Transition metal-free diastereospecific synthesis of (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines by reaction of (Z)-1,2-dibromo-3-aryl-2-propenes with catechols

Article abstract of DOI:10.1016/j.tet.2020.131482

A transition metal-free, diastereospecific reaction between substituted (Z)-1,2-dibromo-3-phenyl-2-propenes and substituted catechols using Cs₂CO₃ as a base at 140 °C for 18 h delivers exclusively substituted (Z)-2-arylidene-2,3-dihy

Full text of DOI:10.1016/j.tet.2020.131482

Journal Pre-proof
Transition metal-free diastereospecific synthesis of (Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxines by reaction of (Z)-1,2-dibromo-3-aryl-2-propenes with
catechols
Szymon P. Rekowski, Aabid A. Wani, Jürgen Conrad, Prasad V. Bharatam, Wolfgang
Frey, Uwe Beifuss
PII:
S0040-4020(20)30662-1
https://doi.org/10.1016/j.tet.2020.131482
TET 131482
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 27 April 2020
Revised Date: 31 July 2020
Accepted Date: 4 August 2020
Please cite this article as: Rekowski SP, Wani AA, Conrad Jü, Bharatam PV, Frey W, Beifuss U,
Transition metal-free diastereospecific synthesis of (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines
by reaction of (Z)-1,2-dibromo-3-aryl-2-propenes with catechols, Tetrahedron (2020), doi: https://
doi.org/10.1016/j.tet.2020.131482.
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Graphical Abstract
Leave this area blank for abstract info.
Transition metal-free diastereospecific synthesis of
(Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines by
reaction of (Z)-1,2-dibromo- 3-aryl-2-propenes with
catechols
Szymon P. Rekowski a, Aabid A.Wani b, Jürgen Conrad a, Prasad V. Bharatamb, Wolfgang Frey c, Uwe
Beifuss a*
1

Tetrahedron
journal homepage: www.elsevier.com
Transition metal-free diastereospecific synthesis of (Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxines by reaction of (Z)-1,2-dibromo-3-aryl-2-
propenes with catechols
Szymon P. Rekowski a, Aabid A. Wani b, Jürgen Conrad a, Prasad V. Bharatam b, Wolfgang
Frey c, Uwe Beifuss a,*
a
Bioorganische Chemie, Institut für Chemie, Universität Hohenheim, Garbenstraße 30, D-
70599 Stuttgart, Germany
b
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and
Research (NIPER), Sector 67, S.A.S. Nagar, 160 062, Punjab, India
c
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, D-70569
Stuttgart, Germany
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A transition metal-free, diastereospecific reaction between
substituted
(Z)-1,2-dibromo-3-phenyl-2-propenes
and
substituted catechols using Cs2CO3 as a base at 140 °C for 18
hours delivers exclusively substituted (Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxines in yields up to 89%.
Experiments as well as quantum chemical calculations support
the assumption that the one pot transformation proceeds as an
intermolecular O-allylation/intramolecular O-vinylation.
Available online
Key words:
O-Allylation
O-Vinylation
Benzodioxine
Diastereospecific synthesis
DFT
2009 Elsevier Ltd. All rights reserved
.
*
Corresponding author.
E-mail address: ubeifuss@uni-hohenheim.de (U. Beifuss).
2

1. Introduction
Benzo[1,4]dioxines and 2,3-dihydro[1,4]benzodioxines are important oxygen containing
heterocycles since they exhibit a wide range of biological and pharmaceutical properties [1].
Among the most prominent examples are the mesylate of doxazosin (CARDURA®) (A),
which is used as an antihypertensive agent [2], piperoxan (B) being a potent α-adrenergic
blocking agent [3] and fluparoxan (C) with antidepressant effects [4] (Fig. 1). A number of
2,3-dihydro[1,4]benzodioxines like D, which are derived from isovanillin, are known for their
strong sweetening properties [5]. In addition, there is also a number of naturally occurring
2,3-dihydro[1,4]benzodioxines [6]. The most popular are the diastereomeric flavolignans
silybin A (E) and silybin B (F), isolated from silybum marianum, which are known for their
antihepatotoxic activities [7].
Fig. 1. Examples of biologically active benzo[1,4]dioxine derivatives.
Due to the marked interest in biological active benzo[1,4]-dioxines and 2,3-
dihydrobenzo[1,4]dioxines, a number of synthetic methods for their preparation has been
developed [1,8]. In contrast, the number of synthetic approaches to 2-(ylidene)-2,3-
dihydrobenzo[b][1,4]dioxines is rather limited (Scheme 1) [9]. Most of them are based on
transition metal-catalyzed 6-exo-dig-type cyclizations of 2-[(3-arylprop-2-yn-1-
3

yl)oxy]phenols (Scheme 1). As catalysts, palladium [9a,b], iron [9c], silver [9d] and even
mercury [9e] compounds have found application. Most of them deliver the corresponding
cyclization products with (Z)-configuration around the newly formed exocyclic double bond.
The 2-[(3-arylprop-2-yn-1-yl)oxy]phenols can be synthesized either by Sonogashira coupling
using monoprop-2-ynylated catechols and aryl halides as substrates [9a,e] or by
propargylation of a catechol with the corresponding aryl-substituted propargyl halide under
basic conditions [9b,d,e]. In addition, the palladium-catalyzed reaction between substituted
propargyl carbonates and catechols has also been developed for the synthesis of 2-(ylidene)-
2,3-dihydrobenzo[b][1,4]dioxines [9f] (Scheme 1).
Scheme 1. Different approaches for the synthesis of 2-ylidene-2,3-dihydrobenzo[b][1,4]dioxines.
4

Cu(I)-catalyzed cross-couplings between bisfunctionalized substrates have proven extremely
valuable for the synthesis of a plethora of heterocyclic as well as carbocyclic systems [10].
We could successfully demonstrate that Cu(I)-catalyzed reactions of aromatic biselectrophiles
such as 1,2-dihalobenzenes and ortho-halobenzyl halides with bisnucleophiles allow access to
several carbo- and heterocyclic skeletons [11]. However, Cu(I)-catalyzed cross-couplings are
not restricted to reactions with aryl halides but can also be performed with vinyl halides as
electrophilic substrates [12]. As an example, we reported the Cu(I)-catalyzed reaction
between 1,2-dihalo-2-propenes and 1,3-dicarbonyls which produces trisubstituted furans in a
highly selective and efficient way [13]. Against this background, it was planned to develop a
new approach for the efficient synthesis of 2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxines 3
based on a Cu(I)-catalyzed intermolecular C-allylation/O-vinylation process using 1,2-dihalo-
2-propenes 1 and catechols 2 as substrates. Herein, we disclose our results on the
diastereospecific synthesis of (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3 by
reaction of (Z)-1,2-dibromo-3-aryl-2-propenes (Z)-1 with substituted catechols 2.
2. Results and discussion
2.1. Synthesis
As a model reaction, the transformation between (Z)-1,2-dibromo-3-phenyl-2-propene [(Z)-
1a] [14] and catechol (2a) was chosen. In a first attempt, (Z)-1a and 2a were reacted under
conditions that have been proven successful in a Cu(I)-catalyzed domino intermolecular C-
allylation/O-vinylation reaction established in our laboratory [13]. Accordingly, 1 equiv (Z)-
1,2-dibromo-3-phenyl-2-propene [(Z)-1a] and 6 equiv of catechol (2a) were reacted in the
presence of 10 mol% CuI under basic conditions (4 equiv of Cs2CO3) in DMF at 120 °C for
2.5 h (Table 1, entry 1).
Table 1
Initial experiments for the formation of benzodioxine (Z)-3a under different conditions.a
Entry
2a (equiv) Catalyst
Cs2CO3 (equiv) T (°C)
Yield (Z)-3a
(%)
50
67
29
7
1
2
3
4
5
6
7
6
6
6
6
6
6
6
CuI (10 mol%)b 4c
120
4c
4c
4c
4c
2c
2d
120
100
75
─
─
─
─
─
─
50
─
120
120
67
36
a All reactions were performed with 1 mmol (Z)-1a in 10 mL DMF under argon.
5

b The purity of CuI was >98%.
c The purity of Cs2CO3 was 99%.
d The purity of Cs2CO3 was 99.99%.
To our delight, (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3a] was formed
exclusively in 50% yield under these conditions. Encouraged by this finding the model
reaction was optimized. To verify the role of the CuI as a catalyst, the reaction was run in the
absence of Cu(I) salt. Surprisingly, (Z)-3a was also formed as the sole product and with an
even better yield (67%) (Table 1, entry 2). Next, the impact of the temperature on the yield of
(Z)-3a was studied. For this purpose, the copper-free reaction was run at 100 °C, 75 °C and 50
°C (Table 1, entries 3─5). It could be established that the yields of (Z)-3a decrease
dramatically with decreasing temperatures: at 50 °C, the formation of (Z)-3a could not be
observed. The experiment given in Table 1, entry 6 clearly demonstrated that the excess of
Cs2CO3 could be reduced from 4 equiv to 2 equiv without affecting the yield. To identify
possible effects of transition metal impurities in the Cs2CO3 (99% purity) used, the
transformation was repeated with Cs2CO3 of 99.99% purity (Table 1, entry 7). Since the yield
of (Z)-3a dropped to 36%, it was decided to run the model reaction in the presence of 10
mol% of several transition metal reagents using 2 equiv of Cs2CO3 of 99.99% purity as a
base. The results are given in Table 2.
Table 2
The influence of different transition metal catalysts on the yield of (Z)-3a.a
Entry
1
2
3
4
5
6
7
8
Catalyst
Yield (Z)-3a (%)
CuI
CuBr
Cu(acac)2
Cu(OAc)2
CrCl3 × 6 H2O
Cr(NO3)3 × 9 H2O
Cr2O3
CoCl2 × 6 H2O
CoCl3 × 6 H2O
Co(acac)2
35
36
53
37
35
25
49
35
29
traces
39
31
4
9
10
11
12
13
14
15
16
Fe
FeCl2 × 4 H2O
FeCl3 × 6 H2O
Fe(C2O4) × 2 H2O
FeSO4 × 7 H2O
NiCl2
9
30
30
6

17
18
Pd(OAc)2
Pd(PPh3)4
41
38
a
All reactions
were performed with 1 mmol (Z)-1a, 6 mmol 2a and 2 mmol Cs2CO3 (99.99%) in
10 mL DMF under argon.
In a first set, the reaction was run in the presence of some other Cu(I) and Cu(II) reagents
(Table 2, entries 1─4). Interestingly, the best yield was obtained when the reaction was done
in the presence of 10 mol% Cu(acac)2. With this Cu(II) reagent, (Z)-3a was isolated in 53%
(Table 2, entry 3). Apart from Cu-based reagents, the model reaction was also performed with
a number of Cr(III) reagents (Table 2, entries 5─7), Co(II) and Co(III) reagents (Table 2,
entries 8─10) as well as with elemental iron, Fe(II) and Fe(III) reagents (Table 2, entries
11─15). In addition, NiCl2 (Table 2, entry 16), Pd(OAc)2 and Pd(PPh3)4 (Table 2, entries 17,
18) were tried as catalysts. However, under no circumstances the yield of the model reaction
under transition metal-free conditions could be improved by running the reaction in the
presence of 10 mol% of a transition metal catalyst.
Table 3
Impact of different bases on the outcome of the model reaction under catalyst-free conditions.a
Yield (Z)-3a
Entry Base
(%)
1
2
3
4
5
Cs2CO3
K2CO3
Na2CO3
K3PO4
KOH
67b
39c
12d
tracese
f
─
a All reactions were performed with 1 mmol (Z)-1a, 2 mmol base and 6 mmol 2a in 10 mL DMF under argon.
b The purity of Cs2CO3 was 99%.
c The purity of K2CO3 was 99%.
d The purity of Na2CO3 was 99.5%.
e The purity of K3PO4 was 99.5%.
f The purity of KOH was 85%.
In a next step, the influence of different bases, such as K2CO3, Na2CO3, K3PO4 and KOH, on
the outcome of the model reaction under metal-free conditions was figured out (Table 3). It
was established that Cs2CO3 is by far the best base to facilitate this reaction (Table 3, entry 1;
see also Table 1, entry 2). Finally, the influence of the molar ratio between (Z)-1a and 2a, the
amount of Cs2CO3 and the reaction conditions like reaction time and temperature on the yield
of the model reaction was addressed. First, 1 equiv of (Z)-1a was reacted with 2 equiv of 2a
and 2 equiv Cs2CO3 at different reaction times and reaction temperatures. When the reaction
7

was run at 120 °C for 2.5 h, (Z)-3a was obtained in 59% (Table 4, entry 1). A gradual increase
of reaction time and reaction temperature resulted in an improvement of the yield (Table 4,
entries 1─4). The highest yield (77%) was obtained when the transformation was done at 140
°C for 18 h (Table 4, entry 4). The same yield was achieved when the amounts of 2a and
Cs2CO3 were doubled (Table 4, entry 5). Next, we performed some reactions between 1 equiv
(Z)-1a, 3 equiv 2a and 2 equiv of the base at different reaction temperatures and reaction
times. It was established that the yields of (Z)-3a dramatically decreased with decreasing
temperatures and increasing reaction time (Table 4, entries 6─10). In a final attempt, the
model reaction was run with 2 equiv 2a and 4 equiv Cs2CO3 at 140 °C for 18 h. Under these
conditions, (Z)-3a was isolated in 89% as a single product in diastereomerically pure form.
(Table 4, entry 11).
Table 4
Influence of the molar ratio between (Z)-1a and 2a, the amount of Cs2CO3 and the reaction
conditions on the model reaction.a
Yield (Z)-3a
Entry
2a (equiv)
Cs2CO3 (equiv)
Time (h) T (°C)
(%)
59
65
74
77
77
66
62
71
43
21
89
1
2
3
4
5
6
7
8
2
2
2
2
4
3
3
3
3
3
2
2
2
2
2
4
2
2
2
2
2
4
2.5
2.5
6
18
18
2.5
2.5
4
120
140
140
140
140
140
120
100
90
9
10
11
6
7
18
70
140
a All reactions were performed with 1 mmol (Z)-1a in 10 mL DMF under argon. The purity of Cs2CO3 was 99%.
Encouraged by this result, we embarked on studying scope and limitations of the new method
for the diastereospecific synthesis of (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3.
For this purpose, a number of different (Z)-1,2-dibromo-3-aryl-2-propenes (Z)-1 were reacted
with catechols 2. While the catechols 2a─d were commercially available, the (Z)-1,2-
dibromo-3-aryl-2-propenes (Z)-1a─i had to be synthesized. The preparation of the dibromo
compounds (Z)-1a─i was achieved by a three-step sequence starting from the commercially
available, corresponding aldehydes 4a─i (Scheme 2). Reaction of the aldehydes 4a─i with the
phosphorane 5 [15a,b] according to Thiemann et al. [15c] delivered the corresponding Wittig
8

products 6a─i with yields between 75 and 96%. The Wittig reaction produced predominantly
the α-bromoarylacrylates with (Z)-configuration (Z:E ≥ 4:1). The (Z)- and (E)-diastereomers
can easily be distinguished by 1H NMR spectroscopy. For the (Z)-compounds, 3-H resonates
at chemical shifts δ >8 ppm, while for the (E)-compounds the resonance signal for 3-H is
found at chemical shifts δ <8 ppm [15c]. The diastereomers also differ with respect to the
3
values of their JC=O,
coupling constants which could be determined by HSQMBC
3-H
experiments. For the (Z)-compounds the coupling constants range between 3 and 5 Hz and for
the (E)-isomers the coupling constants are between 7 and 13 Hz [16]. Then, the
diastereomeric mixtures of the α-bromoarylacrylates 6a─i were subjected to reduction to the
corresponding 3-substituted 2-bromopropen-1-ols 7a─i using DIBAL-H as reductant [15d]. At
this stage, minor amounts of the E-isomers of 7a─i were removed by repeated column
chromatography on SiO2. Finally, the diastereomerically pure (Z)-alcohols (Z)-7a─i were
converted into the (Z)-1,2-dibromo-3-aryl-2-propenes (Z)-1a─i with yields up to 91% by using
PPh3/Br2 as reagents [14].
Scheme 2. Synthesis of the substituted 1,2-dibromo-3-aryl-2-propenes (Z)-1a─i.
With the substrates in hand, (Z)-1b─i were reacted with catechols 2 under optimized
conditions. The reaction of the p-alkylaryl substituted (Z)-1,2-dibromo-2-propenes (Z)-1b─d
with catechol (2a) delivered the corresponding (Z)-2-(4-alkylbenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxines (Z)-3b─d in diastereomerically pure form. Best yields were
obtained with (Z)-1,2-dibromo-3p-tolyl-2-propene [(Z)-1b] (88%) (Table 5, entry 1), followed
by (Z)-1,2-dibromo-3-(4-ethylphenyl)-2-propene [(Z)-1c] (77%) (Table 5, entry 2) and (Z)-
1,2-dibromo-3-(4-isopropylphenyl)-2-propene [(Z)-1d] (68%) (Table 5, entry 3) as substrates.
It seems that the size of the p-alkyl substituent has an influence on the yield. Next, the 3-(4-
haloaryl)-substituted 1,2-dibromo-2-propenes (Z)-1e─g were reacted to deliver the (Z)-2-(4-
halobenzylidene)-2,3-dihydrobenzo[b][1,4]benzodioxines (Z)-3e─g with yields between 53
and 63% (Table 5, entries 4─6). When the 3-(m-bromophenyl)-substituted compound (Z)-1h
was employed as substrate, the product (Z)-3h was isolated in comparable yield (55%) than
(Z)-3g (Table 5, entries 6 and 7). The 3-(m-methoxyphenyl)-substituted derivate (Z)-1i
delivered the corresponding product (Z)-3i in 65% yield (Table 5, entry 8). Finally, (Z)-1a
was reacted successfully with 3,4-dichlorocatechol (2b), 3,4-dibromocatechol (2c) and 2,3-
dihydroxynaphthalene (2d) to provide the 6,7-dihalo-2,3-dihydrobenzo[b][1,4]dioxines (Z)-
3j,k and the 2,3-dihydronaptho[2,3-b][1,4]dioxine [(Z)-3l]. It was demonstrated that a range
of (Z)-1,2-dibromo-3-aryl-substituted-2-propenes (Z)-1a─i could be reacted with catechol (2a)
and some catechol derivatives (2b─d) under basic, transition metal-free conditions to give the
9

pure (Z)-2-(arylidene)-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3a─l with yields in the range
between 49 and 89%. When (Z)-1a was treated with 1,2-ethanediol as bisnucleophile under
standard conditions, no transformation could be observed.
Table 5
Substrate scope of the reaction of (Z)-1a─i with 2a─d to the corresponding (Z)-2-benzylidene-
2,3-dihydrobenzo[b][1,4]dioxines (Z)-3b─l under optimized, transition metal-free conditions.a
Entry
R1
Yield (Z)-3 (%)
2
1
2
3
4
5
6
Cl
1f
(Z)-
10

7
8
9
10
11
a All reactions were performed with 1 mmol (Z)-1, 2 mmol 2 and 4 mmol Cs2CO3 (99%) in 10 ml DMF under
argon.
b Reaction was performed with 0.89 mmol (Z)-1i, 1.78 mmol 2a and 3.56 mmol Cs2CO3 (99%) in 10 ml DMF
under argon.
2.2. Structure elucidation
Fig. 2. Some important 1H- and 13C NMR chemical shifts [ppm], 2J- and 3J HMBC correlations from
1-H2 and 3-H of (Z)-3a.
11

Fig. 3. 1D-NOESY spectrum obtained by selective excitation of the signal at δ = 5.51 ppm of (Z)-3a.
H
H
H
3
1
O
O
Fig. 4. 1D-NOESY spectrum obtained by selective excitation of the signal at δ = 4.02 ppm of (Z)-3a.
12

All substrates (Z)-1 and all (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3 were
1
characterized by IR-, H- and 13C NMR spectroscopy as well as mass spectrometry. The
structure elucidation of (Z)-3a─l is mainly based on NMR experiments, including COSY-,
1
HMBC-, HSQC-, HSQMBC- and D NOESY experiments. As an example, signals at δ =
65.88, 144.77, 142.96 and 143.80 ppm in the 13C NMR spectrum of (Z)-3a, which are
assigned unambiguously to C-1, C-2, C-1’’ and C-6’’, respectively, are in accordance with a
2,3-dihydrobenzo[b][1,4]dioxine structure with an exocyclic double bond at C-2 (Fig. 2). This
is supported by the chemical shifts for the allylic protons attached to C-1 and the vinylic
proton at C-3, which resonate as singlets at δ = 4.02 ppm and at δ = 5.11 ppm, respectively. In
case of a 2-benzylbenzo[b][1,4]dioxine with an endocyclic double bond and a benzyl
substituent the protons would be expected to resonate around δ ≈ 5.6 ppm (vinylic proton) and
δ ≈ 3.2 ppm (benzylic protons) [8f]. Unambiguous evidence for the (Z)-configuration of the
1
exocyclic double bond was provided by D NOESY experiments (Figs. 3 and 4). Selective
excitation of the proton attached to C-3 at δ = 5.11 ppm results in an intensity increase of the
signals at δ = 4.02 ppm (1-H2) and δ = 7.71 ppm (2’-H, 6’-H). As expected, excitation of the
two protons attached to C-1 at δ = 4.02 ppm resulted in a strong enhancement of the signal
intensity at δ = 5.11 ppm (3-H). In case of an (E)-configuration no NOE effect between the
protons attached to C-1 and the proton at C-3 would be expected. Strong evidence for the (Z)-
geometry of the exocyclic double bonds came also from the size of the coupling constants 3JC-
1, 3-H. For double bonds with (Z)-configuration the values of this coupling constant are smaller
than 5 Hz while for the corresponding (E)-isomer the values exceed 7 Hz [17]. In all (Z)-2-
3
arylidene-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3a─l, the size of the coupling constants JC-1,
was in the range between 3.5 and 4.5 Hz, which clearly proves the (Z)-geometry of all
3-H
products.
13

Fig. 5. Structure of (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3a], as derived from X-
ray crystal structure analysis.
Unequivocal evidence for the structure of (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine
[(Z)-3a] came from single crystal X-ray diffraction (Fig. 5). The title compound crystallizes
with two independent molecules in the asymmetric unit of the acentric space group P21. Both
conformers show a Z-isomer. The C1-C9 double bond could be clearly identified in both
molecules characterized by distances of 1.325(4) Å and 1.324(4) Å, respectively.
2.3. Reaction mechanism
Scheme 3. Two possible reaction mechanisms: a) the alkene pathway and b) the alkyne pathway.
With regard to the reaction mechanism it is assumed, that the reaction sequence starts with an
intermolecular O-allylation between a 3-aryl-substituted 1,2-dibromo-2-propene (Z)-1 and a
catechol 2 to deliver the corresponding allyl aryl ether (Z)-8 (Scheme 3a). After a second
deprotonation an intramolecular O-vinylation takes place, which results in the highly
diastereospecific formation of the cyclization product,
a
(Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxine (Z)-3. This requires, that the cyclization proceeds with retention
of the configuration of the double bond in (Z)-1. It is also conceivable that under basic
reaction conditions the reaction sequence starts with elimination of HBr from (Z)-1 to form
the aryl propargyl bromide 9 as an intermediate (Scheme 3b). This is followed by an
intermolecular O-propargylation between 9 and a deprotonated catechol 2. After subsequent
deprotonation, the resulting anionic aryl propargyl ether anion of 10 undergoes an
intramolecular 6-exo-dig cyclization which delivers the (Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxine 3 with (Z)-configuration around the exocyclic double bond [18].
14

Scheme 4. Preparation of (Z)-3a by reaction of (3-bromoprop-1-yn-1-yl)benzene (9a) with catechol
(2a) under optimized conditions.
The reaction mechanism via the alkyne 9 (Scheme 3b) cannot be excluded a priori, which was
demonstrated by the outcome of the reaction between phenyl propargyl bromide (9a) and
catechol (2a). When the transformation was run under the conditions optimized for the
reaction between (Z)-1a and 2a, the cyclization product (Z)-3a was isolated as pure (Z)-
diastereomer in 89% yield (Scheme 4). It needs to be highlighted that this experiment clearly
proves that the cyclization of 2-[(3-arylprop-2-yn-1-yl)oxy]phenols can easily be achieved
under transition metal-free conditions (for transition metal-catalyzed cyclizations, see Scheme
1). To decide, whether the reaction proceeds via the alkene pathway (Scheme 3a) or the
alkyne pathway (Scheme 3b) a number of experiments were performed.
15

a) Diastereospecific cyclization of a mixture of (Z)- and (E)-1a
2 equiv 2a,
4 equiv Cs2CO3,
O
O
DMF, 140 °C, 18 h, Ar
Br
Br
+
+
O
O
Br
Br
89%
(Z)-3a
(E)-3a
(E)-1a
(Z)-1a
:
90
92
8
10
:
b) Diastereospecific cyclization of pure (E)-1a
2 equiv 2a,
4 equiv Cs2CO3,
O
O
DMF, 140 °C, 18 h, Ar
Br
Br
+
+
O
O
Br
Br
(Z)-3a
(E)-3a
(E)-1a
(Z)-1a
:
1
0
100
99
:
c) Isomerization experiment of pure (Z)-3a and a mixture of (Z)- and (E)-3a
O
O
4 equiv Cs2CO3,
DMF,140 °C, 18 h, Ar
O
O
+
+
O
O
O
O
93 %
(E)-3a
(Z)-
3a
(Z)-3a
(E)-
3a
:
0
100
92
:
:
0
8
100
92
:
8
Scheme 5. a) Diastereospecific cyclization of a mixture of (Z)- and (E)-1a; b) diastereospecific
cyclization of pure (E)-1a; c) isomerization experiment of pure (Z)-3a and a mixture of (Z)- and (E)-
3a.
First, a 9:1 mixture of (Z)- and (E)-1,2-dibromo-3-phenyl-2-propene [(Z)-1a and (E)-1a] [19]
was reacted under standard conditions (Scheme 5a). This experiment delivered 89% of a 92:8
mixture of (Z)- and (E)- 2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3a and (E)-3a].
This outcome supports that the cyclization of the substrates with (Z)-configuration proceeds
diastereospecifically via the alkene pathway (Scheme 3a) with retention of the configuration
of the double bond. Obviously, this result offers also the opportunity to synthesize
diastereoselective pure (E)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines (E)-3 by employing
the corresponding substrates 1 with (E)-configuration. To prove this hypothesis, it was
decided to synthesize diastereomerically pure (E)-1a and to react it under standard conditions.
For this purpose, pure (Z)-1a was subjected to an iodine-catalyzed double bond isomerization
16

as described in the literature [20]. After chromatography, the (E)-isomer of 1a was obtained in
diastereomerically pure form (Z:E = 1:99). The structure was proven by NMR spectroscopy
[21]. Then, (E)-1a was reacted with 2a using our optimized protocol. It was found that the
reaction of diastereomerically pure (E)-1a delivers diastereomerically pure 3a exclusively.
The structure of 3a has unequivocally been determined by NMR spectroscopy. Due to the
deshielding effect of one of the ring oxygens in the benzodioxine the vinylic proton of (E)-3a
is expected to resonate at lower field (δ = 6.42 ppm) than the vinylic proton of (Z)-3a (δ =
5.11 ppm). This is in full accordance with the literature [9a]. To exclude a subsequent
isomerization of the products with (Z)- and (E)-configuration, pure (Z)-3a as well as a 92:8
mixture of (Z)-3a and (E)-3a were subjected to reaction conditions (Scheme 5c). Under these
conditions no isomerization occurred. It can be concluded that the reaction between (Z)-1a
and 2 proceeds diastereospecifically via the alkene pathway as depicted in Scheme 3a.
2.4. DFT-calculations
Further studies concerning the exclusive formation of products 3 with (Z)-configuration
included quantum chemical calculations which were carried out at the B3LYP/6-31+G(d)
level of theory. The reaction between (Z)-1g and 2a was taken as an example. The
calculations reveal that the overall product formation is endergonic in nature by 21.37
kcal/mol (11.15 + 9.77) (Scheme 6a) for (Z)-3g and 23.78 kcal/mol (11.15 + 12.63) for (E)-
3g. The endergonic character supports the necessity of harsh reaction conditions for the
product formation on a relative scale. The (Z)-isomer 3g is more stable by 2.41 kcal/mol, and
hence, the (E)-isomer 3g is expected to be formed in minor amounts.
17

a) The overall energetics of the reaction between (Z)-1g
and 2a to (Z)- and (E)-3g
O
O
G = 9.77
HBr
Br
Br
O
(Z)-3g
Br
OH
Br
int. A [conf. A of (Z)-8g]
(Z)-1g
HO
G = 11.15
HBr
G = 0.00
Ea = 1.95
O
O
+
G = 12.63
HBr
2a
O
(E)-3g
Br
int. B [conf. B of (Z)-8g]
Br
b) The alkene pathway (neutral):
O
Cyclization
O
O
Br
G = 9.77
Ea = 46.67
(Z)-3g
Br
OH
Br
int. A
b) The alkene pathway (Ionic-base catalysed):
Cs2CO3
O
O
O
Br
G = 9.77
Ea = 11.38
(Z)-3g
Br
OH
Br
int. A
HBr
(deprotonation followed
by debromination catalysed by Cs2CO3)
PES diagram ( Blue-neutral and Purple-Ionic) depicting product formation.
Energies are given in kcal/mol and distances in Angstrom (Å).
c) The alkyne pathway (neutral)
Br
O
G = 39.26
HBr
Cyclization
O
int. A
Br
G = 29.49
Ea = 74.76
HBr
O
(Z)-3g
HO
int. C 9g
Br
O
G = 39.26
HBr
Cs2CO3
O
int. A
Br
G = -29.49
Ea =55.62
(Z)-3g
O
HO
Base catalysed
deprotonation
followed by cyclization
PES diagram ( Blue-neutral and Purple-Ionic) depicting product formation.
Energies are given in kcal/mol and distances in Angstrom (Å).
int. C 9g
Scheme 6. a) The overall energetics of the reaction between (Z)-1g and 2a to form (Z)- and (E)-3g; b)
the alkene pathway; c) the alkyne pathway. All energies are given in kcal/mol and distances in Å.
Corresponding pathways involving intermediate B (int. B) are depicted in ESI (Scheme S1). The
potential energy diagram is included.
It is assumed that the reaction starts with the loss of HBr in the presence of a base like K2CO3,
leading to (Z)-8g. This step is endergonic by 11.15 kcal/mol. (Z)-8g can adopt two
conformational states: int. A and int. B. There is no energy difference between these two
states, one conformer produces the Z-isomer of 3g and the other results in the E-isomer of 3g.
The rotational barrier between the two conformers amounts to 1.95 kcal/mol which is less
18

than 3 kcal/mol. Since the quantum chemical calculations revealed that the energy difference
between the two isomers of the key intermediate is zero, it was concluded that the product
formation is largely governed by steric factors. To understand the mechanism of the
cyclization step, two pathways have been considered: the alkene and the alkyne pathways.
Along the alkene pathway (Scheme 6b), int. A can undergo an intramolecular cyclization by
nucleophilic addition. The cyclization may start either from the neutral or the anionic form of
int. A. Starting from int. A in the neutral form the Ea for the cyclization, which proceeds via
TS-1, has been found to be 46.67 kcal/mol. On the other hand, the Ea for the anionic pathway
starting from the anion of int. A and proceeding via TS-2 amounts to 11.38 kcal/mol.
Remarkably, the activation barrier for the anionic path is considerably lower than that for the
pathway starting with the neutral int. A. The activation barrier values suggest that the
cyclization process can be considered as a base-catalyzed cyclization. In the alkyne pathway
(Scheme 6c), int. A initially undergoes a base-catalyzed abstraction of HBr to form the alkyne
int. C. The formation of int. C is endergonic by 39.26 kcal/mol. Like in the alkene pathway,
the cyclization can also start either from the neutral int. C or the anion of int. C. In case of
the neutral int. C, the cyclization proceeds via TS-3a with an activation barrier of 74.76
kcal/mol. Starting from the anionic form of int. C, the activation barrier amounts to 55.62
kcal/mol via TS-3b. As a result, the alkyne pathway is also accompanied with a reduction of
the activation barrier in the presence of a base. Thus, in the cyclization starting from int. A
(alkene pathway) as well as the cyclization starting from int. C (alkyne pathway) the base
could function as a catalytic agent. However, it can be concluded, that the alkene pathway is
preferred over the alkyne pathway.
3. Conclusions
To summarize, a new and efficient one pot process of the synthesis of (Z)-2-arylidene-2,3-
dihydrobenzo[b][1,4]dioxines (Z)-3 with yields up to 89% has been established. Reaction of a
range of diastereomerically pure (Z)-1,2-dibromo-2-propenes (Z)-1 with catechols 2 under
transition metal-free conditions using Cs2CO3 as a base delivers the diastereomerically pure
(Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxines (Z)-3. It is assumed that the reaction
starts with an intermolecular O-allylation, which is followed by an intramolecular O-
vinylation. The reaction mechanism is supported by experiments as well as by DFT
calculations. Our study has also revealed that the reaction of (E)-1,2-dibromo-2-propene (E)-
1a with catechol (2a) delivers (E)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(E)-3a]
and that the reaction between (3-bromoprop-1-yn-1-yl)benzene (9a) and catechol (2a) yields
the (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4] dioxine [(Z)-3a] under transition metal-free
conditions. The structures of all products were elucidated unequivocally by NMR
spectroscopy.
19

4. Experimental section
4.1 General
All commercially available reagents were used without further purification. Catechol (2a) was
recrystallized from toluene prior to use. DMF used in reactions was distilled prior to use and
stored under argon over molecular sieves 4 Å. Other solvents used in reactions and solvents
used for extraction and purification were distilled prior to use. Reaction temperatures are
reported as bath temperatures. Thin-layer chromatography (TLC) was performed on precoated
aluminum plates (silica gel Macherey-Nagel ALUGRAM® Xtra SIL G/UV254) and visualized
by UV light (254 nm) and/or by immersion in an ethanolic vanillin solution followed by
heating. Products were purified by flash chromatography on silica gel (MN 60, 0.04–0.063
mm; Marcherey-Nagel or by preparative thin layer chromatography (Merck PLC Silica gel 60
F
, 2 mm). Melting points were determined on a Büchi melting point apparatus B-545
1
and are uncorrected. IR spectra were measured on a Bruker Alpha FT-IR spectrometer. H
and 13C NMR spectra were recorded at 300 MHz and 500 MHz on Varian Unity Inova
spectrometers and at 600 MHz on a Bruker Avance III HD spectrometer using CDCl3, C6D6
or pyridine-d5 as the solvent. The H and 13C chemical shifts were referenced to residual
1
solvent signals at
δ H/C 7.26/77.02 (CDCl3), δ H/C 7.16/128.39 (C6D6) and δ H/C
8.74/150.35 (pyridine-d5) relative to TMS as internal standard. COSY-, HSQC-, HMBC-,
1
HSQMBC- and D NOESY-spectra were recorded on Bruker Avance III HD spectrometer at
600 MHz. Coupling constants J [Hz] were directly taken from the spectra and are not
averaged. Splitting patterns are designated as s (singlet), bs (broad singlet), d (doublet), t
(triplet), q (quartet), sep (septet), m (multiplet) and ovl (overlapped). Low-resolution electron
impact mass spectra [MS (EI)] and high-resolution mass electron impact mass spectra [HRMS
(EI)] were obtained at 70 eV using a double focusing sector field mass spectrometer Finnigan
MAT 95. High resolution spectra [HRMS (APCI)] were recorded in the solvent system 0.2 %
formic acid in water (solvent A) and acetonitrile + 0.2 % formic acid in water (solvent B)
using Agilent 1290-APCI (Q Exactive plus, Thermo Fisher Scientific, APCI, pos) with the
following gradient program: 0.00 (min), 0.30 (mL/min), A:B = 90:10; 10.00 (min), 0.30
(mL/min), A:B = 30:70; 15.00 (min), 0.30 (mL/min), A:B = 10:90; 20.00 (min), 0.30
(mL/min), A:B = 90:10; 25.00 (min), 0.30 (mL/min), A:B = 90:10. Intensities are reported as
percentages relative to the base peak (I = 100%).
4.2 Synthesis and characterization of starting materials [(Z)-1a─i]
General procedure I for the synthesis of starting materials (Z)-1a─i [14]
A solution of bromine (1.09 equiv) in dichloromethane (1.63 mL/mmol bromine) was added
dropwise to a stirred solution of a 2-bromo-2-propen-1-ol (Z)-7 (1.0 equiv) and
triphenylphosphine (1.10 equiv) in dichloromethane (3 mL/mmol alcohol) at 0 °C. After
stirring for 3 h at 0 °C the reaction mixture was allowed to warm to room temperature and the
mixture was applied to reduced pressure until a small residue of solvent was left (≈ 5 mL/20
mmol alcohol). The residue was subjected to precipitation with n-pentane (60 mL) and was
20

kept overnight at ─25 °C. The solid triphenylphosphine oxide was filtered over silica and the
filter cake was washed thoroughly with n-pentane (3 × 100 mL). The filtrate was dried over
MgSO4, filtered and the solvents were removed under reduced pressure. The crude product
was purified by column chromatography over silica gel using n-pentane as eluent to afford the
corresponding 1,2-dibromo-3-aryl-2-propene (Z)-1 in analytically pure form.
4.2.1 (Z)-1,2-Dibromo-3-phenyl-2-propene [(Z)-1a] [21]
According to general procedure I, 2-bromo-3-phenyl-prop-2-en-1-ol [(Z)-7a] (2.01 g, 9.43
mmol), triphenylphosphine (2.72 g, 10.38 mmol) in dichloromethane (28 mL) and a solution
of bromine (0.53 mL, 1.66 g, 10.38 mmol) in dichloromethane (17 mL) were reacted for 3 h
at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-phenyl-2-propene [(Z)-1a] was
obtained as a pale yellow oil in 91% yield (2.38 g, 8.60 mmol, Z:E ≥ 95:5); Rf 0.41 (n-
1
pentane); H NMR (300 MHz, CDCl3) δ 4.44 (s, 2H, 1-H), 7.13 (s, 1H, 3-H), 7.36─7.38 (m,
3H, arom. H), 7.66─7.64 (m, 2H, arom. H); 13C NMR (75 MHz, CDCl3) δ 40.65 (C-1), 120.75
(C-3), 128.25 (arom. C), 128.70 (arom. C), 129.06 (arom. C), 132.20 (arom. C), 134.58
(arom. C); MS (EI, 70 eV) m/z (%) 275 (9) [M]+ ≙ [C9H8Br2]+, 195 (30) [M─Br]+ ≙
[C9H8Br]+, 115 (100) [M─2 × Br]+ ≙ [C9H8]+.
4.2.2 (Z)-1,2-Dibromo-3-p-tolyl-2-propene [(Z)-1b] [21]
According to general procedure I, 2-bromo-3-(p-tolyl)prop-2-en-1-ol [(Z)-7b] (4.74 g, 20.00
mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60 mL) and a solution
of bromine (1.12 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were stirred for 3 h at
0 °C. After work-up and purification, (Z)-1,2-dibromo-3-p-tolyl-2-propene [(Z)-1b] was
obtained as a pale yellow oil in 30% yield (1.71 g, 5.88 mmol, Z:E ≥ 95:5 ); Rf 0.43 (n-
pentane); 1H NMR (600 MHz, CDCl3) δ 2.36 (s, 3H, 1’’-H), 4.44 (s, 2H, 1-H), 7.09 (s, 1H, 3-
3
3
H), 7.19 (d like, J(3’-H, 2’-H) = J(5’-H, 6’-H) = 7.5 Hz, 2H, 3’-H and 5’-H), 7.55 (d like,
3J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 7.6 Hz, 2H, 2’-H and 6’-H);13C NMR (125 MHz, CDCl3) δ
21.38 (C-1’’), 41.04 (C-1), 119.80 (C-2), 128.97 (C-2’ and C-6’), 129.03 (C-3’ and C-5’),
131.67 (C-1’), 132.20 (C-3), 138.96 (C-4’); MS (EI, 70 eV) m/z (%) 289 (9) [M]+ ≙
[C10H11Br2]+, 210 (31) [M─Br]+ ≙ [C10H11Br]+, 130 (100) [M─2 × Br]+ ≙ [C10H11]+, 115 (49),
64 (10).
4.2.3 (Z)-1,2-Dibromo-3-(4-ethylphenyl)-2-propene [(Z)-1c]
According to general procedure I, (Z)-2-bromo-3-(4-ethylphenyl)prop-2-en-1-ol [(Z)-7c] (4.82
g, 20.00 mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60mL) and a
solution of bromine (1.12 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were stirred
21

for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(4-ethylphenyl)-2-propene
[(Z)-1c] was obtained as a pale yellow oil in 57% yield (3.44 g, 11.32 mmol, Z:E ≥ 95:5); Rf
0.46 (n-pentane); IR (ATR) ν 2962, 2929, 2870, 1607, 1509, 1454, 1413, 1285, 1206, 1184,
1131, 1071, 1019, 899, 870, 819, 619, 533 cm-1; 1H NMR (600 MHz, CDCl3) δ 1.27 (t, 3J(2’’-
H, 1’’-H) = 7.5 Hz, 3H, 2’’-H), 2.68 (q, 3J(1’’-H, 2’’-H) = 7.5 Hz, 2H, 1’’-H), 4.46 (s, 2H, 1-
H), 7.12 (s, 1H, 3-H), 7.24 (d like, 3J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.0 Hz, 2H, 3’-H and 5’-
H), 7.62 (d like 3J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 8.0 Hz, 2H, 2’-H and 6’-H); 13C NMR (125
MHz, CDCl3) δ 15.27 (C-2’’), 28.70 (C-1’’), 41.08 (C-1), 119.75 (C-2), 127.75 (C-3’ and C-
5’), 129.11 (C-2’ and C-6’), 131.86 (C-1’), 132.19 (C-3), 145.24 (C-4’); MS (EI, 70 eV) m/z
(%) 303 (11) [M]+ ≙ [C11H13Br2]+, 223 (41) [M─Br]+ ≙ [C11H13Br]+, 144 (100) [M─2 × Br]+
≙ [C11H13]+, 129 (92), 115 (38), 105 (15), 79 (29); HRMS (EI, M+) calculated for
[C11H12Br2]+ 303.9286 found 303.9347.
4.2.4 (Z)-1,2-Dibromo-3-(4-isopropylphenyl)-2-propene [(Z)-1d]
According to general procedure I, (Z)-2-bromo-3-(4-isopropylphenyl)prop-2-en-1-ol [(Z)-7d]
(5.10 g, 20.00 mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60 mL)
and a solution of bromine (1.12 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were
stirred for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(4-
isopropylphenyl)-2-propene [(Z)-1d] was obtained as a light yellow oil in 47% yield (3.01 g,
9.45 mmol, Z:E ≥ 95:5); Rf 0.50 (n-pentane); IR (ATR) ν 2958, 2867, 1607, 1508, 1458,
1
1414, 1278, 1206, 1052, 1017, 899, 870, 818, 620, 556, 499, 431 cm-1; H NMR (600 MHz,
3
3
CDCl3) δ 1.25 (d, J(1’’-H, 2’’-H) = J(3’’-H, 2’’-H) = 6.9 Hz, 6H, 1’’-H and 3’’-H), 2.91
(sep, 3J(2’’-H, 1’’-H) = 3J(2’’-H, 3’’-H) = 6.9 Hz, 1H, 2’’-H), 4.44 (s, 2H, 1-H), 7.09 (s, 1H,
3-H), 7.23 (d like, 3J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.2 Hz, 2H, 3’-H and 5’-H), 7.61 (d like,
3J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 8.2 Hz, 2H, 2’-H and 6’-H); 13C NMR (125 MHz, CDCl3) δ
23.77 (C-1’’ and C-3’’), 33.99 (C-2’’), 41.13 (C-1), 119.72 (C-2), 126.35 (C-3’ and C-5’),
129.15 (C-2’ and C-6’), 131.99 (C-1’), 132.18 (C-3), 149.87 (C-4’); MS (EI, 70 eV) m/z (%)
317 (14) [M]+ ≙ [C12H15Br2]+, 237 (27) [M─Br]+ ≙ [C12H15Br]+, 194 (43), 157 (71) [M─2 ×
Br]+ ≙ [C12H15]+, 143 (100), 128 (80), 115 (68), 91 (14) ≙ [C7H7]+; HRMS (EI, M+)
calculated for [C12H14Br2]+ 317.9442 found 317.9468.
4.2.5 (Z)-1,2-Dibromo-3-(4-fluorophenyl)-2-propene [(Z)-1e] [21]
According to general procedure I, (Z)-2-bromo-3-(4-fluorophenyl)prop-2-en-1-ol [(Z)-7e]
(1.16 g, 5 mmol), triphenylphosphine (1.58 g, 6.00 mmol) in dichloromethane (15 mL) and a
solution of bromine (0.31 mL, 0.96 g, 6.00 mmol) in dichloromethane (10 mL) were stirred
for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(4-fluorophenyl)-2-
propene [(Z)-1e] was obtained as a light yellow oil in 77% yield (1.13 g, 3.82 mmol, Z:E ≥
22

95:5); Rf 0.41 (n-pentane); 1H NMR (600 MHz, C6D6) δ 3.77 (s, 2H, 1-H), 6.32 (s, 1H, 3-H),
6.70 (d like, 3J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.0 Hz, 2H, 3’-H and 5’-H), 7.19 (d like, 3J(2’-
H, 3’-H) = 3J(6’-H, 5’-H) = 8.5 Hz, 2H, 2’-H and 6’-H); 13C NMR (125 MHz, C6D6) δ 40.10
2
2
(C-1), 115.0 (d, J(4’-F, C-3’) = J(4’-F, C-5’) = 21.9 Hz, C-3’ and C-5’), 120.77 (C-2),
130.62 (d, 4J(4’-F, C-1’) = 3.3 Hz, C-1’), 130.73 (C-3), 130.90 (d, 3J(4’-F, C-2’) = 3J(4’-F, C-
6’) = 8.7 Hz, C-2’ and C-6’), 162.64 (d, 1J(4’-F, C-4’) = 250.1 Hz, C-4’); MS (EI, 70 eV) m/z
(%) 293(14) [M]+ ≙ [C9H7Br2F]+, 212 (47) [M─Br]+ ≙ [C9H7BrF]+, 134 (100) [M─2 × Br]+ ≙
[C9H7F]+.
4.2.6 (Z)-1,2-Dibromo-3-(4-chlorophenyl)-2-propene [(Z)-1f] [21]
According to general procedure I, (Z)-2-bromo-3-(4-chlorophenyl)prop-2-en-1-ol [(Z)-7f]
(4.95 g, 20 mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60 mL) and
a solution of bromine (0.31 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were stirred
for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(4-chlorophenyl)-2-
propene [(Z)-1f] was obtained as a light yellow oil in 61% yield (3.76 g, 12.12 mmol, Z:E ≥
95:5); Rf 0.44 (n-pentane); 1H NMR (600 MHz, CDCl3) δ 4.42 (s, 2H, 1-H), 7.08 (s, 1H, 3-H),
7.34 (d like, 3J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.0 Hz, 2H, 3’-H and 5’-H), 7.57 (d like, 3J(2’-
H, 3’-H) = 3J(6’-H, 5’-H) = 8.5 Hz, 2H, 2’-H and 6’-H); 13C NMR (125 MHz, CDCl3) δ 40.26
(C-1), 121.49 (C-2), 128.50 (C-3’ and C-5’), 130.31 (C-2’ and C-6’), 130.94 (C-3), 132.98
(C-1’), 134.59 (C-4’); MS (EI, 70 eV) m/z (%) 309 (12) [M]+ ≙ [C9H7Br2Cl]+, 230 (44)
[M─Br]+ ≙ [C9H7BrCl]+, 150 (69) [M─2 × Br]+ ≙ [C9H7Cl]+, 115 (100) ≙ [C9H7]+.
4.2.7 (Z)-1,2-Dibromo-3-(4-bromophenyl)-2-propene [(Z)-1g]
According to general procedure I, (Z)-2-bromo-3-(4-bromophenyl)prop-2-en-1-ol [(Z)-7g]
(5.84 g, 20 mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60 mL) and
a solution of bromine (0.31 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were stirred
for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(4-bromophenyl)-2-
propene [(Z)-1g] was obtained as a light yellow oil in 47% yield (3.36 g, 9.46 mmol, Z:E ≥
95:5); Rf 0.50 (n-pentane); IR (ATR) ν 2921, 2851, 1615, 1584, 1484, 1398, 1275, 1199,
1123, 1071, 1006, 902, 880, 809, 674, 636, 611, 557, 514, 498, 429 cm-1; 1H NMR (600 MHz,
3
3
pyridine-d5) δ 6.81 (s, 1H, 1-H), 7.49 (d like, J(2’-H, 3’-H) = J(6’-H, 5’-H) = 8.5 Hz, 2H,
3
3
2’-H and 6’-H), 7.70 (d like, J(3’-H, 2’-H) = J(5’-H, 6’-H) = 8.0 Hz, 2H, 3’-H and 5’-H),
13
8.82 (s, 1H, 3-H); C NMR (125 MHz, pyridine-d5) δ 68.48 (C-1), 117.59 (C-2), 131.28 (C-
2’ and C-6’), 131.58 (C-3’ and C-5’), 133.47 (C-1’), 135.63 (C-3), 136.84 (C-4’); MS (EI, 70
eV) m/z (%) 353 (13) [M]+ ≙ [C9H7Br3]+, 274 (34) [M─Br]+ ≙ [C9H7Br2]+, 193 (71) [M─2 ×
Br]+ ≙ [C9H7Br]+, 115 (100) [M─3 × Br]+ ≙ [C9H7]+, 69 (11); HRMS (APCI, 5 kV, [M+H]+)
calculated for [C9H7Br3]+ 352.8171 found 352.8170.
23

4.2.8 (Z)-1,2-Dibromo-3-(3-bromophenyl)-2-propene [(Z)-1h]
According to general procedure I, (Z)-2-bromo-3-(3-bromophenyl)prop-2-en-1-ol [(Z)-7h]
(5.84 g, 20.00 mmol), triphenylphosphine (5.77 g, 22.00 mmol) in dichloromethane (60 mL)
and a solution of bromine (0.31 mL, 3.52 g, 22.00 mmol) in dichloromethane (36 mL) were
stirred for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(3-bromophenyl)-2-
propene [(Z)-1h] was obtained as a light yellow oil in 45% yield (3.19 g, 8.98 mmol, Z:E ≥
95:5); Rf 0.50 (n-pentane); IR (ATR) ν 2956, 2925, 1589, 1558, 1470, 1405, 1276, 1204,
1
1070, 995, 912, 885, 777, 679, 623, 562, 475, 436 cm-1; H NMR (600 MHz, CDCl3) δ 4.60
(s, 2H, 1-H), 7.26 (s, 1H, 3-H), 7.44 (t like, 3J(5’-H, 4’-H) = 3J(5’-H, 6’-H) = 7.9 Hz, 1H, 5’-
H), 7.66 (d like, 3J(6’-H, 5’-H) = 7.9 Hz, 1H, 6’-H), 7.73 (d like, 3J(4’-H, 5’-H) = 7.9 Hz, 1H,
13
4’-H), 7.98 (s, 1H, 2’-H); C NMR (125 MHz, CDCl3) δ 39.91 (C-1), 122.31 (C-2), 122.39
(C-1’), 127.64 (C-6’), 129.77 (C-5’), 130.67 (C-3), 131.66 (C-4’), 131.79 (C-2’), 136.66 (C-
3’); MS (EI, 70 eV) m/z (%) 353 (12) [M]+ ≙ [C9H7Br3]+, 274 (29) [M─Br]+ ≙ [C9H7Br2]+,
243 (10), 193 (64) [M─2 × Br]+ ≙ [C9H7Br]+, 115 (100) [M─3 × Br]+ ≙ [C9H7]+, 57 (12);
HRMS (EI, M+) calculated for [C9H7Br3]+ 353.8049 found 353.8072.
4.2.9 (Z)-1,2-Dibromo-3-(3-methoxyphenyl)-2-propene [(Z)-1i]
According to general procedure I, (Z)-2-bromo-3-(3-methoxyphenyl) prop-2-en-1-ol [(Z)-7i]
(0.73 g, 3.00 mmol), triphenylphosphine (0.87 g, 3.30 mmol) in dichloromethane (9 mL) and
a solution of bromine (0.17 mL, 0.53 g, 3.30 mmol) in dichloromethane (5.5 mL) were stirred
for 3 h at 0 °C. After work-up and purification, (Z)-1,2-dibromo-3-(3-methoxyphenyl)-2-
propene [(Z)-1i] was obtained as a light yellow oil in 47% yield (0.15 g, 1.41 mmol, Z:E ≥
95:5); Rf 0.35 (n-pentane); IR (ATR) ν 3000, 2956, 2935, 2832, 1596, 1575, 1485,1454, 1421,
1320, 1260, 1208, 1039, 940, 865, 778, 688, 624, 479, 456 cm-1; 1H NMR (600 MHz, CDCl3)
δ 3.83 (s, 3H, 1’’-H), 4.43 (s, 2H, 1-H), 6.89 (d like, 3J(4’-H, 5’-H) = 7.6 Hz, 1H, 4’-H), 7.11
(s, 1H, 3-H), 7.17 (d like, 3J(6’-H, 5’-H) = 7.6 Hz, 1H, 6’-H), 7.25 (s, 1H, 2’-H), 7.28 (t like,
3
13
3J(5’-H, 4’-H) = J (5’-H, 6’-H) = 7.6 Hz, 1H, 5’-H); C NMR (125 MHz, CDCl3) δ 40.61
(C-1), 55.29 (C-1’’), 114.13 (C-2’), 114.67 (C-4’), 120.91 (C-2), 121.77 (C-6’), 129.26 (C-
5’), 132.09 (C-3), 135.82 (C-1’), 159.35 (C-3’); MS (EI, 70 eV) m/z (%) 305 (14) [M]+ ≙
[C10H10Br2O]+, 224 (36) [M─Br]+ ≙ [C10H10BrO]+, 146 (100) [M─2 × Br]+ ≙ [C10H10O]+, 131
(31) ≙ [C9H7O]+, 103 (40) ≙ [C8H7]+, 77 (14) [C6H5]+; HRMS (EI, M+) calculated for
[C9H7Br3]+ 305.9046 found 305.9073.
4.3 Synthesis and characterization of products [(Z)-3a─l]
General procedure II for the synthesis of (Z)-3a─l
A two-necked round-bottom flask was charged with a 1,2-dibromo-3-aryl-2-propene (Z)-1 (1
mmol, 1 equiv), a catechol 2 (2 mmol, 2 equiv), Cs2CO3 (4 mmol, 4 equiv) and DMF (10 mL)
under argon. The reaction mixture was vigorously stirred for 18 h at 140 °C. After cooling to
24

100 °C, the reaction mixture was quenched with 2 M HCl (2.5 mL) and then allowed to cool
to room temperature. The reaction mixture was diluted with H2O (25 mL) and extracted with
Et2O (3 × 20 mL). The combined organic layers were washed with brine (3 × 15 mL), dried
over MgSO4, filtered and concentrated under reduced pressure. The crude product was
purified by column chromatography on silica gel using mixtures of n-hexane and ethyl acetate
as eluents to afford the corresponding 2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine (Z)-3
in pure form.
4.3.1 (Z)-2-Benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3a] [9a-d,f]
According to general procedure II, (Z)-1,2-dibromo-3-phenyl-2-propene [(Z)-1a] (276 mg, 1
mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were reacted for 18
h at 140 °C in DMF. After work-up and purification by column chromatography (SiO2, n-
hexane:ethyl acetate = 49:1) (Z)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3a] was
obtained as a white solid in 89% yield (199 mg, 0.89 mmol, Z:E ≥ 95:5); Rf 0.40 (n-
1
hexane:ethyl acetate = 49:1); H NMR (600 MHz, C6D6) δ 4.02 (s, 2H, 1-H), 5.11 (s, 1H, 3-
H), 6.67─6.69 (m, 1H, 3’’-H), 6.69─6.71 (m, 1H, 4’’-H), 6.91─6.92 (m, 1H, 2’’-H), 6.92─6.93
(m, 1H, 5’’-H), 7.09 (t like, 3J(4’-H, 3’-H) = 3J(4’-H, 5’-H) = 7.4 Hz, 1H, 4’-H), 7.25 (t like,
3J(3’-H, 2’-H) = 3J(3’-H, 4’-H) = 3J(5’-H, 4’-H) = 3J(5’-H, 6’-H) = 7.4 Hz, 2H, 3’-H and 5’-
H), 7.71 ( d like, 3J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 7.4 Hz, 2H, 2’-H and 6’-H; 13C NMR (125
MHz, C6D6) δ 65.88 (C-1), 107.30 (C-3), 116.99 (C-2’’), 117.74 (C-5’’), 122.46 (C-3’’),
122.86 (C-4’’), 127.12 (C-4’), 128.61 (C-3’ and C-5’), 129.32 (C-2’ and C-6’), 134.88 (C-1’),
142.96 (C-1’’), 143.80 (C-6’’), 144.77 (C-2); HRMS (APCI, 5 kV, [M+H]+) calculated for
[C15H13O2]+ 225.0917 found 225.0916.
4.3.2 (E)-2-Benzylidene-2,3-dihydrobenzo[b][1,4]dioxine [(E)-3a] [9e]
According to general procedure II, (E)-1,2-dibromo-3-phenyl-2-propene [(E)-1a] (25 mg, 90
µmol), catechol (2a) (20 mg, 180 µmol) and Cs2CO3 (117 mg, 360 µmol) were reacted for 18
h at 140 °C in DMF. After work-up and purification by preparative thin layer chromatography
(SiO2, n-hexane:ethyl acetate = 49:1) (E)-2-benzylidene-2,3-dihydrobenzo[b][1,4]dioxine
[(E)-3a] was obtained as a white solid in 35% yield (7 mg, 31 µmol, Z:E = 0:100); Rf 0.42 (n-
1
hexane:ethyl acetate = 49:1); H NMR (600 MHz, C6D6) δ 4.44 (s, 2H, 1-H), 6.42 (s, 1H, 3-
H), 6.67─6.69 (m, 1H, arom. H), 6.69─6.71 (m, 1H, arom. H), 6.82─6.86 (m, 2H, arom. H),
6.90─6.94 (m, 1H, arom. H), 6.97─7.06 (m, 4H, arom. H). 13C NMR (125 MHz, C6D6) δ 59.67
(C-1), 108.54 (C-3), 115.58 (arom. C), 116.44 (arom. C), 121.28 (arom. C), 121.44 (arom. C),
125.78 (arom. C), 127.54 (arom. C), 127.98 (arom. C), 133.35 (arom. C), 142.22 (arom. C),
25

143.63 (arom. C), 144.91 (arom. C); HRMS (APCI, 5 kV, [M+H]+) calculated for
[C15H13O2]+ 225.0917 found 225.0916.
4.3.3 (Z)-2-(4-Methylbenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3b] [9a,c,d]
According to general procedure II, (Z)-1,2-dibromo-3-p-tolyl-2-propene [(Z)-1b] (290 mg, 1
mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were reacted for 18
h at 140 °C in DMF. After work-up and purification by column chromatography (SiO2, n-
hexane: ethyl acetate = 49:1) (Z)-2-(4-methylbenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine
[(Z)-3b] was obtained as a white solid in 88% yield (213 mg, 0.89 mmol, Z:E ≥ 95:5); Rf 0.42
1
(n-hexane:ethyl acetate = 49:1); H NMR (600 MHz, C6D6) δ 2.16 (s, 3H, 1’’’-H), 4.05 (s,
2H, 1-H), 5.15 (s, 1H, 3-H), 6.67─6.68 (m, 1H, 3’’-H), 6.68─6.69 (m, 1H, 4’’-H), 6.93─6.94
3
(m, 1H, 2’’-H), 6.94─6.95 (m, 1H, 5’’-H), 7.10 (d like, J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 7.5
Hz, 2H, 3’-H and 5’-H), 7.67 (d like, 3J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 7.6 Hz, 2H, 2’-H and
13
6’-H); C NMR (125 MHz, C6D6) δ 20.07 (C-1’’’), 64.82 (C-1), 106.26 (C-3), 115.83 (C-
3’’), 116.62 (C-4’’), 121.28 (C-2’’), 121.62 (C-5’’), 128.20 (C-2’ and C-6’), 128.22 (C-3’ and
C-5’), 130.98 (C-1’), 135.57 (C-4’), 141.93 (C-2), 142.04 (C-6’’), 143.68 (C-1’’); MS (EI, 70
eV) m/z (%) 238 (100) [M]+ ≙ [C16H14O2]+, 223 (22) [M─CH3]+ ≙ [C15H12O2]+, 129 (98) ≙
[C6H5O]+, 105 (58), 91 (15), 79 (10).
4.3.4 (Z)-2-(4-Ethylbenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3c]
According to general procedure II, (Z)-1,2-dibromo-3-(4-ethylphenyl)-2-propene [(Z)-1c]
(304 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 49:1) (Z)-2-(4-ethylbenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3c] was obtained as a white solid in 77% yield (194 mg,
0.77 mmol, Z:E ≥ 95:5); mp 97–98 °C; Rf 0.46 (n-hexane:ethyl acetate = 49:1); IR (ATR) ν
2962, 1678, 1593, 1490, 1460, 1374, 1347, 1258, 1168, 1104, 1027, 995, 925, 853, 768, 744,
1
3
571, 528, 474 cm-1; H NMR (600 MHz, C6D6) δ 1.11 (t, J(2’’’-H, 1’’’-H) = 8.0 Hz, 3H,
2’’’-H), 2.48 (q, 3J(1’’’-H, 2’’’-H) = 8.0 Hz, 2H, 1’’’-H), 4.06 (s, 2H, 1-H), 5.17 (s, 1H, 3-H),
6.67─6.69 (m, 1H, 3’’-H), 6.69─6.71 (m, 1H, 4’’-H), 6.92─6.95 (m, 1H, 2’’-H), 6.96─6.99 (m,
1H, 5’’-H), 7.13 (d like, 3J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.2 Hz, 2H, 3’-H and 5’-H), 7.70 (d
26

3
3
like, J(2’-H, 3’-H) = J(6’-H, 5’-H) = 8.2 Hz, 2H, 2’-H and 6’-H); 13C NMR (125 MHz,
C6D6) δ 15.73 (C-2’’’), 28.96 (C-1’’’), 65.96 (C-1), 107.43 (C-3), 116.97 (C-2’’), 117.77 (C-
5’’), 122.43 (C-3’’), 122.78 (C-4’’), 128.16 (C-3’ and C-5’), 129.44 (C-2’ and C-6’), 132.37
(C-1’), 143.22 (C-4’), 144.10 (C-6’’), 143.10 (C-2), 143.08 (C-1’’); MS (EI, 70 eV) m/z (%)
252 (100) [M]+ ≙ [C17H16O2]+, 205 (14), 151 (10), 144 (65), 129 (70) ≙ [C6H5O]+, 97 (37),
95 (40), 85 (51), 83 (54), 71 (78), 57 (88); HRMS (EI, M+) calculated for [C17H16O2]+
252.1150 found 252.1152.
4.3.5 (Z)-2-(4-isopropylbenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3d]
3
1
2'
1'
2
3'
4'
O
1''
1'''
2'''
6'
O
2''
3''
6''
5''
5'
3'''
4''
According to general procedure II, (Z)-1,2-dibromo-3-(4-isopropylphenyl)-2-propene [(Z)-1d]
(304 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 49:1) (Z)-2-(4-isopropylbenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-1d] was obtained as a white solid in 68% yield (194 mg,
0.77 mmol, Z:E ≥ 95:5); mp 96–97 °C; Rf 0.49 (n-hexane:ethyl acetate = 49:1); IR (ATR) ν
[cm-1] 2957, 2865, 1680, 1593, 1489, 1461, 1346, 1307, 1278, 1256, 1169, 1104, 1053, 1028,
992, 925, 854, 767, 745, 574, 486, 402; 1H NMR (600 MHz, C6D6) δ 1.17 (d, 3J(1’’-H, 2’’-H)
3
3
3
= J(3’’’-H, 2’’’-H) = 6.9 Hz, 6H, 1’’’-H and 3’’’-H), 2.75 (sep, J(2’’’-H, 1’’’-H) = J(2’’’-
H, 3’’’-H) = 6.9 Hz, 1H, 2’’’-H), 4.06 (s, 2H, 1-H), 5.17 (s, 1H, 3-H), 6.69─6.71 (m, 1H, 3’’-
H), 6.71─6.73 (m, 1H, 4’’-H), 6.92─6.95 (m, 1H, 5’’-H), 6.96─7.01 (m, 1H, 2’’-H), 7.13 (d
3
3
3
like, J(3’-H, 2’-H) = J(5’-H, 6’-H) = 8.2 Hz, 2H, 3’-H and 5’-H), 7.70 (d like, J(2’-H, 3’-
3
13
H) = J(6’-H, 5’-H) = 8.2 Hz, 2H, 2’-H and 6’-H); C NMR (125 MHz, C6D6) δ 24.05 (C-
1’’’ and C-3’’’), 34.21 (C-2’’’), 65.95 (C-1), 107.42 (C-3), 116.96 (C-3’’), 117.99 (C-4’’),
122.43 (C-2’’), 122.78 (C-5’’), 126.70 (C-3’ and C-5’), 129.46 (C-2’ and C-6’), 132.50 (C-
1’), 143.09 (C-1’’), 143.23 (C-2), 144.82 (C-6’’), 147.72 (C-4’); MS (EI, 70 eV) m/z (%) 266
(100) [M]+ ≙ [C18H18O2]+, 251 (72), 223 (14), 158 (27), 143 (73), 128 (33), 115 (38), 91 (51)
≙ [C7H7]+; HRMS (EI, M+) calculated for [C18H18O2]+ 266.1306, found 266.1307.
4.3.6 (Z)-2-(4-Fluorobenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3e]
According to general procedure II, (Z)-1,2-dibromo-3-(4-fluorophenyl)-2-propene [(Z)-1e]
(294 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 29:1) (Z)-2-(4-fluorobenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3e] was obtained as a pale yellow oil in 63% yield (153 mg,
0.63 mmol, Z:E ≥ 95:5); Rf 0.51 (n-hexane:ethyl acetate = 29:1); IR (ATR) ν 3042, 2852,
1682, 1599, 1490, 1463, 1347, 1306, 1258, 1225, 1159, 1106, 1029, 997, 928, 842, 746, 572,
27

1
524, 480, 419 cm-1; H NMR (600 MHz, C6D6) δ 4.00 (s, 2H, 1-H), 4.96 (s, 1H, 3-H),
6.68─6.69 (m, 1H, 3’’-H), 6.69─6.70 (m, 1H, 4’’-H), 6.86─6.90 (ovl, m, 1H, 5’’-H), 6.86─6.90
(ovl, m, 2H, 3’-H and 5’-H), 6.92─6.93 (m, 1H, 2’’-H), 7.45─7.49 (m, 2H, 2’-H and 6’-H);
2
2
13C NMR (125 MHz, C6D6) δ 65.79 (C-1), 106.05 (C-3), 115.44 (d, J(4’-F, C-3’) = J(4’-F,
C-5’) = 21.2 Hz, C-3’ and C-5’), 116.92 (C-5’’), 117.79 (C-2’’), 122.50 (C-3’’), 122.97 (C-
3
3
4’’), 130.89 (d, J(4’-F, C-2’) = J(4’-F, C-6’) = 7.8 Hz, C-2’ and C-6’), 130.95 (C-1’),
142.84 (C-6’’), 143.40 (d, 6J(4’-F’, C-2) = 2.0 Hz, C-2), 144.73 (C-1’’), 162.00 (d, 1J(4’-F, C-
4’) = 246.5 Hz, C-4’); MS (EI, 70 eV) m/z (%) 242 (100) [M]+ ≙ [C15H11O2F]+, 134 (68), 121
(10); HRMS (EI, M+) calculated for [C15H11O2F]+ 242.0738 found 242.0725.
4.3.7 (Z)-2-(4-Chlorobenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3f] [9c,d]
According to general procedure II, (Z)-1,2-dibromo-3-(4-chlorophenyl)-2-propene [(Z)-1f]
(310 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 29:1) (Z)-2-(4-chlorobenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3f] was obtained as a white solid in 54% yield (141 mg,
0.54 mmol, Z:E ≥ 95:5); Rf 0.53 (n-hexane:ethyl acetate = 19:1); 1H NMR (600 MHz, C6D6) δ
3.96 (s, 2H, 1-H), 4.90 (s, 1H, 3-H), 6.67─6.79 (m, 1H, 3’’-H), 6.69─6.71 (m, 1H, 4’’-H),
3
3
6.86─6.88 (m, 1H, 2’’-H), 6.91─6.93 (m, 1H, 5’’-H), 7.20 (d like, J(3’-H, 2’-H) = J(5’-H,
3
3
6’-H) = 8.2 Hz, 2H, 3’-H and 5’-H), 7.41 (d like, J(2’-H, 3’-H) = J(6’-H, 5’-H) = 8.2 Hz,
2H, 2’-H and 6’-H); 13C NMR (125 MHz, C6D6) δ 65.72 (C-1), 105.90 (C-3), 116.92 (C-2’’),
117.77 (C-5’’), 122.55 (C-4’’), 123.07 (C-3’’), 128.76 (C-3’ and C-5’), 130.47 (C-2’ and C-
6’), 132.68 (C-4’). 133.27 (C-1’), 142.74 (C-6’’), 144.23 (C-2), 144.68 (C-1’’); MS (EI, 70
eV) m/z (%) 258 (100) [M]+ ≙ [C15H11O2Cl]+, 223 [M─Cl]+ ≙ [C15H11O2Cl]+ (14), 150 (60),
129 (15), 115 (89), 97 (11), 63 (10).
4.3.8 (Z)-2-(4-Bromobenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3g]
According to general procedure II, (Z)-1,2-dibromo-3-(4-bromophenyl)-2-propene [(Z)-1g]
(355 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 29:1) (Z)-2-(4-bromobenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3g] was obtained as a white solid in 53% yield (161 mg,
0.53 mmol, Z:E ≥ 95:5); mp 90–91 °C; Rf 0.56 (n-hexane:ethyl acetate = 29:1); IR (ATR) ν
3056, 2839, 1672, 1594, 1482, 1401, 1343, 1304, 1279, 1262, 1189, 1106, 1068, 995, 867,
853, 824, 766, 741, 657, 568, 509, 469 cm-1; 1H NMR (600 MHz, pyridine-d5) δ 4.64 (s, 2H,
1-H), 5.65 (s, 1H, 3-H), 6.97─6.99 (m, 1H, 3’’-H), 6.99─7.02 (m, 1H, 4’’-H), 7.08─7.11 (m,
28

3
1H, 2’’-H), 7.21─7.23 (m, 1H, 5’’-H), 7.59 (d like, J(3’-H, 2’-H) = 3J(5’-H, 6’-H) = 8.5 Hz,
3
2H, 3’-H and 5’-H), 7.71 (d like, J(2’-H, 3’-H) = 3J(6’-H, 5’-H) = 8.5 Hz, 2H, 2’-H and 6’-
H); 13C NMR (125 MHz, pyridine-d5) δ 65.99 (C-1), 106.00 (C-3), 117.18 (C-2’’), 117.92 (C-
6’’), 120.78 (C-1’), 122.82 (C-3’’), 123.82 (C-4’’), 131.09 (C-3’ and C-5’), 131.89 (C-2’ and
C-6’), 134.10 (C-4’). 142.78 (C-6’’), 142.89 (C-2), 144.89 (C-1’’); MS (EI, 70 eV) m/z (%)
301 (100) [M]+ ≙ [C15H11O2Br]+, 223 [M─Br]+ ≙ [C15H11O2Br]+ (19), 193 (34), 115 (66);
HRMS (EI, M+) calculated for [C15H11O2Br]+ 301.9937 found 301.9924.
4.3.9 (Z)-2-(3-Bromobenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3h]
According to general procedure II, (Z)-1,2-dibromo-3-(3-bromophenyl)-2-propene [(Z)-1h]
(355 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 29:1) (Z)-2-(3-bromobenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3h] was obtained as a white solid in 55% yield (168 mg,
0.55 mmol, Z:E ≥ 95:5); mp 90–91 °C; Rf 0.56 (n-hexane:ethyl acetate = 29:1); IR (ATR) ν
3001, 2857, 1673, 1585, 1492, 1461, 1417, 1353, 1269, 1171, 1105, 1073, 1029, 994, 937,
878, 839, 824, 779, 748, 717, 675, 581, 500, 451, 435, 411 cm-1; 1H NMR (600 MHz, C6D6) δ
3.93 (s, 2H, 1-H), 4.83 (s, 1H, 3-H), 6.64─6.67 (m, 1H, 3’’-H), 6.67─6.69 (m, 1H, 4’’-H), 6.84
3
3
( t like J(5’-H, 4’-H) = J(5’-H, 6’-H) = 7.8 Hz, 1H, 5’-H), 6.85─6.87 (m, 1H, 2’’-H),
6.89─6.91 (m, 1H, 5’’-H), 7.19 (d like, 3J(4’-H, 5’-H) = 7.8 Hz, 1H, 4’-H), 7.44 (d like, 3J(2’-
13
H, 3’-H) = 7.8 Hz, 1H, 6’-H), 7.87 (s, 1H, 2’-H); C NMR (125 MHz, C6D6) δ 65.32 (C-1),
105.24 (C-3), 116.69 (C-2’’), 117.38 (C-5’’), 122.31 (C-3’’), 122.54 (C-1’), 122.78 (C-4’’),
127.25 (C-6’), 129.61 (C-5’), 129.70 (C-4’), 131.78 (C-2’), 136.65 (C-3’), 142.33 (C-6’’),
144.30 (C-1’’), 144.57 (C-2); MS (EI, 70 eV) m/z (%) 301 (100) [M]+ ≙ [C15H11O2Br]+, 223
[M─Br]+ ≙ [C15H11O2]+ (14), 194 (34), 147 (10), 115 (68); HRMS (EI, M+) calculated for
[C15H11O2Br]+ 301.9937 found 301.9913.
4.3.10 (Z)-2-(3-Methoxybenzylidene)-2,3-dihydrobenzo[b][1,4]dioxine [(Z)-3i]
According to general procedure 4, (Z)-1,2-dibromo-3-(3-methoxyphenyl)-2-propene [(Z)-1i]
(355 mg, 1 mmol), catechol (2a) (221 mg, 2 mmol) and Cs2CO3 (1.31 g, 4.00 mmol) were
reacted for 18 h at 140 °C in DMF. After work-up and purification by column
chromatography (SiO2, n-hexane:ethyl acetate = 49:1) (Z)-2-(3-methoxybenzylidene)-2,3-
dihydrobenzo[b][1,4]dioxine [(Z)-3i] was obtained as a white solid in 65% yield (147 mg,
0.55 mmol, Z:E ≥ 95:5); mp 85–86 °C; Rf 0.54 (n-hexane:ethyl acetate = 49:1); IR (ATR) ν
2997, 2910, 1674, 1594, 1488, 1459, 1349, 1300, 1254, 1206, 1170, 1103, 1037, 998, 949,
1
906, 863, 784, 772, 746, 688, 627, 507, 456, 410 cm-1; H NMR (600 MHz, C6D6) δ 3.41 (s,
29