Visible Light-Mediated [2 + 2] Cycloaddition Reactions of 1,4-Quinones and Terminal Alkynes

Article abstract of DOI:10.1021/acs.joc.9b00855

A single-step synthesis of 4-hydroxy-functionalized bi-aryl and aryl/alkyl ketones via oxidative coupling of terminal alkynes with benzoquinones is reported. Furthermore, with naphthoquinones, owing to the cross-resonance of carbonyl with the aromatic ring, alkene-alkyne cycloaddition is more favored to give four-membered carbocyclic adducts, thereby precluding the requirement of preactivated alkynes.

Full text of DOI:10.1021/acs.joc.9b00855

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Article
Visible Light Mediated [2+2] Cycloaddition
Reactions of 1,4-Quinones and Terminal Alkynes
Shaista Sultan, Muneer-Ul-Shafi Bhat, Masood Ahmad Rizvi, and Bhahwal Ali Shah
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00855 • Publication Date (Web): 17 Jun 2019
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The Journal of Organic Chemistry
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Visible Light Mediated [2+2] Cycloaddition Reactions of 1,4-
Quinones and Terminal Alkynes
Shaista Sultan,a,† Muneer-ul-Shafi Bhat, a,† Masood Ahmad Rizvi,*,‡ and Bhahwal Ali Shah*,†
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†AcSIR and Natural Product Microbes, CSIR-Indian Institute of Integrative Medicine, Jammu-180001,
‡Department of Chemistry, University of Kashmir, Srinagar, 190006
a Both authors contributed equally
Supporting Information Placeholder
O
R
[2+2] Patterno-Buchi
n*
HO
4-hydroxy ketones
25 examples
O
O
blue
LEDS
O
O
+
O
R
R1
R
*
R= aliphatic/
aromatic
R1
O
[2+2] alkene-alkyne
cycloaddition
cyclobutenes
22 examples
ABSTRACT: A single-step synthesis of 4-hydroxy functionalized bi-aryl and aryl-alkyl ketones via oxidative coupling of terminal
alkynes with benzoquinones is reported. Furthermore, with naphthoquinones, owing to cross-resonance of carbonyl with aromatic
ring, alkene-alkyne cycloaddition is more favoured to give 4-membered carbocyclic adducts, thereby precluding the requirement of
preactivated alkynes.
challenge.10 Conventionally, 4-hydroxy functional group is
INTRODUCTION
introduced indirectly via hydroxylation of halo-aryl ketones
and deprotection of alkoxy substituted aryl ketones.11 The only
direct method for their synthesis was recently reported by
Hwang and co-workers12 using visible light mediated coupling
of phenols and terminal alkynes.
Ketones are valuable intermediates and core structural
components in a diverse array of pharmaceuticals, natural
products,
organic
materials,
agrochemicals
and
photosensitizers.1,2 The synthesis of ketones particularly aryl
ketones is one of the most addressed problems in the synthetic
organic chemistry (Fig. 1). They are generally accessed via
Friedel-Craft's acylation reaction,3 which notably requires
creation of high energy acylating reagents. Other approaches
to access ketones include: (a) addition of organomettalic
reagents over activated carboxylic acid derivatives like
Weinreb amides, anhydrides, acid chlorides and acyl silanes;4
(b) transition metal catalyzed cross-coupling acylation
reactions such as Kumada-arylation and Suzuki-Miyaura
1. Photoredox methods of ketone synthesis
b) Oxidative coupling:
a) C-H activation:
O
IrIII, Ni
HAT
O
CuCl, O2
R
R
R
R
OH
R
Y
R
H
Terminal
alkynes
R = Ar
Y = Cl, Br
benzophenones/
aryl-alkyl ketones
Aldehyde
2. This work
O
[2+2]
Patterno-Buchi
25 examples
O
air
R
O
reactions employing use of activated arenes like boronic acids,
organoborates, organotriflates and halides;
O
HO
5,6
4-hydroxy ketones
n*
(c)
K2S2O8, TFA
blue LEDs
O
O
R1
+
decarboxylative addition of benzoic acids and α-
oxocarboxylates;7 (d) carbonylation of arene C-H bonds; 8 (e)
photoredox catalysis involving the C-H arylation/alkylation of
aldehydes with aryl/alkyl bromides and cross-coupling of
alkenes or halides with silyl enol ethers, aryl boronic acids and
salicylate esters and carboxylic acids.9 In this regard, synthesis
of 4-hydroxy functionalized aryl/alkyl ketones, precursor to
pharmaceutically important molecules like pitofenone,
tamoxifen, ospemifene, clomefine, finofibrate, antibiotics,
anticholesteremic agents, acetylcholinesterase inhibitors and
leukotriene A4 hydrolase inhibitors represents an interesting
[2+2]
alkene-alkyne
cycloaddition
O
R
R
22 examples
O
R1
R= aliphatic/
aromatic
O
*
R1 = H, Me, OMe
R1
cyclobutenes
Figure 1. Synthesis of aryl ketones and cyclobutenes.
Thus, in continuation of our interests13 and inspired by
recent advancements in radical reactions,14 particularly
photoredox catalysis,15 we envisaged the use of 1,4-
benzoquinones as they have an innate capability of producing
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4-hydroxy functionality post-aromatization. Herein, we report (persulfate) or light source (Table 1, entries 7-9). Reaction in
1
2
3
4
5
6
7
8
a photoredox catalyzed approach for oxidative coupling of
acetylenes with 1,4-benzoquinones to synthesize various 4-
hydroxy functionalized aryl/alkyl ketones. However, with
naphthoquinone the formation of 4-membered carbocycles
was more favourable owing to participation of ππ* excited
state of C-C double bond rather than nπ* of carbonyl group,16
which may be attributed to the cross-resonance of carbonyl
with aromatic ring. To the best of our knowledge synthesis of
this class of cylcobutenes is hitherto unreported. Also, this
observation is significant as such reactions are difficult to
achieve using unactivated terminal alkynes given the fact that
two coupling partners should either be electrophilic or
nucleophilic, so as to match their frontier molecular orbitals.17
presence of sodium and ammonium persulfate also gave the
product 3 in 84 and 75% yields respectively (Table 1, entries
10-11). Furthermore, there was no product formation in
absence of atmospheric oxygen, under argon atmosphere with
degassed solvent system (Table 1, entries 10-11).
The reaction conditions thus optimized were applied to a
series of phenylacetylenes using benzoquinone 1 for the
synthesis of diverse benzophenones (Scheme 1). The products
(4-7) with 4-methyl, propyl, pentyl and tert-butyl
phenylacetylenes were synthesized in 85-90% yields. The
reaction with various halo-substituted phenylacetylenes
ranging from 4-bromo, 4-fluoro, 3-fluoro, 2-fluoro, 3,5-
difluoro, 4-chloro and 3-chloro phenylacetylene gave
corresponding products (8-14) in 79-90% yields. The electron
deficient 4-trifluoromethylphenylacetylene produced 15 in
91% yields. The reaction of phenylacetylene was also feasible
with substituted benzoquinones viz., 2-methyl and 2-chloro
benzoquinone giving benzophenones (16-17) in 84 and 90%
yields respectively.
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RESULTS AND DISCUSSION
Table 1. Optimization of Reaction Conditionsa
O
O
K2S2O8, light source
TFA, solvent, rt
+
HO
Scheme 1. Synthesis of benzophenones
O
3
1
2
K2S2O8 (3 mmol)
TFA (1 mmol)
MeCN/H2O (1:1)
blue LEDs
O
O
+
R
R
O
entry
1
oxidant
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
-
light source
CFL
solvent
acid source
TFA
TFA
TFA
TFA
TFA
TFA
-
yield (%)
2a
(1.2 mmol)
1a
(1 mmol)
HO
3-17
MeCN/H2O
MeCN/H2O
MeOH/H2O
DCE
71
O
O
O
2
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
blue LEDs
no light
88
3
-
-
HO
HO
HO
5
, 90% 7 h
O
3
, 88% 8 h
4
, 87% 8 h
4
precursor to tamoxifen,
ospemifene, clomifene
(Ref. 10c, 10e)
5
DMSO
-
O
O
6
CH2Cl2/H2O
MeCN/H2O
MeCN/H2O
MeCN/H2O
MeCN/H2O
MeCN/H2O
MeCN/H2O
traces
traces
-
HO
4
HO
HO
Br
HO
HO
7
8
, 81% 7 h
7
, 85% 8 h
O
6
, 88% 8 h
O
8
TFA
TFA
TFA
TFA
TFA
O
F
F
9
K2S2O8
Na2S2O8
(NH4)2S2O8
K2S2O8
traces
84
F
HO
10
11
12b
blue LEDs
blue LEDs
blue LEDs
9
, 79% 7 h
O
10
, 85% 6 h
O
11
, 88% 8 h
O
75
F
Cl
traces
HO
HO
HO
Cl
a1 (1 mmol), 2 (1.2 mmol), oxidant (3 mmol), trifluoroacetic acid (TFA, 1
mmol), solvent (4 mL), rt = 25 C. The reactions was carried out under
argon atmosphere with degassed solvent system (freeze-thaw process).
Note: The reactions were monitored upto 10 h reaction time.
HO
F
14
, 87% 6 h
O
13
, 90% 6 h
12
o
b
, 85% 6 h
O
precursor to fenofibrate
Ref. 10d
O
Cl
Preliminary studies using benzoquinone
1
and
CF3
HO
phenylacetylene 2 as model substrates in the presence of
various oxidants and acid sources showed that the
combination of potassium persulfate, trifluoroacetic acid
(TFA) and visible light was required for synthesis of
benzophenones (Table 1). The irradiation of the reaction
mixture with CFL in presence of MeCN:H2O as solvent
afforded the 4-hydroxy benzophenone 3 in 71% yields (Table
1, entry 1), albeit with side product formation possibly
because of the heat generated by CFL. Nevertheless, the use of
blue light not only improved the reaction yields to 88%, but
also showed no side product formation (Table 1, entry 2).
Furthermore, screening of different solvents like MeOH/H2O,
DCE, DMSO and CH2Cl2/H2O resulted in no product
formation (Table 1, entries 3-6). Moreover, the ketone could
not be isolated in absence of acid source (TFA), oxidant
HO
15
, 91% 7 h
16
, 84% 8 h
17
, 90% 6 h
We further examined the scope of this reaction with aliphatic
acetylenes for the synthesis of aryl-alkyl ketones (Scheme 2).
Aliphatic alkynes like cyclopropylacetylene, 1-pentyne, 1-
hexyne and 1-heptyne also underwent coupling with
benzoquinone to generate corresponding products (18-21) in
85-90% yields. Similarly, long chain alkynes like 1-octyne
and 1-nonyne also produced ketones (22-23) in 88 and 87%
yields respectively. Also, 2-methyl and 2-chloro benzoquinone
with 1-heptyne and 1-octyne produced substituted aryl-alkyl
ketones (24-27) in 81-87% yields.
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The Journal of Organic Chemistry
oxidative conditions,20 and in our observation these dyes
displayed a sequential decrease in the absorbance at their
corresponding λmax with the increasing irradiation time in
presence of K2S2O8 (See supporting information for details).
Scheme 2. Synthesis of aryl-alkyl ketones
O
K2S2O8 (3 mmol)
TFA (1 mmol)
MeCN/H2O (1:1)
blue LEDs
O
+
R
R
O
HO
R = aliphatic
1a
(1 mmol)
2b
(1.2 mmol)
Scheme 3. Synthesis of cyclobutenes
18-27
O
O
O
K2S2O8 (3 mmol),TFA (1 mmol)
MeCN:H2O (1:1), blue LEDs
O
O
+
R
R1
R
8
9
R1
2a
1b
O
O
HO
HO
HO
HO
R1 = H, Me, OMe
28-49
19,
90% 8 h
O
18,
88% 6 h
20,
87% 8 h
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50
51
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53
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60
precursor to
O
O
O
O
histamine subtype 3
receptor (Ref. 12b)
O
O
F
O
O
HO
HO
28
31
, 89%, 8 h
29
, 85%, 8 h
O
30
, 88%, 8 h
O
F
23
, 87% 7 h
22
, 88% 8 h
21
, 85% 7 h
O
O
CF3
O
HO
Cl
O
25
, 83% 9 h
F
Cl
O
O
O
Cl
HO
32
, 80%, 8 h
, 79%, 8 h
33
, 77%, 8 h
O
O
HO
F
O
O
27
, 82% 7 h
24
, 87% 8 h
Cl
HO
26
, 81% 7 h
OMe
O
OMe
O
OMe
O
To expand the utility of this methodology, we directed our
efforts towards probing the reaction scope with 1,4-
naphthoquinones. However, under standard conditions, instead
of 4-hydroxy ketones, it produced alkene-alkyne cycloaddition
product 28 in 89% yields. Notably, 4-membered ring of
cyclobutanes and cyclobutenes are important precursor for the
synthesis of natural products and pharmaceuticals and also
utilized as important intermediate during ring expansion
reactions.18 The 4-membered carbocycles are mostly accessed
via thermal and photochemical [2+2] cycloaddition
reactions.19 The reaction of 1,4-naphthoquinone proceeded
efficiently with halo-substituted (3-fluoro, 4- fluoro, 3,5-
difluoro, and 3-chloro) and electron deficient 4-
trifluoromethyl phenylacetylene to generate cyclobutenes (29-
33) in excellent yields (Scheme 3). Also, 2-methoxy
naphthoquinone appeared to be a suitable coupling partner
with a range of phenylacetylenes viz., phenylacetylene, halo-
substituted (4- fluoro and 2-chloro), electron deficient (2-
trifluoromethyl), alkyl substituted (4-ethyl, 4-tert-butyl, 4-
pentyl) and electron rich 3-methoxy phenylacetylene to afford
carbocycles (34-41) in 62-84% yields. Similarly, 2-methyl
naphthoquinone (menadione) participated in [2+2]
cycloaddition reaction with 2-trifluoromethyl and 3-methoxy
phenylacetylene generating (42-43) in 77-78% yields. As
demonstrated, the reaction of 2-methoxy naphthoquinone also
proceeded efficiently with aliphatic acetylenes like 1-
ethynylcyclohexene, cyclopropylacetylene, 1-pentyne, 1-
octyne and 1-nonyne to produce (44-48) in excellent yields.
Also, reaction of menadione with 1-octyne gave 49 in 79%
yields.
34
, 84%, 8 h
36
35
F
, 81%, 8 h
O
, 79%, 8 h
O
O
CF3
OMe
OMe
OMe
O
O
O
38
, 80%, 8 h
37
, 79%, 8 h
O
39
, 75%, 8 h
O
O
CF3
OMe
O
OMe
OMe
O
O
40
, 63%, 8 h
41
, 62%, 8 h
42
, 78%, 8 h
4
O
O
O
OMe
OMe
OMe
O
O
O
44
, 66%, 8 h
45
, 85%, 8 h
43
, 77%, 8 h
O
O
O
O
OMe
O
47
, 80%, 8 h
O
OMe
O
46
, 89%, 8 h
49
, 79%, 8 h
OMe
O
48
, 83%, 8 h
A recent work by Xia and co-workers21 also presented a
To get an insight about the plausible mechanism of the
reaction, physico-chemical investigations like cyclic
voltammetry (CV) and spectrophotometric dye-degradation
studies were conducted as parallel experiments for
mechanistic support. The dye-degradation study of eosin,
malachite green and Rose Bengal was conducted to confirm
2-
visible light mediated cleavage of SO4 to SO4•−. The CV
studies were also performed to ascertain the thermodynamic
feasibility of the proposed reaction between the
photochemically generated SO4•− and phenylacetylene. The
observed CV plot for phenylacetylene depicts an irreversible
redox behavior with only single oxidation peak current
starting at a potential close to 1.9 V (vs. SCE) and no
2-
the visible light mediated cleavage of SO4 to sulfate radical
anion (SO4•−). These dyes are known to degrade under
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reduction peak. The onset of oxidation peak is close to 1.9 V and axial hydrogens of cyclopropyl and cyclohexene, which
1
2
3
4
5
6
7
8
and it maximizes around 2.4 V (vs. SCE). The results suggest
a single redox system of irreversible nature which in turn
implies a single electron transfer (SET) reaction. The
calculated formal potentials of phenylacetylene (1.9-2.4 vs.
SCE) show that it can be oxidized by the photochemically
unlike other interactions is not of stabilizing nature owing to
lower electronegativity of sp3 carbon bonded hydrogen atom,
due to which steric interactions predominate and invert the
regioselectivity. Notably, the reaction in absence of persulfate
salt didn’t yield desired product.
•−
generated SO4 having a higher reduction potential (2.6 V vs.
SCE).22 Moreover, inhibition of the reaction in presence of
radical-quencher TEMPO also indicates its radical nature
which goes inconformity with the CV studies (See supporting
information for details).
CONCLUSION
In conclusion, we have developed a visible-light mediated
synthesis of 4-hydroxy functionalized ketones using 1,4-
benzoquinones and terminal alkynes. Moreover the 1,4-
naphthoquinones undergo [2+2] alkene-alkyne cycloaddition
with acetylenes to afford 4-membered carbocycles in high
yields. The protocol presents a mild and efficient system
which offers a viable method for generation of 4-hydroxy
benzophenones, aryl-alkyl ketones and carbocycles. Further
applicability of this method is under investigation in our
laboratory.
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44
45
46
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50
51
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57
58
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60
Scheme 4. Plausible mechanism
a) Synthesis of ketones:
2-
blue LEDs
S2O8
OSO3H
[2+2]
cycloaddition
O
OSO3H
-H+
O2
O
OSO3H
SO4
+H+
O2
51
O
50
52
O
EXPERIMENTAL SECTION
O
O
O
O
O
O
O
General Information. All reactions were conducted in oven-
dried glassware. The reactions were irradiated using regular blue
light-emitting diode (LED) array (30 lamps, power density:
40mW/cm2 at 460 nm). Irradiation occurred along the sides at a
uniform distance of 5 cm. 1H and 13C NMR spectra were recorded
on FT-NMR 500 and 400 MHz instruments. Chemical data for
protons are reported in parts per million (ppm) downfield from
tetramethylsilane and are referenced to the residual proton in the
NMR solvent (CDCl3, 7.26 ppm). Carbon nuclear magnetic
resonance spectra (13C NMR) were recorded at 125 MHz or 100
MHz: chemical data for carbons are reported in parts per million
HO
+H+
O
OSO3H
OH
CO2
SO4
O2
55
3
56
OH
O
53
54
b) Synthesis of cyclobutene adducts:
O
SO3H
O
O
O
SO4H
OSO3H
R
R
R
R1
R1
R1
O
O
O
50
28
57
Based on control experiments and literature precedence a
plausible reaction mechanism is proposed (Scheme 4a). The
(ppm,
δ scale) downfield from tetramethylsilane and are
referenced to the carbon resonance of the solvent. Mass spectra
were obtained by using Q-TOF-LC-MS Spectrometer using
electron spray ionization.
reaction possibly initiates by the homolysis of persulfate to
•− 21
SO4
.
As suggested by the redox potentials of
phenylacetylene and sulfate radical anion, and based on earlier
General Procedure for the Synthesis of Ketones. To a 30
mL glass vial was added benzoquinone (1.0 equiv.) in 4 mL
MeCN:H2O (1:1), followed by addition of terminal alkyne (1.2
equiv.), potassium persulfate K2S2O8 (3 equiv.) and trifluoroacetic
acid TFA (1 equiv.). The reaction mixture was then irradiated
with continuous stirring under blue LEDs for a period of 8 h. The
progress of reaction was monitored by TLC. After completion of
reaction, the crude reaction mixture was extracted with ethyl
acetate (10 mL×3) and water (10 mL). The aqueous layers were
then washed with saturated sodium bicarbonate (NaHCO3) (5 mL)
and again extracted with ethyl acetate (10 mL). The combined
organic layers were dried over sodium sulfate (Na2SO4) and
concentrated under vacuum. The crude mixture was purified by
silica gel column chromatography using ethyl acetate/hexane as
solvent system.
•−
reports,23 the SO4 adds to the C-C triple bond of terminal
alkyne, thereby generating transitory vinyl radical adduct 50
which after SET with molecular oxygen produces
comparatively stable intermediate 51. A [2+2] Patterno-Buchi
reaction between intermediate 51 and carbonyl group of
benzoquinone generates a 4-membered oxetene derivative 52
which rearranges via cycloreversion reaction to yield
intermediate 53. Rapid fragmentation of this intermediate to
•−
release SO4
gives an acyl radical intermediate 54.
Subsequent reaction with oxygen radical anion and
protonation assisted by TFA leads to the formation of peracid
intermediate 55. Thereafter, decarboxylation followed by
Keto-enol tautomerism of quinone methide 56 affords the final
product. However with naphthoquinones, the free-radical of
intermediate 50 possibly attacks the C-C double bond of
naphthoquinone leading to the formation of 57, which on loss
of sulfate radical anion gives the cyclobutene 28 (Scheme 4b).
Mechanistically, we believe the predominant formation of syn-
isomers in case of 2-substituted naphthoquinones is possibly
because sulfate part of 50 interacts with the carbonyl oxygen
of naphthoquinone from the less hindered side. The structure
of these cyclobutene adducts were found to be in accordance
with the reported NMR data,24 wherein the coupling constants
(J value) between 1-2 Hz are characteristics of syn-isomer.
However, in case of compound 44 and 45, no coupling was
observed between the H atoms, indicating that these two
products are anti-isomers. This may be because of nature of
axial-axial interaction between methoxy of naphthoquinone
(4-hydroxyphenyl)(phenyl)methanone (3). The
title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol),
phenylacetylene (110 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7
mmol) and TFA (70 µL, 0.9 mmol) and purified by column
chromatography (hexane:EA = 80:20) as yellow solid (161 mg,
o
1
88%), mp 132-135 C. H NMR (400 MHz, CDCl3) δ 7.95 (s,
1H), 7.76 (dd, J = 11.6, 4.9 Hz, 4H), 7.58 (t, J = 7.4 Hz, 1H), 7.48
(t, J = 7.6 Hz, 2H), 6.96 (d , J = 8.7 Hz, 2H); 13C {1H} NMR (100
MHz, CDCl3) δ 197.2, 161.1, 138.0, 133.3(2C), 132.3, 129.9(2C),
129.4, 128.3(2C), 115.5(2C). HRMS (ESI) (m/z): [M+H]+
calculated for C13H11O2, 199.0754; found, 199.0754. The
observed characterization data (1H & 13C) was consistent with that
previously reported in the literature.12
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The Journal of Organic Chemistry
The observed characterization data (1H & 13C) was consistent
(4-hydroxyphenyl)(p-tolyl)methanone (4). The
title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol), 4-
ethynyltoluene (137 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol)
and TFA (70 µL, 0.9 mmol) and purified by column
chromatography (hexane:EA = 80:20) as white solid (171 mg,
87%), mp 174-176 oC. 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J =
8.6 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H),
6.85 (d, J = 8.6 Hz, 2H), 3.30 (s, 1H), 2.38 (s, 3H); 13C {1H}
NMR (125 MHz, CDCl3) δ 196.6, 161.3, 142.9, 135.4, 132.9(2C),
130.1(2C), 129.3, 128.9(2C), 115.2(2C), 21.6. HRMS (ESI)
(m/z): [M+H]+ calculated for C14H13O2, 213.0910; found,
213.0913. The observed characterization data (1H & 13C) was
consistent with that previously reported in the literature.11j
1
2
3
4
5
6
7
8
with that previously reported in the literature.12
(4-fluorophenyl)(4-hydroxyphenyl)methanone (9). The title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-
ethynyl-4-fluorobenzene (129 µL, 1.08 mmol), K2S2O8 (730 mg,
2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by column
1
chromatography (hexane:EA = 78:22) (158 mg, 79%). H NMR
(400 MHz, CDCl3) δ 7.76 (dd, J = 8.4, 5.6 Hz, 2H), 7.69 (d, J =
8.6 Hz, 2H), 7.12 (t, J = 8.6 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H).;
13C {1H} NMR (125 MHz, CDCl3 and MeOD) δ 194.8, 165.1 (d,
J = 253.26 Hz), 161.5, 134.5 (d, J = 2.52 Hz), 132.8, 132.3 (d, J
= 8.82 Hz), 128.9, 115.4, 115.2. HRMS (ESI) (m/z): [M-H]-
calculated for C13H8FO2, 215.0508; found, 215.0529. The
observed characterization data (1H & 13C) was consistent with that
previously reported in the literature.11j
(3-fluorophenyl)(4-hydroxyphenyl)methanone (10). The
title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-ethynyl-3-fluorobenzene (129 µL, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by
column chromatography (hexane:EA = 78:22) (170 mg, 85%).1H
NMR (400 MHz, CDCl3) δ 8.26 – 7.95 (brs, 1H), 7.77 (d, J = 8.7
Hz, 2H), 7.52 (d, J = 7.8 Hz, 1H), 7.48 – 7.41 (m, 2H), 7.29 –
7.23 (m, 1H), 6.97 (d, J = 8.7 Hz, 2H); 13C {1H} NMR (125 MHz,
CDCl3) δ 195.7, 162.4 (d, J = 247.5 Hz), 161.5, 140.1 (d, J =
6.25 Hz), 133.3(2C), 130.1 (d, J = 10.0 Hz), 128.7, 125.6 (d, J =
2.5 Hz), 119.3 (d, J = 21.25 Hz), 116.6 (d, J = 22.5 Hz),
115.7(2C). HRMS (ESI) (m/z): [M+H]+ calculated for C13H10FO2,
217.0659; found, 217.0639. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature.11g
(2-fluorophenyl)(4-hydroxyphenyl)methanone (11). The
title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-ethynyl-2-fluorobenzene (129 µL, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by
column chromatography (hexane:EA = 78:22) (176 mg, 88%).
1H NMR (400 MHz, CDCl3) δ 7.77 (t, J = 12.2 Hz, 2H), 7.57 –
7.42 (m, 2H), 7.26 (m, 1H), 7.17 (t, J = 9.2 Hz, 1H), 6.99 – 6.89
(m, 2H); 13C {1H} NMR (125 MHz, CDCl3) δ 193.5, 161.9, 159.8
(d, J = 250 Hz), 133.0(2C), 132.9 (d, J = 5.0 Hz), 130.4 (d, J =
3.75 Hz), 129.4, 127.1 (d, J = 15 Hz), 124.3 (d, J = 3.75 Hz),
116.3 (d, J = 22.5 Hz), 115.7(2C). HRMS (ESI) (m/z): [M+H]+
calculated for C13H10FO2, 217.0659; found, 217.0640.
(3,5-difluorophenyl)(4-hydroxyphenyl)methanone (12):
The title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-ethynyl-3,5-difluorobenzene (128 µl, 1.08 mmol),
K2S2O8 (730 mg, 2.7 mmol) and TFA (70 µl, 0.9 mmol) and
purified by column chromatography (hexane:EA = 75:25) as
white solid (184 mg, 85%), mp 130-132 oC. 1H NMR (400 MHz,
CDCl3) δ 7.70 (d, J = 8.7 Hz, 2H), 7.24 – 7.18 (m, 2H), 6.98 (m,
1H), 6.88 (d, J = 8.7 Hz, 2H); 13C {1H}NMR (125 MHz, CDCl3)
δ 193.4, 162.5 (dd, J = 250, 11.3 Hz, 2C), 162.1, 141.3 (t, J = 7.7
Hz), 133.0, 127.9, 115.5, 112.6 (dd, J = 19.9, 6.5 Hz), 107.1 (t, J
= 25.3 Hz). HRMS (ESI) (m/z): [M-H]- calculated for C13H7F2O2,
233.0420; found, 233.0417.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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31
32
33
34
35
36
37
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47
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60
(4-hydroxyphenyl)(4-propylphenyl)methanone (5). The title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-
ethyl-4-propylbenzene (155 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7
mmol) and TFA (70 µL, 0.9 mmol) and purified by column
chromatography (hexane:EA = 82:18) as white solid (199 mg,
90%), mp 122-124 oC. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.6 Hz, 2H), 7.69 (t, J = 8.3 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H),
6.96 (d, J = 8.7 Hz, 2H), 2.69 – 2.63 (m, 2H), 1.68 (dd, J = 15.1,
7.5 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H); 13C {1H} NMR (125 MHz,
CDCl3) δ 197.1, 161.1, 147.9, 135.5, 133.1(2C), 130.2(2C),
129.5, 128.4(2C), 115.5(2C), 38.1, 24.9, 13.8. HRMS (ESI)
(m/z): [M+H]+ calculated for C16H17O2, 241.1223; found,
241.1226.
(4-hydroxyphenyl)(4-pentylphenyl)methanone (6). The title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-
ethyl-4-pentylbenzene (185 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7
mmol) and TFA (70 µL, 0.9 mmol) and purified by column
chromatography (hexane:EA = 80:20) as white solid (218 mg,
88%), mp 128-130 oC. 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
8.6 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H),
6.95 (d, J = 8.6 Hz, 2H), 2.70 – 2.65 (m, 2H), 1.65 (dd, J = 15.0,
7.4 Hz, 2H), 1.37 – 1.31 (m, 4H), 0.90 (t, J = 6.9 Hz, 3H); 13C
{1H} NMR (125 MHz, CDCl3) δ 197.0, 160.9, 148.1, 135.4,
133.1(2C), 130.2(2C), 129.7, 128.4(2C), 115.4(2C), 36.0, 31.5,
30.9, 22.5, 14.0. HRMS (ESI) (m/z): [M+H]+ calculated for
C18H21O2, 269.1536; found, 269.1541.
(4-(tert-butyl)phenyl)(4-hydroxyphenyl)methanone (7). The
title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 4-tert-butylphenylacetylene (170 µL, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by
column chromatography (hexane:EA = 82:18) as white solid (199
mg, 85%), mp 103-105 oC. 1H NMR (400 MHz, CDCl3) δ 7.79 (d,
J = 8.6 Hz, 2H), 7.72 (d, J = 8.4 Hz, 2H), 7.49 (d, J = 8.4 Hz,
2H), 6.93 (d, J = 8.6 Hz, 2H), 1.36 (s, 9H); 13C {1H} NMR (125
MHz, CDCl3) δ 196.3, 160.3, 155.9, 135.3, 133.0(2C), 130.1,
130.0(2C), 125.2(2C), 115.3(2C), 35.1, 31.2(3C). HRMS (ESI)
(m/z): [M+H]+ calculated for C17H19O2, 255.1380; found,
255.1375. The observed characterization data (1H & 13C) was
consistent with that previously reported in the literature.12
(4-bromophenyl)(4-hydroxyphenyl)methanone (8).
The title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-ethynyl-4-bromobenzene (195 µl, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µl, 0.9 mmol) and purified by
column chromatography (hexane:EA = 75:25) as white solid
(4-chlorophenyl)(4-hydroxyphenyl)methanone (13). The
title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-chloro-4-ethynylbenzene (128 µL, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by
column chromatography (hexane:EA = 78:22) as white solid
(193 mg, 90%), mp 179-181 oC. 1H NMR (400 MHz, CDCl3 and
MeOD) δ 7.54 (dd, J = 13.1, 8.6 Hz, 5H), 7.30 (d, J = 8.4 Hz,
1H), 6.74 (s, 2H); 13C {1H} NMR (125 MHz, CDCl3 and MeOD)
o
(208 mg, 81%), mp 190-193 C. 1H NMR (400 MHz, CDCl3) δ
7.78 – 7.73 (m, 2H), 7.63 (s, 4H), 6.94-6.89 (m, 2H); 13C
{1H}NMR (125 MHz, CDCl3) δ 194.7, 160.0, 136.9, 132.9(2C),
131.6(2C), 131.3(2C), 129.6, 127.0, 115.3(2C); HRMS (ESI) m/z:
[M-H]- calculated for C13H8BrO2, 274.9713; found, 274.9717.
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δ 195.4, 162.1, 138.3, 136.6, 132.9(2C), 131.1(2C), 128.5(2C),
mmol) and TFA (70 µL, 0.9 mmol) and purified by column
1
2
3
4
5
6
7
8
128.3, 115.3(2C). HRMS (ESI) (m/z): [M+H]+ calculated for
C13H10ClO2, 233.0364; found, 233.0353. The observed
characterization data (1H & 13C) was consistent with that
previously reported in the literature.12
chromatography (hexane:EA = 90:10) as yellow solid (132 mg,
88%), mp 105-107 oC. 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J
= 18.3 Hz, 1H), 6.92 (d, J = 8.7 Hz, 2H), 2.66 (m, 1H), 1.25 (m,
2H), 1.04 (m, 2H); 13C {1H} NMR (125 MHz, CDCl3) δ 201.0,
161.2, 140.0, 130.8(2C), 130.3, 115.5, 17.0, 11.8(2C). HRMS
(ESI) m/z: [M+H]+ calculated for C10H11O2, 163.0754; found,
163.0754. The observed characterization data (1H & 13C) was
consistent with that previously reported in the literature.11b
(3-chlorophenyl)(4-hydroxyphenyl)methanone (14). The
title compound was prepared according to the general
procedure described above using 1,4-benzoquinone (100 mg, 0.9
mmol), 1-chloro-3-ethynylbenzene (128 µL, 1.08 mmol), K2S2O8
(730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol) and purified by
column chromatography (hexane:EA = 78:22) as white solid
1-(4-hydroxyphenyl)butan-1-one (19). The title compound
was prepared according to the general procedure described
above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-pentyne
(61 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70
µL, 0.9 mmol) and purified by column chromatography
(hexane:EA = 88:12) (137 mg, 90%). 1H NMR (400 MHz,
CDCl3) δ 7.93 (d, J = 8.7 Hz, 2H), 6.96 (d, J = 8.7 Hz, 2H), 2.94
9
o
1
(187 mg, 87%), mp 168-170 C. H NMR (400 MHz, CDCl3 and
MeOD) δ 7.69 (dd, J = 14.1, 5.1 Hz, 3H), 7.58 (d, J = 7.6 Hz,
1H), 7.55 – 7.50 (m, 1H), 6.89 (d, J = 8.7 Hz, 3H); 13C {1H}
NMR (125 MHz, CDCl3 and MeOD) δ 195.0, 162.3, 140.0,
134.3, 133.0(2C), 131.8, 129.6, 129.4, 128.1, 127.7, 115.3(2C).
HRMS (ESI) m/z: [M+H]+ calculated for C13H10ClO2, 233.0364;
found, 233.0362. The observed characterization data (1H & 13C)
was consistent with that previously reported in the literature.11h
(4-hydroxyphenyl)(4-(trifluoromethyl)phenyl)methanone
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
30
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59
60
(t, J = 7.4 Hz, 2H), 1.85 – 1.72 (m, 2H), 1.11 – 0.97 (m, 3H); 13
C
{1H} NMR (125 MHz, CDCl3) δ 201.0, 161.2, 130.9(2C), 129.5,
115.6(2C), 40.3, 18.3, 13.9. HRMS (ESI) (m/z): [M+H]+
calculated for C10H13O2, 165.0910; found, 165.0895. The
observed characterization data (1H & 13C) was consistent with that
previously reported in the literature.12
(15). The title compound was prepared according to the
general procedure described above using 1,4-benzoquinone (100
mg, 0.9 mmol), 4-trifluoromethylphenylacetylene (183 µL, 1.08
mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70 µL, 0.9 mmol)
and purified by column chromatography (hexane:EA = 70:30)
1-(4-hydroxyphenyl)pentan-1-one (20). The title compound
was prepared according to the general procedure described
above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-hexyne (88
µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70 µL,
1
(224 mg, 91%). H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.1
Hz, 2H), 7.72 – 7.66 (m, 4H), 6.87 (d, J = 8.5 Hz, 2H); 13C {1H}
NMR (125 MHz, CDCl3) δ 195.4, 162.3, 141.5, 133.1(2C),
129.7(2C), 128.1, 125.2 (q, J = 11.25 Hz, 2C), 123.7 (q, J =
271.25 Hz), 115.5(2C). HRMS (ESI) (m/z): [M-H]- calculated for
C14H8F3O2, 265.0476; found, 265.0496. The observed
characterization data (1H & 13C) was consistent with that
previously reported in the literature.11j
0.9 mmol) and
purified
by
column
chromatography
(hexane:EA = 88:12) as yellow solid (143 mg, 87%), mp 62-63
oC. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.7 Hz, 2H), 6.95
(d, J = 8.7 Hz, 2H), 2.99 – 2.88 (m, 2H), 1.71 (dt, J = 15.2, 7.5
Hz, 2H), 1.41 (dt, J = 14.9, 7.4 Hz, 2H), 0.93 (t, J = 7.3 Hz, 3H);
13C {1H} NMR (125 MHz, CDCl3) δ 201.5, 161.4, 140.7, 131.0,
129.3, 122.4, 115.6, 38.1, 27.1, 22.5, 13.9; HRMS (ESI) m/z:
[M+H]+calculated for C11H15O2, 179.1067; found, 179.1067. The
observed characterization data (1H & 13C) was consistent with that
previously reported in the literature.12
1-(4-hydroxyphenyl)hexan-1-one (21). The title compound
was prepared according to the general procedure described
above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-heptyne
(104 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70
µL, 0.9 mmol) and purified by column chromatography
(hexane:EA = 88:12) as yellow solid (151 mg, 85%), mp 61-63
oC. 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.5 Hz, 2H), 6.93
(t, J = 9.0 Hz, 2H), 2.96 – 2.88 (m, 2H), 1.72 (dd, J = 14.6, 7.3
Hz, 2H), 1.37 – 1.31 (m, 4H), 0.89 (t, J = 6.9 Hz, 3H); 13C {1H}
NMR (125 MHz, CDCl3) δ 201.5, 161.4, 131.0(2C), 129.4,
115.6(2C), 38.4, 31.6, 24.7, 22.5, 13.9. HRMS (ESI) m/z:
[M+H]+ calculated for C12H17O2, 193.1223; found, 193.1207.
The observed characterization data (1H & 13C) was consistent
with that previously reported in the literature.11e
(4-hydroxy-3-methylphenyl)(phenyl)methanone (16). The
title compound was prepared according to the general
procedure described above using methyl-p-benzoquinone (100
mg, 0.8 mmol), phenylacetylene (98 µL, 0.96 mmol), K2S2O8
(649 mg, 2.4 mmol) and TFA (61 µL, 0.8 mmol) and purified by
column chromatography as white solid (hexane:EA = 80:20)
(146 mg, 84%), mp 163-165 oC. 1H NMR (400 MHz, CDCl3 and
MeOD) δ 7.78 – 7.70 (m, 2H), 7.65 (s, 1H), 7.60 – 7.53 (m, 2H),
7.49 – 7.44 (m, 2H), 6.84 (d, J = 8.4 Hz, 1H), 2.26 (s, 3H); 13C
{1H} NMR (125 MHz, CDCl3 and MeOD ) δ 196.8, 159.9, 138.5,
133.8, 131.8, 130.6, 130.0, 129.7, 128.8, 128.3, 128.1, 124.7,
114.2, 15.9; HRMS (ESI) m/z: [M+H]+ calculated for C14H13O2,
213.0910; found, 213.0908. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature.12
(3-chloro-4-hydroxyphenyl)(phenyl)methanone (17). The
title compound was prepared according to the general
procedure described above using 2-chloro-1,4-benzoquinone (100
mg, 0.7 mmol), phenylacetylene (86 µL, 0.84 mmol), K2S2O8
(568 mg, 2.1 mmol) and TFA (53 µL, 0.7 mmol) and purified by
column chromatography (hexane:EA = 78:22) as white solid
1-(4-hydroxyphenyl)heptan-1-one (22). The title compound
was prepared according to the general procedure described
above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-octyne
(119 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70
µL, 0.9 mmol) and purified by column chromatography
(hexane:EA = 90:10) as yellow solid (168 mg, 88%), mp 92-93
o
(147 mg, 90%), mp 180-181 C. 1H NMR (400 MHz, CDCl3) δ
7.91 – 7.79 (m, 1H), 7.73 (ddd, J = 6.2, 4.3, 2.0 Hz, 2H), 7.67 –
7.56 (m, 2H), 7.53 – 7.46 (m, 2H), 7.02 (dd, J = 8.4, 3.6 Hz, 1H);
13C {1H} NMR (125 MHz, CDCl3 and MeOD) δ 195.4, 157.3,
137.6, 132.6, 132.3, 130.8, 129.7, 129.6(2C), 128.3(2C), 120.8,
116.0. HRMS (ESI) m/z: [M+H]+ calculated for C13H10ClO2,
233.0364; found, 233.0353. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature .11a
cyclopropyl(4-hydroxyphenyl)methanone (18). The title
compound was prepared according to the general procedure
described above using 1,4-benzoquinone (100 mg, 0.9 mmol),
cyclopropylacetylene (71 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7
1
oC. H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.6 Hz, 2H), 6.95
(d, J = 8.6 Hz, 2H), 2.93 (t, J = 7.5 Hz, 2H), 1.71 (dd, J = 14.9,
7.6 Hz, 2H), 1.36 (dd, J = 13.3, 5.2 Hz, 2H), 1.32 – 1.27 (m, 4H),
0.87 (t, J = 7.0 Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ
201.5, 161.3, 131.0(2C), 129.3, 115.6(2C), 38.4, 31.6, 29.1, 25.0,
22.5, 14.0. HRMS (ESI) m/z: [M+H]+ calculated for C13H19O2,
207.1380; found, 207.1360. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature.12
1-(4-hydroxyphenyl)octan-1-one (23). The title compound
was prepared according to the general procedure described
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above using 1,4-benzoquinone (100 mg, 0.9 mmol), 1-nonyne
(m/z): [M+H]+ calculated for C12H16ClO2, 227.0833; found,
1
2
3
4
5
6
7
8
(134 µL, 1.08 mmol), K2S2O8 (730 mg, 2.7 mmol) and TFA (70
µL, 0.9 mmol) and purified by column chromatography
(hexane:EA = 90:10) as yellow solid (177 mg, 87%), mp 60-62
227.0816.
General Procedure for the Synthesis of Cyclobutenes. To
a 30 mL glass vial was added 1,4-naphthoquinone (1.0 equiv.) in
4 mL MeCN:H2O (1:1), followed by addition of terminal alkyne
(2 equiv.), potassium persulfate K2S2O8 (3 equiv.) and
trifluoroacetic acid TFA (1 equiv.). The reaction mixture was then
irradiated with continuous stirring under blue LEDs for a period
of 8 h. The progress of reaction was monitored by TLC. After
completion of reaction, the crude reaction mixture was extracted
with ethyl acetate (10 mL×3) and water (10 mL). The aqueous
layers were washed with saturated sodium bicarbonate (NaHCO3)
(5 mL) and again extracted with ethyl acetate (10 mL). The
combined organic layers were dried over sodium sulfate (Na2SO4)
and concentrated under vacuum. The crude mixture was purified
by silica gel column chromatography using EtOAc/Hexane as
solvent system
1
oC. H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 2H), 6.94
(d, J = 8.3 Hz, 2H), 2.92 (t, J = 7.5 Hz, 2H), 1.78 – 1.66 (m, 2H),
1.34 – 1.23 (m, 8H), 0.86 (t, J = 6.8 Hz, 3H); 13C {1H} NMR
(125 MHz, CDCl3) δ 201.3, 161.3, 140.7, 131.0, 129.4, 116.1,
115.6, 38.4, 31.7, 29.4, 29.1, 25.0, 22.6, 14.1. HRMS (ESI) m/z:
[M+H]+ calculated for C14H21O2, 221.1536; found, 221.1532.
The observed characterization data (1H & 13C) was consistent
with that previously reported in the literature.11d
1-(3-chloro-4-hydroxyphenyl)heptan-1-one (24). The title
compound was prepared according to the general procedure
described above using 2-chloro-1,4-benzoquinone (100 mg, 0.7
mmol), 1-octyne (92 µL, 0.84 mmol), K2S2O8 (568 mg, 2.1
mmol) and TFA (53 µL, 0.7 mmol) and purified by column
chromatography (hexane:EA = 86:14) (147 mg, 87%). 1H NMR
(400 MHz, CDCl3) δ 8.01 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 8.5,
2.1 Hz, 1H), 7.11 – 7.07 (m, 1H), 2.93 – 2.89 (m, 2H), 1.73 (dd, J
= 14.1, 6.7 Hz, 2H), 1.39 – 1.30 (m, 6H), 0.91 (dd, J = 9.0, 4.8
Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 198.4, 155.4,
131.0, 129.7, 129.0, 120.5, 116.1, 38.3, 31.6, 29.0, 24.4, 22.5,
14.0. HRMS (ESI) (m/z): [M-H]- calculated for C13H16ClO2,
239.0839; found, 239.0864.
1-(4-hydroxy-3-methylphenyl)heptan-1-one (25). The title
compound was prepared according to the general procedure
described above using methyl-p-benzoquinone (100 mg, 0.8
mmol), 1-octyne (106 µL, 0.96 mmol), K2S2O8 (649 mg, 2.4
mmol) and TFA (61 µL, 0.8 mmol) and purified by column
chromatography (hexane:EA = 90:10) (150 mg, 83%). 1H NMR
(400 MHz, CDCl3) δ 7.81 (d, J = 1.5 Hz, 1H), 7.76 (dd, J = 8.3,
2.1 Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 2.95 – 2.91 (m, 2H), 2.32
(s, 3H), 1.77 – 1.71 (m, 2H), 1.38 – 1.29 (m, 6H), 0.91 (t, J = 7.0
Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 200.4, 158.7,
131.7, 129.9, 128.3, 124.2, 114.7, 38.3, 31.7, 29.1, 24.8, 22.5,
15.8, 14.0. HRMS (ESI) (m/z): [M+H]+ calculated for C14H21O2,
221.1536; found, 221.1505. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature.11e
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18
19
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24
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33
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36
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1-phenyl-2a,8a-dihydrocyclobuta[b]naphthalene-3,8-dione
(28). The title compound was prepared according to the
general procedure described above using 1,4-naphthoquinone
(100 mg, 0.6 mmol), phenylacetylene (122 µL, 1.2 mmol),
K2S2O8 (486 mg, 1.8 mmol) and TFA (46 µL, 0.6 mmol) and
purified by column chromatography (hexane:EA = 95:05) (147
1
mg, 89%). H NMR (400 MHz, CDCl3) δ 8.13 – 8.06 (m, 1H),
8.03 (dd, J = 7.4, 1.6 Hz, 1H), 7.77 – 7.70 (m, 2H), 7.58 – 7.53
(m, 2H), 7.39 – 7.28 (m, 3H), 6.57 (d, J = 0.9 Hz, 1H), 4.53 (d, J
= 3.8 Hz, 1H), 4.14 (dd, J = 3.7, 1.6 Hz, 1H).; 13C {1H} NMR
(125 MHz, CDCl3) δ 195.7, 195.7, 149.2, 134.6, 134.6, 133.9,
133.7, 132.0, 129.2, 128.6, 128.6(2C), 127.8, 127.6, 125.5(2C),
52.2, 49.1. HRMS (ESI) (m/z): [M+H]+ calculated for C18H13O2,
261.0910; found, 261.0896.
1-(3-fluorophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-
3,8-dione (29). The title compound was prepared according
to
the
general procedure described above using 1,4-
naphthoquinone (100 mg, 0.6 mmol), 1-ethynyl-3-fluorobenzene
(144 µL, 1.2 mmol), K2S2O8 (486 mg, 1.8 mmol) and TFA (46
µL, 0.6 mmol) and purified by column chromatography
(hexane:EA = 94:06) as brown semi-solid (149 mg, 85%). H
NMR (400 MHz, CDCl3) δ 8.13 – 8.09 (m, 1H), 8.08 – 8.04 (m,
1
1H), 7.80 – 7.72 (m, 2H), 7.40 – 7.26 (m, 3H), 7.00 (m, 1H), 6.61
1-(4-hydroxy-3-methylphenyl)hexan-1-one (26). The title
compound was prepared according to the general procedure
described above using methyl-p-benzoquinone (100 mg, 0.8
mmol), 1-heptyne (92 µL, 0.96 mmol), K2S2O8 (649 mg, 2.4
mmol) and TFA (61 µL, 0.8 mmol) and purified by column
(d, J = 1.1 Hz, 1H), 4.51 (d, J = 3.8 Hz, 1H), 4.16 (m, 1H); 13
C
{1H} NMR (125 MHz, CDCl3) δ 195.3, 195.3, 162.8 (d, J =
246.25 Hz), 147.9 (d, J = 2.5 Hz), 134.7 (d, J = 6.25 Hz, 2C),
133.9 (d, J = 8.75 Hz), 133.9 (d, J = 27.5 Hz), 130.2 (d, J = 8.75
Hz, 2C), 130.1(2C), 127.5 (d, J = 28.75 Hz, 2C), 121.4 (d, J = 2.5
Hz), 116.2 (d, J = 21.25 Hz), 112.4 (d, J = 22.5 Hz), 52.1, 49.1.
HRMS (ESI) m/z: [M+H]+ calculated for C18H12FO2, 279.0816;
found, 279.0800.
1
chromatography (hexane:EA = 88:12) (137 mg, 81%). H NMR
(400 MHz, CDCl3) δ 7.81 (d, J = 1.5 Hz, 1H), 7.75 (dd, J = 8.4,
2.1 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 2.96 – 2.91 (m, 2H), 2.32
(s, 3H), 1.79 – 1.71 (m, 2H), 1.38 (td, J = 7.1, 3.6 Hz, 4H), 0.92
(t, J = 7.0 Hz, 3H); 13C {1H} NMR (125 MHz, CDCl3) δ 200.8,
159.0, 131.7, 129.7, 128.3, 124.3, 114.8, 38.3, 31.6, 24.6, 22.5,
15.9, 13.9. HRMS (ESI) (m/z): [M-H]- calculated for C13H17O2,
205.1229; found, 205.1252. The observed characterization data
(1H & 13C) was consistent with that previously reported in the
literature.11e
1-(4-fluorophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-
3,8-dione (30). The title compound was prepared according
to
the
general procedure described above using 1,4-
naphthoquinone (100 mg, 0.6 mmol), 1-ethynyl-4-fluorobenzene
(144 µL, 1.2 mmol), K2S2O8 (486 mg, 1.8 mmol) and TFA (46
µL, 0.6 mmol) and purified by column chromatography
1
(hexane:EA = 94:06) as dark red semi-solid (154 mg, 88%). H
1-(3-chloro-4-hydroxyphenyl)hexan-1-one (27). The title
compound was prepared according to the general procedure
described above using 2-chloro-1,4-benzoquinone (100 mg, 0.7
mmol), 1-heptyne (81 µL, 0.84 mmol), K2S2O8 (568 mg, 2.1
mmol) and TFA (53 µL, 0.7 mmol) and purified by column
NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.0 Hz, 1H), 8.04 (d, J =
7.0 Hz, 1H), 7.78 – 7.70 (m, 2H), 7.54 (dd, J = 8.3, 5.6 Hz, 2H),
7.03 (t, J = 8.6 Hz, 2H), 6.50 (s, 1H), 4.50 (d, J = 3.6 Hz, 1H),
4.13 (s, 1H); 13C {1H} NMR (125 MHz, CDCl3) δ 195.5(2C),
163.1 (d, J = 248.75 Hz), 148.0, 134.7 (d, J = 12.5 Hz, 2C), 133.8
(d, J = 20.0 Hz), 128.3 (d, J = 3.75 Hz), 127.9 (d, J = 2.5 Hz),
127.8(2C), 127.6 (d, J = 3.75 Hz, 2C), 127.5, 115.7 (d, J = 21.25,
2C), 52.1, 48.9. HRMS (ESI) m/z: [M+H]+ calculated for
C18H12FO2, 279.0816; found, 279.0794.
1
chromatography (hexane:EA = 86:14) (130 mg, 82%). H NMR
(400 MHz, CDCl3) δ 8.01 (d, J = 2.1 Hz, 1H), 7.84 (dd, J = 8.5,
2.1 Hz, 1H), 7.11 – 7.07 (m, 1H), 2.93 – 2.89 (m, 2H), 1.78 – 1.70
(m, 2H), 1.40 – 1.35 (m, 4H), 0.93 (dd, J = 9.4, 4.6 Hz, 3H); 13C
{1H} NMR (125 MHz, CDCl3) δ 198.4, 155.5, 131.0, 129.7,
129.0, 120.5, 116.1, 38.3, 31.5, 24.2, 22.5, 13.9. HRMS (ESI)
1-(3,5-difluorophenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (31). The title
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Page 8 of 12
compound was prepared according to the general procedure
column chromatography (hexane:EA = 92:08) (198 mg, 79%). 1H
1
2
3
4
5
6
7
8
described above using 1,4-naphthoquinone (100 mg, 0.6 mmol),
1-ethynyl-3,5-difluorobenzene (165 µL, 1.2 mmol), K2S2O8 (486
mg, 1.8 mmol) and TFA (46 µL, 0.6 mmol) and purified by
column chromatography (hexane:EA = 94:06) as pale yellow
NMR (400 MHz, CDCl3) δ 8.13 – 8.10 (m, 1H), 8.06 – 8.01 (m,
1H), 7.82 – 7.74 (m, 2H), 7.64 – 7.57 (m, 2H), 7.09 – 7.02 (m,
2H), 6.71 (d, J = 1.5 Hz, 1H), 4.16 (s, 1H), 3.50 (s, 3H).; 13C {1H}
NMR (125 MHz, CDCl3) δ 195.6, 194.7, 163.3 (d, J = 250 Hz),
149.2, 134.7 (d, J = 46.6 Hz), 133.2 (d, J = 17.6 Hz), 130.8 (d, J =
1.3 Hz), 128.2 (d, J = 16.4 Hz), 128.2, 127.2, 126.8 (d, J = 2.52
Hz), 115.8 (d, J = 22.7), 85.7, 55.3, 53.4. HRMS (ESI) (m/z):
[M+H]+ calculated for C19H14FO3, 309.0921; found, 309.0900.
1-(2-chlorophenyl)-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (36). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-chloro-2-ethynylbenzene (136 µL, 1 mmol),
K2S2O8 (405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and
purified by column chromatography (hexane:EA = 94:06) as
yellow semi-solid (139 mg, 81%). 1H NMR (400 MHz, CDCl3) δ
8.29 – 7.83 (m, 3H), 7.77 (m, 2H), 7.40 – 7.31 (m, 2H), 7.25 (m,
1H), 7.18 (d, J = 1.7 Hz, 1H), 4.22 (d, J = 3.3 Hz, 1H), 3.50 (s,
3H); 13C {1H} NMR (125 MHz, CDCl3) δ 195.2, 194.6, 146.9,
138.6, 134.9, 134.5, 133.4, 133.3, 133.3, 130.4, 130.4, 129.9,
128.3, 128.3, 127.1, 127.1, 86.5, 56.4, 53.2. HRMS (ESI) m/z:
[M+H]+ calculated for C19H14ClO3, 325.0626; found, 325.0619.
8a-methoxy-1-(2-(trifluoromethyl)phenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (37). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 2-trifluoromethylphenylacetylene (170 µL, 1 mmol),
K2S2O8 (405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and
purified by column chromatography (hexane:EA = 91:09) as
yellow semi-solid (150 mg, 79%). 1H NMR (400 MHz, CDCl3) δ
8.17 – 7.98 (m, 3H), 7.78 (m, 2H), 7.65 (dd, J = 14.1, 7.7 Hz,
2H), 7.44 (t, J = 7.7 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 4.17 (d, J =
1.6 Hz, 1H), 3.51 (s, 3H).; 13C {1H} NMR (125 MHz, CDCl3) δ
195.0, 194.7, 145.7, 139.0 (q, J = 5.0 Hz), 134.9(2C), 134.6(2C),
133.3, 133.3, 132.2, 130.6, 129.0, 128.2, 127.1, 126.3 (q, J = 6.25
Hz), 125.5 (q, J = 228.75 Hz), 86.7, 55.7, 53.4. HRMS (ESI) m/z:
[M+H]+ calculated for C20H14F3O3, 359.0890; found, 359.0903.
1-(4-ethylphenyl)-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (38). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-ethyl-4-ethynylbenzene (130 µL, 1 mmol), K2S2O8
(405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by
column chromatography (hexane:EA = 92:08) as brown semi-
solid (135 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J =
7.6, 1.1 Hz, 1H), 8.02 (dd, J = 7.6, 1.1 Hz, 1H), 7.80 – 7.71 (m,
2H), 7.52 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 6.71 (d, J
= 1.6 Hz, 1H), 4.17 (d, J = 1.3 Hz, 1H), 3.51 (s, 3H), 2.65 (q, J =
7.6 Hz, 2H), 1.23 (t, J = 7.6 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 195.9, 194.8, 150.3, 146.1, 134.7, 134.4, 133.3, 133.3,
130.3, 128.3, 128.2(2C), 128.1, 127.0, 126.1, 85.9, 55.3, 53.2,
30.9, 28.8, 15.3. HRMS (ESI) m/z: [M+H]+ calculated for
C21H19O3, 319.1329; found, 319.1322.
1
semi-solid (148 mg, 79%). H NMR (400 MHz, CDCl3) δ 8.14 –
8.05 (m, 2H), 7.76 (m, 2H), 7.13 – 7.06 (m, 2H), 6.75 (m, 1H),
6.64 (d, J = 1.2 Hz, 1H), 4.48 (d, J = 3.7 Hz, 1H), 4.16 (dd, J =
3.8, 1.7 Hz, 1H); 13C {1H} NMR (125 MHz, CDCl3) δ 194.8,
194.8, 163.1 (dd, J = 250.1, 12.1 Hz, 2C), 146.9, 134.8 (d, J =
10.0 Hz, 2C), 133.7 (d, J = 20.2 Hz, 2C) , 131.4 (2C), 127.8 (d, J
= 27.3 Hz, 2C), 108.6 (dd, J = 19.9, 6.3 Hz, 2C), 104.6 (t, J =
25.4 Hz), 52.0, 49.0; HRMS (ESI) m/z: [M+H]+ calculated for
C18H11F2O2, 297.0722; found, 297.0725.
9
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17
18
19
20
21
22
23
24
25
26
27
28
29
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31
32
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34
35
36
37
38
39
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44
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48
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58
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1-(3-chlorophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-
3,8-dione (32). The title compound was prepared according
to
the
general procedure described above using 1,4-
naphthoquinone (100 mg, 0.6 mmol), 1-chloro-3-ethynylbenzene
(163 µL, 1.2 mmol), K2S2O8 (486 mg, 1.8 mmol) and TFA (46
µL, 0.6 mmol) and purified by column chromatography
1
(hexane:EA = 95:05) as dark red semi-solid (148 mg, 80%). H
NMR (400 MHz, CDCl3) δ 8.12 – 8.07 (m, 1H), 8.07 – 8.02 (m,
1H), 7.78 – 7.71 (m, 2H), 7.52 (s, 1H), 7.47 – 7.42 (m, 1H), 7.31
– 7.25 (m, 2H), 6.60 (d, J = 1.1 Hz, 1H), 4.50 (d, J = 3.7 Hz, 1H),
4.14 (dd, J = 3.7, 1.6 Hz, 1H); 13C {1H} NMR (125 MHz, CDCl3)
δ 195.2, 195.1, 147.7, 134.7(2C), 134.6, 133.9, 133.7, 133.6,
130.2, 129.9, 129.2, 127.8, 127.6, 125.5, 123.8, 52.1, 49.1. HRMS
(ESI) m/z: [M+H]+ calculated for C18H12ClO2, 295.0520; found,
295.0498.
1-(2-(trifluoromethyl)phenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (33). The title
compound was prepared according to the general procedure
described above using 1,4-naphthoquinone (100 mg, 0.6 mmol),
2-trifluoromethylphenylacetylene (204 µL, 1.2 mmol), K2S2O8
(486 mg, 1.8 mmol) and TFA (46 µL, 0.6 mmol) and purified by
column chromatography (hexane:EA = 91:09) as whitish yellow
1
semi-solid (159 mg, 77%). H NMR (400 MHz, CDCl3) δ 8.14
(dd, J = 7.6, 1.0 Hz, 1H), 8.02 (dd, J = 7.5, 1.2 Hz, 1H), 7.78 (m,
3H), 7.68 (d, J = 7.9 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.44 (t, J =
7.7 Hz, 1H), 6.71 (s, 1H), 4.63 (d, J = 3.7 Hz, 1H), 4.18 (dd, J =
3.7, 1.5 Hz, 1H); 13C {1H} NMR (125 MHz, CDCl3) δ 195.2,
195.1, 145.2, 136.0 (q, J = 5.0 Hz), 134.7(2C), 134.6(2C), 133.8
(d. J = 27.5 Hz), 132.0, 130.0(2C), 128.8, 127.7, 127.6, 126.4 (q,
J = 6.25 Hz), 126.2 (q, J = 256.25 Hz), 53.3, 49.1. HRMS (ESI)
m/z: [M+H] calculated for C19H12F3O2, 329.0784; found,
329.0771.
8a-methoxy-1-phenyl-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (34). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), phenylacetylene (102 µL, 1 mmol), K2S2O8 (405 mg,
1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by column
chromatography (hexane:EA = 93:07) as pale yellow semi-solid
1
(126 mg, 84%). H NMR (400 MHz, CDCl3) δ 8.08 (dd, J = 7.6,
1.3 Hz, 1H), 8.00 (dd, J = 7.6, 1.3 Hz, 1H), 7.78 – 7.70 (m, 2H),
7.58 (dd, J = 8.0, 1.3 Hz, 2H), 7.37 – 7.30 (m, 3H), 6.75 (d, J =
1.6 Hz, 1H), 4.15 (d, J = 1.5 Hz, 1H), 3.48 (s, 3H).; 13C {1H}
NMR (100 MHz, CDCl3) δ 195.7, 194.7, 150.4, 134.7, 134.4,
133.4, 131.5, 130.6, 129.6, 128.7, 128.3, 127.1, 126.1, 85.9, 55.4,
53.3, 29.7. HRMS (ESI) m/z: [M+H]+ calculated for C19H15O3,
291.1016; found, 291.1005.
1-(4-(tert-butyl)phenyl)-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (39). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 4-tert-butylphenylacetylene (158 µL, 1 mmol),
K2S2O8 (405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and
purified by column chromatography (hexane:EA = 92:08) as
brown semi-solid (138 mg, 75%). 1H NMR (400 MHz, CDCl3) δ
8.10 (dd, J = 7.6, 1.3 Hz, 1H), 8.02 (dd, J = 7.6, 1.3 Hz, 1H), 7.79
– 7.71 (m, 2H), 7.54 (d, J = 8.4 Hz, 2H), 7.41 – 7.38 (m, 2H),
6.72 (d, J = 1.7 Hz, 1H), 4.17 (d, J = 1.6 Hz, 1H), 3.51 (s, 3H),
1.32 (s, 9H).; 13C {1H} NMR (125 MHz, CDCl3) δ 195.9, 194.8,
152.9, 150.3, 134.7, 134.4, 133.3, 133.3, 130.5, 128.3, 128.1,
1-(4-fluorophenyl)-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (35). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-ethynyl-4-fluorobenzene (120 µL, 1 mmol), K2S2O8
(405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by
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The Journal of Organic Chemistry
127.9, 127.7, 127.0, 125.8, 125.6, 85.9, 55.3, 53.3, 34.8, 31.1(3C).
1-(cyclohex-1-en-1-yl)-2a-methoxy-2a,8a-
1
2
3
4
5
6
7
8
HRMS (ESI) m/z: [M+H]+ calculated for C23H23O3, 347.1642;
found, 347.1628.
dihydrocyclobuta[b]naphthalene-3,8-dione (44). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol),1-ethynylcyclohexene (106 µL, 1 mmol), K2S2O8 (405
mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by
column chromatography (hexane:EA = 93:07) (103 mg, 66%).
1H NMR (400 MHz, CDCl3) δ 8.16 – 8.13 (m, 1H), 8.04 – 7.97
(m, 1H), 7.81 – 7.75 (m, 2H), 6.37 (s, 1H), 6.22 (s, 1H), 4.01 (s,
1H), 3.45 (s, 3H), 2.18 (s, 2H), 1.66 – 1.54 (m, 6H); 13C {1H}
NMR (125 MHz, CDCl3) δ 196.2, 194.9, 151.9, 134.6, 134.3,
133.5, 133.3, 132.3, 129.5, 128.6, 128.2, 127.1, 85.9, 55.2, 53.3,
25.5, 23.6, 21.8(2C). HRMS (ESI) m/z: [M+H]+ calculated for
C19H19O3, 295.1329; found, 295.1308.
8a-methoxy-1-(4-pentylphenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (40). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-ethyl-4-pentylbenzene (172 µL, 1 mmol), K2S2O8
(405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by
column chromatography (hexane:EA = 93:07) as brown semi-
solid (120 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 8.10 (dd, J =
7.6, 1.2 Hz, 1H), 8.03 (dd, J = 7.6, 1.2 Hz, 1H), 7.76 (m, 2H),
7.51 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 6.71 (d, J = 1.6
Hz, 1H), 4.16 (d, J = 1.4 Hz, 1H), 3.51 (s, 3H), 2.65 – 2.55 (m,
2H), 1.61 (s, 2H), 1.37 – 1.29 (m, 4H), 0.90 (t, J = 6.9 Hz, 3H);
13C {1H} NMR (125 MHz, CDCl3) δ 195.9, 194.8, 150.4, 144.9,
134.7, 134.4, 133.3, 130.3(2C), 128.7(2C), 128.3, 128.1, 127.0,
125.9(2C), 85.9, 55.3, 53.3, 35.9, 31.4, 30.9, 22.5, 14.0. HRMS
(ESI) m/z: [M+H]+ calculated for C24H25O3, 361.1798; found,
361.1782.
9
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12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-cyclopropyl-2a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (45). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), cyclopropylacetylene (66 µL, 1 mmol), K2S2O8 (405
mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and purified by
column chromatography (hexane:EA = 93:07) (115 mg, 85%).
1H NMR (400 MHz, CDCl3) δ 8.21 – 8.12 (m, 1H), 8.04 – 7.97
(m, 1H), 7.82 – 7.76 (m, 2H), 6.14 (s, 1H), 3.90 (s, 1H), 3.46 (s,
3H), 1.46 – 1.38 (m, 1H), 0.81 – 0.74 (m, 2H), 0.68 – 0.61 (m,
2H); 13C {1H} NMR (125 MHz, CDCl3) δ 196.5, 195.4, 156.8,
134.7, 134.4, 133.5, 133.2, 131.0, 127.9, 127.2, 85.9, 54.7, 53.6,
9.0, 6.9, 6.8. HRMS (ESI) m/z: [M+H]+ calculated for C16H15O3,
255.1016; found, 255.1014.
8a-methoxy-1-(3-methoxyphenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (41). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 3-methoxyphenylacetylene (132 µL, 1 mmol),
K2S2O8 (405 mg, 1.5 mmol) and TFA (38 µL, 0.5 mmol) and
purified by column chromatography (hexane:EA = 90:10) as
yellowish semi-solid (105 mg, 62%). 1H NMR (400 MHz, CDCl3)
δ 8.11 (dd, J = 7.6, 1.3 Hz, 1H), 8.03 (dd, J = 7.5, 1.2 Hz, 1H),
7.83 – 7.72 (m, 2H), 7.27 (s, 1H), 7.20 (d, J = 7.7 Hz, 1H), 7.15
(d, J = 2.2 Hz, 1H), 6.89 (dd, J = 8.1, 2.0 Hz, 1H), 6.77 (d, J = 1.7
8a-methoxy-1-propyl-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (46). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol),1-pentyne (68 µL, 1 mmol), K2S2O8 (405 mg, 1.5
mmol) and TFA (38 µL, 0.5 mmol) and purified by column
chromatography (hexane:EA = 94:06) (121 mg, 89%). 1H NMR
(400 MHz, CDCl3) δ 8.23 – 8.10 (m, 1H), 8.07 – 7.98 (m, 1H),
7.83 – 7.76 (m, 2H), 6.32 (d, J = 1.5 Hz, 1H), 3.94 (d, J = 1.2 Hz,
1H), 3.42 (s, 3H), 2.17 – 2.09 (m, 1H), 2.05 – 1.97 (m, 1H), 1.51
– 1.42 (m, 2H), 0.86 (t, J = 7.4 Hz, 3H); 13C {1H} NMR (125
MHz, CDCl3) δ 196.5, 195.3, 155.5, 134.8, 134.4, 134.3, 133.3,
133.2, 127.8, 127.3, 85.9, 55.2, 53.8, 29.1, 18.9, 13.8. HRMS
(ESI) m/z: [M+H]+ calculated for C16H17O3, 257.1172; found,
257.1160.
Hz, 1H), 4.17 (d, J = 1.5 Hz, 1H), 3.85 (s, 3H), 3.51 (s, 3H).; 13
C
{1H} NMR (125 MHz, CDCl3) δ 195.7, 194.6, 159.7, 150.3,
134.8, 134.5, 133.3, 131.9, 131.7, 129.8, 128.3, 127.1, 118.5,
115.8, 110.9, 85.8, 55.3, 53.3. HRMS (ESI) m/z: [M+H]+
calculated for C20H17O4, 321.1121; found, 321.1117.
8a-methyl-1-(2-(trifluoromethyl)phenyl)-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (42). The title
compound was prepared according to the general procedure
described above using menadione (100 mg, 0.6 mmol), 2-
trifluoromethylphenylacetylene (204 µL, 1.2 mmol), K2S2O8
(486 mg, 1.8 mmol) and TFA (46 µL, 0.6 mmol) and purified by
column chromatography (hexane:EA = 92:08) (156 mg, 78%).
1H NMR (400 MHz, CDCl3) δ 8.11 (m, 2H), 7.78 (m, 2H), 7.69
(d, J = 7.8 Hz, 1H), 7.60 – 7.55 (m, 2H), 7.42 (m, 1H), 6.66 (d, J
= 1.8 Hz, 1H), 3.84 (d, J = 1.7 Hz, 1H), 1.82 (s, 3H).; 13C {1H}
NMR (125 MHz, CDCl3) δ 198.5, 196.1, 149.3, 135.5 (q, J = 5.0
Hz), 134.6, 134.5, 133.8, 133.8, 131.8, 130.9 (q, J=76.9 Hz),
129.0, 128.6, 127.9, 127.1, 126.6 (q, J = 6.25 Hz), 125.7 (q, J =
272.5 Hz), 58.9, 57.6, 19.9. HRMS (ESI) (m/z): [M+H]+
calculated for C20H14F3O2, 343.0940; found, 343.0919.
1-hexyl-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (47). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-octyne (110 µL, 1 mmol), K2S2O8 (405 mg, 1.5
mmol) and TFA (38 µL, 0.5 mmol) and purified by column
1
1-(3-methoxyphenyl)-8a-methyl-2a,8a-
chromatography (hexane:EA = 94:06) (128 mg, 80%). H NMR
(400 MHz, CDCl3) δ 8.18 – 8.13 (m, 1H), 8.05 – 8.01 (m, 1H),
7.82 – 7.76 (m, 2H), 6.31 (d, J = 1.4 Hz, 1H), 3.94 (d, J = 1.2 Hz,
1H), 3.42 (s, 3H), 2.19 – 2.09 (m, 1H), 2.07 – 1.97 (m, 1H), 1.47
dihydrocyclobuta[b]naphthalene-3,8-dione (43). The title
compound was prepared according to the general procedure
described above using menadione (100 mg, 0.6 mmol), 3-
methoxyphenylacetylene (158 µL, 1.2 mmol), K2S2O8 (486 mg,
1.8 mmol) and TFA (46 µL, 0.6 mmol) and purified by column
– 1.38 (m, 2H), 1.27 – 1.18 (m, 6H), 0.84 (t, J = 6.8 Hz, 3H)..; 13
C
{1H} NMR (125 MHz, CDCl3) δ 196.5, 195.3, 155.7, 134.8,
134.4, 134.2, 133.4, 133.2, 127.8, 127.3, 85.9, 55.2, 53.8, 31.4,
28.9, 27.0, 25.3, 22.5, 13.9. HRMS (ESI) m/z: [M+H]+ calculated
for C19H23O3, 299.1642; found, 299.1619.
1
chromatography (hexane:EA = 92:08) (136 mg, 77%). H NMR
(400 MHz, CDCl3) δ 8.13 – 8.03 (m, 2H), 7.77 – 7.73 (m, 2H),
7.27 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 7.7 Hz, 1H), 7.08 (d, J = 2.0
Hz, 1H), 6.87 (m, 1H), 6.58 (d, J = 1.7 Hz, 1H), 3.84 (s, 3H), 3.81
(d, J = 1.6 Hz, 1H), 1.86 (s, 3H); 13C {1H} NMR (125 MHz,
CDCl3) δ 198.4, 196.7, 159.7, 153.3, 134.5, 134.4, 133.7, 133.6,
132.8, 129.7, 128.0, 127.9, 127.0, 118.0, 115.1, 110.6, 57.4, 57.1,
55.3, 19.9. HRMS (ESI) (m/z): [M+H]+ calculated for C20H17O3,
305.1172; found, 305.1143.
1-heptyl-8a-methoxy-2a,8a-
dihydrocyclobuta[b]naphthalene-3,8-dione (48). The title
compound was prepared according to the general procedure
described above using 2-methoxy-1,4-naphthoquinone (100 mg,
0.5 mmol), 1-nonyne (124 µL, 1 mmol), K2S2O8 (405 mg, 1.5
mmol) and TFA (38 µL, 0.5 mmol) and purified by column
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Page 10 of 12
chromatography (hexane:EA = 94:06) (141 mg, 83%). 1H NMR
(400 MHz, CDCl3) δ 8.20 – 8.12 (m, 1H), 8.06 – 7.98 (m, 1H),
7.82 – 7.75 (m, 2H), 6.30 (d, J = 1.4 Hz, 1H), 3.93 (d, J = 1.2 Hz,
1H), 3.42 (s, 3H), 2.18 – 2.10 (m, 1H), 2.06 – 1.97 (m, 1H), 1.48
Arylation of Aldehydes to Bis-heteroaryl Ketones. J. Am. Chem. Soc.
2013, 135, 3772. and references cited therein.
1
2
3
4
5
6
7
8
(2) (a) Dugas, H.; Bioorganic Chemistry, 3rd ed.; Ed.; Springer
Verlag: New York, 1996. (b) Smith, M. B.; March, J. Advanced
Organic Chemistry. Wiley: New York, 2007.
(3) Friedel-Craft's acylation for synthesis of ketones: (a) Nahm, S.;
Weinreb, S. M. N-methoxy-n-methylamides as effective acylating
agents. Tetrahedron Lett. 1981, 22, 3815. (b) Sartori, G.; Maggi, R.
Use of Solid Catalysts in Friedel−Crafts Acylation Reactions. Use of
Solid Catalysts in Friedel−Crafts Acylation Reactions. Chem. Rev.
2006, 106, 1077. and references cited therein.
(4) Organomettalic addition reactions: (a) Brunet, J. J.; Chauvin, R.
Synthesis of diarylketones through carbonylative coupling. Chem.
Soc. Rev. 1995, 24, 89. (b) Dieter, R. K. Reaction of Acyl Chlorides
with Organometallic Reagents: A Banquet Table of Metals for Ketone
Synthesis. Tetrahedron 1999, 55, 4177. (c) Bechara, W. S.; Pelletier,
G.; Charette, A. B. Chemoselective synthesis of ketones and
ketimines by addition of organometallic reagents to secondary
amides. Nat. Chem. 2012, 4, 228. (d) Senatore, R.; Castoldi, L.; Ielo,
L.; Holzer, W.; Pace, V. Expeditious and Chemoselective Synthesis
of α-Aryl and α-Alkyl Selenomethylketones via Homologation
Chemistry.
– 1.34 (m, 2H), 1.30 – 1.15 (m, 8H), 0.86 (t, J = 6.9 Hz, 3H); 13
C
{1H} NMR (125 MHz, CDCl3) δ 196.5, 195.3, 155.7, 134.8,
134.4, 134.2, 133.4, 133.2, 127.8, 127.3, 85.9, 55.2, 53.8, 31.7,
29.2, 28.9, 27.0, 25.4, 22.6, 14.1. HRMS (ESI) m/z: [M+H]+
calculated for C20H25O3, 313.1798; found, 313.1778.
1-hexyl-8a-methyl-2a,8a-dihydrocyclobuta[b]naphthalene-
9
3,8-dione (49). The title compound was prepared according
to the general procedure described above using menadione (100
mg, 0.6 mmol), 1-octyne (132 µL, 1.2 mmol), K2S2O8 (486 mg,
1.8 mmol) and TFA (46 µL, 0.6 mmol) and purified by column
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13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
chromatography (hexane:EA = 94:06) (129 mg, 79%). H NMR
(400 MHz, CDCl3) δ 8.15 – 8.09 (m, 1H), 8.10 – 8.02 (m, 1H),
7.81 – 7.73 (m, 2H), 6.04 (d, J = 1.5 Hz, 1H), 3.64 (d, J = 1.3 Hz,
1H), 2.11 – 2.03 (m, 1H), 2.01 – 1.92 (m, 1H), 1.61 (s, 3H), 1.45
– 1.35 (m, 2H), 1.29 – 1.19 (m, 6H), 0.85 (t, J = 5.2 Hz, 3H); 13
C
{1H} NMR (125 MHz, CDCl3) δ 198.1, 197.7, 159.2, 134.4,
134.3, 133.7, 133.4, 128.8, 127.6, 127.1, 57.9, 57.0, 31.5, 28.9,
27.3, 25.3, 22.5, 18.9, 14.0. HRMS (ESI) m/z: [M+H]+ calculated
for C19H23O2, 283.1693; found, 283.1676.
Org. Lett. 2018, 20, 2685. and references cited therein.
(5) Selected reviews on transition metal catalyzed acylation
reactions, see (a) Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-
Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995,
95, 2457. (b) Willis, M. C. Transition Metal Catalyzed Alkene and
Alkyne Hydroacylation. Chem. Rev. 2010, 110, 725. (c) Wu, X. F.;
Neumann, H.; Beller, M. Palladium-catalyzed carbonylative coupling
reactions between Ar-X and carbon nucleophiles. Chem. Soc. Rev.
2011, 40, 4986. (d) Moragas, T.; Correa, A.; Martin, R. Metal-
Catalyzed Reductive Coupling Reactions of Organic Halides with
Carbonyl-Type Compounds. Chem. Eur. J. 2014, 20, 8242.
ASSOCIATED CONTENT
Supporting Information
1H and 13C NMR spectra of all compounds, dye-degradation
experiment and cyclic voltammetry. This material is available free
of charge via the Internet at http://pubs.acs.org.
(6) For selected examples on transition metal catalyzed acylation
reactions, see: (a) Takemiya, A.; Hartwig, J. F. Palladium-Catalyzed
Synthesis of Aryl Ketones by Coupling of Aryl Bromides with an
Acyl Anion Equivalent. J. Am. Chem. Soc. 2006, 128, 14800. (b)
Goossen, L. J.; Rudolphi, F.; Oppel, C.; Rodríguez, N. Synthesis of
ketones from alpha-oxocarboxylates and aryl bromides by Cu/Pd-
catalyzed decarboxylative cross-coupling. Angew. Chem. Int. Ed.
2008, 47, 3043. (c) Weires, N. A.; Baker, E. L.; Garg, N. K. Nickel-
catalysed Suzuki-Miyaura coupling of amides. Nat. Chem. 2016, 8,
75. (d) Amani, J.; Molander, G. A. Synergistic Photoredox/Nickel
Coupling of Acyl Chlorides with Secondary Alkyltrifluoroborates:
Dialkyl Ketone Synthesis. J. Org. Chem. 2017, 82, 1856. (e) Wakaki,
T.; Togo, T.; Yoshidome, D.; Kuninobu, Y.; Kanai, M. Palladium-
Catalyzed Synthesis of Diaryl Ketones from Aldehydes and
(Hetero)Aryl Halides via C–H Bond Activation. ACS Catal. 2018, 8,
3123. and references cited therein.
(7) For selected examples on decarboxylative additions reactions,
see: (a) Goossen, L. J.; Rudolphi, F.; Oppel, C.; Rodríguez, N.
Synthesis of ketones from alpha-oxocarboxylates and aryl bromides
by Cu/Pd-catalyzed decarboxylative cross-coupling. Angew. Chem.
Int. Ed. 2008, 47, 3043. (b) Lindh, J.; Sjoberg, P. J. R.; Larhed, M.
Synthesis of aryl ketones by palladium(II)-catalyzed decarboxylative
addition of benzoic acids to nitriles. Angew. Chem. Int. Ed. 2010, 49,
7733.
(8) For selected examples on carbonylation of arene C-H for
synthesis of ketones, see: (a) Brunet, J. J.; Chauvin, R.. Synthesis of
diarylketones through carbonylative coupling. Chem. Soc. Rev. 1995,
24, 89. (b) Brennfuhrer, A.; Neumann, H.; Beller, M. Palladium-
Catalyzed Carbonylation Reactions of Aryl Halides and Related
Compounds. Angew. Chem. Int. Ed. 2009, 48, 4114. (c) Wu, X. F.;
Neumann, H.; Beller, M. Palladium-catalyzed carbonylative coupling
reactions between Ar–X and carbon nucleophiles. Chem. Soc. Rev.
2011, 40, 4986. (d) Magano, J.; Dunetz, J. R. Large-Scale
Applications of Transition Metal-Catalyzed Couplings for the
Synthesis of Pharmaceuticals. Chem. Rev. 2011, 111, 2177. (e) Wu,
X. F.; Neumann, H.; Beller, M. Synthesis of Heterocycles via
Palladium-Catalyzed Carbonylations. Chem. Rev. 2013, 113, 1. (f)
Kinney, R. G.; Tjutrins, J.; Torres, G. M.; Liu, N. J.; Kulkarni, O.;
Arndtsen, B. A. A general approach to intermolecular carbonylation
AUTHOR INFORMATION
Corresponding Author
E-mail: bashah@iiim.ac.in, masoodku2@gmail.com
Orcid ID: 0000-0003-0041-5049 (SS); 0000-0003-0470-6329
(MAR); 0000-0001-6629-0002 (BAS)
ACKNOWLEDGMENT
BAS thank CSIR for Young Scientist Award Grant (P-81-113)
and DBT (1151/2016), New Delhi for financial assistance. SS
thanks CSIR for Senior Research Fellowship. IIIM
communication No. 2299/2019
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synthesis of α-trifluoromethyl carbonyl compounds. Angew. Chem.
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Functionalization To Achieve Sterically Controlled Regioselectivity
in Arene Acylation. J. Am. Chem. Soc. 2018, 140, 10025. (c) Zhang,
M.; Xie, J.; Zhu, C. A general deoxygenation approach for synthesis
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Acyl Radicals from Acylsilanes: Photoredox-Catalyzed Synthesis of
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