The E/Z ratio was determined product), 6.78 (s, CH for the Z-product). Signals of the E-isomer:
based on the characteristic olefinic signals of the two isomers. 7.67 (dd, J = 7.6, 1.5 Hz, 2H), 7.49 (s, 2H), 7.25-7.21 (m, 2H), 6.99-
1H NMR (CDCl3, 400 MHz, 300K): δ = 7.01 (d, 3J = 16.3 Hz, CH for 6.96 (m, 2H), 6.91-6.86 (m2H), 3.88 (s, 6H). Signals of the Z-
3
the E-product), 6.62 (d, J = 12.3 Hz, CH for the Z-product). isomer: 7.20 – 7.15 (m, 2H), 7.14 (dd, J = 7.6, 1.7 Hz, 2H), 6.92 –
Signals of the E-isomer: 7.66-7.64 (m, 1H), 7.58-7.56 (m, 2H), 6.84 (m, 2H), 6.78 (s, 2H), 6.71 (td, J = 7.5, 1.0 Hz, 2H), 3.83 (s,
3
7.43-7.37 (m, 3H), 7.33-7.19 (m, 4H), 7.01 (d, J = 16.3 Hz, 1H), 6H).
(E-Z) 1-bromo-2-(4-methoxystyryl)benzene (Scheme 3a)
2.48 (s, 3H). Signals of the Z-isomer: 7.33-7.19 (m, 9H), 6.64 (d,
3J = 12.3 Hz, 1H), 6.62 (d, 3J = 12.3 Hz, 1H), 2.32 (s, 3H).
(E-Z) 1-methoxy-2-styrylbenzene (table 2, entry 6)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as a mixture of E-
The product was purified via silica gel column chromatography and Z-olefins with a total yield of 54%, 96 mg, pale yellow solid.
with 6% EtOAc in heptane and it was isolated as a mixture of E- Analytical data of the compounds are in agreement with the
and Z- olefins with a total yield of 57%, 55 mg, yellow oil. reported literature values.55 The E/Z ratio was determined
Analytical data of the compounds are in agreement with the based on the characteristic olefinic signals of the two isomers.
reported literature values.50 The E/Z ratio was determined 1H NMR (CDCl3, 400 MHz, 300K): δ = 7.32 (d, 3J = 16.2 Hz, CH for
based on the characteristic olefinic signals of the two isomers. the E-product), 6.99 (d, 3J = 16.2 Hz, CH for the E-product), 6.62
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3
2
3
4
5
6
7
J. Jiang, C. Zheng, K. Zhu, J. Liu, N. Sun, C. Wang, H. Jiang, J.
Zhu, C. Luo and Y. Zhou, J. Med. Chem.D, O20I:1105.,10538V9,ie/2Dw50A3Ort8iBc-l0e21O513n4l96inH.e
M. Cushman, D. Nagarathnam, D. Gopal, A. K. Chakraborti, C.
M. Lin and E. Hamel, J. Med. Chem., 1991, 34, 2579-2588.
M. Cushman, D. Nagarathnam, D. Gopal, H. M. He, C. M. Lin
and E. Hamel, J. Med. Chem., 1992, 35, 2293-2306.
C. Rivière, A. D. Pawlus and J.-M. Mérillon, Nat. Prod. Rep.,
2012, 29, 1317-1333.
(d, J = 12.1 Hz, CH for the Z-product), 6.50 (d, J = 12.1 Hz, CH
for the Z-product). Signals of the E-isomer: 7.64 (dd, 4J = 7.9, 1.6
Hz, 1H), 7.56 (dd, 4J = 7.9, 1.6 Hz, 1H), 7.51 – 7.46 (m, 2H), 7.32
3
(d, J = 16.2 Hz, 1H), 7.29 – 7.26 (m, 1H), 7.12 – 7.05 (m, 1H),
6.99 (d, 3J = 16.2 Hz, 1H), 6.93 – 6.87 (m, 2H), 3.83 (s, 3H). Signals
of the Z-isomer: 7.61-7.59 (m, 1H), 7.24-7.22 (m, 1H), 7.13-7.06
(m, 4H), 6.73-6.99 (m, 2H), 6.62 (d, 3J = 12.1 Hz, 1H), 6.50 (d, 3J
= 12.1 Hz, 1H), 3.76 (s, 3H).
S. R. Marder, D. N. Beratan and L.-T. Cheng, Science, 1991,
252, 103-106.
B. De Filippis, A. Ammazzalorso, M. Fantacuzzi, L. Giampietro,
(E)-1-bromo-2-(4-methoxystyryl)benzene (Scheme 3b)
C. Maccallini and R. Amoroso, Chem. Med. Chem, 2017, 12
558-570.
,
The product was purified via silica gel column chromatography
with 6% of EtOAc in heptane and it was isolated as pure E-olefin,
yield 34%, 52 mg, pale yellow solid. Analytical data of the
compound are in agreement with the reported literature
values.55 1H NMR (CDCl3, 400 MHz, 300K) δ : 7.64 (dd, J = 7.9,
1.6 Hz, 1H), 7.56 (dd, J = 7.9, 1.6 Hz, 1H), 7.51 – 7.46 (m, 2H),
7.32 (d, J = 16.2 Hz, 1H), 7.29 – 7.26 (m, 1H), 7.12 – 7.05 (m,
1H), 6.99 (d, 3J = 16.2 Hz, 1H), 6.93 – 6.87 (m, 2H), 3.83 (s, 3H).
(E-Z)-4-(4-(2-bromostyryl)phenyl)morpholine (Scheme 3c)
8
9
J. Wang, Stereoselective Alkene Synthesis, Springer-Verlag,
Berlin Heidelberg, 2012.
T. Takeda, Modern Carbonyl Olefination, Wiley-VCH Verlag
GmbH & Co. KGaA, Weinheim, 2004.
4
4
10 G. Wittig and G. Geissler, Liebigs Ann. Chem., 1953, 580, 44-
57.
11 G. Wittig, Science, 1980, 210, 600-604.
12 J. Boutagy and R. Thomas, Chem. Rev., 1974, 74, 87-99.
13 L. F. v. Staden, D. Gravestock and D. J. Ager, Chem. Soc. Rev.,
2002, 31, 195-200.
14 O. M. Ogba, N. C. Warner, D. J. O’Leary and R. H. Grubbs,
Chem. Soc. Rev., 2018, 47, 4510-4544.
3
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as a mixture of E-
and Z-olefins with a total yield of 48%, 93 mg, colorless oil. The
E/Z ratio was determined based on the characteristic olefinic
signals of the two isomers. 1H NMR (CDCl3, 400 MHz, 300K): δ =
6.97 (d, 3J = 16.1 Hz, CH for the E-product), 6.47 (d, 3J = 12.1 Hz,
CH for the Z-product). Signals of the E-isomer: 7.65 – 7.63 (m,
1H), 7.57 – 7.55 (m, 1H), 7.48 – 7.46 (m, 2H), 7.33 – 7.26 (m, 2H),
7.09 – 7.05 (m, 1H), 6.97 (d, 3J = 16.1 Hz, 1H), 6.92 – 6.90 (broad
m, 2H), 3.88 – 3.86 (m, 4H), 3.22 – 3.19 (m, 4H). Signals of the
Z-isomer: 7.59 (dd, J = 7.6, 1.6 Hz, 1H), 7.13 – 7.03 (m, 5H), 6.78
– 6.66 (broad m, 2H), 6.58 (d, 3J = 12.1 Hz, 1H), 6.47 (d, 3J = 12.1
Hz, 1H), 3.85 – 3.70 (m, 4H), 3.17 – 3.07 (m, 4H).
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(E)-4-(4-(2-bromostyryl)phenyl)morpholine (Scheme 3d)
The product was purified via silica gel column chromatography
with 6% EtOAc in heptane and it was isolated as pure E-olefin,
yield 45%, 54 mg, white solid. 1H NMR (CDCl3, 400 MHz, 300K) δ
: 7.65 – 7.63 (m, 1H), 7.57 – 7.55 (m, 1H), 7.48 – 7.46 (m, 2H),
,
3
7.33 – 7.26 (m, 2H), 7.09 – 7.05 (m, 1H), 6.97 (d, J = 16.1 Hz,
1H), 6.92 – 6.90 (broad m, 2H), 3.88 – 3.86 (m, 4H), 3.22 – 3.19
(m, 4H). 13C NMR (CDCl3, 101 MHz, 300K) δ: 137.6, 133.1, 131.1,
130.2, 128.4, 128.0, 127.6, 126.5, 124.0, 115.6, 66.80, 49.1. HR-
MS/QTOF (+): m/z
[C18H19NOBr]+ = 344.0650.
,
=
344.0657 [M+H]+, calculated
7312-7317.
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Conflicts of interest
There are no conflicts to declare.
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Financial support for the work was provided by the Swedish
Research Council and Uppsala University.
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