A one-pot oxidation/cycloaddition cascade synthesis of 2,4-diaryl chromans via ortho-quinone methides

Article abstract of DOI:10.1016/j.tet.2015.12.011

A one-pot oxidation/cycloaddition cascade for the synthesis of 2,4-diaryl chromans is developed. The reaction involves in situ oxidative generation of the unstable o-quinone methides followed by endo selective [4+2] cycloaddition with styrenes.

Full text of DOI:10.1016/j.tet.2015.12.011

Accepted Manuscript
A One-Pot Oxidation/Cycloaddition Cascade Synthesis of 2,4-Diaryl Chromans via
ortho-Qunione Methides
Yuk Fai Wong, Zhaobin Wang, Wen-Xu Hong, Jianwei Sun
PII:
S0040-4020(15)30267-2
10.1016/j.tet.2015.12.011
TET 27337
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 September 2015
Revised Date: 3 December 2015
Accepted Date: 7 December 2015
Please cite this article as: Wong YF, Wang Z, Hong W-X, Sun J, A One-Pot Oxidation/Cycloaddition
Cascade Synthesis of 2,4-Diaryl Chromans via ortho-Qunione Methides, Tetrahedron (2016), doi:
10.1016/j.tet.2015.12.011.
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A One-Pot Oxidation/Cycloaddition Cascade
Synthesis of 2,4-Diaryl Chromans via ortho-
Qunione Methides
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Yuk Fai Wong, Zhaobin Wang, Wen-Xu Hong, and Jianwei Sun
Department of Chemistry, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon,
Hong Kong SAR, China; Shenzhen Research Institute of Population and Family Planning, Shenzhen, China

1
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Tetrahedron
journal homepage: www.elsevier.com
A One-Pot Oxidation/Cycloaddition Cascade Synthesis of 2,4-Diaryl Chromans via
ortho-Qunione Methides
Yuk Fai Wong,a Zhaobin Wang,a Wen-Xu Hong,b and Jianwei Sun a,
aDepartment of Chemistry, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China
b Shenzhen Research Institute of Population and Family Planning, Shenzhen, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A one-pot oxidation/cycloaddition cascade for the synthesis of 2,4-diaryl chromans is
developed. The reaction involves in situ oxidative generation of the unstable o-quinone methides
followed by endo selective [4+2] cycloaddition with styrenes.
2009 Elsevier Ltd. All rights reserved
.
Available online
Keywords:
chroman
cascade
cycloaddition
quinone methide
———
Corresponding author. Tel.: +852-2358-7351; fax: +842-2358-1594; e-mail: sunjw@ust.hk

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
Chroman is an important structural framework present in a
wide range of natural products and biologically active unnatural
molecules.1 For example, myristinin B and their analogues, a
family of 2,4-dirayl chromans, exhibit selective inhibitory
activities against various enzymes including cyclooxygenase-2,
DNA polymerase β, etc.2 Diinsininol is a biflavonoid natural
product with anti-inflammatory activity (Fig. 1).3 As a result of
their wide occurrence and important utility, various strategies for
the synthesis of the chroman skeleton have been developed.4
Among them, the [4+2] cycloaddition of ortho-quinone methides
(o-QMs) and alkenes represents a facile and convergent strategy
that allows flexible substitution of the chroman products.5,6
Scheme 1. One-pot synthesis of chromans via o-QMs
2. Results and discussion
We employed substituted phenol 1a as the o-QM precursor
and styrene 2a as the cycloaddition partner. Initial preliminary
condition evaluation indicated that the reaction at room
temperature did not proceed. After substantial effort, we were
delighted to find that certain oxidants can promote the formation
Fig. 1. Useful chroman-containing molecules
o
of the desired chroman product 3a at 100 C in toluene with 4Å
Although o-QMs have been recognized as useful synthetic
intermediates for more than a century, their high reactivity and
instability have impeded their characterization and application
organic synthesis.6 To date, only very few o-QMs stabilized with
electron-donating groups have been synthesized and purified.7
Nevertheless, even with these few pure o-QMs, various useful
reactions have been developed. However, the scope of these
reactions have been extremely narrow due to the lack of pure o-
QMs that can be used.7 In this context, in situ generation of o-
QMs for one-pot reactions has been a pursuit of organic chemists
to expand their utility. Thus, the compatibility of the o-QM
generation and subsequent reaction is the key issue to address. In
the past few decades, significant progress has been achieved.5,6
However, there remain great challenges and high demand in
effective utilization of the in situ generated o-QMs. In
continuation of our interest in the studies of o-QMs,8 here we
report a one-pot stereoselective synthesis of 2,4-diaryl chromans
by an oxidation/cycloaddition cascade via o-QMs.
molecular sieves as additive. As shown in Table 1, among all the
examined oxidants, MnO2, Ag2CO3, and Ag2O behave similarly
well. Ag2O provided the best reaction efficiency. Evaluation of
different solvents indicated that xylene can slight improve the
results.11
Table 1. Evaluation of oxidants
PMP
O
oxidant
PMP
O
O
+
Ph
O
toluene, 4Å MS
100 oC, 21 h
OH
Ph
O
1a
2a
3a
drb
entry
1
oxidant
yieldb
<10%
tBuOOH
H2O2
−
2
3
<10%
<10%
<10%
<10%
70%
−
−
−
PCC
It has been previously demonstrated that in situ generation of
o-QMs either by addition of an organometallic reagent (such as
alkyl/aryl lithium or Grignard reagents) to a salicylaldehyde
derivative (path a, Scheme 1) or by acid-promoted elimination of
an o-hydroxybenzyl alcohol derivative is compatible with the
subsequent [4+2] cycloaddition with an alkene to form
substituted chromans.5 However, these acidic and strong basic
conditions may have compatibility issues with certain labile
functional groups. Therefore, the generation of o-QMs by
oxidation of the non-functionalized benzylic position provides a
complementary one-pot approach to chroman synthesis (path
c).7,9-10 In addition to the previously explored cases with β-
unsubstituted o-QMs (R1 = H),9 here we describe the synthesis
of 2,4-diaryl chromans from β-substituted o-QMs with regio- and
stereoselectivity.
4
Oxone
K2S2O8
MnO2
5
−
6
4.6:1
4.3:1
4.3:1
4.6:1
Ag2CO3
Ag2O
7
63%
8
9c
78%
Ag2O
79%
a Reaction scale: phenol (0.1 mmol), styrene (1.0 mmol), oxidant
b
(0.15 mmol), solvent (1.0 mL).
Yield and dr value were
determined by 1H NMR with CH2Br2 as internal standard. Run
with xylene as solvent.
c
With the standard conditions established in entry 9 of Table 1,
we then examined the reaction scope. As shown in Table 2, a
range of 2,4-diaryl chromans can be synthesized with moderate
to high efficiency and diastereoselectivity. Substrates with
electron-withdrawing and electron-donating groups are all
suitable. The reaction is not limited to mono-substituted styrenes.
1,2-Disubstituted olefins with Z and E configuration can both
give the desired products (3h and 3i). 1,1-Disbustitutend olefins
also reacted smoothly with high efficiency. Notably, in view of

3
the multiple bond cleavage/formation events, including C−H
bond cleavage as well as C−C and C−O bond formation, our one-
pot protocol is an expedient and efficient strategy for multi-
substituted chroman synthesis. It is probably worth noting that
although we chose Ag2O as the oxidant in view of overall
reaction efficiency, MnO2 is also a good choice if price is taken
into consideration.
chromans, a family of useful molecules of broad utility in
ACCEPTED MANUSCRIPT
medicinal chemistry. Our approach involves an in situ oxidative
generation of unstable o-QMs, which is complementary not only
to those strategies requiring pre-synthesis of o-QMs, but also to
the previously reported acidic and organometallic conditions for
one-pot synthesis of chromans. Further investigations to extend
this cascade strategy to catalytic asymmetric synthesis of 2,4-
diaryl chromans are underway.
Table 2. Reaction scopea
4. Experimental section
4.1. General
All air moisture sensitive reactions were conducted in oven-
dried glassware under nitrogen atmosphere using dry solvents.
Flash column chromatography was performed over silica gel
(230-400 mesh) purchased from Qindao Puke Co., China.
Anhydrous tetrahydrofuran, diethyl ether, acetonitrile, and
toluene were purified by the Innovative® solvent purification
system. Cyclopentyl methyl ether (CPME) and xylene were
purchased from Sigma-Aldrich and Riedel-de Haën, respectively,
1
and used as received. H and 13C NMR were collected on a
Bruker AV 400 MHz NMR spectrometer using residue solvent
peaks as an internal standard (1H NMR: CDCl3 at 7.26 ppm, 13C
NMR: CDCl3 at 77.2 ppm).
4.2. Procedures
4.2.1. General procedure for the one-pot preparation of 2,4-
diaryl chromans (3a-3j).At room temperature, a 4-mL vial was
charged with a mixture of phenol (0.4 mmol), styrene (4 mmol),
Ag2O (0.6 mmol), 4Å MS (40 mg), and xylene (2.0 mL). The
o
reaction mixture was heated to 100 C and stirred at the same
temperature for 21 h. After cooling, the mixture was purified by
silica gel column chromatography to afford the desired product.
a
Isolated yield. The dr value was determined by NMR analysis
of the crude mixture.
4.2.1.1.
cis-8-(4-Methoxyphenyl)-6-phenyl-7,8-dihydro-6H-
[1,3]dioxolo[4,5-g]chromene (3a) was synthesized as white solid
according to the General Procedure (100.7 mg, 70% yield, 4.3:1
dr, purified by column chromatography, eluent: hexane/Et2O =
8:1). 1H NMR (400 MHz, CDCl3) δ 7.50 (d. J = 7.2 Hz, 2H), 7.42
(t, J = 7.2 Hz, 2H), 7.37 – 7.33 (m, 1H), 7.16 (d, J = 8.8 Hz, 2H),
6.89 (d, J = 8.8 Hz, 2H), 6.53 (s, 1H), 6.27 (s, 1H), 5.86 (d, J =
6.0 Hz, 2H), 5.15 (d, J = 11.2 Hz, 1H), 4.24 (dd, J = 12.0, 6.0 Hz,
1H), 3.82 (s, 3H), 2.41 – 2.37 (m, 1H), 2.26 – 2.17 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 158.6, 150.4, 146.8, 141.7, 141.3,
136.9, 129.5, 128.7, 128.2, 126.2, 117.9, 114.2, 109.2, 101.0,
98.7, 78.4, 55.4, 42.8, 41.0.
The major products from the one-pot reaction generally have
cis relative stereochemistry for the 2,4-diaryl substituents. To
rationalize the observation, we proposed two possible transition
states TS1 and TS2, corresponding to endo and exo selectivity,
respectively. We believe that in TS1 there is secondary orbital
overlap between the aryl group of the styrene and the π system of
the o-QM intermediate, which provides stabilization of this
transition state and thus results in a lower barrier than that with
TS2. This analysis is consistent with the observation of endo
product (via TS1) as the major diastereomer.
4.2.1.2
cis-6,8-Diphenyl-7,8-dihydro-6H-[1,3]dioxolo[4,5-
g]chromene (3b) was synthesized as yellow oil according to the
General Procedure (70.4 mg, 53% yield, 4.3:1 dr, purified by
1
column chromatography, eluent: hexanes/Et2O = 8:1). H NMR
(400 MHz, CDCl3) δ 7.47 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 7.2 Hz,
2H), 7.34 – 7.30 (m, 3H), 7.24 – 7.21 (m, 3H), 6.51 (s, 1H), 6.22
(s, 1H), 5.84 (d, J = 6.4 Hz, 2H), 5.13 (d, J = 11.6 Hz, 1H), 4.27
(dd, J = 12.0, 6.0 Hz, 1H), 2.41 – 3.36 (m, 1H), 2.26 – 2.16 (m,
1H). 13C NMR (100 MHz, CDCl3) δ 150.5, 147.4, 144.9, 141.8,
141.3, 128.9, 128.7, 128.6, 128.2, 127.0, 126.3, 117.5, 108.6,
101.1, 98.8, 78.4, 43.7, 40.9. IR (neat, cm-1) 2879, 1630, 1479,
1148. HRMS (EI+) calculated for C22H18O3 [M+]: 330.1256,
found: 330.1256.
Fig. 2. Endo and exo transition states
3. Conclusions
In
summary,
we
have
developed
a
one-pot
4.2.1.3
cis-8-(4-Fluorophenyl)-6-phenyl-7,8-dihydro-6H-
oxidation/cycloaddition cascade for the synthesis of 2,4-diaryl
[1,3]dioxolo[4,5-g]chromene (3c) was synthesized as yellow oil

4
Tetrahedron
according to the General Procedure (107.6 mg, 77% yield, 4.6:1
128.2, 127.9, 126.3, 126.2, 125.1, 124.3, 117.9, 114.3, 108.6,
ACCEPTED MANUSCRIPT
dr, purified by column chromatography, eluent: hexanes/Et2O =
8:1). H NMR (400 MHz, CDCl3) δ 7.48 – 7.33 (m, 5H), 7.21 –
101.0, 98.8, 78.5, 55.4, 42.9, 40.9. IR (neat, cm-1) 2880, 1630,
1477, 1247, 1149. HRMS (EI+) calculated for C27H22O4 [M+]:
410.1518, found: 410.1517.
1
7.18 (m, 2H), 7.03 (t, J = 8.4 Hz, 2H), 6.53 (s, 1H), 6.22 (s, 1H),
5.87 (d, J = 7.2 Hz, 2H), 5.14 (d, J = 11.2 Hz, 1H), 4.28 (dd, J =
12.0, 6.0 Hz, 1H), 2.41 – 2.37 (m, 1H), 2.23 – 2.14 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 161.9 (d, JC-F = 243 Hz), 150.5, 147.0,
141.9, 141.2, 140.6 (d, JC-F = 3 Hz), 130.0 (d, JC-F = 8 Hz), 128.7,
128.3, 126.2, 117.2, 115.7 (d, JC-F = 21 Hz), 108.4, 101.1, 98.9,
78.3, 42.9, 41.1. IR (neat, cm-1) 2879, 1634, 1479, 1226, 1151.
HRMS (EI+) calculated for C22H17FO3 [M+]: 348.1162, found:
348.1168.
4.2.1.8. cis-11-(4-Methoxyphenyl)-5a,10,10a,11-tetrahydro-
[1,3]dioxolo[4,5-g]indeno[1,2-b]chromene (3h) was synthesized
as yellow solid according to the General Procedure (54.5 mg, 37%
yield, 7.3:1 dr, purified by column chromatography, eluent:
1
hexanes/Et2O = 8:1). H NMR (400 MHz, CDCl3) δ 7.57 – 7.55
(m, 1H), 7.31 – 7.26 (m, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.21 –
7.18 (m, 1H), 6.94 (d, J = 8.4 Hz, 2H), 6.43 (d, J = 4.4 Hz, 2H),
5.86 (d, J = 3.6 Hz, 2H), 5.46 (d, J = 4.8 Hz, 1H), 4.54 (d, J = 6.0
Hz, 1H), 3.87 (s, 3H), 3.08 – 3.03 (m, 1H), 2.99 – 2.92 (m, 1H),
2.56 – 2.50 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 158.6, 150.9,
146.5, 144.6, 142.5, 141.7, 134.2, 130.4, 129.3, 126.9, 125.4,
125.2, 116.7, 114.1, 108.2, 101.0, 99.2, 81.8, 55.5, 45.9, 42.6,
33.8. IR (neat, cm-1) 2897, 1506, 1474, 1243, 1145. HRMS (EI+)
calculated for C24H20O4 [M+]: 372.1362, found: 372.1365.
4.2.1.4. cis-8-(4-Methoxyphenyl)-6-(p-tolyl)-7,8-dihydro-6H-
[1,3]dioxolo[4,5-g]chromene (3d) was synthesized as pale
yellow solid according to the General Procedure (111.9 mg, 75%
yield, 4.3:1 dr, purified by column chromatography, eluent:
1
hexane/Et2O = 8:1). H NMR (400 MHz, CDCl3) δ 7.42 (d. J =
8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H),
6.92 (d, J = 8.4 Hz, 2H), 6.55 (s, 1H), 6.30 (s, 1H), 5.88 (d, J =
5.6 Hz, 2H), 5.14 (d, J = 11.2 Hz, 1H), 4.26 (dd, J = 12.0, 6.0 Hz,
1H), 3.85 (s, 3H), 2.42 – 2.40 (m, 4H), 2.30 – 2.18 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 158.6, 150.5, 146.8, 141.7, 138.6,
137.9, 137.0, 129.5, 129.4, 126.3, 117.9, 114.2, 108.5, 101.0,
98.7, 78.3, 55.4, 42.9, 40.8, 21.3. IR (neat, cm-1) 2879, 1610,
1474, 1146. HRMS (EI+) calculated for C24H22O4 [M+]:
374.1518, found: 374.1513.
4.2.1.9.
cis-8-(4-Methoxyphenyl)-7-methyl-6-phenyl-7,8-
dihydro-6H-[1,3]dioxolo[4,5-g]chromene (3i) was synthesized as
yellow solid according to the General Procedure (49.9 mg, 33%
yield, 3.3:1 dr, purified by column chromatography:
1
hexanes/Et2O = 8:1). H NMR (400 MHz, CDCl3) δ 7.45 – 7.40
(m, 3H), 7.39 – 7.31 (m, 2H), 7.11 (d, J = 8.4 Hz, 2H), 6.88 (d, J
= 8.4 Hz, 2H), 6.45 (s, 1H), 6.14 (s, 1H), 5.83 (d, J = 5.2 Hz, 2H),
4.68 (d, J = 10.0 Hz, 1H), 3.82 (s, 3H), 2.26 – 2.15 (m, 1H), 1.19
(d, J = 6.4 Hz, 1H), 0.59 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ 158.3, 150.3, 146.6, 141.8, 140.1, 136.2, 131.6, 128.7,
4.2.1.5.
cis-6-(4-Fluorophenyl)-8-(4-methoxyphenyl)-7,8-
dihydro-6H-[1,3]dioxolo[4,5-g]chromene (3e) was synthesized
as yellow solid according to the General Procedure (106.8 mg, 71% 128.6, 128.4, 127.7, 114.2, 108.9, 101.0, 98.4, 84.7, 55.4, 50.5,
yield, 4.9:1 dr, purified by column chromatography, eluent:
hexanes/Et2O = 8:1). 1H NMR (400 MHz, CDCl3) δ 7.45 (dd, J =
8.4, 5.2 Hz, 2H), 7.15 – 7.03 (m, 4H), 6.88 (d, J = 8.4 Hz, 2H),
6.49 (s, 1H), 6.25 (s, 1H), 5.85 (d, J = 5.2 Hz, 2H), 5.11 (d, J =
11.2 Hz, 1H), 4.22 (dd, J = 12.0 Hz, 6.0 Hz, 1H), 3.81 (s, 3H),
2.37 – 2.32 (m, 1H), 2.21 – 2.12 (m, 1H). 13C NMR (100 MHz,
CDCl3) δ 162.6 (d, JC-F = 245 Hz), 158.6, 150.3, 146.9, 151.9,
137.2 (d, JC-F = 3 Hz), 136.8, 129.5, 128.0 (d, JC-F = 8 Hz), 117.8,
155.6 (d, JC-F = 22 Hz), 114.3, 108.5, 101.1, 98.7, 77.7, 55.4, 42.8,
41.0.
41.4, 15.8. IR (neat, cm-1) 2897, 1507, 1476, 1245, 1151. HRMS
(EI+) calculated for C24H22O4 [M+]: 374.1518, found: 374.1525.
4.2.1.10.
cis-8-(4-Methoxyphenyl)-6-methyl-6-phenyl-7,8-
dihydro-6H-[1,3]dioxolo[4,5-g]chromene (3j) was synthesized as
yellow oil yellow oil according to the General Procedure (144.0
mg, 96% yield, 5.3:1 dr, purified by column chromatography,
1
eluent: hexanes/Et2O = 8:1). H NMR (400 MHz, CDCl3) δ 7.57
(d, J = 7.6 Hz, 2H), 7.42 – 7.34 (m, 2H), 7.29 (t, J = 7.2 Hz, 1H),
7.12 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 6.60 (s, 1H),
6.30 (s, 1H), 5.87 (d, J = 7.2 Hz, 2H), 4.13 (dd, J = 12.0, 6.0 Hz,
1H), 3.81 (s, 3H), 2.39 – 2.34 (m, 1H), 2.16 (t, J = 12.4 Hz, 1H),
1.71 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 158.5, 148.6, 147.1,
147.0, 141.5, 136.8, 129.7, 128.4, 127.1, 124.5, 116.7, 114.1,
108.5, 100.9, 99.2, 77.8, 55.4, 44.6, 39.5, 24.7. IR (neat, cm-1)
2976, 1611, 1508, 1378, 1274, 1153. HRMS (EI+) calculated for
C24H22O4 [M+]: 374.1518, found: 374.1512.
4.2.1.6.
4-(cis-8-(4-Methoxyphenyl)-7,8-dihydro-6H-
[1,3]dioxolo[4,5-g]chromen-6-yl)phenyl acetate (3f) was
synthesized as yellow solid according to the General Procedure
(93.2 mg, 56% yield, 6.1:1 dr, purified by column
1
chromatography, eluent: hexanes/Et2O = 5:1). H NMR (400
MHz, CDCl3) δ 7.49 (d, J = 21 Hz, 2H), 7.14 – 7.11 (m, 4H),
6.87 (d, J = 21 Hz, 2H), 6.49 (s, 1H), 6.24 (s, 1H), 5.84 (d, J =
6.0 Hz, 2H), 5.12 (d, J = 10.8 Hz, 1H), 4.21 (dd, J = 12.0, 6.0 Hz,
1H), 3.81 (s, 3H), 2.38 – 2.33 (m, 1H), 2.31 (s, 3H), 2.21 – 2.10
(m, 1H). 13C NMR (100 MHz, CDCl3) δ 169.6, 158.6, 150.4,
150.2, 146.8, 141.8, 138.9, 136.7, 129.5, 127.3, 121.8, 117.8,
141.2, 108.5, 101.0, 98.7, 77.8, 55.4, 42.7, 40.9, 21.3. IR (neat,
cm-1) 2881, 1634, 1508, 1478, 1184. HRMS (EI+) calculated for
C25H22O6 [M+]: 418.1416, found: 418.1409.
Acknowledgments
Financial support was provided by Hong Kong RGC
(GRF604513, M-HKUST607/12, and ECS605812) and the
Medical Scientific Research Foundation of Guangdong Province
(20132016).
4.2.1.7.
cis-8-(4-Methoxyphenyl)-6-(naphthalen-2-yl)-7,8-
Supplementary data
dihydro-6H-[1,3]dioxolo[4,5-g]chromene (3g) was synthesized
as yellow solid according to the General Procedure (135.7 mg, 83%
yield, 24:1 dr, purified by column chromatography, eluent:
hexanes/Et2O = 8:1). 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H),
7.91 – 7.86 (m, 3H), 7.61 (d, J = 8.4 Hz, 1H), 7.55 – 7.49 (m,
2H), 7.19 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 6.60 (s,
1H), 6.31 (s, 1H), 5.88 (d, J = 5.2 Hz, 2H), 5.31 (d, J = 10.8 Hz,
1H), 4.28 (dd, J = 12.0, 6.0 Hz, 1H), 3.82 (s, 3H), 2.50 – 2.45 (m,
1H), 2.36 – 2.26 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 158.6,
150.4, 146.9, 141.8, 138.7, 136.9, 133.5, 133.3, 129.5, 128.5,
The procedures for the synthesis of substrates together with 1H
and 13C NMR spectra for compounds the new compounds.
Supplementary data associated with this article can be found in
the online version.
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4. Reviews and selective examples of different synthetic strategies:
(a) Shi, Y.-L.; Shi, M. Org. Biomol. Chem. 2007, 5, 1499; (b)
Masesane, I. B.; Desta, Z. Y. Beilstein J. Org. Chem. 2012, 8,
2166; (c) Selenski, C.; Pettus, T. R. R. Tetrahedron, 2006, 62,
5298; (d) Maloney, D. J.; Chen, S.; Hecht, S. M. Org. Lett. 2006,
8, 1925; (e) Li, K.; Vanka, K.; Thompson, W. H.; Tunge, J. A.
Org. Lett. 2006, 8, 4711; (f) Pagar, V. V.; Tseng, C.-C.; Liu, R.-S.
Chem. Eur. J. 2014, 20, 10519.
5. Examples of the synthesis of benzopyrans by [4+2] cycloaddition
of o-QMs: (a) Jones, R. M.; Selenski, C.; Pettus, T. R. R. J. Org.
Chem. 2002, 67, 6911; (b) Batsomboon, P.; Phakhodee, W.;
Ruchirawat, S.; Ployradith, P. J. Org. Chem. 2009, 74, 4009; (c)
Gharpure, S. J.; Sathiyanarayanan, A. M.; Vuram, P. K. RSC Adv.
2013, 3, 18279; (d) Zhao, J.-J.; Sun, S.-B.; He, S.-H.; Wu, Q.; Shi,
F. Angew. Chem., Int. Ed. 2015, 54, 5460; (e) Saha, S.; Schneider,
C. Chem. – Eur. J. 2015, 21, 2348; (f) Saha, S.; Schneider, C. Org.
Lett. 2015, 17, 648; (g) Hsiao, C.-C.; Raja, S.; Liao, H.-H.;
Atodiresei, I.; Rueping, M. Angew. Chem., Int. Ed. 2015, 54, 5762.
6. For pioneering studies on o-QMs, see: (a) Fries, K.; Kann, K. I.
Liebigs Ann. Chem. 1907, 353, 335; (b) Arduini, A.; Pochini, A.;
Ungaro, R.; Domiano, P. J. Chem. Soc., Perkin Trans. 1 1986,
1391; For selected reviews about o-QMs, see: (c) Amouri, H.; Le
Bras, J. Acc. Chem. Res. 2002, 35, 501; (d) Van De Water, R. W.;
Pettus, T. R. R. Tetrahedron 2002, 58, 5367; (e) Quinone
Methides (Ed.: S. E. Rokita), Wiley, Hoboken, NJ, 2009; (f)
Pathak, T. P.; Sigman, M. S. J. Org. Chem. 2011, 76, 9210; (e)
Willis, N. J.; Bray, C. D. Chem. Eur. J. 2012, 18, 9160; (g) Bai,
W. J.; David, J. G.; Feng, Z. G.; Weaver, M. G.; Wu, K. L.;
Pettus, T. R. Acc. Chem. Res. 2014, 47, 3655; (h) Caruana, L.;
Fochi, M.; Bernardi, L. Molecules 2015, 20, 11733; (i) Wang, Z.;
Sun, J. Synthesis 2015, 47, 3629.
7. Pre-synthesis of o-QMs by oxidation is known, but due to
instability of most o-QMs, it was only used for relatively stable
ones bearing electron-donating groups: (a) Jurd, L. Tetrahedron
1977, 33, 163; (b) Lv, H.; Jia, W.-Q.; Sun, L.-H.; Ye, S. Angew.
Chem., Int. Ed. 2013, 52, 8607; (c) Alden-Danforth, E.; Scerba, M.
T.; Lectka, T. Org. Lett. 2008, 10, 4951; (d) Hu, H.; Liu, Y.; Guo,
J.; Lin, L.; Xu, Y.; Liu, X.; Feng, X. Chem. Commun. 2015, 51,
3835.
8. Our effort on o-QMs: (a) Zhao, J.-J.; Sun, S.-B.; He, S.-H.; Wu,
Q.; Shi, F. Angew. Chem. Int. Ed. 2015, 54, 5460; (b) Wang, Z.;
Ai, F.; Wang, Z.; Zhao, W.; Zhu, G.; Lin, Z.; Sun, J. J. Am. Chem.
Soc. 2015, 137, 383.
9. For examples of oxidation of an ortho-methyl group, but not
larger groups, to generate o-QMs for one-pot [4+2] cycloaddition:
(a) Bolon, D. A. J. Org. Chem. 1970, 35, 715; (b) Bolon, D. A. J.
Org. Chem. 1970, 35, 3666; (c) Liebner, F.; Schmid, P.;
Adelwohrer, C.; Rosenau, T. Tetrahedron 2007, 63, 11817; (d)
Patel, A.; Netscher, T.; Rosenau, T. Tetrahedron Lett. 2008, 49,
2442; (e) Bohmdorfer, S.; Patel, A.; Netscher, T.; Gille, L.;
Rosenau, T. Tetrahedron 2011, 67, 4858; (f) Liao, D.; Li, H.; Lei,
X. Org. Lett. 2012, 14, 18.
10. For an example of one-pot o-QM generation by oxidation and
formal [4+1] cyclization, see: Wu, B.; Chen, M.-W.; Ye, Z.-S.; Yu,
C.-B.; Zhou, Y.-G. Adv. Synth. Catal. 2014, 356, 383.
11. The xylene is a mixture of o-, m-, and p-xylenes.