Ru-Catalyzed δ-Arylation of para-Quninone Methides with Aryl Diazonium Salts to Synthesize Fuchsones

Article abstract of DOI:10.1021/acs.joc.0c00621

A novel reaction mode and efficient ruthenium-catalyzed Matsuda-Heck-type arylation of para-quinone methides (p-QMs) with aryl diazonium salts has been developed for the synthesis of symmetrical or unsymmetrical δ,δ′-diaryl quinone methides (fuchsones). Aryl groups are introduced at the δ-position of p-QMs via tandem olefin insertion reaction/β-H elimination processes. This reaction features advantages such as mild and green conditions, broad reactant scope, and high yields.

Full text of DOI:10.1021/acs.joc.0c00621

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Article
Ru-Catalyzed #-Arylation of para-Quninone Methides
with Aryl Diazonium Salts to Synthesize Fuchsones
Lei Dai, kaimin Mao, Ge Zhang, Chang Wang, Yun Liu, Liangce Rong, and Jinpeng Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00621 • Publication Date (Web): 08 May 2020
Downloaded from pubs.acs.org on May 12, 2020
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Ru-Catalyzed δ-Arylation of para-Quninone Methides with Aryl Diazonium
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Salts to Synthesize Fuchsones
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Lei Dai†, Kaimin Mao†, Ge Zhang†, Chang Wang†, Yun Liu†, Liangce Rong*,†, Jinpeng Zhang*,‡
†Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, School of
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Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu, PR China
‡Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University,
Xuzhou, 221004, Jiangsu, PR China
E-mail. lcrong@jsnu.edu.cn; xiaopangpeng@126.com
ABSTRACT: A novel reaction mode and efficient ruthenium-catalyzed Matsuda−Heck-type
arylation of para-quinone methides (p-QMs) with aryl diazonium salts has been developed for the
synthesis of symmetrical or unsymmetrical δ,δ’-diaryl quinone methides (fuchsones). Aryl groups
are introduced at the δ-position of p-QMs via tandem olefin insertion reaction/β-H elimination
processes. This reaction features advantages such as mild and green conditions, broad reactants
scope and high yields.
INTRODUCTION
As a special structural system, fuchsones have been found to be able to rapidly interconvert chiral
conformers in the liquid or solution state,1 which were elicited interest from people because of
their photochromic properties and utility in dyes, photographic printing, and to stabilize radicals,2
etc. Recent study have shown that they can also be used as novel nonpeptide inhibitor of
Caspase-3.3 The traditional method for the synthesis of fuchsones was a two-step reaction. First,
the substituted 4-hydroxytriphenylmethanes was obtained by the condensation reaction of
substituted phenols and benzhydrol, and then fuchsones was formed by the oxidation of active
manganese dioxide, nickel peroxide, or lead dioxide in benzene solution (Scheme 1, Previous
work).4 Other reported synthesis methods almost have been developed on the basis of this
reaction.1,5 Surprisingly, few new and effective methods for the synthesis of fuchsones have been
reported so far.
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para-Quinone methides (p-QMs) have been recognized for more than one century.6 This motif
exists in a variety of biologically active compounds7 and is a key intermediates of versatile
medicinal and biological processes.8 Consequently, there are great demands to explore new
reaction of p-QMs. Up to now, many reactions have been accomplished by employing p-QMs as
the substrates and the main reaction modes involve reduction,9 cyclization10-13 and 1,6-conjugate
addition.14-22 Although great progress has been made, there are still some limitations needing to be
overcome. i) The reported reactions of p-QMs generally led to aromatic products, whereas
dearomatized products were rarely obtained. ii) The new reaction mode has not broken through.
iii) To the best of our knowledge, there is no report of aryl diazonium salts to react with p-QMs so
far. Hence, there are great demands to synthesize dearomatic products via olefin insertion
reaction/ β-H elimination processes of p-QMs as well as to introduce aryl groups at the δ-position
of p-QMs.
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In the past decades, aryl diazonium salts have been widely used in organic synthesis.23,24
Among these, transition-metal catalyzed Matsuda−Heck reaction is a typical application which
reacted arenediazonium salts with alkenes in the aid of palladium catalyst.25 Compared with
traditional electrophiles as aryl halides and aryl triflates, aryl diazonium salts generate nitrogen as
the only byproduct and are more eco-friendly. Although some alkenes were applied as the
coupling partners in Matsuda−Heck reaction, p-QMs had never being investigated yet. Herein, we
reported a novel reaction mode and highly regioselective ruthenium-catalyzed δ-arylation of
p-QMs with aryldiazonium salts to synthesize fuchsone derivatives (Scheme 1, This work). This
reaction proceeds under mild conditions and give the symmetrical or unsymmetrical fuchsones in
high yields.
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Previous work
:
OH
R1
R2
(step 1)
OH
R1
R2
HOAc
Ar
Ar
OH
H
+
H2SO4
Ar
Ar
H
O
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OH
R1
R2
R1
R2
(step 2)
MnO2
benzene
Ar
Ar
H
Ar
Ar
This work
:
O
O
tBu
But
+
tBu
But
Ru cat.
-
+ BF4
Ar2 N2
Ar1
Ar1
Ar2
Scheme 1. Synthesis of fuchsone derivatives (Previous work and This work)
RESULTS AND DISCUSSION
For
the
optimization
of
reaction
conditions,
we
chose
2,6-di-tert-butyl-4-
(4-fluorobenzylidene)cyclohexa-2,5-dien-1-one 1a and 4-methoxyphenyl diazonium salt 2a as the
model reactants, and the results were listed in Table 1. Initially, by heating the mixture of 1a (0.3
mmol), 2a (0.6 mmol), palladium acetate.(10 mol%), potassium carbonate (0.3 mmol) in
acetonitrile (2 mL) under nitrogen atmosphere for 6 hours in a Schlenk tube, we isolated target
product 3a in 42% yields (Table 1, entry 1). Different metal catalysts were then examined, and
ruthenium chloride performed the best and afforded product 3a in 79 % yield (Table1, entries
2-7). With RuCl3 as the catalyst, we tried other base instead of K2CO3, but did not get better result
(Table 1, entries 8-13). On the basis of this, we further investigated the effect of different solvents.
The results showed acetonitrile was the best choice (Table1, entries 14-18). For the loading of
catalyst and base, it showed that 10 mol% ruthenium catalyst and 1 equiv of K2CO3 was enough to
ensure the high yield of 3a (Table 1, entries 19-23). In addition, the reaction yield decreased
obviously with decreasing the reaction temperature, but the yield of the reaction did not increase
significantly with the increase of reaction temperature (Table1, entries 24, 25). Finally, we carried
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out this reaction in the air, and isolated 3a only in 30% yield (Table1, entry 26). It is probably due
to diazonium salt 2a is reactive in the air and tends to decompose. Therefore, the optimized
conditions were set to heating the mixture of 1a (0.3 mmol), 2a (0.6 mmol) in acetonitrile at 60 oC
for 6 h in a sealed tube with 10 mol% RuCl3 as the catalyst and 1 equiv. of K2CO3 as the base.
Table 1. Optimization of reaction conditionsa
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O
O
N2BF4
+
cat. base
solvent, N2,
50 oC, 6 h
MeO
F
F
OMe
2a
1a
3aa
Entry
1
Cat. (mol%)
Pd(OAc)2 (10)
Pd(pph3)4 (10)
FeCl2 (10)
Base
Solvent
Yield (%)b
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Et3N
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DCE
42
40
30
35
37
79
32
49
60
51
23
30
32
30
18
24
34
trace
2
3
4
CuI (10)
5
Cu(OAc)2 (10)
.
6
RuCl3 3H2O (10)
7
Ru(bpy)3Cl2 (10)
.
8
RuCl3 3H2O (10)
.
9
RuCl3 3H2O (10)
t-BuOK
Cs2CO3
DBU
.
10
11
12
13
14
15
16
17
18
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
KOH
.
RuCl3 3H2O (10)
DABCO
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
DMF
.
RuCl3 3H2O (10)
DMSO
1,4-dioxane
THF
.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
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RuCl3 3H2O (5)
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
28
78
.
RuCl3 3H2O (15)
.
RuCl3 3H2O (20)
79
RuCl3 3H2O (10)
78c
43d
52e
78f
30g
.
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.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
.
RuCl3 3H2O (10)
aReaction conditions: 1a (0.3 mmol), 2a (0.6 mol), catalyst (5%-20%), base (1 eq), solvent (2.0
ml), N2, 50 C, 6h; Isolated yield; 2 equiv of K2CO3. d0.5 equiv of K2CO3. Under 40 C. Under
o
b
c
e
o
f
70 oC. gIn the air.
With the optimal conditions in hand, we then screened the scope of reactants 1 and 2. By
employing 4-methoxy arenediazonium salt 2a as the coupling partner, we firstly investigated the
generality of p-QMs 1 (Table 2). It is found that electronic and steric factors of p-QMs have little
effect to this reaction. For para-substituted p-QMs with electron-donating groups ( OMe, i-Pr) or
with electron-withdrawing groups (F, Cl, NO2), the target products 3aa-3ae were afforded in high
yields. However, it seems that the yield of p-QMs with electron-donating groups is better than that
of with withdrawing groups (3aa-3ac vs 3ad and 3ae). Similarly, ortho-substituted p-QMs
attached with different groups underwent this reaction smoothly as well, giving products 3af-3ah
in 80% to 81% yields. Besides, meta-substituted p-QMs also gived corresponding products with
good yields (3ai, 3aj). It should be noted that the position of substituents has no effect on the yield
of the reaction, which can be seen from the yields of 3ab & 3ag and 3ad & 3aj. In addition, the
multi-substituted and annulated p-QMs were all proven to be good reactant substrates, generating
3ak-3ap in 84% to 92% yields. Moreover, the heterocyclic p-QMs was also be applied to this
synthesis, generating 3aq in 84% yield. In Table 2, we could see compound 3ad is a absolutely
symmetrical structure.
Table 2. Scope of reactant 1a
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O
4
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7
K2CO3 (1 equiv.)
RuCl3.3H2O (10 mol%)
N2BF4
+
CH3CN, N2, 50oC
MeO
R1
8
9
R1
1
2a
3
OMe
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O
O
O
O
O
Me
Cl
OMe
MeO
OMe
OMe
OMe
F
OMe
O2N
b
3ab
3aa
, 78%
3ac,
, 79%
78%
3ad
3ae
, 86%
, 89%
O
Me
O
O
O
O
OMe
OMe
Br
Me
3af
OMe
Cl
3ag
OMe
OMe
, 80%
3ah
Me 3ai, 85%
, 81%
80%
O
3aj
, 86%
OMe
O
O
O
O
MeO
MeO
MeO
OMe
Me
OMe
OMe
OMe
O
OMe
Me
Br
OMe
O
3ak
Me
3am
, 84%
3an
, 90%
OMe
3ao
, 87%
, 92%
3al
, 89%
O
O
S
OMe
OMe
3aq
, 84%
3ap
, 87%
aConditions: 1 (0.3 mmol), 2a (0.6 mol), RuCl3 3H2O (10 mol%), K2CO3 (1 eq), acetonitrile (2.0
.
ml), N2, 50 oC, 6h (monitored by TLC); bIsolated yield.
Subsequently, we investigated the scope of aryl diazonium salts
2 (Table 3).
Different-substituted aryl diazonium salts 2b-2g all showed good reaction activities. For instance,
para-substituted diazonium salts 2b-2e either with electron-withdrawing group (Me) or with
electron-withdrawing groups (F, Cl, Br) reacted with diversified p-QMs 1 well, generating
products 3ba-3ea in high yields. Moreover, ortho-substituted diazonium salt 2f was also well used
in this preferred condition and given 3fa with satisfying yield. Moreover,
benzo[d][1,3]dioxole-5-diazonium salt 2g also performed well in the synthesis, delivering
products 3ga-3gh in 81% to 92% yields. In these this synthetic scope, compounds 3bd, 3db,
and 3gh are the perfectly symmetrical structures.
Table 3. Scope of reactant 2a
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O
4
5
6
7
8
9
K2CO3 (1 equiv.)
RuCl3.3H2O (10 mol%)
N2BF4
+
R2
CH3CN, N2, 50oC, 6 h
R2
R1
R1
2b 2h
-
1
3
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N2BF4
N2BF4
Br
N2BF4
2b
2c
2d
2e
R=Me
R=F
R=Cl
R=Br
R
O
2b 2e
2f
2g
-
O
O
O
O
O
O
Br
3be
OMe
Br
Cl
3bb
b
, 83%
3bd
, 83%
3ba
, 85%
, 83%
3bc
, 80%
O
O
O
O
O
OMe
F
F
Cl
Cl
Cl
OMe
3da
, 77%
Cl
3dc
, 79%
3db
, 75%
3cb
, 80%
3ca
, 78%
O
O
O
O
O
Br
O
O
O
O
O
O
Br
3gb
OMe
3ea
Br
3gc
, 88%
3ga
, 85%
, 82%
3fa
, 81%
, 77%
O
O
O
O
O
Br
O
O
O
O
O
O
O
O
O
O
OMe
O
Br
O
Br
3gg
, 90%
3ge
, 85%
3gh
, 92%
3gd
81%
3gf
, 84%
aConditions: 1 (0.3 mmol), 2 (0.6 mol), RuCl3 3H2O (10 mol%), K2CO3 (1 eq), acetonitrile (2.0
ml), N2, 50 oC, 6h (monitored by TLC); bIsolated yield.
.
To shed light on the reaction mechanism, some control reactions was investigated carefully
(Scheme 2). When RuCl3·3H2O was absent in standard condition, the 3aa was not obtained, which
meant that the catalyst was indispensable. Subsequently, we added 4 equiv of radical scavenger
TEMPO (2,2,6,6-Tetramethylpiperidine 1-oxyl) or BHT (2,6-Di-tert-butyl-4-methyl- phenol) into
the model reaction, and found 3aa was formed in 78% and 76% yields, respectively. These results
illustrated the reaction should occurred via a non-radical pathway. In addition, the successful
completion of gram-scale experiment indicates that this synthesis has a good application prospect.
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O
O
without RuCl3 H2O
-
N2+BF4
K2CO3 (1 equiv)
7
8
+
CH3CN, N2, 50 oC, 6 h
H3CO
9
F
OCH3
F
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3aa
, 0%
2a
2a
2a
1a
O
O
K2CO3 (1 equiv)
-
N2+BF4
RuCl3 3H2O (10mol%)
+
TEMPO (4 equiv.)
CH3CN, N2, 50 oC, 6 h
H3CO
F
OCH3
F
1a
3aa
, 78%
O
O
K2CO3 (1 equiv)
N2+BF4
-
RuCl3 3H2O (10mol%)
+
BHT (4 equiv.)
CH3CN, N2, 50 oC, 6 h
H3CO
F
OCH3
F
1a
3aa
, 76%
O
O
K2CO3 (1 equiv)
N2BF4
RuCl3 3H2O (10mol%)
CH3CN, N2, 50oC
+
H3CO
F
OCH3
3aa
(1.12g, 67%)
F
1a
(4 mmol, 1.25g)
2a
(8 mmol, 1.78g)
Scheme 2. Control and gram-scale experiments
Based on our experimental results, a possible reaction mechanism was proposed as follows
(Scheme 3). At first, aryl diazonium salt was inserted by [Ru] species to generate aryl-ruthenium
intermediate I accompanying removal of N2 and BF3. Through the olefin insertion reaction of I
and p-QMs 1 to afford intermediate II and intermediate III, which finally forms intermediate IV.
The intermediate V is formed by the characteristic of easy coordination of hydrogen atom with
ruthenium, After β-H elimination, the product 3 is obtained, and with the help of K2CO3, [Ru]
species is freshly generated again.
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5
O
t-Bu
t-Bu
t-Bu
O
6
7
8
9
t-Bu
O
N2 + BF3
[Ru]
t-Bu
t-Bu
1
Ar1
Ar2 [Ru]
[Ru]
Ar2
Ar2 N2BF4
[Ru] Ar2
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Ar1
O
Ar1
2
I
III
II
CO2
H2O
KF
O
t-Bu
t-Bu
K2CO3
t-Bu
O
t-Bu
t-Bu
t-Bu
-H Elimination
[Ru]
H
[Ru]
Ar2
[Ru]-H
+
Ar1
Ar1
Ar1
Ar2
Ar2
IV
3
V
Scheme 3. Possible mechanism
CONCLUSION
In conclusion, we have developed a novel reaction mode and efficient ruthenium-catalyzed
arylation of p-QMs with aryl diazonium salts to synthesize fuchsones derivatives. A variety of
reactants survive in the conditions and symmetrical or unsymmetrical products are formed in high
yields. This reaction represents a new Matsuda−Heck-type reaction by employing p-QMs as the
coupling partner to construct Csp2-Csp2 bond with diazonium salts for the first time.
EXPERIMENTAL SECTION
General Information.
Unless stated otherwise, all reactions were conducted in Schlenk tube under nitrogen condition.
All solvents and reagents were received from commercial sources without further purification.
para-Quinone methides26 and aryl diazonium salts27 were synthesized following reported
protocols. All the reactions were monitored by TLC. Silica gel (particle size 10–50 μm ) was used
for flash column chromatography. NMR spectra were recorded on Bruker-400 spectrometer at 400
MHz (1H NMR), 100 MHz (13C NMR). High resolution mass spectra (HRMS) were recorded on a
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Bruker microTOF-Q 134 instrument with Electron Spray Ionization (ESI) resource.
General Procedure for the Synthesis Product 3.
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To a mixture of RuCl3·3H2O (0.03 mmol) and K2CO3 (0.3 mmol) in CH3CN (2.0 mL) under N2
atmosphere, para-quinone methides 1 (0.3 mmol) and aryl diazonium salts 2 (0.6 mmol) were
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added. The system was stirred at 50 C using an oil bath for 6 h (the reaction was monitored by
TLC). After the reaction was completed, the reaction mixture was filtered by diatomite. The filtere
was diluted with brine (10 mL) and extracted with ethyl acetate (5 mL x 3). The organic layer was
washed with water (10 mL), then separated, dried over Na2SO4, and concentrated under vacuum.
The residue was further purified by flash column chromatography on silica gel (petroleum ether:
EtOAc = 40:1) to afford desired product 3 as a yellow solid.
Procedure for the Control Reaction.
To a mixture of RuCl3·3H2O (0.03 mmol) and K2CO3 (0.3 mmol) in CH3CN (2.0 mL) under N2
atmosphere, 2,2,6,6-tetramethylpiperidinooxy (TEMPO) (1.2 mmol) or butylated hydroxytoluene
(BHT) (1.2 mmol), 2,6-di-tert-butyl-4-(4-fluorobenzyli dene)cyclohexa-2,5-dien-1-one 1a (0.3
mmol) and 4-methoxybenzenediazonium salt 2a (0.6 mmol) were added. The system was stirred
at 50 oC for 6 h and the reaction was monitored by TLC.
Procedure for the Synthesis of 3aa on 4 mmol Scale.
To a mixture of RuCl3·3H2O (0.104 g, 0.4 mmol) and K2CO3 (0.55 g, 4 mmol) in CH3CN (10.0
mL) under N2 atmosphere, 2,6-di-tert-butyl-4-(4-fluorobenzylidene) cyclohexa-2,5-dien-1-one 1a
(1.25 g, 4 mmol) and 4-methoxybenzenediazonium salt 2a (1.78 g, 8 mmol) were added. The
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system was stirred at 50 C for 6 h (the reaction was monitored by TLC). After the reaction was
completed, the reaction mixture was filtered by diatomite. The filtere was diluted with brine (40
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mL) and extracted with ethyl acetate (20 mL X 3). The organic layer was washed with water (40
mL), then separated, dried over Na2SO4, and concentrated under vacuum. The residue was further
purified by flash column chromatography on silica gel (petroleum ether: EtOAc = 40:1) to afford
desired product 3aa (1.12 g, 67%) as a yellow solid.
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Characterization Data of Product 3.
2,6-Di-tert-butyl-4-((4-fluorophenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one (3aa)
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1
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 79% (99 mg). mp: 169 - 170 C. H
NMR (400 MHz, CDCl3) δ: 7.30 - 7.26 (m, 3H), 7.23 - 7.20 (m, 2H), 7.18 - 7.13 (m, 3H), 6.99 (d,
J = 8.8 Hz, 2H), 3.93 (s, 3H), 1.31 (s, 9H), 1.29 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ:
186.1, 163.4 (d, JC-F = 249.2 Hz), 160.8, 154.9, 147.3 (double), 137.2 (d, JC-F = 2.9 Hz), 134.1 (d,
JC-F = 8.3 Hz), 133.9, 133.1, 132.2, 132.0, 129.3, 115.2 (d, JC-F = 21.6 Hz), 113.7, 55.5, 35.4
(double), 29.7, 29.6. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C28H31FNaO2 441.2206;
Found 441.2213.
2,6-Di-tert-butyl-4-((4-chlorophenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one (3ab)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 78% (102 mg). mp: 160 - 161 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.44 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 2.8 Hz, 1H), 7.25 - 7.19 (m, 4H),
7.14 (d, J = 2.4 Hz, 1H), 7.01 - 6.96 (m, 2H), 3.93 (s, 3H), 1.31 (s, 9H), 1.29 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ: 186.1, 160.8, 154.5, 147.5, 147.4, 139.6, 135.5, 133.9, 133.4, 132.9,
132.1, 131.7, 129.5, 128.4, 113.7, 55.5, 35.4, 29.7, 29.6. HRMS (ESI-TOF) m/z: [M+Na]+
Calculated for C28H31ClNaO2 457.1910; Found 457.1899.
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(4-nitrophenyl)methylene)cyclohexa-2,5-dien-1-one (3ac)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 78% (104 mg). mp: 197 - 198 oC. 1H
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NMR (400 MHz, CDCl3) δ: 8.32 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.8 Hz,
1H), 7.21 - 7.17 (m, 2H), 7.03 (d, J = 2.8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 1.31 (s,
9H), 1.27 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 161.0, 152.2, 148.4, 148.3, 147.9,
147.8, 133.7, 132.8, 132.2, 131.7, 130.9, 130.7, 123.3, 114.0, 55.6, 35.5, 35.5, 29.7, 29.6. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C28H31NNaO4 468.2151; Found 468.2144.
4-(Bis(4-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3ad)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 86% (111 mg). mp: 178 - 179 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.24 (s, 2H), 7.22 (s, 4H), 7.00 - 6.97 (m, 4H), 3.93 (s, 6H), 1.31 (s,
18H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.0, 160.8, 156.6, 146.7, 134.1, 133.5, 132.5, 128.6,
113.5, 55.5, 35.3, 29.7. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H34NaO3 453.2406;
Found 453.2397.
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2,6-Di-tert-butyl-4-((4-isopropylphenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one
(3ae)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 89% (118 mg). mp: 182 - 183 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.31 (d, J = 7.6 Hz, 2H), 7.27 (d, J = 2.0 Hz, 1H), 7.24 (d, J = 2.0 Hz,
2H), 7.22 (d, J = 2.8 Hz, 2H), 7.20 (s, 1H), 6.98 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 3.02 (dt, J =
13.6, 6.8 Hz, 1H), 1.36 (s, 3H), 1.35 (s, 3H), 1.32 (s, 9H), 1.30 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3) δ: 186.1, 160.6, 156.8, 150.4, 146.9, 146.8, 138.5, 134.0, 133.4, 132.5, 132.4, 128.9, 126.0,
113.4, 55.4, 35.3 (double), 34.0, 29.6 (double), 23.9. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated
for C31H38NaO2 465.2770; Found 465.2768.
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(o-tolyl)methylene)cyclohexa-2,5-dien-1-one (3af)
yellow solid, isolated yield 80% (99 mg). mp: 142 - 143 oC. 1H NMR (400 MHz, CDCl3) δ: 7.46
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(d, J = 2.4 Hz, 1H), 7.39 - 7.35 (m, 1H), 7.31 - 7.27 (m, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.19 - 7.15
(m, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 2.4 Hz, 1H), 3.91 (s, 3H), 2.05 (s, 3H), 1.35 (s, 9H),
1.22 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.3, 160.5, 155.4, 147.5, 147.2, 140.5, 137.1,
133.1, 132.3, 131.9, 131.3, 131.1, 130.5, 129.3, 128.7, 125.4, 113.7, 55.5, 35.4, 35.2, 29.7, 29.5.
HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H34NaO2 437.2457; Found 437.2445.
2,6-Di-tert-butyl-4-((2-chlorophenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one (3ag)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 80% (104 mg). mp: 126 - 127 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.51 (dd, J = 7.6, 2.0 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.42 - 7.38
(m, 2H), 7.29 (dd, J = 7.2, 2.0 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.80 (d,
J = 2.4 Hz, 1H), 3.91 (s, 3H), 1.34 (s, 9H), 1.23 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ:
186.4, 160.4, 151.6, 148.1, 147.5, 139.7, 134.1, 133.0, 132.4, 131.6, 131.4, 131.0, 130.1, 130.0,
129.9, 126.4, 113.7, 55.4, 35.5, 35.2, 29.7, 29.5. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for
C28H31ClNaO2 457.1910; Found 457.1907.
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4-((2-Bromophenyl)(4-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3ah)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 81% (116 mg). mp: 123 - 124 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.71 (d, J = 8.0 Hz, 1H), 7.47 - 7.41 (m, 2H), 7.33 (dd, J = 8.0, 2.0
Hz, 1H), 7.30 (t, J = 2.0 Hz, 1H), 7.27 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.78 (d, J =
13
2.4 Hz, 1H), 3.91 (s, 3H), 1.34 (s, 9H), 1.23 (s, 9H). C{1H} NMR (100 MHz, CDCl3) δ: 186.4,
160.5, 153.0, 148.2, 147.5, 141.7, 133.4, 133.2, 132.4, 131.5, 131.4, 131.1, 130.0, 129.8, 127.1,
124.2, 113.7, 55.5, 35.6, 35.3, 29.8, 29.6. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for
C28H31BrNaO2 501.1405; Found 501.1409.
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(m-tolyl)methylene)cyclohexa-2,5-dien-1-one (3ai)
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 85% (106 mg). mp: 170 - 171 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.34 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 2.8 Hz, 2H), 7.25 - 7.22 (m, 2H),
7.21 (d, J = 2.4 Hz, 1H), 7.09 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 3.93 (s, 3H), 2.42 (s,
3H), 1.32 (s, 9H), 1.29 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.2, 160.7, 156.7, 147.1,
146.9, 141.1, 137.6, 133.9, 133.3, 132.9, 132.5, 132.3, 130.1, 129.5, 129.2, 127.8, 113.5, 55.5,
35.4, 35.3, 29.7, 29.6, 21.4. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H34NaO2
437.2457; Found 437.2466.
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2,6-Di-tert-butyl-4-((3-methoxyphenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one
(3aj)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 86% (111 mg). mp: 174 - 175 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.36 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.23
(s, 2H), 7.02 (dd, J = 8.4, 2.4 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 7.6 Hz, 1H), 6.82 (s,
1H), 3.92 (s, 3H), 3.84 (s, 3H), 1.32 (s, 9H), 1.29 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ:
186.2, 160.7, 159.2, 156.1, 147.3, 147.0, 142.5, 133.9, 133.1, 132.3, 132.2, 129.2, 129.0, 124.8,
117.3, 115.2, 113.5, 55.5, 35.4, 35.4, 29.7 (double). HRMS (ESI-TOF) m/z: [M+Na]+ Calculated
for C29H34NaO3 453.2406; Found 453.2409.
4-((2-Bromo-4-methylphenyl)(4-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-
one (3ak)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 84% (124 mg). mp: 169 - 170 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.53 (s, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.25 (d, J = 8.8 Hz, 2H), 7.22
(s, 1H), 7.15 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 2.4 Hz, 1H), 3.91 (s, 3H),
2.45 (s, 3H), 1.34 (s, 9H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 160.4, 153.3,
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147.9, 147.3, 140.4, 138.7, 133.8, 133.2, 132.2, 131.7, 131.1, 129.8, 127.9, 124.0, 113.6, 55.4,
35.5, 35.2, 29.7, 29.6, 21.0. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H33BrNaO2
515.1562; Found 515.1567.
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2,6-Di-tert-butyl-4-((2,5-dimethoxyphenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one
(3al)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 89% (123 mg). mp: 180 - 181 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 2.8 Hz, 1H), 7.28 - 7.24 (m, 2H), 7.01 (d, J = 2.8 Hz, 1H),
6.98 (d, J = 2.8 Hz, 1H), 6.95 (d, J = 2.8 Hz, 2H), 6.93 (d, J = 3.2 Hz, 1H), 6.74 (d, J = 3.2 Hz,
1H), 3.91 (s, 3H), 3.82 (s, 3H), 3.60 (s, 3H), 1.32 (s, 9H), 1.25 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3) δ: 186.4, 160.2, 153.2, 152.3, 151.8, 147.3, 146.8, 132.9, 132.7, 132.2, 131.4, 131.0, 129.6,
117.9, 115.5, 113.4, 113.2, 56.5, 56.0, 55.4, 35.4, 35.2, 29.7, 29.6. HRMS (ESI-TOF) m/z:
[M+Na]+ Calculated for C30H36NaO4 483.2511; Found 483.2517.
2,6-Di-tert-butyl-4-((3,4-dimethylphenyl)(4-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one
(3am)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 87% (112 mg). mp: 190 - 200 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.26 (s, 2H), 7.22 (t, J = 8.4 Hz, 3H), 7.06 (s, 1H), 7.03 (d, J = 7.6
Hz, 1H), 6.98 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 2.38 (s, 3H), 2.32 (s, 3H), 1.32 (s, 9H), 1.31 (s,
13
9H). C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 160.6, 157.0, 146.8, 146.6, 138.6, 138.3, 136.2,
134.0, 133.6, 133.4, 132.6, 132.4, 130.0, 129.2, 128.8, 113.4, 55.4, 35.3 (double), 29.6 (double)
19.8, 19.7. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C30H36NaO2 451.2613; Found
451.2601.
4-(Benzo[d][1,3]dioxol-5-yl(4-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-o
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 90% (120 mg). mp: 177 - 178 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.24 (d, J = 1.6 Hz, 2H), 7.22 (s, 2H), 6.98 (d, J = 8.4 Hz, 2H), 6.91
(d, J = 8.0 Hz, 1H), 6.84 (dd, J = 8.0, 1.6 Hz, 1H), 6.72 (d, J = 1.2 Hz, 1H), 6.09 (s, 2H), 3.93 (s,
3H), 1.32 (s, 9H), 1.31 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 160.8, 156.1, 148.8,
147.6, 146.9, 146.8, 135.1, 134.0, 133.3, 132.4, 132.3, 129.0, 127.3, 113.5, 112.3, 107.8, 101.6,
55.5, 35.3, 29.7. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H32NaO4 467.2198; Found
467.2193.
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2,6-Di-tert-butyl-4-((4-methoxyphenyl)(3,4,5-trimethoxyphenyl)methylene)cyclohexa-2,5-dien-1-o
ne (3ao)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 92% (135 mg). mp: 136 - 137 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.29 - 7.26 (m, 2H), 7.25 (d, J = 2.8 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H),
6.51 (s, 2H), 3.99 (s, 3H), 3.94 (s, 3H), 3.84 (s, 6H), 1.32 (s, 9H), 1.31 (s, 9H). 13C{1H} NMR
(100 MHz, CDCl3) δ: 186.2, 160.8, 156.3, 152.6, 147.1, 146.9, 139.2, 136.4, 134.1, 132.9, 132.4,
132.3, 129.1, 113.5, 110.0, 61.1, 56.3, 55.5, 35.4, 29.8, 29.7. HRMS (ESI-TOF) m/z: [M+Na]+
Calculated for C31H38NaO5 513.2617; Found 513.2624.
2,6-Di-tert-butyl-4-((4-methoxyphenyl)(naphthalen-2-yl)methylene)cyclohexa-2,5-dien-1-one
(3ap)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 87% (118 mg). mp: 173 - 174 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.96 (dd, J = 11.6, 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 1H), 7.60 - 7.56
(m, 2H), 7.53 - 7.49 (m, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.33 (d, J = 2.0 Hz, 1H), 7.31 (d, J = 2.4
Hz, 1H), 6.95 - 6.92 (m, 2H), 6.79 (d, J = 2.8 Hz, 1H), 3.88 (s, 3H), 1.39 (s, 9H), 1.10 (s, 9H).
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13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 160.5, 153.9, 147.6, 147.0, 138.6, 133.7, 133.1, 132.9,
132.4, 132.2, 131.3, 130.5, 129.3 (double), 128.4, 126.5, 126.3, 126.0, 124.5, 113.7, 55.4, 35.4,
35.1, 29.7, 29.3. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C32H34NaO2 473.2457; Found
473.2448.
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2,6-Di-tert-butyl-4-((4-methoxyphenyl)(thiophen-2-yl)methylene)cyclohexa-2,5-dien-1-one (3aq)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 84% (102 mg). mp: 173 - 174 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.69 (d, J = 2.4 Hz, 1H), 7.64 (dd, J = 4.8, 2.0 Hz, 1H), 7.34 - 7.30
(m, 2H), 7.23 - 7.19 (m, 2H), 7.11 (d, J = 2.8 Hz, 1H), 7.02 - 6.98 (m, 2H), 3.94 (s, 3H), 1.38 (s,
9H), 1.28 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.2, 161.0, 147.9, 147.5, 147.0, 144.1,
133.8, 133.3, 133.2, 132.3, 131.6, 131.1, 129.4, 127.7, 113.5, 55.5, 35.5, 35.4, 29.7, 29.6. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C26H30NaO2S 429.1864; Found 429.1859.
2,6-Di-tert-butyl-4-((2-methoxyphenyl)(p-tolyl)methylene)cyclohexa-2,5-dien-1-one (3ba)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 85% (106 mg). mp: 146 - 147 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.47 - 7.41 (m, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.21 (s, 4H), 7.17 (dd, J
= 7.6, 1.6 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 7.02 - 6.98 (m, 2H), 3.67 (s, 3H), 2.44 (s, 3H), 1.32 (s,
9H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 157.4, 152.9, 147.2, 146.9, 138.7,
137.7, 132.4, 132.1, 131.4, 130.9, 130.4, 130.0, 129.9, 128.6, 120.3, 111.6, 55.7, 35.3, 35.1, 29.6,
29.5, 21.4. HRMS (ESI-TOF) m/z: [M+Na]+ Ccalculated for C29H34NaO2 437.2457; Found
437.2450.
2,6-Di-tert-butyl-4-((2-chlorophenyl)(p-tolyl)methylene)cyclohexa-2,5-dien-1-one (3bb)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 83% (104 mg). mp: 143 - 144 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.53 - 7.49 (m, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.40 (dd, J = 4.0, 2.0 Hz,
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1H), 7.39 - 7.36 (m, 1H), 7.31 - 7.28 (m, 1H), 7.23 (q, J = 8.4 Hz, 4H), 6.82 (d, J = 2.4 Hz, 1H),
2.45 (s, 3H), 1.33 (s, 9H), 1.23 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 151.7, 148.1,
147.7, 139.6, 139.3, 136.2, 134.0, 132.2, 131.3, 131.2, 130.9, 130.3, 130.1, 129.8, 128.9, 126.4,
35.4, 35.2, 29.6, 29.4, 21.4. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C28H31ClNaO
441.1961; Found 441.1958.
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4-((2-Bromophenyl)(p-tolyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3bc)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 80% (111 mg). mp: 145 - 146 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.72 - 7.69 (m, 1H), 7.46 - 7.41 (m, 2H), 7.35 - 7.32 (m, 1H), 7.29 (dd,
J = 7.2, 1.6 Hz, 1H), 7.24 (s, 4H), 6.80 (d, J = 2.4 Hz, 1H), 2.45 (s, 3H), 1.33 (s, 9H), 1.23 (s, 9H).
13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 153.0, 148.2, 147.7, 141.6, 139.3, 135.9, 133.2, 132.2,
131.4, 131.3, 130.9, 130.2, 129.8, 128.9, 127.0, 124.0, 35.4, 35.2, 29.6, 29.4, 21.5. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C28H31BrNaO 485.1456; Found 485.1447.
2,6-Di-tert-butyl-4-(di-p-tolylmethylene)cyclohexa-2,5-dien-1-one (3bd)
o
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 83% (99 mg). mp: 198 - 199 C. H
NMR (400 MHz, CDCl3) δ: 7.26 (s, 2H), 7.25 (d, J = 6.4 Hz, 4H), 7.17 (d, J = 8.0 Hz, 4H), 2.47 (s,
6H), 1.31 (s, 18H). 13C NMR (100 MHz, CDCl3) δ: 186.2, 156.8, 147.0, 139.5, 138.1, 132.3,
132.2, 129.2, 128.7, 35.3, 29.6, 21.5. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H34NaO
421.2507; Found 421.2496.
4-((2-Bromo-4-methylphenyl)(p-tolyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3be)
yellow solid, isolated yield 83% (119 mg). mp: 184 - 185 oC. 1H NMR (400 MHz, CDCl3) δ: 7.53
(s, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.23 (d, J = 3.2 Hz, 5H), 7.15 (d, J = 7.6 Hz, 1H), 6.84 (d, J =
2.8 Hz, 1H), 2.45 (s, 3H), 2.44 (s, 3H), 1.33 (s, 9H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz,
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CDCl3) δ: 186.4, 153.4, 148.0, 147.5, 140.3, 139.3, 138.6, 136.3, 133.8, 132.1, 131.6, 131.5, 131.1,
130.2, 128.9, 127.9, 123.8, 35.5, 35.3, 29.7, 29.6, 21.5, 21.0. HRMS (ESI-TOF) m/z: [M+Na]+
Calculated for C29H33BrNaO 499.1612; Found 499.1605.
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2,6-Di-tert-butyl-4-((4-fluorophenyl)(2-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one (3ca)
o
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 78% (94 mg). mp: 140 - 141 C. H
NMR (400 MHz, CDCl3) δ: 7.48 - 7.43 (m, 1H), 7.31 - 7.27 (m, 3H), 7.19 (dd, J = 7.6, 1.6 Hz,
1H), 7.14 - 7.07 (m, 3H), 7.01 (s, 1H), 7.00 (d, J = 7.6 Hz, 1H), 3.66 (s, 3H), 1.31 (s, 9H), 1.24 (s,
13
9H). C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 162.8 (d, JC-F = 248.1 Hz), 157.4, 151.4, 147.7,
147.3, 136.7 (d, JC-F = 2.6 Hz), 132.6 (d, JC-F = 8.2 Hz), 132.5, 131.9, 130.9, 130.7, 130.3, 129.6,
120.4, 114.9 (d, JC-F = 21.5 Hz), 111.7, 55.6, 35.4, 35.2, 29.6 (double). HRMS (ESI-TOF) m/z:
[M+Na]+ Calculated for C28H31FNaO2 441.2206; Found 441.2199.
2,6-Di-tert-butyl-4-((3,4-dimethylphenyl)(4-fluorophenyl)methylene)cyclohexa-2,5-dien-1-one
(3cb)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 80% (100 mg). mp: 166 - 167 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.30 - 7.25 (m, 3H), 7.22 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 4.4 Hz, 1H),
7.14 (d, J = 8.8 Hz, 2H), 7.04 (s, 1H), 7.01 (d, J = 8.0 Hz, 1H), 2.38 (s, 3H), 2.32 (s, 3H), 1.31 (s,
9H), 1.30 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 163.2 (d, JC-F = 249.1 Hz), 155.3,
147.4, 147.2, 138.5, 138.2, 137.1 (d, JC-F = 3.0 Hz), 136.4, 133.9 (d, JC-F = 8.1 Hz), 133.3, 132.2,
131.8, 129.8, 129.5, 129.4, 115.1 (d, JC-F = 21.4 Hz), 35.3, 29.6 (double), 19.8, 19.7. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C29H33FNaO 439.2413; Found 439.2403.
2,6-Di-tert-butyl-4-((4-chlorophenyl)(2-methoxyphenyl)methylene)cyclohexa-2,5-dien-1-one (3da)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 77% (100 mg). mp: 152 - 153 oC. 1H
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NMR (400 MHz, CDCl3) δ: 7.48 - 7.43 (m, 1H), 7.40 - 7.37 (m, 2H), 7.29 (d, J = 2.4 Hz, 1H),
7.27 - 7.23 (m, 2H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.07 (td, J = 7.2, 0.8 Hz, 1H), 7.01 (s, 1H),
6.99 (d, J = 7.6 Hz, 1H), 3.65 (s, 3H), 1.31 (s, 9H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3)
δ: 186.4, 157.4, 151.1, 147.8, 147.5, 139.1, 134.6, 132.5, 132.1, 131.9, 130.8, 130.7, 130.5, 129.4,
128.1, 120.4, 111.7, 55.6, 35.5, 35.3, 29.7, 29.6. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for
C28H31ClNaO2 457.1910; Found 457.1919.
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4-(Bis(4-chlorophenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3db)
o
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 75% (99 mg). mp: 175 - 176 C. H
NMR (400 MHz, CDCl3) δ: 7.47 - 7.43 (m, 4H), 7.23 - 7.19 (m, 4H), 7.16 (s, 2H), 1.29 (s, 18H).
13C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 152.4, 148.2, 138.9, 135.7, 133.2, 131.3, 130.4, 128.6,
35.5, 29.6. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C27H28Cl2NaO 461.1415; Found
461.1421.
2,6-Di-tert-butyl-4-((4-chlorophenyl)(3,4-dimethylphenyl)methylene)cyclohexa-2,5-dien-1-one
(3de)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 79% (102 mg). mp: 201 - 202 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.45 - 7.41 (m, 2H), 7.28 (d, J = 2.8 Hz, 1H), 7.25 - 7.23 (m, 1H),
7.22 (s, 1H), 7.21 (d, J = 4.4 Hz, 1H), 7.15 (d, J = 2.4 Hz, 1H), 7.03 (s, 1H), 7.00 (d, J = 7.6 Hz,
1H), 2.38 (s, 3H), 2.32 (s, 3H), 1.30 (s, 9H), 1.30 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ:
186.2, 155.0, 147.6, 147.4, 139.5, 138.5, 138.0, 136.5, 135.3, 133.3, 132.2, 131.7, 129.9, 129.7,
129.5, 128.3, 35.4, 29.7, 19.9, 19.8. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for
C29H33ClNaO 455.2118; Found 455.2110.
4-((4-Bromophenyl)(2-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3ea)
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 77% (110 mg). mp: 158 - 159 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.54 (d, J = 8.4 Hz, 2H), 7.48 - 7.43 (m, 1H), 7.28 (d, J = 2.4 Hz, 1H),
7.20 - 7.16 (m, 3H), 7.07 (t, J = 7.2 Hz, 1H), 7.00 (s, 1H), 6.99 (d, J = 5.2 Hz, 1H), 3.66 (s, 3H),
1.31 (s, 9H), 1.24 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.4, 157.4, 151.1, 147.9, 147.5,
139.6, 132.5, 132.3, 131.8, 131.1, 130.7, 130.7, 130.5, 129.3, 122.9, 120.4, 111.7, 55.6, 35.5, 35.3,
29.6, 29.5. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C28H31BrNaO2 501.1405; Found
501.1397.
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4-((2-Bromophenyl)(3,4-dimethylphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one
(3fa)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 81% (116 mg). mp: 140 - 141 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.71 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 2.4 Hz, 1H), 7.43 (t, J = 7.6 Hz,
1H), 7.34 - 7.31 (m, 1H), 7.30 - 7.27 (m, 1H), 7.20 (d, J = 7.6 Hz, 1H), 7.11 (s, 1H), 7.08 (d, J =
7.6 Hz, 1H), 6.78 (d, J = 2.4 Hz, 1H), 2.35 (s, 3H), 2.31 (s, 3H), 1.34 (s, 9H), 1.23 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ: 186.4, 153.3, 148.0, 147.6, 141.7, 138.2, 136.4, 136.3, 133.2, 132.6,
132.2, 131.5, 131.2, 130.1, 129.9, 129.4, 129.2, 127.1, 124.0, 35.5, 35.2, 29.7, 29.5, 19.9. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C29H33BrNaO 499.1612; Found 499.1605.
4-(Benzo[d][1,3]dioxol-5-yl(o-tolyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3ga)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 85% (109 mg). mp: 172 - 173 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.45 (d, J = 2.4 Hz, 1H), 7.39 - 7.34 (m, 1H), 7.31 - 7.26 (m, 2H),
7.16 (d, J = 7.2 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 6.86 (dd, J = 8.4, 1.6 Hz, 1H), 6.82 (d, J = 2.4
Hz, 1H), 6.73 (d, J = 1.2 Hz, 1H), 6.07 (s, 2H), 2.08 (s, 3H), 1.35 (s, 9H), 1.21 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ: 186.3, 154.9, 148.5, 147.7, 147.6, 147.3, 140.3, 137.0, 133.9, 131.8,
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131.0 (double), 130.5, 129.7, 128.8, 126.4, 125.5, 111.3, 108.0, 101.6, 35.4, 35.1, 29.6, 29.5, 20.3.
HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H32NaO3 451.2249; Found 451.2238.
4-(Benzo[d][1,3]dioxol-5-yl(2-bromophenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one
(3gb)
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 82% (121 mg). mp: 168 - 169 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.71 (dd, J = 7.6, 0.8 Hz, 1H), 7.46 - 7.42 (m, 2H), 7.33 (dd, J = 7.6,
1.6 Hz, 1H), 7.28 (dd, J = 7.6, 1.6 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.87 (dd, J = 8.0, 1.6 Hz, 1H),
6.77 (d, J = 1.2 Hz, 1H), 6.75 (d, J = 2.8 Hz, 1H), 6.07 (s, 2H), 1.34 (s, 9H), 1.22 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ: 186.4, 152.5, 148.6, 148.2, 147.7, 147.6, 141.5, 133.3, 132.8, 132.2,
131.4, 130.7, 130.2, 130.0, 127.1, 126.6, 124.0, 111.3, 108.0, 101.6, 35.4, 35.2, 29.6, 29.4. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C28H29BrNaO3 515.1198; Found 515.1192.
4-(Benzo[d][1,3]dioxol-5-yl(p-tolyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3gc)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 88% (113 mg). mp: 167 - 168 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.27 (s, 2H), 7.25 (s, 1H), 7.21 (d, J = 2.8 Hz, 1H), 7.18 (d, J = 8.0 Hz,
2H), 6.91 (d, J = 8.0 Hz, 1H), 6.83 (dd, J = 8.0, 1.6 Hz, 1H), 6.70 (d, J = 1.6 Hz, 1H), 6.08 (s, 2H),
2.47 (s, 3H), 1.32 (s, 9H), 1.29 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ: 186.1, 156.2, 148.7,
147.6, 147.0, 139.6, 138.0, 135.0, 132.3, 132.2, 132.1, 129.3, 128.8, 127.1, 112.1, 107.8, 101.6,
35.3 (double), 29.6 (double), 21.5. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H32NaO3
451.2249; Found 451.2256.
4-(Benzo[d][1,3]dioxol-5-yl(4-bromophenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one
(3gd)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 81% (120 mg). mp: 153 - 154 oC. 1H
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NMR (400 MHz, CDCl3) δ: 7.60 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 2.4 Hz, 1H), 7.17 (d, J = 8.4 Hz,
2H), 7.12 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.81 (dd, J = 8.0, 1.6 Hz, 1H), 6.68 (d, J =
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1.6 Hz, 1H), 6.10 (s, 2H), 1.31 (s, 9H), 1.29 (s, 9H). C{1H} NMR (100 MHz, CDCl3) δ: 186.1,
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154.0, 148.9, 147.8 147.6, 147.5, 139.8, 134.3, 133.5, 131.8, 131.5, 131.3, 129.8, 127.1, 123.8,
112.0, 107.9, 101.7, 35.3, 29.6, 29.5. HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for
C28H29BrNaO3 515.1198; Found 515.1187.
4-(Benzo[d][1,3]dioxol-5-yl(5-bromo-2-methoxyphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5
-dien-1-one (3ge)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 85% (133 mg). mp: 196 - 197 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.54 (dd, J = 8.8, 2.5 Hz, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.28 (d, J =
2.4 Hz, 1H), 6.89 (d, J = 2.4 Hz, 2H), 6.87 (s, 1H), 6.83 (dd, J = 8.0, 1.6 Hz, 1H), 6.74 (d, J = 1.6
Hz, 1H), 6.07 (s, 2H), 3.70 (s, 3H), 1.32 (s, 9H), 1.25 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3) δ:
186.4, 156.5, 149.8, 148.4, 147.7 (double), 147.4, 134.7, 134.0, 133.0, 131.8, 131.6, 130.9, 130.4,
125.8, 113.3, 112.7, 111.0, 108.0, 101.6, 56.0, 35.5, 35.3, 29.7, 29.6. HRMS (ESI-TOF) m/z:
[M+Na]+ Calculated for C29H31BrNaO4 545.1303; Found 545.1307.
4-(Benzo[d][1,3]dioxol-5-yl(2-bromo-4-methylphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-d
ien-1-one (3gf)
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 84% (128 mg). mp: 174 - 175 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.53 (s, 1H), 7.42 (d, J = 2.4 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.14
(d, J = 8.0 Hz, 1H), 6.89 (d, J = 8.0 Hz, 1H), 6.85 (dd, J = 8.0, 1.6 Hz, 1H), 6.80 (d, J = 2.4 Hz,
1H), 6.75 (d, J = 1.6 Hz, 1H), 6.06 (s, 2H), 2.45 (s, 3H), 1.34 (s, 9H), 1.23 (s, 9H). 13C{1H} NMR
(100 MHz, CDCl3) δ: 186.4, 152.8, 148.5, 148.0, 147.7, 147.4, 140.4, 138.5, 133.8, 133.2, 132.2,
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131.6, 130.9, 130.2, 127.9, 126.6, 123.9, 111.4, 108.0, 101.6, 35.4, 35.2, 29.6, 29.5, 21.0. HRMS
(ESI-TOF) m/z: [M+Na]+ Calculated for C29H31BrNaO3 529.1354; Found 529.1346.
4-(Benzo[d][1,3]dioxol-5-yl(3,4-dimethylphenyl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1
-one (3gg)
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yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 90% (119 mg). mp: 202 - 203 oC. 1H
NMR (400 MHz, CDCl3) δ: 7.25 (dd, J = 8.8, 2.4 Hz, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.06 - 7.00 (m,
2H), 6.91 (d, J = 8.0 Hz, 1H), 6.84 (dd, J = 8.0, 1.6 Hz, 1H), 6.71 (d, J = 1.6 Hz, 1H), 6.09 (s, 2H),
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2.38 (s, 3H), 2.32 (s, 3H), 1.32 (s, 9H), 1.30 (s, 9H). C{1H} NMR (100 MHz, CDCl3) δ: 186.1,
156.5, 148.7, 147.6, 146.9, 146.8, 138.4, 138.3, 136.2, 135.0, 133.4, 132.5, 132.2, 129.9, 129.3,
129.2, 127.1, 112.2, 107.7, 101.6, 35.3 (double), 29.6(double), 19.8, 19.7. HRMS (ESI-TOF) m/z:
[M+Na]+ Calculated for C30H34NaO3 465.2406; Found 465.2418.
4-(Bis(benzo[d][1,3]dioxol-5-yl)methylene)-2,6-di-tert-butylcyclohexa-2,5-dien-1-one (3gh)
o
yellow solid (petroleum ether: EtOAc = 40:1), isolated yield 92% (126 mg). mp: 198 - 199 C.
1H NMR (400 MHz, CDCl3) δ: 7.22 (s, 2H), 6.91 (d, J = 8.0 Hz, 2H), 6.84 (dd, J = 8.0, 1.6 Hz,
2H), 6.71 (d, J = 1.6 Hz, 2H), 6.09 (s, 4H), 1.31 (s, 18H). 13C {1H} NMR (100 MHz, CDCl3) δ:
186.1, 155.5, 148.8, 147.6, 146.9, 134.8, 132.1, 129.3, 127.2, 112.1, 107.8, 101.6, 35.3, 29.6.
HRMS (ESI-TOF) m/z: [M+Na]+ Calculated for C29H30NaO5 481.1991; Found: 481.1988.
ASSOCIATED CONTENT
*Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1H NMR, 13C{1H} NMR spectra for all products (PDF).
■ AUTHOR INFORMATION
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Corresponding Author
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*E-mail: lcrong@jsnu.edu.cn; xiaopangpeng@126.com
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ORCID
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Liangce Rong:0000-0003-0561-1137
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to National Natural Science Foundation of China (NSFC) (No. 21571087 and
No.81872647), the Natural Science Foundation of the Jiangsu Higher Education Institutions of
China (No. 17KJB150016, 18KJA150004), and this work was also sponsored by TAPP.
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