Dimethylzinc-Initiated Radical Coupling of β-Bromostyrenes with Ethers and Amines

Article abstract of DOI:10.1002/chem.201502429

A new coupling reaction has been developed in which β-bromostyrenes react with ethers and tertiary amines to introduce the styryl group in the α-position. The transformation is mediated by Me₂Zn/O₂ with 10 % MnCl₂ and is believed to proceed by a radical addition-elimination mechanism. The ether and the amine are employed as solvent and the coupling takes place through the most stable α radical for unsymmetrical substrates. The products are obtained in moderate to good yields as the pure E isomers. The coupling can be achieved with a range of smaller cyclic and acyclic ethers/amines as well as various substituted β-bromostyrenes.

Full text of DOI:10.1002/chem.201502429

DOI: 10.1002/chem.201502429
Full Paper
&
CÀH Bond Activation
Dimethylzinc-Initiated Radical Coupling of b-Bromostyrenes with
Ethers and Amines
[
a]
Amanda Sølvhøj, Andreas Ahlburg, and Robert Madsen*
Abstract: A new coupling reaction has been developed in
which b-bromostyrenes react with ethers and tertiary
amines to introduce the styryl group in the a-position. The
transformation is mediated by Me Zn/O with 10% MnCl
2
vent and the coupling takes place through the most stable
a radical for unsymmetrical substrates. The products are ob-
tained in moderate to good yields as the pure E isomers.
The coupling can be achieved with a range of smaller cyclic
and acyclic ethers/amines as well as various substituted
b-bromostyrenes.
2
2
and is believed to proceed by a radical addition–elimination
mechanism. The ether and the amine are employed as sol-
[
9]
Introduction
same position. b-Nitrostyrenes have been reacted with THF
in the presence of dibenzoyl peroxide to afford styryl tetrahy-
[
10]
a-Alkoxy alkyl and a-amino alkyl radicals are unique intermedi-
ates in organic synthesis and they can react with unsaturated
acceptors to form carbon–carbon bonds under relatively mild
drofurans.
Recently, a copper-catalyzed oxidative coupling
between olefins and ethers to form a-alkenyl ethers was
[
11]
presented, although the mechanism is not known. In most
cases, the substrate scope of these radical addition–elimination
reactions is rather narrow and there is clearly room for further
development of these procedures to install olefins in the a-
position of ethers and amines.
[
1]
conditions. The carbon-centered radicals are nucleophilic and
are typically formed by abstraction of the a-hydrogen from
ethers and tertiary amines. a-Alkoxy alkyl radicals are rather
versatile species and the addition of ethers (and especially tet-
[2]
[3]
[4]
[5]
rahydrofuran) to C=C, CꢀC, C=N, and C=O bonds has
been achieved under different conditions. Typically, the ether
is used as the solvent and the radical is generated with either
Herein, we describe a novel radical coupling between
b-bromostyrenes and ethers/amines mediated by Me Zn and
2
a catalytic amount of MnCl2.
[2–5]
Me Zn/O , Et B/O , or peroxides as the initiator.
a-Amino
2
2
3
2
alkyl radicals, on the other hand, have found fewer synthetic
applications, which is mainly due to difficulties associated with
their generation from tertiary amines because further oxidation
to iminium cations takes place easily. However, the addition of
Results and Discussion
The radical coupling was discovered by serendipity when at-
tempting a cross-coupling reaction between b-bromostyrene
and p-tolylzinc iodide in THF. The Negishi coupling has had
a significant impact on organic synthesis, but the reaction re-
quires the use of expensive and toxic metal palladium as the
[6]
tertiary amines to aldehydes and electron-deficient C=C
[
7]
bonds have been described with either Et B/O or visible
3
2
light photoredox catalysis.
[
12]
Besides addition reactions, addition–elimination reactions
can also be carried out with these radicals, although this sce-
nario is relatively rare. The further development of this trans-
formation is highly attractive because a new functional group
catalyst. It has, however, been shown that the cross coupling
between vinyl halides and Grignard reagents can be catalyzed
[
13]
by the much less expensive and more benign catalyst MnCl2.
The mechanism for this manganese-catalyzed coupling
reaction is not known, but it seemed reasonable to attempt
a similar coupling with an organozinc species. b-Bromostyrene
was selected because it had served as a successful substrate
(
alkene or alkyne) is installed in the ether/amine to furnish the
corresponding allyl/propargyl species. Under photoirradiation
conditions, alkenyl and alkynyl sulfones have been coupled
with ethers and amines to install the alkene/alkyne in the a-
[
13]
for coupling with aryl Grignard reagents.
However, un-
[
8]
position. Phenylethynyl bromide/benziodoxolone have been
converted with ethers to introduce the alkynyl moiety in the
expectedly, the coupling did not occur with the organozinc
reagent, but instead with the solvent THF.
The reaction was very clean and gave 2-styryltetrahydrofuran
in 55% GC yield with the rest being unreacted b-bromostyrene
[
a] Dr. A. Sølvhøj, A. Ahlburg, Prof. Dr. R. Madsen
Department of Chemistry
Technical University of Denmark
(
Table 1, entry 1). In the absence of MnCl the yield dropped to
2
1
3%, which underlines the importance of manganese in com-
2
800 Kgs. Lyngby (Denmark)
bination with the zinc reagent (entry 2). No reaction occurred
E-mail: rm@kemi.dtu.dk
when the organozinc halide was replaced with ZnCl , whereas
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201502429.
2
a low yield was obtained with n-propylzinc bromide (entries 3
Chem. Eur. J. 2015, 21, 16272 – 16279
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Full Paper
Table 1. Radical initiators and additives for the coupling between
b-bromostyrene and THF.
Table 2. Coupling of b-bromostyrene with different substrates.
[a]
Entry
1
RÀH
Temp. [8C]
Product
Yield [%]
47
[a]
Entry
Initiator
X
Additive
Y [%]
Yield [%]
[
[
[
[
b]
b]
b]
b]
1
2
3
4
5
6
7
8
9
1
p-MePhZnI
p-MePhZnI
2
2
2
2
3
3
3
3
3
3
3
2
1
3
3
3
3
3
3
3
3
3
3
3
3
3
MnCl
none
MnCl
MnCl
MnCl
MnCl
None
MnCl
None
MnCl
None
MnCl
MnCl
MnCl
2
None
2
30
–
55
13
0
11
67
35
6
65
ZnCl
n-PrZnBr
Me Zn
2
2
2
2
2
25
30
30
12
–
30
–
30
–
40
35
10
–
10
10
10
10
10
30
30
10
10
20
20
[
b]
2
2
78
88
65
40
Bz
Bz
2
2
O
O
2
[b]
2
[
c]
c]
Et
Et
2
Zn
B
2
5
12
<1
<1
56
31
75
45
62
43
75
58
60
21
28
49
73
62
28
[
3
3
[b]
0
AIBN
AIBN
2
[b]
1
1
1
1
2
3
Me
Me
2
Zn
Zn
2
2
2
4
100
44
1
4
Me
2
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
1
1
1
1
1
2
2
2
2
2
2
2
5
6
7
8
9
0
1
2
3
4
5
6
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
2
2
2
2
2
2
2
2
2
2
2
2
MnBr
Mn(OAc)
Mn(OAc)
2
2
3
31
+
MnBr(CO)
Mn (CO)10
5
5
6
74
82
16
2
FeCl
FeCl
2
3
2
·H O
CuCl
CoCl
2
2
[b]
34
CrCl
2
NaCl
[
a] GC yield. [b] Performed under an argon atmosphere. [c] 1-Phenylbut-1-
7
8
9
35
68
80
67
12
71
ene was formed as a major byproduct.
and 4). Although organozinc halides are known to form
[14]
carbon-centered radicals, the corresponding diorganozinc re-
agents have found much wider applications as radical initiators
[15]
in the presence of air. Indeed, when Me Zn was employed as
2
the zinc reagent, the yield of the coupling product increased
to 67% (entry 5). Several other radical initiators were also in-
vestigated, but the results were poor. The use of Bz O , Et Zn,
[a] Isolated yield. [b] Me Zn (3 equiv) was employed.
2
2
2
2
and Et B all led to low yields of the coupling product, and only
3
traces were observed with AIBN (entries 6–11). Therefore,
of the remaining starting material is not known. b-Bromostyr-
ene is employed as a 6:1 mixture of the E and the Z isomer,
but only (E)-2-styryltetrahydrofuran was isolated as the product
and none of the Z compound was detected. At lower tempera-
ture, the yield was reduced, but the E isomer was still the only
product observed. At 08C, the GC yield was 42%, compared
with 75% at reflux (Table 1, entry 14); no conversion occurred
at À188C.
Me Zn was selected for general use as the initiator. Several ex-
2
periments were performed with different amounts of Me Zn
2
and MnCl , and 3 equiv of the zinc reagent and 10% of the
2
manganese salt seemed to give the best results (entries 12–
1
2
5). A number of other salts were also investigated (entries 16–
6); however, although comparable results were obtained with
both Mn(OAc) and CoCl , MnCl was subsequently employed
3
2
2
for general use.
Full conversion was achieved with 2-methyltetrahydrofuran
Thus, the optimized conditions employ Me Zn and 10%
at reflux with 3 equiv of Me Zn, and 2-methyl-2-styryltetrahy-
2
2
MnCl in the ether as solvent at reflux under air. The conver-
drofuran was isolated in 65% yield (Table 2, entry 2). A small
amount of the isomeric 2-methyl-5-styryl compound was also
detected (as two diastereomers), but these were not isolated.
The ratio between the 2-styryl and the 5-styryl compound was
6.3:1, as determined by GC analysis. This shows that the cou-
pling mainly proceeds through the most stable a-alkoxy alkyl
2
sion of b-bromostyrene was approximately 90% in THF, but
upon scale up the isolated yield of 2-styryltetrahydrofuran was
only 33%. Consequently, it was decided to increase the
amount of Me Zn to 4 equiv, which gave full conversion of b-
2
bromostyrene and an isolated yield of 47% (Table 2, entry 1).
No byproducts could be detected by GC analysis and the fate
radical. In the absence of MnCl , the conversion of b-bromo-
2
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styrene was only around 50% and the ratio between the two
isomeric products dropped to 2.7:1. A similar reactivity was
observed with tetrahydropyran (THP), for which 2-styryltetra-
hydropyran was isolated as the main product in 40% yield
[a]
Table 3. Coupling of substituted b-bromostyrenes with THF.
[b]
Entry
Substrate
Product
Yield [%]
48
(
entry 3). Small amounts of two isomers resulting from reaction
1
in the 3- and 4-position of THP were also observed, but these
were not isolated. 1,4-Dioxane gave the 2-styryl derivative
(
entry 4), whereas 1,3-dioxolane afforded a mixture of the 2-
2
3
48
40
and 4-styryl compound (entry 5). A mixture of the 2- and 4-
derivative was also observed with 2-methyl-1,3-dioxolane in
a 2.9:1 ratio, for which the former was isolated in 34% yield
(
entry 6). When MnCl2 was omitted, the conversion of
b-bromostyrene dropped to below 5% and it was no longer
possible to determine the ratio between the product isomers.
Full conversion of b-bromostyrene was not observed in the
reactions with 1,4-dioxane, 1,3-dioxolane, or 2-methyl-1,3-diox-
olane (Table 2, entries 5–7). The variations in the reactivity and
selectivity correlate reasonably well with the differences be-
tween the calculated CÀH dissociation energies for the cyclic
[c]
4
54
39
39
5
À1
À1
ethers: THF 89.8 kcalmol (H-2), THP 92.1 kcalmol (H-2),
À1
À1
1
,4-dioxane 93.2 kcalmol (H-2), 1,3-dioxolane 90.0 kcalmol
[
[
d]
6
7
8
À1
[16]
(
H-2), and 91.5 kcalmol
(H-4).
As a result, hydrogen
abstraction from THP and 1,3-dioxolane is expected to
occur both from the a-position and (to a lesser degree) from
d]
c]
[
16]
37
54
the other positions.
Acyclic ethers could also be employed in the coupling, as
shown with diethyl ether, which gave the a-styryl product in
[
6
7% yield (Table 2, entry 7). The reaction did not go to com-
pletion because similar conversion was observed for the start-
ing b-bromostyrene. Diisopropyl ether, on the other hand, was
a poor substrate and only gave 12% isolated yield of the prod-
uct with approximately 30% conversion of b-bromostyrene
[
e]
9
1
21
18
(
entry 8). Interestingly, the conditions were also amenable to
tertiary amine because N-methylpyrrolidine gave full
conversion of b-bromostyrene and 71% isolated yield of the
[
c,e]
0
a
[
[
a] Reaction conditions: Me
2
2
Zn (3 equiv), 10% MnCl , THF, 16 h, 658C, air.
2
-styryl product (entry 9).
b] Isolated yield. [c] Reaction time 3 d. [d] Reaction time 2 d. [e] Addition-
Zn (3 equiv) and 10% MnCl were added followed by heating to
reflux for another 16 h.
A range of substituted b-bromostyrenes were then investi-
al Me
2
2
gated as substrates in the reaction with THF (Table 3). The
starting materials were prepared from the corresponding car-
boxylic acids by a Mn(OAc) -catalyzed Hunsdiecker reaction
2
[
17]
with N-bromosuccinimide (NBS). Interestingly, chloro, bromo,
fluoro, methyl, hydroxyl, and ether substituents all gave higher
yields of the coupling products than obtained with the parent
b-bromostyrene under the same conditions (entries 1–8). This
may be due to the enhanced ability of these substituents to
detail. b-Bromo-3,4-methylenedioxystyrene was selected for
these studies because this substrate previously gave the high-
est yield (Table 3). First, the reaction with N-methylpiperidine
was performed at different temperatures, which proved to
have a considerable influence on the outcome. The best result
was obtained when the reaction was performed at 658C;
under these conditions, the 2-piperidyl compound was isolated
in 83% yield and the corresponding N-methyl coupling prod-
uct was obtained in 8% yield (Table 4, entry 1). Decreasing the
temperature gave lower yields (entries 2–4), and almost no
conversion occurred at À208C. The ratio between the two
products was slightly different at lower temperature, but both
compounds were only detected as the E isomers. Increasing
the temperature had a detrimental effect and only 15% yield
of the main product was obtained at 858C (entries 5 and 6).
Attempts to use a co-solvent were unsuccessful; performing
the coupling in benzene, heptane, and pyridine only produced
[
18]
stabilize a benzylic radical compared with a hydrogen atom.
In contrast, bicyclic substrates 2-(2-bromovinyl)naphthalene
and 2-bromoindene reacted very slowly and the coupling
products were only isolated in low yield even after addition of
additional reagent (entries 9 and 10). Notably, all the products
presented in Table 2 and Table 3 were isolated as the E
isomers; the corresponding Z compounds were not detected.
The reaction with a tertiary amine (Table 2, entry 9) deserves
further comment because the use of Me Zn and air has very
2
seldom been employed for generating a-amino alkyl radi-
[19]
cals. As a result, it was decided to investigate the scope of
the coupling with amines and amine derivatives in further
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9
58C (entry 10) and no further experiments were performed to
Table 4. Coupling of b-bromo-3,4-methylenedioxystyrene with tertiary
amines and DMF.
investigate the influence of the temperature. Tri-n-propyl-
amine, on the other hand, gave a disappointing 21% yield at
6
58C and a mere 4% at 958C (entries 11 and 12). Most likely,
the increased steric hindrance in this substrate compared with
that of triethylamine accounts for the significant difference in
yield between the two acyclic amines. This is consistent with
the observation that diethyl ether gave a much higher yield
than diisopropyl ether (Table 2, entries 7 and 8). The reaction
with N-methylmorpholine gave approximately 50% conversion
of b-bromostyrene and afforded a 4:1 mixture of the a-amino
and the a-alkoxy coupling product, from which the former
could be isolated in 25% yield (Table 4, entry 13). In the ab-
[a]
Entry RÀH
Temp. [8C] Product
Yield [%]
[b]
1
2
3
4
5
6
65
55
20
0
75
85
83
77
67
51
66
15
[
[
c]
b]
sence of MnCl , the same experiment gave 34% conversion of
2
58
b-bromostyrene and the two products were formed in a slightly
lower ratio (3:1). N,N-Dimethylformamide (DMF) was a poor
substrate and only furnished about 20% yield, depending on
the temperature (entries 14–16). Heterocyclic amines such as
pyridine, N-methylpyrrole, and N-methylindole did not react in
the coupling and the same was observed with the secondary
amine pyrrolidine. As observed in the ether coupling, all the
products presented in Table 4 were obtained as the pure E
isomers.
7
65
85
+
26
22
8
9
+
31
The mechanism for these coupling reactions has not been
investigated in detail, but all indications are that they proceed
62
by a radical pathway. Studies have shown that Me Zn reacts
2
95
95
+
with O to form a zinc methylperoxide, which is able to break
2
23
down by homolysis to give the oxygen-centered radicals
·
· [20]
MeZnO and MeO. These may react with the ether or the ter-
tiary amine to generate the a-alkoxy or a-amino alkyl radical,
which, upon addition to b-bromostyrene, forms the benzylic
radical (Scheme 1). Final elimination of a bromine radical then
10
95
1
1
65
95
21
4
12
13
65
25
1
1
1
4
5
6
65
85
95
19
22
15
Scheme 1. Proposed mechanism for radical addition–elimination with THF.
[
a] Isolated yield. [b] N-(3,4-Methylenedioxycinnamyl)piperidine was also
isolated in 8% yield. [c] N-(3,4-Methylenedioxycinnamyl)piperidine was
also isolated in 18% yield.
produces the addition–elimination product. The addition of
a stoichiometric amount of 2,2,6,6-tetramethylpiperidine-1-oxyl
(TEMPO) completely blocks the reaction shown in Table 2,
entry 1, which is presumably due to the formation of the com-
approximately 20% yield at 658C (results not shown). Conse-
quently, the coupling reactions with tertiary amines were
performed under the same conditions developed for ethers.
N-Ethylpiperidine also gave a good yield at 658C, but the
ratio between the two coupling products was now about 2:1,
which reflects the similar stability of the two a-amino alkyl
radicals (Table 4, entry 7). No improvement was observed by in-
creasing the temperature to 858C (entry 8). The reaction with
N-ethylpyrrolidine gave a similar result at 658C, whereby the
two coupling products were isolated in 85% overall yield
·
[21]
plex MeZn(TEMPO) with the release of a Me radical, which
would inhibit the formation of the zinc methylperoxide. The
coupling also did not progress when it was run under com-
pletely air-free conditions (and in the absence of MnCl ). The
2
exact role of the added MnCl is not clear. However, it has pre-
2
viously been demonstrated that MnCl , FeCl , and CrCl acceler-
2
3
3
ate the conjugate addition of ethers to benzylidenemalonates
in the presence of Me Zn/O , although the precise behavior of
2
2
[
19]
(
entry 9). Triethylamine afforded one product in 95% yield at
the added salts was not investigated.
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eluting with heptane containing 1% increments of ethyl acetate
per fraction gave the product as a colorless oil. H NMR (400 MHz,
Conclusion
1
CDCl ): d=7.40 (d, J=7.2 Hz, 2H), 7.32 (t, J=7.6 Hz, 2H), 7.22 (t,
J=7.3 Hz, 1H), 6.57 (d, J=16.0 Hz, 1H), 6.26 (d, J=16.0 Hz, 1H),
A new procedure has been developed for introducing a styryl
group at the a-position of ethers and tertiary amines. The
conditions have been optimized and the reaction has been
applied to a variety of substrates. The coupling is believed to
proceed by a radical pathway and takes place through the
most stable a radical in unsymmetrical ethers and amines. The
3
3
1
1
.96 (t, J=6.8 Hz, 2H), 2.04–1.90 (m, 3H), 1.85–1.76 (m, 1H),
13
.43 ppm (s, 3H); C NMR (101 MHz, CDCl ): d=137.2, 135.5, 128.5,
3
27.2, 126.8, 126.4, 82.4, 67.7, 37.9, 26.8, 25.8 ppm; MS: m/z: 188
+
+
[M] ; HRMS: m/z calcd for C H O: 189.1279 [M+H] ; found:
13 17
189.1290.
transformation constitutes a new application of Me Zn and
2
(E)-2-Styryltetrahydropyran: Table 2, entry 3. Prepared by using
highlights the versatile nature of this reagent in organic
synthesis.
procedure A, from b-bromostyrene and THP with Me Zn (4 equiv).
2
DCVC eluting with heptane containing 1% increments of ethyl ace-
1
tate per fraction gave the product as a colorless oil. H NMR
(
400 MHz, CDCl ): d=7.39 (d, J=7.2 Hz, 2H), 7.31 (t, J=7.5 Hz, 2H),
3
7
5
.23 (t, J=7.3 Hz, 1H), 6.60 (d, J=16.1 Hz, 1H), 6.23 (dd, J=16.1,
.8 Hz, 1H), 4.12–4.05 (m, 1H), 4.02–3.95 (m, 1H), 3.60–3.52 (m,
Experimental Section
General methods: Gas chromatography was performed with a
Shimadzu GCMS-QP2010S instrument fitted with an Equity 5,
1H), 1.94–1.86 (m, 1H), 1.79–1.72 (m, 1H), 1.66–1.48 ppm (m, 4H);
13
C NMR (101 MHz, CDCl
126.5, 78.1, 68.5, 32.4, 26.0, 23.6 ppm; MS: m/z: 188 [M] ; NMR
): d=137.1, 131.0, 129.8, 128.6, 127.5,
3
+
3
0 m”0.25 mm”0.25 mm column. Flash column chromatography
[10]
separations were performed on silica gel 60 (40–63 mm). Dry
data are in accordance with the reported values.
E)-2-Styryl-1,4-dioxane: Table 2, entry 4. Prepared by using proce-
dure from b-bromostyrene and 1,4-dioxane with Me Zn
4 equiv). DCVC eluting with heptane containing 1% increments of
[22]
column vacuum chromatography (DCVC) was carried out with
silica gel 60 (15–40 mm). NMR spectra were recorded with a Bruker
Ascend 400 spectrometer. Chemical shifts were measured relative
(
A
2
(
to the signals of residual CHCl3 (d =7.26 ppm) and CDCl3
H
ethyl acetate per fraction gave the product as a colorless oil.
1
(
dC =77.16 ppm). HRMS measurements were made with ESI and
H NMR (400 MHz, CDCl ): d=7.37 (d, J=7.2 Hz, 2H), 7.30 (t, J=
3
TOF detection.
7
.4 Hz, 2H), 7.24 (d, J=7.2 Hz, 1H), 6.68 (d, J=16.0 Hz, 1H), 6.08
General procedure for ether coupling (procedure A): To a 50 mL
round-bottomed flask equipped with a stir bar and a condenser,
(dd, J=16.0, 6.2 Hz, 1H), 4.29–4.21 (m, 1H), 3.90–3.60 (m, 5H),
13
3.46–3.36 ppm (m, 1H); C NMR (101 MHz, CDCl
): d=136.3, 132.6,
3
was added MnCl (12.6 mg, 0.1 mmol), b-bromostyrene (1.0 mmol),
128.5, 127.8, 126.4, 125.0, 76.0, 70.8, 66.5, 66.2 ppm; MS: m/z: 190
2
+
[23]
and the ether (25 mL) as solvent. Me Zn (1.0m in heptanes, 3–
[M] . NMR data are in accordance with the reported values.
E)-2-Styryl-1,3-dioxolane: Table 2, entry 5. Prepared by using pro-
cedure A, from b-bromostyrene and 1,3-dioxolane with Me Zn
2
4
mL, 3–4 mmol) was then added and the mixture was heated to
(
the indicated temperature for 16 h. The reaction was quenched
with 1.0m HCl (10 mL) and the mixture was stirred until both
phases were clear. The phases were separated and the aqueous
2
(
4 equiv). The reaction was worked up with 1.0m NaOH instead of
HCl to avoid formation of cinnemaldehyde. DCVC eluting with hep-
layer was extracted with Et O (2”20 mL). The combined organic
phases were washed with water (20 mL), dried over MgSO4,
2
tane containing 1% increments of ethyl acetate per fraction gave
1
the product as a colorless oil. H NMR (400 MHz, CDCl ): d=7.43 (d,
3
filtered, and concentrated in vacuo to give the crude product,
which was purified by DCVC.
J=7.0 Hz, 2H), 7.34 (t, J=7.2 Hz, 2H), 7.30–7.25 (m, 1H), 6.79 (d,
J=16.0 Hz, 1H), 6.18 (dd, J=16.0, 6.0 Hz, 1H), 5.44 (d, J=6.0 Hz,
13
General procedure for amine coupling (procedure B): To a 25 mL
round-bottomed flask equipped with a stir bar and a condenser,
was added MnCl2 (12.6 mg, 0.1 mmol), b-bromo-3,4-methylene-
dioxystyrene (227 mg, 1.0 mmol) and the tertiary amine (10 mL) as
1H), 4.10–4.02 (m, 2H), 4.01–3.92 ppm (m, 2H); C NMR (101 MHz,
CDCl ): d=135.9, 135.0, 128.7, 128.5, 127.1, 125.2, 104.0, 65.2 ppm;
MS: m/z: 176 [M] ; NMR data are in accordance with the reported
3
+
[3d]
values.
solvent. Me Zn (1.0m in heptanes, 4 mL, 4 mmol) was added and
2
(E)-4-Styryl-1,3-dioxolane: Table 2, entry 5. Prepared by using pro-
the mixture was heated to the indicated temperature for 16 h. The
reaction was quenched with saturated sodium hydroxide (10 mL)
cedure A, from b-bromostyrene and 1,3-dioxolane with Me Zn and
a reaction time of two days. DCVC eluting with heptane containing
2
and the mixture was extracted with CH Cl2 (2”20 mL). The
combined organic phases were concentrated in vacuo to give the
crude product, which was purified by flash chromatography.
2
2% increments of ethyl acetate per fraction gave the product as
1
a colorless oil. H NMR (400 MHz, CDCl ): d=7.33–7.29 (m, 2H),
3
7
.27–7.22 (m, 2H), 7.21–7.15 (m, 1H), 6.60 (d, J=15.0 Hz, 1H), 6.10
(
E)-2-Styryltetrahydrofuran: Table 2, entry 1. Prepared by using
(dd, J=15.0, 7.5 Hz, 1H), 5.05 (s, 1H), 4.92 (s, 1H), 4.53 (q, J=
7.5 Hz, 1H), 4.03 (dd, J=8.0, 6.7 Hz, 1H), 3.55 ppm (dd, J=8.0,
procedure A, from b-bromostyrene and THF with Me Zn (4 equiv).
DCVC eluting with heptane containing 1% increments of ethyl ace-
tate per fraction gave the product as a colorless oil. H NMR
2
13
6.7 Hz, 1H); C NMR (101 MHz, CDCl ): d=136.2, 133.5, 128.2,
3
1
+
126.7, 126.3, 95.6, 77.0, 69.9 ppm; MS: m/z: 176 [M] . HRMS: m/z
+
(
400 MHz, CDCl ): d=7.38 (d, J=7.2 Hz, 2H), 7.30 (t, J=7.5 Hz, 2H),
calcd for C H O : 177.0910 [M+H] ; found: 177.0909.
3
11 13
2
7
6
1
2
1
.22 (t, J=7.3 Hz, 1H), 6.59 (d, J=15.8 Hz, 1H), 6.21 (dd, J=15.8,
.6 Hz, 1H), 4.47 (td, J=7.5, 1.0 Hz, 1H), 3.97 (dd, J=14.2, 7.7 Hz,
H), 3.84 (td, J=7.9, 6.2 Hz, 1H), 2.19–2.05 (m, 1H), 2.04–1.85 (m,
(
E)-2-Methyl-2-styryl-1,3-dioxolane: Table 2, entry 6. Prepared by
using procedure A, from b-bromostyrene and 2-methyl-1,3-dioxo-
lane with Me Zn (3 equiv). The reaction was worked up with 1.0m
NaOH instead of HCl to avoid formation of 4-phenylbut-3-en-2-
one. DCVC eluting with heptane containing 1% increments of
2
1
3
H), 1.77–1.64 ppm (m, 1H); C NMR (101 MHz, CDCl ): d=136.9,
3
30.6, 130.5, 128.6, 127.5, 126.5, 79.7, 68.2, 32.5, 26.0 ppm; MS: m/
+
z: 174 [M] ; NMR data are in accordance with the reported val-
ues.
ethyl acetate per fraction gave the product as a colorless oil.
[
3d]
1
H NMR (400 MHz, CDCl ): d=7.40–7.35 (m, 2H), 7.34–7.26 (m, 2H),
3
(
E)-2-Methyl-2-styryltetrahydrofuran: Table 2, entry 2. Prepared by
7.26–7.19 (m, 1H), 6.69 (d, J=16.0 Hz, 1H), 6.14 (d, J=16.0 Hz, 1H),
13
using procedure A, from b-bromostyrene and 2-methyltetrahydro-
4.02–3.89 (m, 4H), 1.55 ppm (s, 3H); C NMR (101 MHz, CDCl ): d=
3
furan with Me Zn (3 equiv) and a reaction time of two days. DCVC
136.3, 129.9, 129.8, 128.7, 128.0, 126.8, 107.7, 64.7, 25.3 ppm; MS:
2
Chem. Eur. J. 2015, 21, 16272 – 16279
www.chemeurj.org
16276
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
+
1
m/z: 190 [M] . NMR data are in accordance with the reported
values.
as a colorless oil. H NMR (400 MHz, CDCl ): d=7.33 (dd, J=8.7,
3
[24]
5.4 Hz, 2H), 6.98 (t, J=8.7 Hz, 2H), 6.54 (d, J=15.8 Hz, 1H), 6.12
(
dd, J=15.8, 6.6 Hz, 1H), 4.45 (q, J=6.7 Hz, 1H), 3.96 (q, J=7.5 Hz,
(
E)-(3-Ethoxybut-1-en-1-yl)benzene: Table 2, entry 7. Prepared by
1
1
2
H), 3.83 (q, J=7.9 Hz, 1H), 2.17–2.06 (m, 1H), 2.04–1.87 (m, 2H),
using procedure A, from b-bromostyrene and diethyl ether with
Me Zn (4 equiv) and a reaction time of two days. DCVC eluting
with heptane containing 1% increments of ethyl acetate per frac-
tion gave the product as a pale-yellow oil. H NMR (400 MHz,
CDCl ): d=7.38 (d, J=7.3 Hz, 2H), 7.30 (t, J=7.5 Hz, 2H), 7.22 (t,
J=7.3 Hz, 1H), 6.51 (d, J=15.9 Hz, 1H), 6.12 (dd, J=15.9, 7.5 Hz,
13
.75–1.64 ppm (m, 1H); C NMR (101 MHz, CDCl ): d=162.3 (d, J=
3
2
46.5 Hz), 133.1 (d, J=3.3 Hz), 130.4 (d, J=2.2 Hz), 129.3, 128.0 (d,
1
J=8.0 Hz), 115.5 (d, J=21.6 Hz), 79.6, 68.2, 32.5, 26.0 ppm; MS: m/
z: 192 [M] . NMR data are in accordance with the reported val-
ues.
+
3
[3d]
1
1
H), 3.99 (p, J=6.7 Hz, 1H), 3.63–3.50 (m, 1H), 3.46–3.35 (m, 1H),
.34 (d, J=6.4 Hz, 3H), 1.21 ppm (t, J=7.0 Hz, 3H); C NMR
(E)-2-(2-Chlorostyryl)tetrahydrofuran: Table 3, entry 4. Prepared
by using procedure A, from (E)-1-(2-bromovinyl)-2-chlorobenzene
13
(
6
101 MHz, CDCl ): d=136.8, 132.2, 130.8, 128.6, 127.6, 126.5, 76.4,
and THF with Me Zn (3 equiv) and a reaction time of three days.
2
3
+
3.6, 21.8, 15.5 ppm; MS: m/z: 176 [M] . NMR data are in accord-
DCVC eluting with heptane containing 1% increments of ethyl ace-
[25]
1
ance with the reported values.
tate per fraction gave the product as a colorless oil. H NMR
(
1
400 MHz, CDCl ): d=7.53 (dd, J=7.6, 1.8 Hz, 1H), 7.33 (dd, J=7.8,
3
.5 Hz, 1H), 7.24–7.10 (m, 2H), 6.98 (d, J=15.8 Hz, 1H), 6.20 (dd,
(
E)-(3-Isopropoxy-3-methylbut-1-en-1-yl)benzene:
Table 2,
entry 8. Prepared by using procedure A, from b-bromostyrene and
diisopropyl ether with Me Zn (4 equiv) and a reaction time of two
days. DCVC eluting with heptane containing 1% increments of
J=15.8, 6.5 Hz, 1H), 4.51 (q, J=6.9 Hz, 1H), 3.97 (dd, J=14.4,
7
1
d=135.0, 133.5, 133.1, 129.7, 128.5, 126.9, 126.8, 126.6, 79.5, 68.2,
3
2
2
.5 Hz, 1H), 3.84 (td, J=7.9, 6.3 Hz, 1H), 2.19–2.08 (m, 1H), 2.04–
13
.87 (m, 2H), 1.77–1.66 ppm (m, 1H); C NMR (101 MHz, CDCl3):
ethyl acetate per fraction gave the product as a colorless oil.
1
H NMR (400 MHz, CDCl ): d=7.32 (d, J=7.3 Hz, 2H), 7.25 (t, J=
3
+
2.4, 25.9 ppm; MS: m/z: 208 [M] ; HRMS: m/z calcd for C H ClO:
12 14
7
1
.6 Hz, 2H), 7.19–7.13 (m, 1H), 6.39 (d, J=16.4 Hz, 1H), 6.19 (d, J=
6.4 Hz, 1H), 3.65 (hept, J=6.2 Hz, 1H), 1.30 (s, 6H), 1.05 ppm (d,
+
09.0733 [M+H] ; found: 209.0731.
1
3
(E)-2-(4-Methylstyryl)tetrahydrofuran: Table 3, entry 5. Prepared
by using procedure A, from (E)-1-(2-bromovinyl)-4-methylbenzene
and THF with Me Zn (3 equiv). DCVC eluting with heptane contain-
ing 1% increments of ethyl acetate per fraction gave the product
as a colorless oil. H NMR (400 MHz, CDCl ): d=7.29 (d, J=8.1 Hz,
2
1
1
2
J=6.2 Hz, 6H); C NMR (101 MHz, CDCl ): d=137.2, 136.6, 128.7,
1
HRMS: m/z calcd for C H O: 205.1582 [M+H] ; found: 205.1582.
3
+
28.4, 127.6, 126.5, 75.4, 65.0, 27.2, 25.2 ppm; MS: m/z: 204 [M] ;
+
2
1
4
21
(E)-1-Methyl-2-styrylpyrrolidine: Table 2, entry 9. Prepared by
1
3
using procedure B, from b-bromostyrene and N-methylpyrrolidine
with Me Zn (4 equiv) and a reaction time of two days to afford the
product as a yellow oil. H NMR (400 MHz, CDCl ): d=7.42–7.37 (m,
2
6
8
1
CDCl ): d=137.0, 132.1, 131.6, 128.5, 127.3, 126.2, 69.6, 56.7, 40.3,
3
1
H), 7.12 (d, J=8.0 Hz, 2H), 6.56 (d, J=15.8 Hz, 1H), 6.17 (dd, J=
5.8, 6.7 Hz, 1H), 4.47 (q, J=7.0 Hz, 1H), 3.98 (dd, J=14.3, 7.5 Hz,
H), 3.84 (td, J=7.9, 6.2 Hz, 1H), 2.34 (s, 3H), 2.19–2.07 (m, 1H),
2
1
3
H), 7.34–7.28 (m, 2H), 7.25–7.19 (m, 1H), 6.51 (d, J=15.8 Hz, 1H),
.12 (dd, J=15.8, 8.4 Hz, 1H), 3.19–3.12 (m, 1H), 2.67 (dd, J=16.2,
.3 Hz, 1H), 2.31 (s, 3H), 2.24–2.20 (m, 1H), 2.06–1.99 (m, 1H),
13
.06–1.88 (m, 2H), 1.78–1.66 ppm (m, 1H); C NMR (101 MHz,
CDCl ): d=137.4, 134.2, 130.5, 129.6, 129.3, 126.5, 79.9, 68.2, 32.5,
2
with the reported values.
3
+
6.0, 21.3 ppm; MS: m/z: 188 [M] ; NMR data are in accordance
1
3
.95–1.85 (m, 1H), 1.81–1.70 ppm (m, 2H); C NMR (101 MHz,
[3d]
3
+
(E)-4-(2-(Tetrahydrofuran-2-yl)vinyl)phenol: Table 3, entry 6. Pre-
pared by using procedure A, from (E)-4-(2-bromovinyl)phenol and
THF with Me Zn (3 equiv) and a reaction time of two days. DCVC
eluting with heptane containing 5% increments of ethyl acetate
per fraction gave the product as a colorless oil. H NMR (400 MHz,
2.2, 22.3 ppm; MS: m/z: 187 [M] . HRMS: m/z calcd for C H N:
13 18
88.1434 [M+H] ; found: 188.1436.
+
2
(E)-2-(4-Chlorostyryl)tetrahydrofuran: Table 3, entry 1. Prepared
by using procedure A, from (E)-1-(2-bromovinyl)-4-chlorobenzene
and THF with Me Zn (3 equiv). DCVC eluting with heptane contain-
ing 2% increments of ethyl acetate per fraction gave the product
as colorless crystals. H NMR (400 MHz, CDCl ): d=7.33–7.24 (m,
4
4
1
CDCl ): d=135.4, 133.1, 131.3, 129.2, 128.7, 127.7, 79.5, 68.3, 32.4,
2
the reported values.
1
2
CDCl ): d=7.16 (d, J=8.5 Hz, 2H), 7.10 (s, 1H), 6.75 (d, J=8.5 Hz,
3
2
H), 6.48 (d, J=15.8 Hz, 1H), 5.99 (dd, J=15.8, 7.2 Hz, 1H), 4.49 (q,
J=6.8 Hz, 1H), 3.99 (dd, J=14.9, 7.1 Hz, 1H), 3.87 (td, J=7.9,
.0 Hz, 1H), 2.19–2.07 (m, 1H), 2.05–1.89 (m, 2H), 1.79–1.65 ppm
1
3
H), 6.54 (d, J=15.9 Hz, 1H), 6.19 (dd, J=15.9, 6.5 Hz, 1H), 4.50–
6
.42 (m, 1H), 4.01–3.92 (m, 1H), 3.89–3.80 (m, 1H), 2.18–2.07 (m,
13
(
1
m, 1H); C NMR (101 MHz, CDCl ): d=156.0, 131.2, 129.0, 127.9,
3
1
3
H), 2.04–1.88 (m, 2H), 1.76–1.64 ppm (m, 1H); C NMR (101 MHz,
+
27.2, 115.7, 80.5, 68.1, 32.5, 26.0 ppm; MS: m/z: 190 [M] ; HRMS:
+
3
m/z calcd for C H O : 191.1067 [M+H] ; found: 191.1067.
12 15 2
+
6.0 ppm; MS: m/z: 208 [M] . NMR data are in accordance with
(
E)-2-(4-Methoxystyryl)tetrahydrofuran: Table 3, entry 7. Prepared
[10]
by using procedure A, from (E)-1-(2-bromovinyl)-4-methoxyben-
(E)-2-(4-Bromostyryl)tetrahydrofuran: Table 3, entry 2. Prepared
zene and THF with Me Zn (3 equiv) and a reaction time of two
2
by using procedure A, from (E)-1-bromo-4-(2-bromovinyl)benzene
days. DCVC eluting with heptane containing 2% increments of
and THF with Me Zn (3 equiv). DCVC eluting with heptane contain-
ethyl acetate per fraction gave the product as a colorless oil;
2
1
ing 1% increments of ethyl acetate per fraction gave the product
H NMR (400 MHz, CDCl ): d=7.31 (d, J=8.7 Hz, 2H), 6.84 (d, J=
3
1
as colorless crystals. H NMR (400 MHz, CDCl ): d=7.45–7.39 (m,
8.8 Hz, 2H), 6.53 (d, J=15.8 Hz, 1H), 6.07 (dd, J=15.8, 6.8 Hz, 1H),
4.44 (q, J=7.0 Hz, 1H), 3.96 (dd, J=14.3, 7.6 Hz, 1H), 3.87–3.79 (m,
1H), 3.78 (s, 3H), 2.17–2.05 (m, 1H), 2.05–1.86 (m, 2H), 1.75–
3
2
6
1
H), 7.26–7.20 (m, 2H), 6.52 (d, J=15.8 Hz, 1H), 6.20 (dd, J=15.8,
.5 Hz, 1H), 4.49–4.41 (m, 1H), 4.02–3.91 (m, 1H), 3.88–3.79 (m,
H), 2.18–2.07 (m, 1H), 2.04–1.88 (m, 2H), 1.76–1.64 ppm (m, 1H);
13
1.64 ppm (m, 1H); C NMR (101 MHz, CDCl ): d=159.2, 130.1,
3
13
C NMR (101 MHz, CDCl ): d=135.9, 131.7, 131.5, 129.3, 128.1,
129.7, 128.3, 127.7, 114.0, 79.9, 68.1, 55.3, 32.5, 26.0 ppm; MS: m/z:
3
+
+
[3c]
1
21.3, 79.6, 68.3, 32.4, 26.0 ppm; MS: m/z: 254, 252 [M] ; NMR
204 [M] . NMR data are in accordance with the reported values.
[3d]
data are in accordance with the reported values.
(E)-2-(3,4-Methylenedioxystyryl)tetrahydrofuran: Table 3, entry 8.
(E)-2-(4-Fluorostyryl)tetrahydrofuran: Table 3, entry 3. Prepared
Prepared by using procedure A, from (E)-5-(2-bromovinyl)benzo[d]
by using procedure A, from (E)-1-(2-bromovinyl)-4-fluorobenzene
[1,3]dioxole and THF with Me Zn (3 equiv) and a reaction time of
2
and THF with Me Zn (3 equiv). DCVC eluting with heptane contain-
ing 1% increments of ethyl acetate per fraction gave the product
three days. DCVC eluting with heptane containing 2% increments
of ethyl acetate per fraction gave the product as a colorless oil.
2
Chem. Eur. J. 2015, 21, 16272 – 16279
www.chemeurj.org
16277
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
H NMR (400 MHz, CDCl ): d=6.91 (d, J=1.5 Hz, 1H), 6.79 (dd, J=
purified by flash chromatography (heptane/Et O/Et N, 96:3:1!
3
2
1
3
8
6
3
2
.0, 1.5 Hz, 1H), 6.72 (d, J=8.0 Hz, 1H), 6.48 (d, J=15.8 Hz, 1H),
.02 (dd, J=15.8, 6.7 Hz, 1H), 5.91 (s, 2H), 4.41 (q, J=7.0 Hz, 1H),
.94 (dd, J=14.4, 7.5 Hz, 1H), 3.81 (td, J=7.9, 6.3 Hz, 1H), 2.15–
95:4:1) to give the product as a brown oil. H NMR (400 MHz,
CDCl ): d=6.90 (d, J=1.5 Hz, 1H), 6.77 (dd, J=8.0, 1.5 Hz, 1H),
3
6.73 (d, J=8.0 Hz, 1H), 6.38 (d, J=15.8 Hz, 1H), 6.00 (d, J=15.8 Hz,
1H), 5.92 (s, 2H), 3.00 (dt, J=11.3, 3.1 Hz, 1H), 2.85 (dq, J=14.6,
7.3 Hz, 1H), 2.75–5.65 (m, 1H), 2.24 (dq, J=13.9, 7.0 Hz, 1H), 2.01
13
.04 (m, 1H), 2.03–1.84 (m, 2H), 1.73–1.61 ppm (m, 1H); C NMR
(
101 MHz, CDCl ): d=148.0, 147.2, 131.4, 130.2, 128.8, 121.1, 108.2,
3
+
1
05.8, 101.1, 79.7, 68.1, 32.5, 26.0 ppm; MS: m/z: 218 [M] ; HRMS:
(dt, J=11.5, 2.9 Hz, 1H), 1.79–1.41 (m, 5H), 1.37–1.19 (m, 1H),
+
13
m/z calcd for C H O : 219.1021 [M+H] ; found: 219.1044.
1.00 ppm (t, J=7.2 Hz, 3H); C NMR (101 MHz, CDCl ): d=148.1,
1
3
15
3
3
1
3
47.1, 131.8, 131.8, 130.1, 120.8, 108.3, 105.7, 101.1, 65.7, 51.5, 49.4,
(
E)-2-(2-(Naphthalen-2-yl)vinyl)tetrahydrofuran: Table 3, entry 9.
+
3.8, 25.9, 24.0, 10.9 ppm; MS: m/z: 259 [M] ; HRMS: m/z calcd for
Prepared by using procedure A, from (E)-2-(2-bromovinyl)naphtha-
lene and THF with initially Me Zn (3 equiv). After heating to reflux
+
C H NO : 260.1645 [M+H] ; found: 260.1643.
16 22
2
2
overnight, additional MnCl (10%) and Me Zn (3 equiv) were added
(E)-N-[1-(3,4-Methylenedioxystyryl)ethyl]piperidine:
Table 4,
2
2
and the reaction was heated to reflux for another 16 h. DCVC elut-
ing with heptane containing 1% increments of ethyl acetate per
fraction gave the product as a pale-yellow solid. H NMR (400 MHz,
entry 7. Prepared by using procedure B from N-ethylpiperidine and
1
isolated as a brown oil. H NMR (400 MHz, CDCl ): d=6.92 (d, J=
3
1
1.4 Hz, 1H), 6.78 (dd, J=8.0, 1.5 Hz, 1H), 6.73 (d, J=8.0 Hz, 1H),
6.33 (d, J=15.8 Hz, 1H), 6.06 (dd, J=15.8, 8.0 Hz, 1H), 5.93 (s, 2H),
3.09–3.02 (m, 1H), 2.57–2.38 (m, 4H), 1.60 (dt, J=11.0, 5.6 Hz, 4H),
CDCl ): d=7.73–7.62 (m, 4H), 7.51 (dd, J=8.6, 1.6 Hz, 1H), 7.39–
3
7
1
.30 (m, 2H), 6.66 (d, J=15.8 Hz, 1H), 6.25 (dd, J=15.8, 6.6 Hz,
H), 4.44 (q, J=6.9 Hz, 1H), 3.91 (dd, J=14.4, 7.5 Hz, 1H), 3.78 (td,
13
1.45–1.41 (m, 2H), 1.24 ppm (d, J=6.6 Hz, 3H); C NMR (101 MHz,
J=7.9, 6.3 Hz, 1H), 2.13–2.01 (m, 1H), 1.97–1.82 (m, 2H), 1.72–
CDCl ): d=148.1, 147.1, 131.8, 130.9, 130.3, 120.9, 108.4, 105.7,
3
1
3
+
1
1
7
.61 ppm (m, 1H); C NMR (101 MHz, CDCl ): d=134.5, 133.7,
101.1, 63.1, 51.1, 26.3, 24.7, 17.8 ppm; MS: m/z: 259 [M] . HRMS:
3
+
33.1, 131.1, 130.7, 128.2, 128.1, 127.8, 126.5, 126.3, 125.9, 123.8,
m/z calcd for C H NO : 260.1645 [M+H] ; found: 260.1649.
16
22
2
+
9.9, 68.3, 32.6, 26.1 ppm; MS: m/z: 224 [M] ; HRMS: m/z calcd for
(E)-1-Ethyl-2-(3,4-methylenedioxystyryl)pyrrolidine:
Table 4,
+
C H O: 225.1274 [M+H] ; found: 225.1275.
16
17
entry 9. Prepared by using procedure B from N-ethylpyrrolidine
2
-(1H-Inden-2-yl)tetrahydrofuran: Table 3, entry 10. Prepared by
and purified by flash chromatography (heptane/Et N, 98:2) to give
3
1
using procedure A, from 2-bromoindene and THF with initially
the product as a brown oil. H NMR (400 MHz, CDCl ): d=6.92 (d,
3
Me Zn (3 equiv). After heating to reflux for three days, additional
J=1.6 Hz, 1H), 6.76 (dd, J=8.0, 1.6 Hz, 1H), 6.72 (d, J=8.0 Hz, 1H),
6.36 (d, J=15.7 Hz, 1H), 5.92 (dd, J=15.6, 8.5 Hz, 1H), 5.91 (s, 2H),
3.22 (dt, J=8.4, 2.4 Hz, 1H), 2.86 (dq, J=12.0, 7.5 Hz, 1H), 2.75 (dd,
J=16.1, 8.4 Hz, 1H), 2.12–1.62 (m, 6H), 1.08 ppm (t, J=7.3 Hz, 3H);
2
MnCl2 (10%) and Me Zn (3 equiv) were added and the reaction
2
was heated to reflux for another 16 h. DCVC eluting with heptane
containing 1% increments of ethyl acetate per fraction gave the
13
product as a colorless oil. In addition, 2-bromoindene was recov-
C NMR (101 MHz, CDCl ): d=148.1, 147.1, 131.7, 131.1, 130.9,
3
1
ered in 28% yield. H NMR (400 MHz, CDCl ): d=7.43 (dd, J=7.3,
120.9, 108.3, 105.8, 101.1, 68.6, 53.1, 48.2, 32.0, 22.2, 13.9 ppm; MS:
3
+
+
0
7
4
2
.5 Hz, 1H), 7.33 (d, J=7.4 Hz, 1H), 7.25 (dd, J=9.3, 5.6 Hz, 1H),
.15 (td, J=7.4, 1.2 Hz, 1H), 6.73 (s, 1H), 4.84 (t, J=7.0 Hz, 1H),
.06–3.97 (m, 1H), 3.93–3.85 (m, 1H), 3.41 (d, J=0.7 Hz, 2H), 2.27–
m/z: 245 [M] ; HRMS: m/z calcd for C H NO : 246.1489 [M+H] ;
15 20 2
found: 246.1492.
(E)-N-[1-(3,4-Methylenedioxystyryl)ethyl]pyrrolidine:
Table 4,
13
.15 (m, 1H), 2.07–1.96 (m, 2H), 1.91–1.82 ppm (m, 1H); C NMR
entry 9. Prepared by using procedure B from N-ethylpyrrolidine
(
1
101 MHz, CDCl ): d=150.6, 144.8, 143.4, 126.8, 126.4, 124.4, 123.8,
1
3
and isolated as a brown oil. H NMR (400 MHz, CDCl ): d=6.84 (d,
3
+
20.8, 77.9, 68.3, 38.2, 32.3, 26.1 ppm; MS: m/z: 186 [M] ; HRMS:
J=1.4 Hz, 1H), 6.71 (dd, J=8.0, 1.5 Hz, 1H), 6.67 (d, J=8.00 Hz,
1H), 6.30 (d, J=15.8 Hz, 1H), 5.98 (dd, J=15.8, 8.5 Hz, 1H), 5.86 (s,
2H), 2.79 (dq, J=13.0, 6.4 Hz, 1H), 2.58–2.40 (m, 4H), 2.00–1.57 (m,
+
m/z calcd for C H O: 187.1117 [M+H] ; found: 187.1119.
1
3
15
(E)-1-Methyl-2-(3,4-methylenedioxystyryl)piperidine:
Table 4,
13
entry 1. Prepared by using procedure B, from N-methylpiperidine
4H), 1.20 ppm (d, J=6.5 Hz, 3H); C NMR (101 MHz, CDCl ): d=
3
and purified by flash chromatography (heptane/Et N, 98:2) to give
148.1, 147.1, 132.5, 131.9, 129.3, 120.9, 108.4, 105.8, 101.1, 63.1,
3
1
+
the product as a colorless solid. H NMR (400 MHz, CDCl ): d=6.91
52.4, 23.5, 21.2 ppm; MS: m/z: 245 [M] ; HRMS: m/z calcd for
3
+
(
d, J=1.4 Hz, 1H), 6.78 (dd, J=8.0, 1.4 Hz, 1H), 6.74 (d, J=8.0 Hz,
C H NO : 246.1489 [M+H] ; found: 246.1486.
15
20
2
1
2
H), 6.39 (d, J=15.8 Hz, 1H), 5.97 (dd, J=16.0, 8.7 Hz, 1H), 5.94 (s,
H), 2.91 (d, J=11.4 Hz, 1H), 2.46–2.38 (m, 1H), 2.23 (s, 3H), 2.02
(
E)-N,N-Diethyl-[1-(3,4-methylenedioxystyryl)ethyl]amine:
Table 4, entry 10. Prepared by using procedure B from triethyla-
mine and purified by flash chromatography (heptane/Et N, 99:1) to
give the product as a brown oil. H NMR (400 MHz, CDCl ): d=6.92
(d, J=1.5 Hz, 1H), 6.79 (dd, J=8.0, 1.5 Hz, 1H), 6.74 (d, J=8.0 Hz,
(
(
(
dt, J=11.6, 3.5 Hz, 1H), 1.75 (dd, J=12.6, 2.9 Hz, 1H), 1.70–1.53
m, 3H), 1.52–1.40 (m, 1H), 1.35–1.24 ppm (m, 1H); C NMR
101 MHz, CDCl ): d=148.1, 147.1, 132.1, 131.8, 130.3, 120.8, 108.4,
3
13
1
3
3
1
05.8, 101.1, 68.2, 56.6, 44.8, 33.7, 26.2, 24.1 ppm; MS: m/z: 245
1
H), 6.34 (d, J=15.9 Hz, 1H), 6.05 (dd, J=15.9, 7.4 Hz, 1H), 5.93 (s,
+
+
[M] . HRMS: m/z calcd for C H NO : 246.1489 [M+H] ; found:
15 20 2
2H), 3.45–3.39 (m, 1H), 2.66–2.50 (m, 4H), 1.21 (d, J=6.6 Hz, 3H),
1
2
46.1490.
13
.04 ppm (t, J=7.1 Hz, 6H); C NMR (101 MHz, CDCl ): d=148.1,
3
(
E)-N-(3,4-Methylenedioxycinnamyl)piperidine: Table 4, entry 1.
147.0, 132.1, 131.7, 129.6, 120.8, 108.4, 105.7, 101.1, 57.5, 43.6, 17.6,
+
Prepared by using procedure B from N-methylpiperidine and isolat-
ed as an orange solid. H NMR (400 MHz, CDCl ): d=6.92 (d, J=
13.2 ppm; MS: m/z: 247 [M] ; HRMS: m/z calcd for C H NO :
1
5
22
2
1
+
248.1645 [M+H] ; found: 248.1646.
3
1
1
6
2
1
.3 Hz, 1H), 6.83–6.76 (m, 1H), 6.74 (d, J=8.0 Hz, 1H), 6.42 (d, J=
5.8 Hz, 1H), 6.15 (dt, J=15.7 Hz, 1H), 5.94 (s, 2H), 3.16 (d, J=
.8 Hz, 2H), 2.50 (br s, 4H), 1.76–1.56 (m, 4H), 1.51–1.41 ppm (m,
(
E)-N,N-Dipropyl-[1-(3,4-methylenedioxystyryl)propyl]amine:
Table 4, entry 11. Prepared by using procedure B from tripropyla-
mine and purified by flash chromatography (heptane/Et O, 4:1) to
give the product as a light-brown oil. H NMR (400 MHz, CDCl3):
d=6.93 (d, J=1.4 Hz, 1H), 6.79 (dd, J=8.0, 1.4 Hz, 1H), 6.75 (d, J=
8.0 Hz, 1H), 6.30 (d, J=15.8 Hz, 1H), 5.96 (dd, J=16.0, 8.7 Hz, 1H),
2
1
3
H); C NMR (101 MHz, CDCl ): d=148.1, 147.3, 143.5, 133.4,
1
3
31.4, 121.1, 108.4, 105.9, 101.2, 61.7, 54.4, 25.6, 24.2 ppm; MS: m/
+
+
z: 245 [M] ; HRMS: m/z calcd for C H NO : 246.1489 [M+H] ;
1
5
20
2
found: 246.1494.
E)-1-Ethyl-2-(3,4-methylenedioxystyryl)piperidine:
entry 7. Prepared by using procedure B from N-ethylpiperidine and
5
.94 (s, 2H), 2.99 (td, J=8.3, 6.3 Hz, 1H), 2.48 (ddd, J=12.9, 8.8,
(
Table 4,
7.0 Hz, 2H), 2.38–2.28 (m, 2H), 1.65 (m, 1H), 1.54–1.35 (m, 5H),
0.92–0.85 ppm (m, 9H); C NMR (101 MHz, CDCl ): d=148.1, 146.9,
13
3
Chem. Eur. J. 2015, 21, 16272 – 16279
www.chemeurj.org
16278
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
1
2
32.2, 131.3, 128.6, 120.8, 108.4, 105.7, 101.1, 65.1, 52.8, 25.9, 22.0,
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+
2.1, 11.6 ppm; MS: m/z: 289 [M] . HRMS: m/z calcd for C H NO :
18
28
2
+
90.2115 [M+H] ; found: 290.2110.
2
6
345; b) T. Yoshimitsu, Y. Arano, H. Nagaoka, J. Org. Chem. 2003, 68,
25–627.
(E)-4-Methyl-2-(3,4-methylenedioxystyryl)morpholine:
Table 4,
entry 13. Prepared by using procedure B from N-methylmorpholine
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and purified by flash chromatography (toluene/Et O/Et N, 20:79:1)
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11610–11611.
2
3
1
[7] a) X. Dai, D. Cheng, B. Guan, W. Mao, X. Xu, X. Li, J. Org. Chem. 2014, 79,
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3
2013, 78, 4107–4114; c) S. Zhu, A. Das, L. Bui, H. Zhou, D. P. Curran, M.
6
.75 (d, J=8.0 Hz, 1H), 6.53 (d, J=15.9 Hz, 1H), 5.95 (s, 2H), 5.83
Rueping, J. Am. Chem. Soc. 2013, 135, 1823–1829; d) Y. Miyake, K. Naka-
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(
dd, J=15.9, 8.7 Hz, 1H), 3.86 (d, J=11.4 Hz, 1H), 3.79–3.67 (m,
2
3
1
5
2
H), 3.42 (t, J=10.6 Hz, 1H), 2.82–2.75 (m, 2H), 2.37 (dt, J=11.6,
1
3
.2 Hz, 1H), 2.30 ppm (s, 3H); C NMR (101 MHz, CDCl ): d=148.2,
3
47.6, 134.1, 131.0, 124.9, 121.3, 108.4, 105.8, 101.3, 71.1, 67.0, 66.8,
4, 1202–1205; g) S. Marinkovic, N. Hoffmann, Int. J. Photoenergy 2003,
+
4.8, 43.7 ppm; MS: m/z: 247 [M] . HRMS: m/z calcd for C H NO :
14
18
3
175–182.
+
48.1281 [M+H] ; found: 248.1283.
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1
1605; b) Y. Amaoka, M. Nagatomo, M. Watanabe, K. Tao, S. Kamijo, M.
(
E)-N-Methyl-N-(3,4-methylenedioxycinnamyl)formamide:
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2
2
Table 4, entry 14. Prepared by using procedure B from N,N-dime-
thylformamide and purified by flash chromatography (heptane/
EtOAc, 3:7) to give the product as a light-brown oil. Major rotamer:
[
1
H NMR (400 MHz, CDCl ): d=8.14 (s, 1H), 6.90 (s, 1H), 6.83–6.71
3
014, 4, 54349–54353; b) J. Zhang, P. Li, L. Wang, Org. Biomol. Chem.
014, 12, 2969–2978; c) Y. Yang, H. Huang, X. Zhang, W. Zeng, Y. Liang,
(
m, 2H), 6.45 (d, J=15.8 Hz, 1H), 6.00–5.83 (m, 3H), 3.95 (d, J=
1
3
5
1
3
1
5
.8 Hz, 2H), 2.86 ppm (s, 3H); C NMR (101 MHz, CDCl ): d=162.8,
Synthesis 2013, 3137–3146.
[10] Y.-J. Jang, Y.-K. Shih, J.-Y. Liu, W.-Y. Kuo, C.-F. Yao, Chem. Eur. J. 2003, 9,
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48.3, 147.8, 133.5, 130.5, 122.2, 121.5, 108.5, 105.8, 101.3, 51.8,
1
4.2 ppm; Minor rotamer: H NMR (400 MHz, CDCl ): d=8.09 (s,
2123–2128.
3
[
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H) 6.90 (s, 1H), 6.83–6.71 (m, 2H), 6.45 (d, J=15.8 Hz, 1H), 6.00–
1
3
.83 (m, 3H), 4.07 (d, J=6.5 Hz, 2H), 2.92 ppm (s, 3H); C NMR
2
(
101 MHz, CDCl ): d=162.5, 148.2, 147.6, 133.4, 130.9, 121.6, 121.3,
3
+
1
08.4, 105.8, 101.3, 46.2, 29.6 ppm; MS: m/z: 219 [M] ; HRMS: m/z
[
14] a) Y. Matsuo, Y. Zhang, E. Nakamura, Org. Lett. 2008, 10, 1251–1254;
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+
calcd for C H NO : 220.0968 [M+H] ; found: 220.0968.
1
2
14
3
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Published online on September 17, 2015
Chem. Eur. J. 2015, 21, 16272 – 16279
www.chemeurj.org
16279
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim