Hydrazone-palladium-catalyzed allylic arylation of cinnamyloxyphenylboronic acid pinacol esters

Article abstract of DOI:10.1021/jo501235w

Allylic arylation of cinnamyloxyphenylboronic acid pinacol esters 3, which have arylboronic acid moiety and allylic ether moiety, using a hydrazone 1d-Pd(OAc)₂ system proceeded and gave the corresponding 1,3-diarylpropene derivatives 4 with a phenolic hydroxyl group via a selective coupling reaction of the π-allyl intermediate to the boron-substituted position of the leaving group.

Full text of DOI:10.1021/jo501235w

Article
pubs.acs.org/joc
Hydrazone−Palladium-Catalyzed Allylic Arylation of
Cinnamyloxyphenylboronic Acid Pinacol Esters
Kohei Watanabe, Takashi Mino,* Taichi Abe, Taketo Kogure, and Masami Sakamoto
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku,
Chiba 263-8522, Japan
S
* Supporting Information
ABSTRACT: Allylic arylation of cinnamyloxyphenylboronic
acid pinacol esters 3, which have arylboronic acid moiety and
allylic ether moiety, using a hydrazone 1d−Pd(OAc)2 system
proceeded and gave the corresponding 1,3-diarylpropene
derivatives 4 with a phenolic hydroxyl group via a selective
coupling reaction of the π-allyl intermediate to the boron-
substituted position of the leaving group.
ether moiety, using bishydrazones 1a−e7b,c,g and monohy-
INTRODUCTION
■
drazones 2a and 2b7b as ligands (Figure 2). This procedure was
1,3-Diarylpropene frameworks constitute many natural com-
pounds.1 In particular, 1,3-diarylpropene derivatives with a
phenolic hydroxyl group are known as versatile building blocks
in natural products and biologically active compounds.2 For
example, obtusastyrene and obtustyrene are isolated from
Dalbergia retusa as natural product (Figure 1).2a Therefore, an
Figure 2. Hydrazones 1 and 2.
Figure 1. 1,3-Diarylpropene derivatives having a phenolic hydroxyl
group.
achieved by a coupling reaction of π-allyl intermediate to the
boron-substituted position of the leaving group and gave 1,3-
diarylpropene derivatives with a phenolic hydroxyl group.
effective approach toward synthesis of these derivatives is very
important in terms of not only organic synthesis but also
biological perspective. The synthesis of 1,3-diarylpropene
RESULTS AND DISCUSSION
■
derivatives via palladium-catalyzed allylic arylation using allylic
bromides3 or vinyl epoxides4 with arylboronic acids were
Initially, we examined the reaction of 2-(4-(cinnamyloxy)-
phenyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (3a) as a
model substrate with 5 mol % of Pd catalyst for 24 h under
reported as pioneering studies. Recently, palladium-catalyzed
allylic arylations of allylic acetates with arylboronic acids for
synthesis of 1,3-diarylpropene derivatives have been reported.5
Although allylic C−H arylation of allylbenzenes were also
reported,6 Heck-type allylic C−H arylation with arylboronic
acids gave the mixture of the double-bond-migrated isomers.6a,c
On the other hand, we demonstrated that easily prepared and
air-stable hydrazones are effective ligands for palladium-
catalyzed C−C bond formation reactions7 including the allylic
arylation of allylic acetates with arylboronic acids.8 More
recently, we also reported allylic arylation of allylic ethers as a
starting material instead of allylic acetates using hydrazone−
palladium catalyst systems.9 Here, we report a new type of
allylic arylation of cinnamyloxyphenylboronic acid pinacol
esters, which have an arylboronic acid moiety and an allylic
Ar atmosphere at 50 °C (Table 1). Using 5 mol % of Pd(OAc)2
and bishydrazone 1a as a ligand, we observed that the reaction
in the presence of Ca(OH)2 as a base in DMA/H2O (9/1) as a
solvent gave corresponding product 4a (obtusastyrene) in a
12% yield (entry 1). We tested various bishydrazones 1b−e
(entries 2−5). When we used bishydrazone 1d, 4a was
obtained in 75% yield (entry 4). We also tested pyridine-type
monohydrazone ligands 2a and 2b. While pyridine−methyl-
type monohydrazone ligand 2a was not effective for this
reaction (entry 6), phenyl−methyl type ligand 2b was effective
Received: June 3, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 1. Optimization of Palladium-Catalyzed Allylic Arylation of Cinnamyloxyphenylboronic Acid Pinacol Ester (3a) Using
a
Hydrazone Ligand
entry
Pd source
Pd(OAc)2
ligand
base
solvent
yield of 3a (%)
1
1a
1b
1c
1d
1e
2a
2b
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
K2CO3
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
2-butanol
DMSO
DMF
THF
12
10
4
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(acac)2
[Pd(η3-allyl)Cl]2
PdCl2
3
4
75
2
5
6
trace
53
trace
29
54
31
53
72
52
27
32
48
59
52
33
7
7
8
9
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
1d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
Pd(tfa)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K3PO4
NaOEt
Na2CO3
CsF
KF
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
Ca(OH)2
46
63
trace
46
22
trace
MeCN
b
DMA
c
DMA
d
DMA
a
Reaction conditions: 3a (0.25 mmol), Pd source (Pd = 5 mol %), ligand (5 mol %), base (0.50 mmol), solvent (0.9 mL), H2O (0.1 mL) at 50 °C
b
c
d
for 24 h under Ar. Concentration of solvent was 0.125 M. Concentration of solvent was 0.5 M. DMA (1.0 mL) was used as solvent in the absence
of water.
and gave the corresponding product in 53% yield (entry 7).
Without ligand, the reaction did not give the desired product
(entry 8). As a result, we decided to use pyridine−methyl-type
bishydrazone ligand 1d as the optimum ligand for this reaction.
Several palladium sources were also tested (entries 4 and 9−
13). Pd(OAc)2 was the most effective palladium source in this
reaction (entry 4). Next, the effects of various bases were
investigated (entries 4 and 14−19). Using Ca(OH)2 led to the
highest yield in this reaction (entry 4). Various solvents were
also tested (entries 4 and 20−24). DMA was the most suitable
solvent for this reaction (entry 4). Additionally, the effect of
concentration of solvent was investigated (entries 4, 25, and
26). When the concentration of solvent was 0.125 or 0.5 M in
the reaction, the yields decreased to 46 and 22%, respectively
(entries 25 and 26). The reaction without water gave the
corresponding product in only trace amounts (entry 27).
Under optimized reaction conditions (Table 1, entry 4), we
investigated the scope and limitation of this reaction using
various substituted cinnamyloxyphenylboronic acid pinacol
esters 3 (Table 2). Using 4-substituted cinnamyloxyphenylbor-
onic acid pinacol esters led to moderate to good yields of the
corresponding products 4b−e (entries 2−5). Next, the reaction
of substrates 3f and 3g, whose electron-donating group was
substituted on phenylboronic acid pinacol ester, also proceeded
smoothly and gave the corresponding products 4f and 4g in
moderate yields (entries 6 and 7). However, in the case of using
chloro-substituted pinacol ester, the desired product 4h was
obtained in low yield. (E,E)-2-Chloro-4-cinnamyl-1-
(cinnamyloxy)benzene (5h), with which π-allyl intermediate
was coupled at the boron-substituted position of starting
material 3h, was also obtained in 23% yield as a byproduct
(entry 8). Pinacol esters with a cinnamyloxy group in the m- or
o-position were also tested. m-Cinnamylphenol (4i) was
obtained in good yield (entry 9). On the other hand, o-
cinnamylphenol (4j) was obtained in 8% yield, and annulate
compound (Z)-3-benzylidene-2,3-dihydrobenzofuran (6) was
also generated as a byproduct in 37% yield (entry 10). When
we tested allyloxyphenylboronic acid pinacol ester 3k as
starting material, 4-allylphenol (4k) was obtained in the same
way (entry 11). Moreover, we tried to synthesize eugenol (4l),
which is known as a medical product,10 using 4-allyloxy-3-
methoxyphenylboronic acid pinacol ester. As a result, we
succeeded in obtaining eugenol in good yield accompanying the
formation of 2-methoxy-4-allyl-1-(allyloxy)benzene (5l), which
B
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
phenoxide ion reacted with water to generate boronic acid
pinacol ester ion, and this ion underwent transmetalation with
palladium complex II to generate π-allyl aryl palladium complex
III, followed by reductive elimination of palladium complex III,
which gave the corresponding phenol product and regenerated
Pd(0)−hydrazone catalyst. Then, the catalytic cycle was
completed. We thought these palladium complexes were
stabilized by hydrazone ligand, and this reaction proceeded
smoothly.
In summary, we developed allylic arylation using hydrazone
1d−Pd(OAc)2 systems as catalyst and cinnamyl- and
allyloxyphenylboronic acid pinacol esters, which have an
arylboronic acid moiety and an allylic ether moiety as
substrates. This reaction gave the desired cinnamyl- and
allylphenol products including natural and medical compounds.
We also certified that the reaction was intermolecular by a
crossover reaction.
Table 2. Scope and Limitations of Palladium-Catalyzed
Allylic Arylation of Pinacol Esters 3 Using Hydrazone
Ligand
a
entry
R1
C6H5
R2
OH
yield of 4 (%)
75 (4a)
1
2
H
H
H
H
H
4-OH
4-OH
4-OH
4-OH
4-OH
4-OH
4-OH
4-OH
3-OH
2-OH
4-OH
4-OH
4-ClC6H4
4-CF3C6H4
4-MeC6H4
4-MeOC6H4
C6H5
80 (4b)
c
3
51 (4c)
c
,
,
f
f
4
5
6
7
58 (4d)
c
46 (4e)
3,5-diMe
3-MeO
3-Cl
47 (4f)
C6H5
55 (4g)
8g
C6H5
38 (4h) + 23 (5h)
79 (4i)
EXPERIMENTAL SECTION
9
C6H5
H
■
10
11
12
C6H5
H
8 (4j) + 37 (6)
43 (4k)
Preparation of Pyridine-2-carboxaldehyde−(Pyridin-2-yl)-
methylhydrazone (2a).11 2-Pyridinecarboxaldehyde (53.6 mg, 0.5
mmol) and 1-methyl-1-(pyridil)hydrazone (61.6 mg, 0.5 mmol) were
added to EtOH (3.0 mL) in a sample tube. After the mixture was
stirred for 3 h at 80 °C, the reaction was quenched with distilled water.
The white solid was precipitated and collected by filtration, washed
with hexane, and dried in vacuo to afford 2a in 53% yield (55.9 mg,
d
,e
H
H
H
3-OMe
57 (4l) + 20 (5l)
a
Reaction conditions: Cynnamyloxy phenyl boronic acid pinacol ester
(0.25 mmol), Pd(OAc)2 (5 mol %), ligand 2d (5 mol %), Ca(OH)2
(0.50 mmol), DMA/H2O (9/1) (1 mL) at 50 °C for 24 h under Ar.
b
c
This reaction was carried out at 60 °C. This reaction was carried out
1
0.26 mmol) as a white solid: mp 105−106 °C; H NMR (CDCl3) δ:
d
e
at 70 °C. This reaction was carried out for 48 h. 10 mol % of catalyst
and ligand were used. Concentration of solvent was 0.125 M.
3.70 (s, 3H), 6.83 (ddd, J = 7.0, 4.9, 0.9 Hz, 1H), 7.19 (ddd, J = 7.4,
5.0, 1.1 Hz, 1H), 7.62 (ddd, J = 7.8, 7.1, 1.9 Hz, 1H), 7.68−7.76 (m,
3H), 8.02 (d, J = 8.04 Hz, 1H) 8.24 (dd, J = 5.0, 1.1 Hz, 1H), 8.56
(ddd, J = 5.0, 1.6, 1.0 Hz, 1H); 13C{1H} NMR (CDCl3) δ 29.6, 110.0,
116.1, 119.3, 122.4, 134.6, 136.3, 137.5, 147.0, 149.1, 155.3, 157.4; EI-
MS m/z (rel intensity) 212 (M+, 10).
f
was a coupling product from π-allyl intermediate and 3l (entry
12). Unfortunately, the reaction using prenyloxyphenylboronic
acid pinacol ester (3m) did not give the corresponding product
(Scheme 1). When we used heterocyclic compound 3n, such as
a pyridine ring, the corresponding product 4n was obtained in
excellent yield for 48 h at 60 °C (Scheme 2).
Next, to confirm whether this reaction is an intermolecular
reaction or intramolecular, a crossover reaction was carried out
using 3a and 3l as starting materials (Scheme 3). The rate of
coupling products in the reaction mixture was determined by
GC−MS analysis. As a result, obtusastyrene (4a) and eugenol
(4l) were detected, and two cross-coupling products 4k and 4h
were also detected. From this result, we concluded this reaction
occurred in an intermolecular fashion. Another coupling
product 7 from 3a and π-allyl intermediate of 3l was also
detected.
A plausible mechanism of allylic arylation of cinnamylox-
yboronic acid pinacol ester is illustrated in Scheme 4. At first,
oxidative addition at the allylic position of the starting material
to Pd(0)−hydrazone complex took place to generate π-allyl
phenoxy complex I. According to formation of compounds 5h
and 5l in Table 2 and the crossover products in Scheme 3, the
complex I exchanged phenoxy ion for hydroxyl ion to become
π-allyl hydroxyl palladium complex II. On the other hand,
Preparation of (E)-2-(4-(Cinnamyloxy)phenyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (3a). 4-(4,4,5,5-Tetramethyl-1,3,2-di-
oxaborolan-2-yl)phenol (0.5502 g, 2.5 mmol), (E)-cinnamyl bromide
(0.4927 g, 2.5 mmol), and potassium carbonate (0.5183 g, 3.75 mmol)
were added to acetone (2.5 mL) in a sample tube. After the mixture
was stirred for 24 h at 50 °C, the reaction was quenched with distilled
water. The solution was extracted with ethyl acetate, washed with
brine, dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography (hexane/ethyl acetate) to afford 3a in 77% yield (650
mg, 1.94 mmol) as a white solid: mp 83−84 °C; 1H NMR (CDCl3) δ
1.33 (s, 12H), 4.73 (dd, J = 5.8 and 1.4 Hz, 2H), 6.37−6.46 (m, 1H),
6.73 (d, J = 15.9 Hz, 1H), 6.95 (d, J = 8.7 Hz, 2H), 7.25−7.42 (m,
5H), 7.76 (d, J = 8.7 Hz, 2H); 13C{1H} NMR (CDCl3) δ 24.8, 68.3,
83.5, 114.1, 124.2, 126.6, 127.9, 128.6, 133.1, 136.4, 136.5, 161.2; EI-
MS m/z (rel intensity) 336 (M+, 2); HRMS (ESI-orbitrap) m/z calcd
for C21H25O3B [M + Na]+ 359.1789, found 359.1771.
Preparation (E)-2-(4-(3-(4-Chlorophenyl)allyl)oxy)-4,4,5,5-
tetramethyl-1,3,2-dioxaborolane (3b). This compound was
synthesized from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
phenol (0.8803 g, 4.0 mmol) and (E)-p-chlorocinnamyl bromide
(0.9261 g, 4.0 mmol) according to the procedure for preparation of 3a
1
in 38% yield (565 mg, 1.52 mmol) as a white solid: mp 111 °C; H
NMR (CDCl3) δ 1.33 (s, 12H), 4.72 (dd, J = 5.7, 1.3 Hz, 2H), 6.34−
Scheme 1. Palladium-Catalyzed Allylic Arylation of Prenyloxyphenylboronic Acid Pinacol Ester (3m)
C
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Scheme 2. Palladium-Catalyzed Allylic Arylation of Heterocyclic Compound (3n)
Scheme 3. Crossover Reaction Using 3a and 3l
Scheme 4. Plausible Reaction Mechanism
6.43 (m, 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.94 (d, J = 8.7 Hz, 2H),
7.27−7.35 (m, 4H), 7.76 (d, J = 8.6 Hz, 2H); 13C{1H} NMR (CDCl3)
δ 24.8, 68.1, 83.6, 114.0, 124.9, 127.8, 128.7, 131.7, 133.5, 134.9, 136.5,
161.0; EI-MS m/z (rel intensity) 370 (M+, 2); HRMS (ESI-orbitrap)
m/z calcd for C21H23O3BCl [M − H]− 369.1423, found 369.1433.
D
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Preparation of (E)-4,4,5,5-Tetramethyl-2-(4-((3-(4-
(trifluoromethyl)phenyl)allyl)oxy)phenyl)-1,3,2-dioxaborolane
(3c). This compound was synthesized from 4-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl) phenol (0.5067 g, 2.3 mmol) and (E)-p-
(trifluoromethyl)cinnamyl chloride (0.5074 g, 2.3 mmol) according to
the procedure for preparation of 3a in 30% yield (278 mg, 0.69 mmol)
as a yellow solid: mp 99 °C; 1H NMR (CDCl3) δ 1.34 (s, 12H), 4.75
(dd, J = 5.4 and 1.4 Hz, 2H), 6.46−6.55 (m, 1H), 6.77 (d, J = 16.1 Hz,
1H), 6.95 (d, J = 8.6 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.3
Hz, 2H), 7.77 (d, J = 8.6 Hz, 2H); 13C{1H} NMR (CDCl3) δ 24.8,
67.9, 83.6, 114.0, 124.1 (q, J = 272.0 Hz), 125.5 (q, J = 3.7 Hz), 126.7,
127.0, 128.7, 129.6 (q, J = 32.3 Hz), 131.2, 136.6, 161.0; EI-MS m/z
(rel intensity) 404 (M+, 7). HRMS (APPI-orbitrap) m/z calcd for
C22H23O3BF3 [M − H]− 403.1687, found 403.1696.
preparation of 3a in 61% yield (446 mg, 1.22 mmol) as a white solid:
mp 77 °C; 1H NMR (CDCl3) δ 1.34 (s, 12H), 2.32 (s, 6H), 4.48 (dd,
J = 6.0 and 1.2 Hz, 2H), 6.42−6.51 (m, 1H), 6.73 (d, J = 15.9 Hz, 1H),
7.25−7.36 (m, 3H), 7.42 (d, J = 7.1 Hz, 2H), 7.51 (s, 2H); 13C{1H}
NMR (CDCl3) δ 16.3, 24.8, 72.8, 83.6, 125.1, 126.5, 127.8, 128.6,
130.5, 132.6, 135.6, 136.6, 158.7; EI-MS m/z (rel intensity) 364 (M+,
1); HRMS (ESI-orbitrap) m/z calcd for C23H30O3B [M + H]+
365.2283, found 365.2282.
Preparation of (E)-2-(4-(Cinnamyloxy)-3-methoxyphenyl)-
4,4,5,5-tetramethyl-1,3,2- dioxaborolane (3g). This compound
was synthesized from 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl) phenol (0.5002 g, 2.0 mmol) and (E)-cinnamyl bromide
(0.3944 g, 2.0 mmol) according to the procedure for preparation of 3a
1
in 33% yield (244 mg, 0.67 mmol) as a white solid: mp 104 °C; H
Preparation of (E)-2-(4-(3-p-Tolylallyl)oxy)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (3d). This compound was synthesized
from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.2110 g,
5.0 mmol) and (E)-p-methylcinnamyl chloride (0.8341 g, 5.5 mmol)
according to the procedure for preparation of 3a in 37% yield (648
mg, 1.85 mmol) as a white solid: mp 121−122 °C; 1H NMR (CDCl3)
δ 1.33 (s, 12H), 2.34 (s, 3H), 4.71 (d, J = 5.9 Hz, 2H), 6.31−6.40 (m,
1H), 6.70 (d, J = 15.9 Hz, 1H), 6.95 (d, J = 8.6 Hz, 2H), 7.13 (d, J =
8.0 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.76 (d, J = 8.6 Hz, 2H);
13C{1H} NMR (CDCl3) δ 21.2, 24.8, 68.5, 83.5, 114.1, 123.0, 126.5,
NMR (CDCl3) δ 1.34 (s, 12H), 3.94 (s, 3H), 4.80 (dd, J = 5.9 and 1.0
Hz, 2H), 6.41−6.50 (m, 1H), 6.72 (d, J = 16.0 Hz, 1H), 6.95 (d, J =
8.0 Hz, 1H), 7.24−7.41(m, 7H); 13C{1H} NMR (CDCl3) δ 24.8, 55.9,
69.3, 83.6, 112.3, 116.9, 124.2, 126.6, 127.9, 128.4, 128.5, 133.4, 136.3,
148.7, 150.6; EI-MS m/z (rel intensity) 366 (M+, 3); HRMS (ESI-
orbitrap) m/z calcd for C22H28O4B [M + H]+ 367.2075, found
367.2072.
Preparation of (E)-2-(3-Chlorophenyl-4-(cinnamyloxy))-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3h). This compound
was synthesized from 3-chloro-4-(4,4,5,5-tetramethyl- 1,3,2-dioxabor-
olan-2-yl) phenol (0.2545 g, 1.0 mmol) and (E)-cinnamyl bromide
(0.1970 g, 1.0 mmol) according to the procedure for preparation of 3a
129.3, 133.1, 133.6, 136.5, 137.8, 161.2; EI-MS m/z (rel intensity) 350
(M+, 1); HRMS (ESI-orbitrap) m/z calcd for C22H28O3B [M +
H]+351.2126, found 351.2122.
1
in 67% yield (249 mg, 0.67 mmol) as a white solid: mp 74 °C; H
Preparation of (E)-2-(4-((3-(4-Methoxyphenyl)allyl)oxy)-
phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3e). This
compound was synthesized via a two-step reaction. First step: A
mixture of 4-(allyloxy)bromobenzene (2.1198 g, 10 mmol), 4-
iodoanisole (2.3404 g, 10 mmol), K3PO4 (2.1227 g, 10 mmol),
Pd(OAc)2 (0.1123 g, 0.5 mmol, 5 mol %), and ligand 1c (0.1250 g, 0.5
mmol, 5 mol %) in DMF (10 mL) at 70 °C under an atmosphere of
air was stirred for 12 h. After the reaction, the reaction was quenched
with distilled water. The solution was extracted with ethyl acetate,
washed with brine, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by decantation with hexane
to afford to (E)-1-bromo- 4-((3-(4-methoxyphenyl)allyl)oxy)benzene
(8) in 39% yield (1.25 g 3.92 mmol) as a brown solid: mp 147−148
NMR (CDCl3) δ 1.33 (s, 12H), 4.81 (dd, J = 5.6 and 1.2 Hz, 2H),
6.37−6.46 (m, 1H), 6.77 (d, J = 16.0 Hz, 1H), 6.97 (d, J = 8.2 Hz,
1H), 7.26−7.35 (m, 3H), 7.41 (d, J = 7.0 Hz, 2H), 7.65 (dd, J = 8.2
and 1.5 Hz, 1H), 7.83 (d, J = 1.5 Hz, 1H); 13C{1H} NMR (CDCl3) δ
24.8, 69.4, 83.9, 112.9, 122.7, 123.6, 126.6, 128.0, 128.6, 133.3, 134.5,
136.2, 136.7, 156.4; EI-MS m/z (rel intensity) 370 (M+, 1); HRMS
(ESI-orbitrap) m/z calcd for C21H25O3ClB [M + H]+ 371.1580, found
371.1583.
Preparation of (E)-2-(3-(Cinnamyloxy)phenyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (3i). This compound was synthesized
from 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (0.8803 g,
4.0 mmol) and (E)-cinnamyl bromide (0.7883 g, 4.0 mmol) according
to the procedure for preparation of 3a in 59% yield (796 mg, 2.37
1
°C; H NMR (CDCl3) δ 3.81 (s, 3H), 4.63 (dd, J = 6.0 and 1.3 Hz,
1
mmol) as a white solid: mp 84−85 °C; H NMR (CDCl3) δ 1.35 (s,
2H), 6.20−6.30 (m, 1H), 6.75 (d, J = 15.9 Hz, 1H), 6.85 (tt, J = 8.9
and 2.1 Hz, 4H), 7.36 (tt, J = 9.4 and 2.8 Hz, 4H); 13C{1H} NMR
(CDCl3) δ 55.3, 69.1, 112.9, 114.0, 116.6, 121.5, 127.8, 129.0, 132.2,
133.1, 157.7, 159.5; HRMS (ESI-orbitrap) m/z calcd for C16H15O2Br
[M − H]− 317.0172, found 317.0174. Second step: (E)-1-Bromo-4-
((3-(4-methoxyphenyl)allyl)oxy)benzene (8) (0.4457 g, 1.4 mmol)
was added to THF (5.6 mL), the solution was stirred for 15 min at
−78 °C under an Ar atmosphere, n-butyllithium (1.81 mmol) in
hexane (1.00 mL, 1.81 M) was added gradually, and the solution was
stirred at −78 °C. After 2 h, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (0.37 mL, 1.82 mmol) was added gradually, the mixture
was stirred at room temperature 24 h, and the reaction was quenched
with distilled water. The solution was extracted with ethyl acetate,
washed with brine, dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane/ethyl acetate) to afford 3e
in 43% yield (0.204 g, 0.61 mmol) as a white solid: mp 142−143 °C;
1H NMR (CDCl3) δ 1.33 (s, 12H), 3.81 (s, 3H), 4.70 (d, J = 4.9 Hz,
2H), 6.24−6.33 (m, 1H), 6.68 (d, J = 16.0 Hz, 1H), 6.86 (d, J = 8.7
Hz, 2H), 6.95 (d, J = 8.6 Hz, 2H), 7.35 (d, J = 8.7 Hz, 2H), 7.76 (d, J
= 8.6 Hz, 2H); 13C{1H} NMR (CDCl3) δ 24.8, 55.3, 68.9, 83.5, 113.9,
114.1, 121.8, 127.8, 129.1, 132.9, 136.5, 159.4, 161.2; EI-MS m/z (rel
intensity) 366 (M+, 2); HRMS (APPI-orbitrap) m/z calcd for
C22H28O4B [M + H]+ 367.2075, found 367.2061.
Preparation of (E)-2-(4-(Cinnamyloxy)-3,5-dimethylphenyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3f). This compound
was synthesized from 3,5-dimethyl-4-(4,4,5,5- tetramethyl-1,3,2-
dioxaborolan-2-yl) phenol (0.4963 g, 2.0 mmol) and (E)-cinnamyl
bromide (0.3941 g, 2.0 mmol) according to the procedure for
12H), 4.73 (dd, J = 5.7 and 1.3 Hz, 2H), 6.38−6.47 (m, 1H), 6.75 (d, J
= 15.9 Hz, 1H), 7.07 (ddd, J = 8.2 and 2.7 and 1.1 Hz, 1H), 7.25−7.43
(m, 8H); 13C{1H} NMR (CDCl3) δ 24.8, 68.5, 83.8, 118.5, 119.8,
124.6, 126.5, 127.4, 127.8, 128.5, 129.0, 132.8, 136.5, 158.1; EI-MS m/
z (rel intensity) 336 (M+, 2); HRMS (ESI-orbitrap) m/z calcd for
C21H25O3BNa [M + Na]+ 359.1789, found 359.1786.
Preparation of (E)-2-(2-(Cinnamyloxy)phenyl)-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (3j). This compound was synthesized
from 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.1004 g,
5.0 mmol) and (E)-cinnamyl bromide (0.9843 g, 5.0 mmol) according
to the procedure for preparation of 3a, and the residue after the
concentration under reduced pressure was purified by decantation
with hexane to afford 3j in 14% yield (243 mg, 0.75 mmol) as a white
solid: mp 158−159 °C; 1H NMR (CDCl3) δ 1.38 (s, 12H), 4.72 (dd, J
= 4.6 and 1.8 Hz, 2H), 6.41 (dt, J = 15.9 and 4.6 Hz 1H), 6.88−7.04
(m, 3H), 7.22−7.44 (m, 6H), 7.71 (dd, J = 7.3 and 1.7 Hz, 1H);
13C{1H} NMR (CDCl3) δ 24.9, 68.5, 83.5, 112.0, 120.6, 125.0, 126.4,
127.4, 128.5, 131.0, 132.5, 136.7, 137.2, 163.2; EI-MS m/z (rel
intensity) 336 (M+, 2); HRMS (ESI-orbitrap) m/z calcd for
C21H25O3BNa [M +Na]+ 359.1789, found 359.1786.
Preparation of 2-(4-(Allyloxy)phenyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (3k).12 This compound was synthesized from
4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.1004 g, 5.0
mmol) and allyl bromide (0.6049 g, 5.0 mmol) according to the
procedure for preparation of 3a in 40% yield (517 mg, 2.37 mmol) as a
colorless oil: 1H NMR (CDCl3) δ 1.33 (s, 12H), 4.56 (dt, J = 5.3 and
1.4 Hz, 2H), 5.28 (dd, J = 10.5 and 1.4 Hz, 1H), 5.41 (dd, J = 17.2 and
1.5 Hz, 1H), 5.99−6.12 (m, 1H), 6.91 (d, J = 8.7 Hz, 2H), 7.74 (d, J =
E
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
8.6 Hz, 2H); 13C{1H} NMR (CDCl3) δ 24.8, 68.5, 83.5, 114.0, 117.7,
133.0, 136.5, 161.1; EI-MS m/z (rel intensity) 260 (M+, 42).
procedure (60 °C) in 51% yield (35.8 mg, 0.129 mmol) as a brown
solid: mp 45−46 °C; IR (KBr, cm−1) 3352 (Ar-OH); 1H NMR
(CDCl3) δ 3.50 (d, J = 4.0 Hz, 2H), 4.84 (s, 1H), 6.44 (t, J = 3.6 Hz,
2H), 6.79 (dt, J = 8.5 and 2.0 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 7.43
(d, J = 8.2 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H); 13C{1H} NMR (CDCl3)
δ 38.4, 115.4, 124.2 (q, J = 271.8 Hz), 125.4 (q, J = 3.8 Hz), 126.2,
128.8 (q, J = 32.7 Hz), 129.5, 129.8, 131.6, 132.5, 140.9 (q, J = 1.3
Hz), 154.0; EI-MS m/z (rel intensity) 278 (M+, 100); HRMS (ESI-
orbitrap) m/z calcd for C16H13OF3-H [M − H]− 277.0846, found
277.0855.
(E)-4-(3-p-Tolylallyl)phenol (4d) (Table 2, Entry 4). Compound
4d was obtained according to the general procedure (10 mol % of
Pd(OAc)2 and 1d, 60 °C) in 58% yield (32.3 mg, 0.144 mmol) as a
yellow solid: mp 81−82 °C; IR (KBr, cm−1) 3231 (Ar-OH); 1H NMR
(CDCl3) δ 2.32 (s, 3H), 3.45 (d, J = 6,5 Hz, 2H), 4.86 (s, 1H), 6.22−
6.31 (m, 1H), 6.39 (d, J = 15.9 Hz 1H), 6.77 (dt, J = 8.5 and 2.9 Hz,
2H), 7.09 (d, J = 8.1 Hz, 4H), 7.24 (d, J = 3.8 Hz, 2H); 13C{1H} NMR
(CDCl3) δ 21,1, 38.4, 115.2, 126.0, 128.5, 129.2, 129.8, 130.6, 132.5,
134.7, 136.8, 153.8; EI-MS m/z (rel intensity) 224 (M+, 100); HRMS
(ESI-orbitrap) m/z calcd for C16H16O-H [M − H]− 223.1128, found
223.1130.
(E)-4-(3-(4-(Methoxyphenyl)allyl)phenol (4e) (Table 2, Entry 5).
Compound 4e was obtained according to the general procedure (10
mol % of Pd(OAc)2 and 1d, 60 °C) in 46% yield (27.9 mg, 0.116
mmol) as a cream solid: mp 62−63 °C; IR (KBr, cm−1) 3372 (Ar-
OH); 1H NMR (CDCl3) δ 3.45 (d, J = 6.7 Hz, 2H), 3.79 (s, 3H), 4.76
(s, 1H), 6.13−6.40 (m, 1H), 6.37 (d, J = 15.8 Hz, 1H), 6.77 (dt, J =
8.5 and 2.0 Hz, 2H), 6.83 (d, J = 8.7 and 1.9 Hz, 2H), 7.10 (d, J = 8.4
Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H); 13C{1H} NMR (CDCl3) δ 38.4,
55.3, 113.9, 115.2, 127.2, 127.4, 129.7, 130.1, 130.3, 132.5, 153.9,
158.7; EI-MS m/z (rel intensity) 240 (M+, 100); HRMS (APPI-
orbitrap) m/z calcd for C16H16O2 [M]+ 240.1145, found 240.1139.
(E)-4-Cinnamyl-2,6-dimethylphenol (4f) (Table 2, Entry 6).
Compound 4f was obtained according to the general procedure in
47% yield (27.8 mg, 0.117 mmol) as a brown oil: IR (neat, cm−1) 3479
(Ar-OH); 1H NMR (CDCl3) δ 2.22, (s, 6H), 3.40 (d, J = 6.4 Hz, 2H),
4.52 (s, 1H), 6.27−6.36 (m, 1H), 6.43 (d, J = 15.9 Hz, 1H), 6.84 (s,
2H), 7.19−7.37 (m, 5H); 13C{1H} NMR (CDCl3) δ 15.9, 38.5, 123.0,
126.1, 127.0, 128.4, 128.7, 129.9, 130.5, 131.6, 137.6, 150.5; EI-MS m/
z (rel intensity) 238 (M+, 100); HRMS (APCI-orbitrap) m/z calcd for
C17H18O + Na [M + Na]+ 261.1250, found 261.1243.
(E)-4-Cinnamyl-2-methoxyphenol (4g) (Table 2, Entry 7).
Compound 4g was obtained according to the general procedure in
55% yield (33.3 mg, 0.139 mmol) as a brown oil: IR (neat, cm−1) 3518
(Ar-OH); 1H NMR (CDCl3) δ 3.48 (d, J = 6.3 Hz, 2H), 3.87 (s, 3H),
5.51 (s, 1H), 6.28−6.38 (m, 1H), 6.44 (d, J = 15.9 Hz, 1H), 6.74 (d, J
= 7.0 Hz, 2H), 6.86 (d, J = 6.3 Hz, 1H), 7.28 (m, 5H); 13C{1H} NMR
(CDCl3) δ 39.0, 55.9, 111.1, 114.3, 121.3, 126.1, 127.1, 128.5, 129.6,
130.7, 132.0, 137.5, 144.0, 146.5; EI-MS m/z (rel intensity) 240 (M+,
100); HRMS (ESI-orbitrap) m/z calcd for C16H16O2-H [M − H]−
239.1067, found 239.1066.
Preparation of 2-(4-(Allyloxy)-3-methoxyphenyl)-4,4,5,5-tet-
ramethyl-1,3,2-dioxaborolane (3l). This compound was synthe-
sized from 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-
yl)phenol (0.5001 g, 2.0 mmol) and allyl bromide (0.2420 g, 2.0
mmol) according to the procedure for preparation of 3a in 73% yield
1
(423 mg, 1.46 mmol) as a colorless oil: H NMR (CDCl3) δ 1.34 (s,
12H), 3.92 (s, 3H), 4.65 (dt, J = 5.4 and 1.4 Hz, 2H), 5.28 (dd, J =
10.5 and 1.4 Hz, 1H), 5.40 (dd, J = 18.7 and 1.4 Hz, 1H), 6.02−6.15
(m, 1H), 6.88 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 1.1 Hz, 1H), 7.40 (dd, J
= 8.0 and 1.3 Hz, 1H); 13C{1H} NMR (CDCl3) δ 24.8, 55.9, 69.5,
83.6, 112.3, 117.0, 118.1, 128.3, 133.0, 148.7, 150.6; EI-MS m/z (rel
intensity) 290 (M+, 63); HRMS (ESI-orbitrap) m/z calcd for
C16H24O4B [M + H]+ 291.1762, found 291.1763.
Preparation of 2-(4-(Prenyloxy)phenyl)-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (3m). This compound was synthesized from 4-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.1004 g, 5.0
mmol) and prenyl bromide (0.7452 g, 5.0 mmol) according to the
procedure for preparation of 3a in 63% yield (906 mg, 3.14 mmol) as a
colorless oil: 1H NMR (CDCl3) δ 1.33 (s, 12H), 1.74 (s, 3H), 1.79 (s,
3H), 4.53 (d, J = 6.8 Hz, 2H), 5.49 (dt, J = 6.8 and 1.3 Hz, 1H), 6.90
(d, J = 8.7 Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H); 13C{1H} NMR (CDCl3)
δ 18.2, 24.8, 25.8, 64.5, 83.5, 114.0, 119.5, 136.4, 138.2, 161.4; EI-MS
m/z (rel intensity) 288 (M+, 3); HRMS (ESI-orbitrap) m/z calcd for
C17H25O3BNa [M + Na]+ 311.1789, found 311.1787.
Preparation of (E)-2-(Cinnamyloxy)-5-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)pyridine (3n). This compound was
synthesized from 5-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-
pyridin-2-ol (0.2209 g, 1.0 mmol) and (E)-cinnamyl bromide
(0.1973 g, 1.0 mmol) according to the procedure for preparation of
3a ,and the residue after the concentration under reduced pressure was
purified by decantation with hexane to afford 3n in 75% yield (251 mg,
0.75 mmol) as a white solid: mp 141 °C; 1H NMR (CDCl3) δ 1.30 (s,
12H), 4.72 (dd, J = 6.3 and 0.8 Hz, 2H), 6.28−6.38 (m, 1H), 6.55−
6.62 (m, 2H), 7.22−7.39 (m, 5H), 7.62 (dd, J = 9.1 and 1.9 Hz, 1H),
7.78 (d, J = 1.8 Hz, 1H); 13C{1H} NMR (CDCl3) δ 24.7, 51.3, 84.0,
119.9, 123.4, 126.6, 128.0, 128.6, 133.8, 136.0, 143.8, 145.3, 162.9; EI-
MS m/z (rel intensity) 337 (M+, 41); HRMS (ESI-orbitrap) m/z calcd
for C20H25O3NB [M + H]+ 338.1933, found 338.1919.
General Procedure for Palladium-Catalyzed Allylic Arylation
of Cinnamyl- or Allyloxyphenylboronic Acid Pinacol Esters. A
mixture of cinnamyl- or allyloxyphenylboronic acid pinacol ester 3
(0.25 mmol), Ca(OH)2 (0.5 mmol), Pd(OAc)2 (12.5 μmol, 5 mol %),
and ligand 1d (12.5 μmol, 5 mol %) in DMA/H2O (9/1) (1.0 mL) at
50 °C under an Ar atomosphere was stirred for 24 h. After the
reaction, the reaction was quenched with distilled water. The solution
was extracted with ethyl acetate, washed with brine, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by
silica gel chromatography (hexane/ethyl acetate).
(E)-4-Cinnamylphenol (Obtusastyrene) (4a)13 (Table 1, Entry 4).
Compound 4a was obtained according to the general procedure in
75% yield (39.5 mg, 0.188 mmol) as a yellow solid: mp 64 °C; IR
(neat, cm−1): 3226 (Ar-OH); 1H NMR (CDCl3) δ 3.47 (d, J = 6.3 Hz,
2H), 4.75 (s, 1H), 6.27−6.37 (m, 1H), 6.43 (d, J = 15.9 Hz, 1H), 6.77
(d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.5 Hz, 2H), 7.17−7.36 (m, 5H);
13C{1H} NMR (CDCl3) δ 38.4, 115.3, 126.1, 127.0, 128.5, 129.6,
(E)-2-Chloro-4-cinnamylphenol (4h) (Table 2, Entry 8). Com-
pound 4h was obtained according to the general procedure (0.125 M)
in 38% (23.2 mg, 0.095 mmol) as a colorless oil: IR (neat, cm−1) 3524
(Ar-OH); 1H NMR (CDCl3) δ 3.45 (d, J = 6.6 Hz, 2H), 5.49 (s, 1H),
6.24−6.33 (m, 1H), 6.43 (d, J = 15.8 Hz, 1H), 6.95 (d, J = 8.3 Hz,
1H), 7.04 (dd, J = 8.3 and 2.0 Hz, 1H), 7.18−7.37 (m, 6H); 13C{1H}
NMR (CDCl3) δ 38.2, 116.1, 119.7, 126.1, 127.2, 128.5, 128.62,
128.63, 128.8 131.3, 133.4, 137.2, 140.7; EI-MS m/z (rel intensity)
244 (M+, 100); HRMS (ESI-orbitrap) m/z calcd for C15H13OCl-H [M
− H]− 243.0582, found 243.0590.
(E,E)-2-Chloro-4-cinnamyl-1-(cinnamyloxy)benzene (5h) (Table 2,
Entry 8). Compound 5h was obtained according to the general
procedure (0.125 M) in 23% yield (20.7 mg, 0.057 mmol) as a yellow
solid: mp 106−107 °C; 1H NMR (CDCl3) δ 3.46 (d, J = 6.6 Hz, 2H),
4.76 (dd, J = 5.7 and 1.4 Hz, 2H), 6.27−6.46 (m, 3H), 6.75 (d, J =
16.0 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 7.06 (dd, J = 8.4 and 2.1 Hz,
1H), 7.20−7.43 (m, 11H); 13C{1H} NMR (CDCl3) δ 38.1, 69.9,
114.1, 123.0, 124.0, 126.1, 126.6, 127.2, 127.7, 127.9, 128.5, 128.6,
128.7, 130.4, 131.3, 133.1, 133.7, 136.3, 137.2, 152.5; EI-MS m/z (rel
129.8, 130.7, 132.3, 137.5, 153.8; EI-MS m/z (rel intensity) 210 (M+,
100).
(E)-4-(3-(4-Chlorophenyl)allyl)phenol (4b) (Table 2, Entry 2).
Compound 4b was obtained according to the general procedure in
80% yield (48.8 mg, 0.199 mmol) as a yellow solid: mp 71−72 °C; IR
(KBr, cm−1) 3215 (Ar-OH); 1H NMR (CDCl3) δ 3.46 (d, J = 5.5 Hz,
2H), 4.84 (s, 1H), 6.25−6.40 (m, 2H), 6.78 (d, J = 8.5 Hz, 2H), 7.09
(d, J = 8.4 Hz, 2H), 7.22−7.29 (m, 4H); 13C{1H} NMR (CDCl3) δ
38.4, 115.3, 127.3, 128.6, 129.5, 129.8, 130.4, 132.0, 132.6, 136.0,
153.9; EI-MS m/z (rel intensity) 244 (M+, 100); HRMS (APPI-
orbitrap) m/z calcd for C15H13OCl [M]+ 244.0649, found 244.0642.
(E)-4-(3-(4-(Trifluoromethyl)phenyl)allyl)phenol (4c) (Table 2,
Entry 3). Compound 4c was obtained according to the general
F
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
intensity) 360 (M+, 2); HRMS (ESI-orbitrap) m/z calcd for
C24H21OCl + H [M + H]+ 361.1354, found 361.1350.
reduced pressure. The residue was purified by silica gel chromatog-
raphy (hexane/ethyl acetate) to afford 1-allyl-4-(cinnamyloxy)benzene
(7) in 29% yield (18.4 mg, 0.074 mmol) as a cream solid: mp 44−45
(E)-3-Cinnamylphenol (4i) (Table 2, Entry 9). Compound 4i was
obtained according to the general procedure in 79% yield (41.6 mg,
0.198 mmol) as a brown oil: IR (neat, cm−1) 3291 (Ar-OH); 1H NMR
(CDCl3) δ 3.49 (d, J = 6.6 Hz, 2H), 4.90 (s, 1H), 6.27−6.37 (m, 1H),
6.45 (d, J = 15.9 Hz, 1H), 6.69 (d, J = 11.7 Hz, 2H), 6.81 (d, J = 7.6
Hz, 1H), 7.14−7.36 (m, 6H); 13C{1H} NMR (CDCl3) δ 39.1, 113.1,
115.5, 121.1, 126.1, 127.1, 128.5, 128.8, 129.7, 131.2, 137.4, 142.1,
155.6; EI-MS m/z (rel intensity) 210 (M+, 100); HRMS (ESI-
orbitrap) m/z calcd for C15H14O + Na [M + Na]+ 233.0937, found
233.0933.
1
°C; H NMR (CDCl3) δ 3.33 (d, J = 6.7 Hz, 2H), 4.68 (dd, J = 5.8
and 1.4 Hz, 2H), 5.02−5.10 (m, 2H), 5.89−6.02 (m, 1H), 6.37−6.46
(m, 1H), 6.73 (d, J = 16.0 Hz, 1H), 6.90 (dt, J = 8.7 and 2.1 Hz, 2H),
7.11 (d, J = 8.7 Hz, 2H), 7.22−7.35 (m, 3H), 7.41 (dd, J = 8.6 and 1.5
Hz, 2H); 13C{1H} NMR (CDCl3) δ 39.3, 68.7, 114.7, 115.4, 124.6,
126.5, 127.8, 128.6, 129.5, 132.4, 132.9, 136.5, 137.8, 157.0; EI-MS m/
z (rel intensity) 250 (M+, 3); HRMS (ESI-orbitrap) m/z calcd for
C18H18O + H [M + H]+ 251.1430, found 251.1426.
(E)-2-Cinnamylphenol (4j)13 (Table 2, Entry 10). Compound 4j
was obtained according to the general procedure 8% (4.4 mg, 0.021
ASSOCIATED CONTENT
■
S
* Supporting Information
1
mmol) as a brown oil: IR (neat, cm−1) 3334 (Ar-OH); H NMR
1H and 13C NMR spectra for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(CDCl3) δ 3.57 (d, J = 6.1 Hz, 2H), 4.95 (s, 1H), 6.34−6.44 (m, 1H),
6.51 (d, J = 15.9 Hz, 1H), 6.82 (d, J = 7.9 Hz, 1H), 6.91 (td, J = 8.4
and 1.0 Hz, 1H), 7.12−7.37 (m, 7H); 13C{1H} NMR (CDCl3) δ 34.1,
115.7, 121.0, 125.6, 126.2, 127.3, 127.88, 127.91, 128.5, 130.5, 131.5,
137.0, 154.0; EI-MS m/z (rel intensity) 210 (M+, 100).
AUTHOR INFORMATION
Corresponding Author
*E-mail: tmino@faculty.chiba-u.jp.
■
(Z)-3-Benzylidene-2,3-dihydrobenzofuran (6)14 (Table 2, Entry
10). Compound 6 was obtained according to the general procedure in
37% yield (19.0 mg, 0.091 mmol) as a white solid: mp 129−131 °C;
1H NMR (CDCl3) δ 5.43 (d, J = 3.1 Hz, 2H), 6.84 (t, J = 3.1 Hz, 1H),
6.95 (q, J = 8.0 Hz, 2H), 7.20−7.28 (m, 4H), 7.41 (t, J = 7.5 Hz, 2H),
7.53 (d, J = 7.5 Hz, 1H); 13C{1H} NMR (CDCl3) δ 74.6, 110.4, 116.6,
120.2, 120.9, 126.7, 127.0, 128.0, 128.8, 130.2, 136.6, 136.9, 162.5; EI-
MS m/z (rel intensity) 208 (M+, 86); HRMS (ESI-orbitrap) m/z calcd
for C15H12O + H [M + H] 209.0961, found 290.0960.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the COE Program in Chiba
University.
■
4-Allylphenol (4k)15 (Table 2, Entry 11). Compound 4k was
obtained according to the general procedure (48 h, 70 °C) in 43%
yield (14.3 mg, 0.107 mmol) as a colorless oil: IR (neat, cm−1) 3536
(Ar-OH); 1H NMR (CDCl3) δ 3.31(d, J = 6.7 Hz, 2H), 5.02−5.09 (m,
3H), 5.88−6.01 (m, 1H), 6.77 (dt, J = 8.5 and 2.5 Hz, 2H), 7.05 (d, J
= 8.5 Hz, 2H); 13C{1H} NMR (CDCl3) δ 39.3, 115.2, 115.4, 129.7,
132.2, 137.8, 153.8; EI-MS m/z (rel intensity) 134 (M+, 100).
4-Allyl-2-methoxyphenol (Eugenol) (4l)16 (Table 2, Entry 12).
Compound 4l was obtained according to the general procedure in 57%
yield (23.2 mg, 0.141 mmol) as a colorless oil: IR (neat, cm−1) 3523
(Ar-OH); 1H NMR (CDCl3) δ 3.32 (d, J = 6.7 Hz, 2H), 3.87 (s, 3H),
5.07 (t, J = 7.0 Hz, 2H), 5.50 (s, 1H), 5.88−6.01 (m, 1H), 6.68 (q, J =
2.4 Hz, 2H), 6.84 (t, J = 4.3 Hz, 1H); 13C{1H} NMR (CDCl3) δ 39.9,
55.8, 111.1, 114.2, 115.5, 121.1, 131.9, 137.8, 143.9, 146.4; EI-MS m/z
(rel intensity) 164 (M+, 100).
REFERENCES
■
(1) (a) Kramer, B.; Waldvogel, S. R. Angew. Chem. 2004, 116, 2501−
2503; Angew. Chem., Int. Ed. 2004, 43, 2446−2449. (b) Anderson, J.
C.; Headley, C.; Stepleton, P. D.; Taylor, P. W. Tetrahedron 2005, 61,
7703−7711. (c) Belley, M.; Chan, C. C.; Gareau, Y.; Gallant, M.;
Juteau, H.; Houde, K.; Lachance, N.; Labelle, M.; Sawyer, N.;
̀
Tremblay, N.; Limontage, S.; Carriere, M.-C.; Denis, D.; Greig, G. M.;
Slipez, D.; Gordon, R.; Chauret, N.; Li, C.; Zamboni, R. J.; Metters, K.
M. Bioorg. Med. Chem. Lett. 2006, 16, 5639−5642. (d) Abdel Bar, F.
M.; Khanfar, M. A.; Elnagar, A. Y.; Badria, F. A.; Zaghloul, A. M.;
Ahmad, K. F.; Sylvester, P. W.; El Sayed, K. A. Bioorg. Med. Chem.
2010, 18, 496−507. (e) Anderson, J. C.; McCarthy, R. A.; Paulin, S.;
Taylor, W. Bioorg. Med. Chem. Lett. 2011, 21, 6996−7000.
(2) (a) Gergson, M.; Ollis, W. D.; Redman, B. T.; Sutherland, I. O.;
Dietrchs, H. H.; Gottieb, O. R. Phytochemistry 1978, 17, 1395−1400.
(b) Lynn, D. G.; Steffens, J. C.; Kamut, V. S.; Graden, D. W.;
Shabanowitz, J.; Riopel, J. L. J. Am. Chem. Soc. 1981, 103, 1868−1870.
(c) Carlson, R. E.; Dolphin, D. H. Phytochemistry 1982, 21, 1733−
1736. (d) Goda, Y.; Katayama, M.; Ichikawa, K.; Shibuya, M.; Kiuchi,
F.; Sankawa, U. Chem. Pharm. Bull. 1985, 33, 5606−5609.
2-Methoxy-4-allyl-1-(allyloxy) benzene (5l)17 (Table 2, Entry 12).
Compound 5l was obtained according to the general procedure in 20%
1
yield (10.5 mg, 0.051 mmol) as a colorless oil: H NMR (CDCl3) δ
3.33 (d, J = 6.7 Hz, 2H), 3.86 (s, 3H), 4.59 (d, J = 5.4 Hz, 2H), 5.08
(td, J = 8.9 and 1.2 Hz, 2H), 5.27 (dd, J = 10.5 and 1.3 Hz, 1H), 5.39
(dd, J = 17.2 and 1.5 Hz, 1H), 5.89−6.15 (m, 2H), 6.70 (d, J = 9.2 Hz,
2H), 6.82 (d, J = 7.9 Hz, 1H); 13C{1H} NMR (CDCl3) δ 39.8, 55.8,
70.0, 112.2, 113.5, 115.6, 117.8, 120.3, 133.1, 133.5, 137.6, 146.3,
149.3; EI-MS m/z (rel intensity) 204 (M+, 45).
(e) Achenbach, H.; Stocker, M.; Constenla, M. A. Phytochemistry
̈
1988, 27, 1835−1841. (f) Yuda, M.; Ohtani, K.; Mizutani, K.; Kasai,
R.; Tanaka, O.; Jia, M.-R.; Ling, Y.-R.; Pu, X.-F.; Saruwatari, Y.-I.
Phytochemistry 1990, 29, 1989−1993. (g) Goda, Y.; Kiuchi, F.;
Shibuya, M.; Sankawa, U. Chem. Pharm. Bull. 1992, 40, 2452−2457.
(h) Iinuma, M.; Okawa, Y.; Tanaka, T. Phytochemistry 1994, 37, 1153−
1155. (i) Leong, Y.-W.; Harrison, L. J.; Kadir, A. A.; Connolly, J. D.
Phytochemistry 1998, 49, 2141−2143. (j) Lien, T. P.; Porzel, A.;
Schmidt, J.; Sung, T. V.; Adam, G. Phytochemistry 2000, 53, 991−995.
(k) Ito, C.; Itoigawa, M.; Kanematsu, T.; Ruangrungsi, N.;
Higashihara, H.; Tokuda, H.; Nishino, H.; Furukawa, H. J. Nat.
Prod. 2003, 66, 1574−1577. (l) Shen, C.-C.; Wang, S.-T.; Tsai, S.-Y.;
Yang, H.-C.; Shieh, B.-J.; Chen, C.-C. J. Nat. Prod. 2005, 68, 791−793.
(m) Su, C.-R.; Shen, Y.-C.; Kuo, P.-C.; Leu, Y.-L.; Damu, A. G.; Wang,
Y.-H.; Wu, T.-S. Bioorg. Med. Chem. Lett. 2006, 16, 6155−6160.
(n) Ito, C.; Itoigawa, M.; Kanematsu, T.; Imamura, Y.; Tokuda, H.;
Nishino, H.; Furukawa, H. Eur. J. Med. Chem. 2007, 42, 902−909.
(o) Cheenpracha, S.; Karalai, C.; Ponglimanont, C.; Kanjana-Opas, A.
J. Nat. Med. 2011, 65, 313−321. (p) Umehara, K.; Nemoto, K.;
Matsushita, A.; Terada, E.; Monthakantirat, O.; De-Eknamkul, W.;
(E)-5-Cinnamylpyridine-2-ol (4n) (Scheme 2). Compound 4n was
obtained according to the general procedure (60 °C, 48 h) 84% (44.5
1
mg, 0.211 mmol) as a gray oil: IR (neat, cm−1) 3462 (Ar-OH); H
NMR (CDCl3) δ 4.73 (dd, J = 6.4 and 1.2 Hz, 2H), 6.19 (td, J = 6.7
and 1.3 Hz, 1H), 6.27−6.36 (m, 1H), 6.56−6.63 (m, 2H), 7.22−7.39
(m, 7H); 13C{1H} NMR (CDCl3) δ 50.6, 106.2, 121.0, 123.5, 126.5,
128.1, 128.6, 134.0, 135.9, 136.9, 139.5, 162.5; EI-MS m/z (rel
intensity) 211 (M+, 33); HRMS (ESI-orbitrap) m/z calcd for
C14H13NO + H [M + H]+ 212.1070, found 212.1068.
Preparation of 7 for Authentic Sample. A mixture of
(cinnamyloxy)phenylboronic acid pinacol ester 3a (0.0841 g, 0.25
mmol), allylic acetate (0.0300 g, 0.30 mmol), Ca(OH)2 (0.0370 g, 0.5
mmol), Pd(OAc)2 (2.81 mg, 12.5 μmol, 5 mol %), and ligand 1d (3.35
mg, 12.5 μmol, 5 mol %) in DMA/H2O (9/1) (1.0 mL) at 20 °C
under an Ar atomosphere was stirred for 6 h, and the reaction was
quenched with distilled water. The solution was extracted with ethyl
acetate, washed with brine, dried over MgSO4, and concentrated under
G
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Miyase, T.; Warashita, T.; Degawa, M.; Noguchi, H. J. Nat. Prod. 2009,
72, 2163−2168. (q) Mewett, K. N.; Fernadez, S. P.; Pasricha, A. K.;
Pong, A.; Devenish, S. O.; Hibbs, D. E.; Chebib, M.; Johnston, G. A.
R.; Hanrahan, J. R. Bioorg. Med. Chem. 2009, 17, 7156−7173.
(r) Moriyasu, M.; Nakatani, N.; Ichimaru, M.; Nishiyama, Y.; Kato, A.;
Mathenge, S. G.; Juma, F. D.; Mutiso, P. B. C. J. Nat. Med. 2011, 65,
313−321. (s) Kongkammerd, J.; Milani, A.; Cattoli, G.; Terregino, C.;
Capua, I.; Beneduce, L.; Gallotta, A.; Pengo, P.; Fassina, G.;
Monthakantirat, O.; Umehara, K.; De-Eknamkul, W.; Miertus, S. J.
Biomol. Screen. 2011, 16, 755−764.
(3) Moreno-Manas, M.; Pajuelo, F.; Pleixats, R. J. Org. Chem. 1995,
̃
60, 2396−2397.
́
(4) Kjellgren, J.; Aydin, J.; Wallner, O. A.; Saltnava, I. V.; Szabo, K.
Chem.Eur. J. 2005, 11, 5260−5268.
(5) (a) Bouyssi, D.; Gerusz, V.; Balme, G. Eur. J. Org. Chem. 2002,
2445−2448. (b) Ortar, G. Tetrahedron Lett. 2003, 44, 4311−4314.
(c) Polackova, V.; Toma, S.; Kappe, O. Tetrahedron 2007, 63, 8742−
8745. (d) Sarkar, S. M.; Uozumi, Y.; Yamada, Y. M. A. Angew. Chem.,
Int. Ed. 2011, 50, 9347−9441. (e) Yao, B.; Liu, Y.; Wang, M.-D.; Li, J.-
H.; Tang, R.-Y.; Zhang, X.-G.; Deng, C.-L. Adv. Synth. Catal. 2012,
354, 1069−1076.
(6) (a) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung, K. W. Org. Lett.
2003, 5, 2231−2234. (b) Berthiol, F.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2003, 44, 1221−1225. (c) Bar, F. M. A.; Khanfar, M.
A.; Elnagar, A. Y.; Badria, F. A.; Zaghloul, A. M.; Ahmad, K. F.;
Sylvester, P. W.; El Sayed, K. A. Bioorg. Med. Chem. 2010, 18, 496−
507. (d) Sawant, D.; Wagh, Y.; Bhatte, K.; Panda, A.; Bhanage, B.
Tetrahedron Lett. 2011, 52, 2390−2393. (e) Jiang, C.; Covell, D. J.;
Stepan, A. F.; Plummer, M. S.; White, M. C. Org. Lett. 2012, 14,
1386−1389. (f) Werner, E. W.; Sigman, M. S. J. Am. Chem. Soc. 2011,
133, 9692−9695. (g) Wang, G.-W.; Zhou, A.-X.; Li, S.-X.; Yang, S.-D.
Org. Lett. 2014, 16, 3118−3121.
(7) (a) Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. Synlett 2003, 6,
882−884. (b) Mino, T.; Shirae, Y.; Sakamoto, M.; Fujita, T. J. Org.
Chem. 2005, 70, 2191−2194. (c) Mino, T.; Shirae, Y.; Sasai, Y.;
Sakamoto, M.; Fujita, T. J. Org. Chem. 2006, 71, 6834−6839.
(d) Mino, T.; Shirae, Y.; Saito, T.; Sakamoto, M.; Fujita, T. J. Org.
Chem. 2006, 71, 9499−9502. (e) Mino, T.; Shindo, H.; Kaneda, T.;
Koizumi, T.; Kasashima, Y.; Sakamoto, M.; Fujita, T. Tetrahedron Lett.
2009, 50, 5358−5360. (f) Mino, T.; Suzuki, S.; Hirai, K.; Sakamoto,
M.; Fujita, T. Synlett 2011, 9, 1277−1280. (g) Mino, T.; Shibuya, M.;
Suzuki, S.; Hirai, K.; Sakamoto, M.; Fujita, T. Tetrahedron 2012, 68,
429−432. (h) Mino, T.; Watanabe, K.; Abe, T.; Kogure, T.; Sakamoto,
M. Heterocycles 2013, 87, 2015−2021.
(8) (a) Mino, T.; Kajiwara, K.; Shirae, Y.; Sakamoto, M.; Fujita, T.
Synlett 2008, 17, 2711−2715. (b) Mino, T.; Koizumi, T.; Suzuki, S.;
Hirai, K.; Kajiwara, K.; Sakamoto, M.; Fujita, T. Eur. J. Org. Chem.
2012, 678−680.
(9) Mino, T.; Kogure, T.; Abe, T.; Koizumi, T.; Fujita, T.; Sakamoto,
M. Eur. J. Org. Chem. 2013, 1501−1505.
(10) Smiley, P. M.; Miles, W. H. J. Chem. Educ. 2002, 79, 90.
(11) Stadler, A. M.; Kyritsakas, N.; Graff, R.; Lehn, J. M. Chem.Eur.
J. 2006, 12, 4503−4522.
(12) Nagashima, Y.; Takita, R.; Yoshida, K.; Hirano, K.; Uchiyama,
M. J. Am. Chem. Soc. 2013, 135, 18730−18733.
(13) Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell, W. L.;
Kocovsky, P. J. Org. Chem. 1999, 64, 2751−2764.
(14) Durandetti, M.; Hardou, L.; Clement, M.; Maddaluno, J. Chem.
Commun. 2009, 4753−4755.
(15) Denton, R. M.; Scragg, J. T.; Saska, J. Tetrahedron Lett. 2011, 52,
2554−2556.
(16) Larsen, C. R.; Grotjahn, D. B. J. Am. Chem. Soc. 2012, 134,
10357−10360.
(17) Gartner, D.; Konnerth, H.; von Wangelin, A. J. Catal. Sci. Tecnol.
2013, 3, 2541−2545.
H
dx.doi.org/10.1021/jo501235w | J. Org. Chem. XXXX, XXX, XXX−XXX