Palladium-Catalyzed Asymmetric Dihydroxylation of 1,3-Dienes with Catechols

Article abstract of DOI:10.1002/cjoc.201800540

A palladium-catalyzed asymmetric dihydroxylation of 1,3-dienes with catechols is developed using chiral pyridinebis(oxazoline) ligands. Various chiral 2-substituted 1,4-benzodioxanes could be synthesized with moderate to high yields and enantioselectivities from readily available starting materials. The reaction is proposed to proceed through a cascade Wacker-type hydroxypalladation/asymmetric allylation process.

Full text of DOI:10.1002/cjoc.201800540

Palladium-Catalyzed Asymmetric Dihydroxylation of 1,3-Dienes with
Catechols
Tao Fan,a Hong-Cheng Shen, a Zhi-Yong Han,*,a Liu-Zhu Gong*,a
a Hefei National Laboratory for Physical Sciences at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei,
230026, China
Cite this paper: Fan, T.; Shen, H.; Han, Z.; Gong, L. Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion A palladium-catalyzed asymmetric dihydroxylation of 1,3-dienes with catechols is developed using chiral
pyridinebis(oxazoline) ligand. Various chiral 2-substituted 1,4-benzodioxanes could be synthesized with moderate to high yields and enantioselectivities
from readily available starting materials. The reaction is proposed to proceed through a cascade Wacker-type hydroxypalladation /asymmetric allylation
process.
Background and Originality Content
Chiral 2-substituted 1,4-benzodioxane motifs have widely been
found in bioactive natural products and molecules with significant
biological activities, as exemplified by antidepressant MKC-242,[1]
antihypertensive
agent
IDR-16084,[2]
potent
α1D-adrenergicantagonist WB4101,[3] and the antihypertensive
drug (R)-doxazosin[4] (Figure 1a). In the recent decades, global
efforts have been devoted to this field, culminating in a variety of
protocols to access chiral 2,3-dihydro-1,4-benzodioxane skeletons,
including enzymatic[5] and chemical[6] resolution of racemic
1,4-benzodioxan-2-carboxylic acid derivatives and asymmetric
synthesis from chiral pools.[7] In 2001, Buchwald reported a
palladium-catalyzed intramolecular C-O bond formation reaction
using a chiral alcohol substrate to synthesize 1,4-benzodioxane
derivatives.[8] Cai and co-workers provided
a
highly
enantioselective synthesis of 2-hydroxymethyl-1,4-benzodioxanes
via Pd-catalyzed asymmetric C−O coupling reaction.[9] Recently,
Zhang, Yang and co-workers reported an Ir-catalyzed asymmetric
hydrogenation of benzo[b][1,4]dioxine derivatives,[10] and Zhang’s
group established a process enabled by a chiral rhodium catalyst
to give high yields and excellent enantioselectivities.[11] Although
these processes are robust for the construction of the
1,4-benzodioxane structures, they still have drawbacks, such as
the use of relatively complex substrates or chiral starting materials.
Asymmetric hydrogenation reactions also rely on the pre-synthesis
of the benzo[b][1,4]dioxine core. Thus, catalytic approaches to
access chiral 1,4-benzodioxane from simple and inexpensive
starting materials are highly desirable.
Figure
1
Representative bioactive compounds containing
2,3-dihydro-1,4-benzodioxane skeleton (a) and our synthetic approach (b).
Recently, our group has developed Pd(II)-catalyzed asymmetric
aminohydroxylation and diamination reactions of 1,3-dienes with
N-tosyl-2-aminophenol derivatives and ureas, respectively, via a
cascade aza-Wacker/asymmetric allylation process.[12,13] Zhang and
co-workers also reported the palladium-catalyzed diamination[14]
and aminohydroxylation[15] reactions of 1,3-dienes. We envisioned
that in the presence of an appropriate chiral Pd(II) catalyst,
catechols and 1,3-dienes might undergo a cascade Wacker-type[16]
hydroxypalladation/asymmetric allylation process,[17] thus
Results and Discussion
Our investigation started with a reaction between catechol 1a
and (E)-buta-1,3-dien-1-ylbenzene 2a catalyzed by a palladium
complex (Table 1). Initially, the reaction was carried out at 50 °C
for 22 hours in the presence of 10 mol % of Pd(OAc)2,
2,5-dimethylbenzoquinone (DMBQ) and 4Å molecular sieves in
toluene without a ligand. Encouragingly, the racemic reaction
provided 3a in 10 % yield (entry 1). Next, a number of chiral
ligands were evaluated for the reaction. Gratifyingly, the
pyridinebis(oxazoline) (pybox) ligand L1, the optimal ligand used
in our asymmetric aminohydroxylation reaction,[12a] exhibited high
reactivity and enantioselectivity (entry 2, 82% yield and 89:11 e.r.).
Variation of the substituents on the pybox ligands[18] all led to
unproductive reactions (entries 3-5), indicating that the diphenyl
substituents on the pybox ligand are crucial to achieve high
reactivity and enantioselectivity. Interestingly, varying one of the
phenyl group to dimethyl group provided the same
enantioselectivity and slightly lower yield (entry 6, L5). None of
chiral sulfoxide-oxazoline ligand L6,[19] Quinox L7, electron-poor
pyridine-oxazoline ligands L8-L9, and bisoxazoline L10 was able to
accelerate the reaction, although some of the ligands such as L7
providing
a
general and efficient synthesis of chiral
1,4-benzodioxanes from simple starting materials (Fig. 1b).
Compared to our previous work using N-tosyl-2-aminophenol
substrates,[12] the main challenge is to ensure both the reactivity
of the Wacker-type process and the enantioselectivity of the
asymmetric allylation step, given the fact that phenol groups are
less reactive than aryl N-tosylamide group under our reaction
conditions.[12]
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exerted a considerable effect on the stereocontrol. Afterwards, a
number of solvents were tested and their consequences were
unsatisfactory (shown in the Supporting Information). The oxidant
also had considerable effect on both the yield and the
enantioselectivity of the dihydroxylation reaction (entries 12-14),
and 2,5-dimethylbenzoquinone still proved to be the optimal one
(entry 2). Next, different palladium sources were examined, and it
was found that Pd2dba3 could give higher enantioselectivity, which
might be related to the effect of counter anions (entries 15-16).
Table 2 Substrate scope a
o
Performing the reaction at 40 or 70 C led to the decrease in both
the yield and enantioselectivity (entries 17-18). The yield also
dropped when a less amount of diene was employed (entry 19).
Table 1 Optimization of the reaction conditions a
Entry
1
2
3
4
5
6
7
8
Pd
Ligand
--
L1
L2
L3
L4
L5
L6
L7
L8
L9
L10
L1
L1
L1
L1
L1
L1
3a(%)b
10
82
<5
<5
<5
78
<5
<5
<5
<5
<5
33
7
e.r.(3a)c
50:50
89:11
80.5:19.5
58:42
64:36
89:11
58:42
74.5:25.5
--
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
Pd(acac)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
9
a
Unless noted otherwise, the reaction of 1 (0.1 mmol) and 2 (0.5 mmol)
10
11
12d
13e
14f
15
16g
17h
18i
19j
--
--
were carried out with Pd2dba3 (0.005 mmol), L1 (0.012 mmol), 2,5-DMBQ
(0.11 mmol) and 4Å molecular sieves (40 mg) in toluene (0.5 mL) at 50 °C .
b Pd2dba3 (0.01 mmol), L1 (0.024 mmol) were used.
89:11
66:34
76:24
80:20
93:7
92:8
90.5:9.5
92:8
5
With the optimized conditions in hand, we explored possible
variations of the substrate. Firstly, we evaluated a variety of
(E)-1-aryl-1,3-butadienes for the reaction with catechol 1a. As
shown in Table 2, various aryl groups, bearing either
electron-donating or –withdrawing substituents, could be well
tolerated. For example, ortho-, meta- and para-methyl or chloro
substituted substrates all provided corresponding products with
good yields and enantioselectivities. Notably, in the case of 3c,
95:5 er could be achieved. Generally, (E)-1-aryl-1,3-butadienes
bearing electron-donating groups led to higher yield and
enantioselectivity than those with electron-withdrawing
substituents. We next turned our attention to the generality of
88
87
77
54
60
L1
L1
a Unless noted otherwise, the reaction of 1a (0.1 mmol) and 2a (0.5 mmol)
were carried out with Pd (0.01 mmol), ligand (0.012 mmol), 2,5-DMBQ (0.1
mmol) and 4Å molecular sieves (40 mg) in toluene (0.5 mL) at 50 °C for
b
22h. The yields were determined by 1H-NMR analysis of the crude
c
product based on internal standard. The e.r. value of 3a was determined
by HPLC analysis. 2,6-DMBQ was used instead of 2,5-DMBQ. BQ was
used instead of 2,5-DMBQ. O2 (1 atm) was used instead of 2,5-DMBQ.
When Pd2(dba)3 was used, the amount of DMBQ was 0.11 mmol. The
reaction was carried out at 40 °C. i The reaction was carried out at 70 °C. j
The amount of 2a was 0.3 mmol.
d
e
f
g
this
dihydroxylation
reaction
group-substituted
for
catechols.
An
h
electron-withdrawing
pyrocatechol,
4,5-difluorobenzene-1,2-diol (3n), only provided the product in a
low yield and moderate enantioselectivity. The reaction of
2,3-dihydro-1H-indene-5,6-diol with the diene 2a gave a higher
yield and stereoselectivity (3o). Then, this catechol derivative was
subjected to the reactions with a number of other dienes (3p-3s).
Among them, the highest enantiomeric ratio (96.5:3.5) could be
obtained for the reaction yielding 3p.
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Scheme 2 Proposed mechanism.
Scheme 1 Gram-scale reaction and synthetic applications of the
products.
Conclusions
In summary, we have developed
a palladium-catalyzed
asymmetric dihydroxylation of 1,3-dienes with catechols utilizing
chiral pyridinebis(oxazoline) ligand. The reaction is proposed to
proceed via
a
cascade Wacker-type hydroxypalladation
The palladium-catalyzed asymmetric dihydroxylation reaction
of 1,3-dienes with catechols could be readily utilized for
gram-scale synthesis, without notable erosion of the yield and
enantioselectivity (Scheme 1a). The chiral 2-substituted
1,4-benzodioxane products could also undergo further
transformations. The alkene moiety in 3a could be readily
hydrogenated to give compound 4 in 99% yield (Scheme 1b).
Ozonolysis and reduction workup of 3a furnished a chiral alcohol 5
in an excellent yield and with maintained enantioselectivity. The
compound 5 could be then readily transformed to a number of
bioactive compounds, such as MKC-242 and WB4101, following a
reported procedure (Scheme 1c).[9]
/asymmetric allylation process. This methodology provides a
direct and straightforward synthesis to prepare chiral
2-substituted 1,4-benzodioxane motifs in moderate to good yield
and enantioselectivity from readily available starting materials.
Experimental
General Information. NMR spectra were recorded on a
Bruker-400 MHz spectrometer. Chemical shifts (δ) are given in
ppm relative to TMS. The residual solvent signals were used as
references and the chemical shifts converted to the TMS scale
(CDCl3: δH = 7.26 ppm, δC = 77.16 ppm). The high resolution mass
spectra were recorded on a Thermo LTQ Orbitrap XL (ESI+) or a
P-SIMS-Gly of Bruker DaltonicsInc (EI+). Infrared spectra were
recorded on a Nicolet MX-1E FT-IR spectrometer. Enantiomeric
As shown in Scheme 2, possible catalytic cycle for the
Pd(II)-catalyzed asymmetric dihydroxylation of 1,3-dienes with
catechols was proposed according to previous related
reports.[12,14-15] First, Pd2dba3 is oxidized by DMBQ to form Pd(II)
excesses were performed on Waters-Breeze (2487 Dual
λ
complex I bearing
a three-coordinated Pybox ligand. The
Absorbance Detector and 1525 Binary HPLC Pump, UV detection
monitored at 254 nm or 220nm). Chiralpak OD-H columns were
purchased from Daicel Chemical Industries, LTD. Optical rotations
were determined at 589 nm (sodium
Perkin-Elmer-343 polarimeter.
Pd(II)-complex could exist as an equilibrium mixture of tri- and
bidentate isomers I and II in solution.[20] Subsequently, the
five-membered palladacycle III could be generated, which might
then be converted to an intermediate IV via ligand exchange.
Through a hydroxypalladation process, the intermediate IV then
transforms into π-allyl-Pd intermediate V, which might exist in
equilibrium with η1-allyl complex V’. Finally, back attack of the
oxygen nucleophile on the π-allyl palladium moiety would
generate product 3a. Alternatively, the syn-oxygenation process
of V’ is also a possible pathway to form 3a.[17,21] A possible
explanation for the excellent E-selectivity of the reaction is the
σ-interconversion during complexation of the palladium-ligand,[22,
23] and the E-π-palladium complex, which leads to the E-product, is
more stable due to steric hindrance.
D
line) by using
a
General Experimental Procedure. To
a flame-dried and
Ar-purged Schlenk tube (10 mL) were added Pd2dba3 (0.005 mmol,
4.6 mg), 1 (0.1 mmol, 11.0 mg), L1 (0.012mmol, 6.3 mg), 2,
5-DMBQ (0.11 mmol, 15.0 mg), 4Å (40 mg) and a stirring bar. The
Schlenk tube was then evacuated and filled with argon. This cycle
was repeated three times and followed by addition of 1, 3-diene 2
(0.5 mmol) and toluene (0.5 mL) via syringe. The mixture was
o
stirred at 50 C for 22 h. After that, the mixture was filtrated by
silica gel and washed with EtOAc (3 ×10 mL). The combined
organic layers were concentrated under vacuum. After 1H-NMR
analysis, the residue was purified by flash column
chromatography on silica gel (petroleum ether/ ethyl acetate =
10:1) to afford the 3.
(S,E)-2-styryl-2,3-dihydrobenzo[b][1,4]dioxine (3a). Yield: 87%;
1H NMR (400 MHz, CDCl3) δ 7.39 – 7.30 (m, 2H), 7.28 – 7.22 (m,
2H), 7.19 (dt, J = 20.9, 9.9 Hz, 1H), 6.91 – 6.85 (m, 1H), 6.85 – 6.76
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(m, 3H), 6.74 (d, J = 15.6 Hz, 1H), 6.14 (dd, J = 16.0, 6.6 Hz, 1H),
4.79 – 4.59 (m, 1H), 4.23 (dd, J = 11.3, 2.4 Hz, 1H), 3.90 (dd, J =
11.3, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 142.16, 142.00,
134.83, 133.25, 127.62, 127.30, 125.68, 122.04, 120.61, 120.42,
116.38, 116.07, 72.66, 66.80; IR (CH2Cl2) γ 3027, 2922, 1593, 1493,
1465, 1264, 1064, 967, 743 cm-1; HRMS (ESI) m/z (M+H)+:
129.33, 127.02, 126.94, 126.07, 121.72, 121.54, 117.49, 117.15,
73.63, 67.77; IR (CH2Cl2) γ 3038, 2924, 1593, 1493, 1264, 1246,
1036, 960, 746 cm-1; HRMS (ESI) m/z (M+H)+: calculated for
20
C16H13ClO2: 273.0682, found: 273.0680; *α+D = 10.8 (c = 0.22,
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 89:11 e.r. (CHIRALPAK OD-H, hexane/i-PrOH =
90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) = 7.73
min, tR (minor) = 6.83 min; the absolute configuration was
assigned by analogy.
20
calculated for C16H14O2: 239.1072, found: 239.1055; *α+D = 30.4
(c = 0.68, CHCl3); the product was analyzed by HPLC to determine
the enantiomeric ratio: 93:7 e.r. (CHIRALPAK OD-H, hexane/i-PrOH
= 90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
8.34 min, tR (minor) = 6.71 min; the absolute configuration was
determined to be S based on the absolute configuration of
compound 5.
(S,E)-2-(3-methylstyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3f).
Yield: 70%; 1H NMR (400 MHz, CDCl3) δ 7.18 – 7.13 (m, 3H), 7.05 –
6.99 (m, 1H), 6.90 – 6.85 (m, 1H), 6.85 – 6.81 (m, 1H), 6.81 – 6.76
(m, 2H), 6.72 (dd, J = 16.0, 1.1 Hz, 1H), 6.14 (dd, J = 16.0, 6.6 Hz,
1H), 4.74 – 4.67 (m, 1H), 4.24 (dd, J = 11.3, 2.4 Hz, 1H), 3.92 (dd, J
= 11.3, 8.0 Hz, 1H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
142.20, 142.02, 137.21, 134.80, 133.39, 128.11, 127.52, 126.38,
122.87, 121.84, 120.61, 120.40, 116.40, 116.07, 72.73, 66.85,
20.34; IR (CH2Cl2) γ 3041, 2963, 2922, 1593, 1493, 1264, 1063, 966,
747 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for C17H16O2:
(S,E)-2-(2-methoxystyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3b)
1
Yield: 72%; H NMR (400 MHz, CDCl3) δ 7.38 (dd, J = 7.6, 1.2 Hz,
1H), 7.15-7.22 (1H), 7.07 (d, J = 16.2 Hz, 1H), 6.90 – 6.81 (m, 2H),
6.81 – 6.74 (m, 4H), 6.19 (dd, J = 16.2, 6.9 Hz, 1H), 4.81 – 4.58 (m,
1H), 4.25 (dd, J = 11.3, 2.4 Hz, 1H), 3.93 (dd, J = 11.3, 8.2 Hz, 1H),
3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 155.97, 142.32, 142.04,
128.56, 128.41, 126.28, 123.78, 122.59, 120.53, 120.31, 119.60,
116.43, 116.01, 109.85, 73.25, 66.96, 54.40; IR (CH2Cl2) γ 3043,
2923, 2852, 1593, 1492, 1464, 1266, 1246, 1196, 1051, 1027, 975,
747 cm-1; HRMS (ESI) m/z (M+H)+: calculated for C17H16O3:
20
253.1229, found: 253.1229; *α+D = 29.9 (c = 0.36, CHCl3); the
product was analyzed by HPLC to determine the enantiomeric
ratio: 94:6 e.r. (CHIRALPAK OD-H, hexane/i-PrOH = 90/10, flow
rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) = 6.84 min, tR
(minor) = 5.83 min; the absolute configuration was assigned by
analogy.
20
269.1178, found: 269.1177; *α+D = 16.2 (c = 0.39, CHCl3); the
product was analyzed by HPLC to determine the enantiomeric
ratio: 94:6 e.r. (CHIRALPAK OD-H, hexane/i-PrOH = 90/10, flow
rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) = 9.30 min, tR
(minor) = 8.79 min; the absolute configuration was assigned by
analogy.
(S,E)-2-(3-chlorostyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3g).
Yield: 65%; 1H NMR (400 MHz, CDCl3) δ 7.34 – 7.32 (m, 1H), 7.21 –
7.16 (m, 3H), 6.91 – 6.85 (m, 1H), 6.85 – 6.76 (m, 3H), 6.70 (dd, J =
16.0, 1.1 Hz, 1H), 6.17 (dd, J = 16.0, 6.3 Hz, 1H), 4.77 – 4.69 (m,
1H), 4.25 (dd, J = 11.3, 2.4 Hz, 1H), 3.91 (dd, J = 11.3, 7.8 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 142.01, 141.96, 136.73, 133.60,
131.68, 128.86, 127.22, 125.58, 123.91, 123.67, 120.70, 120.53,
116.38, 116.12, 72.33, 66.66; IR (CH2Cl2) γ 3042, 2917, 2850, 1593,
1492, 1263, 1038, 963, 746 cm-1; HRMS (ESI) m/z (M+H)+:
calculated for C16H13ClO2: 273.0682, found: 273.0677; *α+D20 = 31.0
(c = 0.36, CHCl3); the product was analyzed by HPLC to determine
the enantiomeric ratio: 88:12 e.r. (CHIRALPAK OD-H,
hexane/i-PrOH = 90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm),
tR (major) = 8.50 min, tR (minor) = 6.69 min; the absolute
configuration was assigned by analogy.
(S,E)-2-(2-methylstyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3c).
Yield: 71%; 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.44 (m, 1H),
7.18-7.22 (m, 3H), 7.07 (d, J = 15.9 Hz, 1H), 7.00 – 6.95 (m, 1H),
6.90 (m, 3H), 6.13 (dd, J = 15.9, 6.6 Hz, 1H), 4.83 (t, J = 7.1 Hz, 1H),
4.34 (dd, J = 11.3, 2.4 Hz, 1H), 4.03 (dd, J = 11.3, 7.9 Hz, 1H), 2.37
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.19, 142.05, 134.79,
134.02, 131.15, 129.37, 127.16, 125.14, 124.75, 123.41, 120.61,
120.42, 116.40, 116.07, 72.82, 66.91, 18.73.; IR (CH2Cl2) γ 3040,
2922, 1593, 1493, 1265, 1248, 1027, 967, 745 cm-1 ; HRMS (ESI)
m/z (M+H)+ : calculated for C17H16O2: 253.1229, found: 253.1220;
20
*α+D = 13.0 (c = 0.32, CHCl3); the product was analyzed by HPLC
to determine the enantiomeric ratio: 95:5 e.r. (CHIRALPAK OD-H,
hexane/i-PrOH = 90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm),
tR (major) = 7.84 min, tR (minor) = 7.12 min; the absolute
configuration was assigned by analogy.
(S,E)-2-(3-(trifluoromethyl)styryl)-2,3-dihydrobenzo[b][1,4]
dioxine (3h). Yield: 78%; H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H),
1
7.63 – 7.39 (m, 3H), 7.02 – 6.79 (m, 5H), 6.33 (dd, J = 16.0, 6.2 Hz,
1H), 4.99 – 4.69 (m, 1H), 4.35 (dd, J = 11.3, 2.4 Hz, 1H), 4.02 (dd, J
= 11.3, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 143.17, 143.16,
136.87, 132.73, 131.29 (q, J = 32.34 Hz), 130.01, 130.00, 129.30,
125.39, 124.96 (q, J = 3.76 Hz), 123.50 (q, J = 3.82 Hz), 122.79,
121.92, 121.75, 117.56, 117.33, 73.45, 67.81; IR (CH2Cl2) γ 3044,
2919, 2850, 1593, 1493, 1264, 1128, 1072, 965, 747 cm-1; HRMS
(ESI) m/z (M+H)+ : calculated for C17H13ClO2: 307.0946, found:
307.0953; *α+D20 = 27.0 (c = 0.36, CHCl3); the product was analyzed
by HPLC to determine the enantiomeric ratio: 88:12 e.r.
(CHIRALPAK OD-H, hexane/i-PrOH = 90/10, flow rate: 1.0 mL/min,
(S,E)-2-(2-fluorostyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3d).
1
Yield: 50%; H NMR (400 MHz, CDCl3) δ 7.40 (td, J = 7.7, 1.6 Hz,
1H), 7.21 – 7.14 (m, 1H), 7.07 – 7.01 (m, 1H), 7.01 – 6.95 (m, 1H),
6.94 – 6.86 (m, 2H), 6.86 – 6.78 (m, 3H), 6.27 (dd, J = 16.2, 6.5 Hz,
1H), 4.80 – 4.68 (m, 1H), 4.26 (dd, J = 11.3, 2.4 Hz, 1H), 3.93 (dd, J
= 11.3, 8.0 Hz, 1H).; 13C NMR (100 MHz, CDCl3) δ 157.94 (d, J =
250.37 Hz), 142.11, 142.02, 128.63 (d, J = 8.5 Hz), 126.77(d, J =
3.52Hz), 125.81 (d, J = 3.4 Hz), 124.77 (d, J = 5.5 Hz), 123.17(d, J =
3.60Hz), 122.72 (d, J = 12.0 Hz), 120.66, 120.48, 116.42, 116.10,
114.85 (d, J = 22.0 Hz), 72.73, 66.76; IR (CH2Cl2) γ 3042, 2922, 2854, T = 30°C, 254 nm), tR (major) = 6.48 min, tR (minor) = 5.94 min; the
1593, 1493, 1265, 1246, 1065, 968, 748 cm-1 ; HRMS (ESI) m/z
absolute configuration was assigned by analogy.
(M+H)+ : calculated for C16H13FO2: 257.0978, found: 257.0978;
(S,E)-2-(4-methoxystyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3i).
Yield: 73%; 1H NMR (400 MHz, CDCl3) δ 7.42 – 7.33 (m, 2H), 6.98 –
6.94 (m, 1H), 6.94 – 6.90 (m, 1H), 6.90 – 6.84 (m, 4H), 6.78 (d, J =
15.9 Hz, 1H), 6.10 (dd, J = 16.0, 6.9 Hz, 1H), 4.77 (dddd, J = 8.1, 6.9,
2.4, 1.2 Hz, 1H), 4.32 (dd, J = 11.3, 2.4 Hz, 1H), 4.00 (dd, J = 11.3,
8.1 Hz, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.91,
20
*α+D = 17.5 (c = 0.29, CHCl3); the product was analyzed by HPLC
to determine the enantiomeric ratio: 85.5:14.5 e.r. (CHIRALPAK
OD-H, hexane/i-PrOH = 90/10, flow rate: 1.0 mL/min, T = 30°C,
254 nm), tR (major) = 5.90 min, tR (minor) = 5.55 min; the absolute
configuration was assigned by analogy.
(S,E)-2-(2-methoxystyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3e). 143.42, 143.18, 134.16, 128.75, 128.14, 121.74, 121.53, 120.83,
Yield: 51%; 1H NMR (400 MHz, CDCl3) δ 7.57 – 7.54 (m, 1H), 7.40 –
7.34 (m, 1H), 7.25 – 7.19 (m, 3H), 6.99 – 6.94 (m, 1H), 6.93 – 6.86
(m, 3H), 6.23 (dd, J = 16.0, 6.6 Hz, 1H), 4.89 – 4.82 (m, 1H), 4.35
(dd, J = 11.3, 2.4 Hz, 1H), 4.03 (dd, J = 11.3, 7.8 Hz, 1H); 13C NMR
117.55, 117.21, 114.18, 74.09, 68.09, 55.43; IR (CH2Cl2) γ 3041,
2962, 2923, 2853, 1655, 1608, 1493, 1261, 1020, 800, 746 cm-1;
HRMS (ESI) m/z (M+H)+: calculated for C17H16O3: 269.1178, found:
269.1174; *α+D20 = 26.4 (c = 0.37, CHCl3); the product was analyzed
(100 MHz, CDCl3) δ 143.11, 143.06, 134.14, 133.47, 130.49, 129.84, by HPLC to determine the enantiomeric ratio: 94:6 e.r.
This article is protected by copyright. All rights reserved.

(CHIRALPAK OD-H, hexane/i-PrOH = 99/1, flow rate: 1.0 mL/min, T
= 30°C, 254 nm), tR (major) = 33.89 min, tR (minor) = 33.16 min;
the absolute configuration was assigned by analogy.
1H), 2.82 (t, J = 7.4 Hz, 4H), 2.05 (p, J = 7.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ 140.47, 140.34, 136.23, 136.01, 134.96, 133.05,
127.60, 127.23, 125.68, 122.40, 111.86, 111.55, 72.63, 66.85,
31.43, 31.41, 24.95; IR (CH2Cl2) γ 3027, 2927, 1590, 1488, 1450,
(S,E)-2-(4-methylstyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3j).
1
Yield: 77%; H NMR (400 MHz, CDCl3) δ 7.24 (d, J = 8.1 Hz, 2H),
1324, 1285, 1155, 964, 744 cm-1; HRMS (ESI) m/z (M+H)+
:
20
7.07 (d, J = 8.0 Hz, 2H), 6.93 – 6.85 (m, 1H), 6.85 – 6.81 (m, 1H),
6.81 – 6.76 (m, 2H), 6.72 (d, J = 16.0 Hz, 1H), 6.10 (dd, J = 16.0, 6.8
Hz, 1H), 4.83 – 4.58 (m, 1H), 4.24 (dd, J = 11.3, 2.4 Hz, 1H), 3.92
(dd, J = 11.3, 8.1 Hz, 1H), 2.27 (s, 3H).; 13C NMR (100 MHz, CDCl3) δ
143.30, 143.09, 138.34, 134.36, 133.14, 129.39, 126.68, 122.01,
121.65, 121.45, 117.46, 117.12, 73.89, 67.96, 21.29; IR (CH2Cl2) γ
3043, 2920, 1593, 1493, 1265, 1249, 1061, 969, 747 cm-1; HRMS
(ESI) m/z (M+H)+ : calculated for C17H16O2: 253.1229, found:
253.1222; *α+D20 = 33.9 (c = 0.32, CHCl3); the product was analyzed
by HPLC to determine the enantiomeric ratio: 90:10 e.r.
(CHIRALPAK OD-H, hexane/i-PrOH = 99/1, flow rate: 1.0 mL/min, T
= 30°C, 254 nm), tR (major) = 12.96 min, tR (minor) = 11.46 min;
the absolute configuration was assigned by analogy.
calculated for C19H18O2: 279.1385, found: 279.1381; *α+D = 24.6
(c = 0.27, CHCl3); the product was analyzed by HPLC to determine
the enantiomeric ratio: 91:9 e.r. (CHIRALPAK OD-H, hexane/i-PrOH
= 90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
7.67 min, tR (minor) = 6.58 min; the absolute configuration was
assigned by analogy.
(S,E)-2-(2-methylstyryl)-2,3,7,8-tetrahydro-6H-indeno[5,6-b][1,
4]dioxine (3o). Yield: 33%; 1H NMR (400 MHz, CDCl3) δ 7.52 – 7.42
(m, 1H), 7.21 – 7.11 (m, 3H), 7.05 (d, J = 15.9 Hz, 1H), 6.82 (s, 1H),
6.77 (s, 1H), 6.13 (dd, J = 15.9, 6.6 Hz, 1H), 4.90 – 4.64 (m, 1H),
4.30 (dd, J = 11.3, 2.4 Hz, 1H), 3.97 (dd, J = 11.3, 7.9 Hz, 1H), 2.82
(t, J = 7.4 Hz, 4H), 2.36 (s, 3H), 2.06 (p, J = 7.4 Hz, 2H).; 13C NMR
(100 MHz, CDCl3) δ 140.47, 140.34, 136.23, 136.01, 134.96, 133.05,
127.60, 127.23, 125.68, 122.40, 111.86, 111.55, 72.63, 66.85,
31.43, 31.41, 24.95; IR (CH2Cl2) γ 3042, 2926, 1637, 1485, 1439,
1320, 1246, 1155, 1028, 952, 738 cm-1; HRMS (ESI) m/z (M+H)+ :
(S,E)-2-(4-chlorostyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3k).
Yield: 64%; 1H NMR (400 MHz, CDCl3) δ 7.38 – 7.28 (m, 4H), 6.98 –
6.85 (m, 4H), 6.22 (dd, J = 16.0, 6.5 Hz, 1H), 4.82 – 4.77 (m, 1H),
4.33 (dd, J = 11.3, 2.4 Hz, 1H), 4.00 (dd, J = 11.3, 7.9 Hz, 1H).; 13C
NMR (100 MHz, CDCl3) δ 143.12, 143.04, 134.43, 134.06, 132.99,
128.88, 127.95, 123.83, 121.74, 121.56, 117.43, 117.16, 73.54,
67.77; IR (CH2Cl2) γ 3042, 2921, 1593, 1493, 1264, 1249, 1090,
1064, 968, 748 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for
20
calculated for C20H20O2: 293.1542, found: 293.1533; *α+D = 11.1
(c = 0.21, CHCl3); the product was analyzed by HPLC to determine
the enantiomeric ratio: 96.5:3.5 e.r. (CHIRALPAK OD-H,
hexane/i-PrOH = 99/1, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR
(major) = 17.41 min, tR (minor) = 15.96 min; the absolute
configuration was assigned by analogy.
20
C16H13ClO2: 273.0682, found: 273.0673; *α+D = 35.6 (c = 0.25,
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 85:15 e.r. (CHIRALPAK OD-H, hexane/i-PrOH =
99.7/0.3, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
26.56 min, tR (minor) = 29.27 min; the absolute configuration was
assigned by analogy.
(S,E)-2-(3-methylstyryl)-2,3,7,8-tetrahydro-6H-indeno[5,6-b][1,
4]dioxine (3p). Yield: 36%; 1H NMR (400 MHz, CDCl3) δ 7.25 – 7.16
(m, 3H), 7.13 – 7.04 (m, 1H), 6.78 (d, J = 15.8 Hz, 3H), 6.22 (dd, J =
16.0, 6.7 Hz, 1H), 4.86 – 4.63 (m, 1H), 4.27 (dd, J = 11.3, 2.4 Hz,
1H), 3.96 (dd, J = 11.3, 7.9 Hz, 1H), 2.82 (t, J = 7.4 Hz, 4H), 2.35 (s,
3H), 2.05 (p, J = 7.4 Hz, 2H).; 13C NMR (100 MHz, CDCl3) δ 140.50,
140.34, 137.19, 136.22, 135.99, 134.90, 133.17, 128.03, 127.50,
126.36, 122.87, 122.18, 111.86, 111.55, 72.68, 66.88, 31.43, 31.41,
24.96, 20.34; IR (CH2Cl2) γ 3029, 2922, 2847, 1590, 1487, 1325,
(S,E)-2-(4-bromostyryl)-2,3-dihydrobenzo[b][1,4]dioxine (3l).
1
Yield: 75%; H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 8.4 Hz, 2H),
7.36 – 7.16 (m, 2H), 6.99 – 6.92 (m, 1H), 6.92 – 6.83 (m, 3H), 6.76
(d, J = 16.0 Hz, 1H), 6.22 (dd, J = 16.0, 6.4 Hz, 1H), 4.78 (dd, J = 9.4,
4.0 Hz, 1H), 4.31 (dd, J = 11.3, 2.4 Hz, 1H), 3.99 (dd, J = 11.3, 7.9 Hz, 1287, 1154, 1054, 966, 774 cm-1; HRMS (ESI) m/z (M+H)+
:
1H); 13C NMR (100 MHz, CDCl3) δ 143.22, 143.15, 134.99, 133.15,
131.95, 128.36, 124.07, 122.36, 121.86, 121.69, 117.55, 117.29,
73.65, 67.85; IR (CH2Cl2) γ 3041, 2922, 2869, 1592, 1490, 1262,
1071, 1008, 967, 747 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for
calculated for C20H20O2: 293.1542, found: 293.1533; *α+D = 29.4
20
(c = 0.20, CHCl3); the product was analyzed by HPLC to determine
the enantiomeric ratio: 91:9 e.r. (CHIRALPAK OD-H, hexane/i-PrOH
= 90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
6.85 min, tR (minor) = 5.91 min; the absolute configuration was
assigned by analogy.
20
C16H13BrO2: 317.0177, found: 317.0172; *α+D = 20.6 (c = 0.46,
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 78:22 e.r. (CHIRALPAK OD-H, hexane/i-PrOH =
99.7/0.3, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
39.54 min, tR (minor) = 43.14 min; the absolute configuration was
assigned by analogy.
(S,E)-2-(4-fluorostyryl)-2,3,7,8-tetrahydro-6H-indeno[5,6-b][1,
1
4]dioxine (3q). Yield: 49%; H NMR (400 MHz, CDCl3) δ 7.39 (dd, J
= 8.7, 5.4 Hz, 2H), 7.03 (t, J = 8.7 Hz, 2H), 6.86 – 6.73 (m, 3H), 6.16
(dd, J = 16.0, 6.6 Hz, 1H), 4.86 – 4.56 (m, 1H), 4.28 (dd, J = 11.3, 2.4
Hz, 1H), 3.96 (dd, J = 11.3, 7.8 Hz, 1H), 2.82 (t, J = 7.4 Hz, 4H), 2.06
(dq, J = 14.7, 7.4 Hz, 2H).; 13C NMR (100 MHz, CDCl3) δ 162.70 (d, J
= 247.8 Hz), 141.41(d, J = 10.0 Hz), 137.33, 137.12, 132.92,
132.20(d, J = 3.34 Hz), 128.32(d, J = 8.2 Hz), 123.23, 123.21,
(S,E)-6,7-difluoro-2-(3-methylstyryl)-2,3-dihydrobenzo[b][1,4]
1
dioxine (3m). Yield: 25%; H NMR (400 MHz, CDCl3) δ 7.25 – 7.19
(m, 3H), 7.11 (d, J = 6.8 Hz, 1H), 6.82 – 6.69 (m, 3H), 6.17 (dd, J =
16.0, 6.6 Hz, 1H), 4.81 – 4.71 (m, 1H), 4.29 (dd, J = 11.4, 2.4 Hz,
1H), 3.96 (dd, J = 11.4, 7.9 Hz, 1H), 2.36 (s, 3H); 13C NMR (100 MHz, 115.73, 115.51, 112.89, 112.63, 73.59, 67.84, 32.48, 32.46, 26.00;
CDCl3) δ 146.01, 143.44, 138.58 (d, J = 9.4 Hz), 135.61, 134.88,
129.33, 128.62, 127.44, 123.92, 122.10, 105.71(dd, J = 21.0, 26.6
Hz), 73.77, 67.76, 21.38; IR (CH2Cl2) γ 3043, 2923, 1513, 1208,
1165, 966, 776 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for
IR (CH2Cl2) γ 3042, 2925, 2871, 1589, 1510, 1487, 1327, 1156,
1053, 969, 867 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for
20
C20H17FO2: 297.1291, found: 297.1273; *α+D = 32.7 (c = 0.30,
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 92.5:7.5 e.r. (CHIRALPAK OD-H, hexane/i-PrOH
= 99/1, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) =
11.69 min, tR (minor) = 12.60 min; the absolute configuration was
assigned by analogy.
20
C17H14F2O2: 289.1040, found: 289.1043; *α+D = 17.8 (c = 0.13,
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 80:20 e.r. (CHIRALPAK OD-H, hexane/i-PrOH =
90/10, flow rate: 1.0 mL/min, T = 30°C, 254 nm), tR (major) = 7.99
min, tR (minor) = 6.74 min; the absolute configuration was
assigned by analogy.
(S,E)-2-(4-methoxystyryl)-2,3,7,8-tetrahydro-6H-indeno[5,6-b][
1
1,4]dioxine (3r). Yield: 57%; H NMR (400 MHz, CDCl3) δ 7.36 (d, J
(S,E)-2-styryl-2,3,7,8-tetrahydro-6H-indeno[5,6-b][1,4] dioxine
(3n). Yield: 52%; H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 7.1 Hz,
2H), 7.33 (t, J = 7.3 Hz, 2H), 7.30 – 7.24 (m, 1H), 6.80 (dd, J = 16.3,
11.3 Hz, 2H), 6.24 (dd, J = 16.0, 6.6 Hz, 1H), 4.75 (ddd, J = 6.7, 3.9,
= 8.7 Hz, 2H), 6.92 – 6.84 (m, 2H), 6.77 (dd, J = 15.0, 10.4 Hz, 3H),
6.10 (dd, J = 16.0, 6.9 Hz, 1H), 4.77 – 4.70 (m, 1H), 4.28 (dd, J =
11.3, 2.4 Hz, 1H), 3.96 (dd, J = 11.3, 8.0 Hz, 1H), 3.82 (s, 3H), 2.82
(t, J = 7.4 Hz, 4H), 2.06 (p, J = 7.4 Hz, 2H).; 13C NMR (100 MHz,
1
1.0 Hz, 1H), 4.28 (dd, J = 11.3, 2.4 Hz, 1H), 3.96 (dd, J = 11.3, 7.9 Hz, CDCl3) δ 140.47, 140.34, 136.23, 136.01, 134.96, 133.05, 127.60,
This article is protected by copyright. All rights reserved.

127.23, 125.68, 122.40, 111.86, 111.55, 72.63, 66.85, 31.43, 31.41,
24.95; IR (CH2Cl2) γ 3031, 2931, 2845, 1606, 1512, 1487, 1326,
1250, 1155, 969, 764 cm-1; HRMS (ESI) m/z (M+H)+ : calculated for
Pressure and Urinary Bladder Pressure in Anesthetized Rats. Acta
Pharmacol. Sin. 2006, 27, 1423-1430.
[5] (a) Antus, S.; Gottsegen, A.; Kajtár, J.; Kovács, T.; Tóth, T. S.; Wagner, H.
20
C20H20O3: 309.1491, found: 309.1486; *α+D = 29.8 (c = 0.31,
Lipase-catalyzed
Kinetic
Resolution
of
CHCl3); the product was analyzed by HPLC to determine the
enantiomeric ratio: 93:7 e.r. (CHIRALPAK OD-H, hexane/i-PrOH =
90/10, flow rate: 1.0 mL/min, T = 30°C, 220 nm), tR (major) = 7.81
min, tR (minor) = 7.20 min; the absolute configuration was
assigned by analogy.
(±)-2-hydroxymethyl-1,4-benzodioxane. Tetrahedron: Asymmetry
1993, 4, 339-344. (b) Sakai, T.; Hayashi, K.; Yano, F.; Takami, M.; Ino,
M.; Korenaga, T.; Ema, T. Enhancement of the Efficiency of the Low
Temperature Method for Kinetic Resolution of Primary Alcohols by
Optimizing the Organic Bridges in Porous Ceramic-Immobilized
Lipase Bull. Chem. Soc. Jpn. 2003, 76, 1441-1446. (c) Rouf, A.; Gupta,
P.; Aga, M. A.; Kumar, B.; Chaubey, A.; Parshad, R.; Taneja, S. C.
Chemoenzymatic Synthesis of Piperoxan, Prosympal, Dibozane, and
Doxazosin. Tetrahedron: Asymmetry. 2012, 23, 1615-1623.
(S)-2-phenethyl-2,3-dihydrobenzo[b][1,4]dioxine (4). Yield:
99%; 1H NMR (400 MHz, CDCl3) δ 7.31 -7.26 (m, 2H), 7.23 -7.18 (m,
3H), 6.93 – 6.88 (m, 1H), 6.87 – 6.79 (m, 3H), 4.17 (dd, J = 11.2, 2.2
Hz, 1H), 4.12 – 4.05 (m, 1H), 3.88 (dd, J = 11.2, 7.6 Hz, 1H), 2.85
(dddd, J = 16.2, 13.9, 8.9, 6.6 Hz, 2H), 2.00 (ddd, J = 17.4, 8.7, 5.5
Hz, 1H), 1.92 – 1.78 (m, 1H).; 13C NMR (100 MHz, CDCl3) δ 142.30,
142.22, 140.02, 127.48, 127.46, 125.09, 120.42, 120.19, 116.29,
115.95, 70.93, 66.91, 31.46, 29.99; IR (CH2Cl2) γ 3026, 2925, 2869,
1592, 1493, 1454, 1268, 1099, 1043, 907, 748, 700 cm-1; HRMS
(ESI) m/z (M+Na)+ : calculated for C16H16O2: 263.1064, found:
[6] Bolchi, C.; Pallavicini, M.; Fumagalli, L.; Marchini, N.; Moroni, B.;
Rusconi, C.; Valoti, E. Highly Efficient Resolutions of
1,4-benzodioxane-2-carboxylic
Acid
with
Para-substituted
1-phenylethylamines. Tetrahedron: Asymmetry 2005, 16, 1639-1643.
20
263.1064; *α+D = -75.6 (c = 0.96, CHCl3); the product was
[7] (a) Nelson, W. L.; Wennerstrom, J. E. Absolute Configuration of
analyzed by HPLC to determine the enantiomeric ratio: 93:7 e.r.
(CHIRALPAK OD-H, hexane/i-PrOH = 90/10, flow rate: 1.0 mL/min,
T = 30°C, 254 nm), tR (major) = 8.00 min, tR (minor) = 6.95 min; the
absolute configuration was assigned by analogy.
2-alkylaminomethylbenzodioxans,
Competitive
α-adrenergic
Antagonists. J. Chem. Soc., Chem. Commun. 1976, 921-922. (b) Valoti,
E.; Pallavicini, M.; Villa, L.; Pezzetta, D. Synthesis of Homochiral 5-and
(S)-(2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol (5). Yield:
95%; H NMR (400 MHz, CDCl3) δ 6.93 – 6.82 (m, 4H), 4.33 – 4.23
8-Substituted
2-[((2-(2,
6-dimethoxyphenoxy)-ethyl)
amino)
1
methyl]-1, 4-benzodioxanes and Electrophoretic Determination of
Their Enantiomeric Excess. J. Org. Chem. 2001, 66, 1018-1025. (c)
Rouf, A.; Aga, M. A.; Kumar, B.; Taneja, S. C. A Facile Approach to
Chiral 1, 4-benzodioxane toward the Syntheses of Doxazosin,
Prosympal, Piperoxan, and Dibozane. Tetrahedron Lett. 2013, 54,
6420-6422.
(m, 2H), 4.16 – 4.07 (m, 1H), 3.94 – 3.80 (m, 2H), 2.29 – 2.11 (m,
1H).; 13C NMR (100 MHz, CDCl3) δ 142.06, 141.95, 120.63, 120.55,
116.26, 116.19, 72.37, 64.09, 60.75; IR (CH2Cl2) γ 3426, 3044, 2927,
2883, 1593, 1493, 1266, 1102, 1042, 940, 747 cm-1; HRMS (ESI)
m/z (M+H)+: calculated for C9H10O3: 167.0708, found: 167.0704;
20
*α+D = -28.9 (c = 0.32, CHCl3); the product was analyzed by HPLC
to determine the enantiomeric ratio: 92:8 e.r. (CHIRALPAK OD-H,
hexane/i-PrOH = 95/5, flow rate: 1.0 mL/min, T = 30°C, 220 nm), tR
(major) = 14.65 min, tR (minor) = 15.93 min; the absolute
configuration of 5 was assigned to be S by comparing the optical
rotation data with literature reports[24] (see details in the
Supporting Information).
[8] Kuwabe, S.; Torraca, K. E.; Buchwald, S. L. Palladium-Catalyzed
Intramolecular C−O Bond Formation. J. Am. Chem. Soc. 2001, 123,
12202-12206.
[9] Shi, J.; Wang, T.; Huang, Y.; Zhang, X.; Wu, Y.-D.; Cai, Q. Pd-Catalyzed
Asymmetric Intramolecular Aryl C–O Bond Formation with SDP(O)
Ligand:
Enantioselective
Synthesis
of
(2,3-Dihydrobenzo[b][1,4]dioxin
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
-2-yl)methanols. Org. Lett. 2015, 17, 840-843.
[10] Wang, Y.; Xia, J.; Yang, G.; Zhang, W. Iridium-catalyzed Asymmetric
Hydrogenation of 2-Substituted 1,4-Benzodioxines. Tetrahedron
2018, 74, 477-482.
Acknowledgement
We are grateful for the financial support from NSFC (Grants
21672197, 21772184) and Natural Science Foundation of Anhui
Province (BJ2060190066).
[11] Yin, X.; Huang, Y.; Chen, Z.; Hu, Y.; Tao, L.; Zhao, Q.; Dong, X.-Q.;
Zhang, X. Enantioselective Access to Chiral 2-Substituted
2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed
Asymmetric Hydrogenation. Org. Lett. 2018, 20, 4173-4177.
[12] (a) Shen, H.-C.; Wu, Y.-F.; Zhang, Y.; Fan, L.-F.; Han, Z.-Y.; Gong, L.-Z.
Palladium-Catalyzed Asymmetric Aminohydroxylation of 1,3-Dienes.
Angew. Chem., Int. Ed. 2018, 57, 2372-2376; Angew. Chem. 2018,
130, 2396-2400. (b) Wu, M.-S.; Fan, T.; Chen, S.-S.; Han, Z.-Y.; Gong,
L.-Z. Pd(II)-Catalyzed Asymmetric Oxidative 1,2-Diamination of
Conjugated Dienes with Ureas. Org. Lett. 2018, 20, 2485-2489.
[13] (a) Bäckvall, J. E. Palladium in Some Selective Oxidation Reactions.
Acc. Chem. Res. 1983, 16, 335-342. (b) Bäckvall, J. E. In Metal‐
Catalyzed Cross‐Coupling Reactions and More; Meijere, A. d., Bräse,
S., Oestreich, M., Eds.; Wiley-VCH: Weinheim, 2014, pp 875-923. (c)
Zhu, Y.; Cornwall, R. G.; Du, H.; Zhao, B.; Shi, Y. Catalytic Diamination
of Olefins via N–N Bond Activation. Acc. Chem. Res. 2014, 47,
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(The following will be filled in by the editorial staff)
Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
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Entry for the Table of Contents
Page No.
Title Palladium-Catalyzed Asymmetric
Dihydroxylation of 1,3-Dienes with
Catechols
A Pd(II)-catalyzed asymmetric dihydroxylation of 1,3-dienes with catechols was developed for the
efficient synthesis of chiral 1,4-benzodioxanes.
Tao Fan, Hong-Cheng Shen, Zhi-Yong Han*,
Liu-Zhu Gong*
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