PPh3·HBr-DMSO: A Reagent System for Diverse Chemoselective Transformations

Article abstract of DOI:10.1021/acs.joc.5b00846

The broad applicability of the hitherto unexplored reagent combination PPh₃·HBr-DMSO is exemplified with multiple highly diverse one-step transformations to synthetically useful building blocks, such as flavones, 4H-thiochromen-4-ones, α-hydroxy ketones, 1,4-naphthoquinones (including vitamin K₃), 2-bromo-3-substituted-1H-1-indenones, 2-methylthio-1H-1-indenones, 3-butyne-1,2-dione, and 4-pentene-2,3-diones. The simple and mild reaction conditions make the reagent superior in terms of yield and substrate scope in comparison with the existing alternatives.

Full text of DOI:10.1021/acs.joc.5b00846

Article
pubs.acs.org/joc
PPh3·HBr−DMSO: A Reagent System for Diverse Chemoselective
Transformations
Kanchan Mal,‡ Amanpreet Kaur,‡ Fazle Haque, and Indrajit Das*
Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata 700 032, India
S
* Supporting Information
ABSTRACT: The broad applicability of the hitherto unexplored
reagent combination PPh3·HBr−DMSO is exemplified with multiple
highly diverse one-step transformations to synthetically useful building
blocks, such as flavones, 4H-thiochromen-4-ones, α-hydroxy ketones,
1,4-naphthoquinones (including vitamin K3), 2-bromo-3-substituted-
1H-1-indenones, 2-methylthio-1H-1-indenones, 3-butyne-1,2-dione,
and 4-pentene-2,3-diones. The simple and mild reaction conditions
make the reagent superior in terms of yield and substrate scope in
comparison with the existing alternatives.
PPh3·HBr−DMSO eliminates the need to handle highly
corrosive and toxic bromine.
In our previous work with PPh3·HBr−DMSO, we transformed
α,β-unsaturated ketomethyl derivatives to γ-substituted β,γ-
unsaturated α-ketomethyl thioesters (Scheme 1, eq 1).1t
INTRODUCTION
■
The oxidative bromination, with in situ generation of an active
brominating species/molecular bromine from hydrobromic acid
(HBr)/bromide salts and hydrogen peroxide, is regarded as an
efficient and viable alternative to the existing procedures utilizing
molecular bromine for the synthesis of bromide derivatives.1a−k
Currently, depending on this concept, several elegant approaches
have been documented in the literature.1e−k However, HBr-
mediated oxidative bromination suffers from environmental,
health, and safety issues due to its hazardous nature.
Scheme 1. Synthesis of α-Ketothioesters from Ketomethyl
Derivatives by Using PPh3·HBr−DMSO
On the other hand, dimethyl sulfoxide (DMSO), an
inexpensive and less toxic solvent than other members of this
category, such as N,N-dimethylformamide (DMF) and hexam-
ethylphosphoramide (HMPA), is extensively employed as an
effective oxidant in traditional named reactions, such as Swern
oxidation and its variants, and as a useful oxygen source in
Kornblum oxidation as well as hydroxylation reaction.1l,m
Moreover, the combination of HBr or Br2 with DMSO is
generally pertinent in a variety of oxidative brominations
followed by DMSO-based oxidation reactions.1n−s Despite its
wide applicability in chemical transformations, this reagent
combination fails to circumvent the aforementioned issues.
However, PPh3·HBr−DMSO is such a reagent system, which
eliminates the ecological and operational concerns.
Herein, we report the PPh3·HBr−DMSO-mediated highly
diverse and chemoselective one-step transformation of keto-
methylene derivatives into flavones, 4H-thiochromen-4-ones, α-
hydroxy ketones, 1,4-naphthoquinones, 2-bromo-3-substituted-
1-indenones, 2-methylthio-1-indenones, ynedione, and ene-
diones. The present method involving simple reaction conditions
and the readily available and relatively green reagent combination
make these transformations more convenient than the reported
ones. Furthermore, the in situ generation of bromine by using
Importantly, we did not observe any bromination at the aromatic
ring or at the alkenyl/alkynyl olefinic bond. Intrigued by this
finding and to further explore the potential of the PPh3·HBr−
DMSO reagent system, we initiated a systematic study with
compounds containing the ketomethylene group (Scheme 1, eq
2).
RESULTS AND DISCUSSION
■
Based on our previous report,1t we began the investigation for
optimal reaction conditions with 1f using 2.0 equiv of PPh3·HBr
Received: April 16, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00846
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a
Table 1. Dehydrogenation Using PPh3·HBr−DMSO
a
By stirring a mixture of 1 (0.05 g, 1.0 equiv) and PPh3·HBr (2.0 equiv) in dry DMSO (2.0 mL) under an Ar atmosphere at 50 °C, employing time
b
as noted, isolated yield. The reaction was carried out at 100 °C. In addition to product 2g, other unidentified products were isolated.
in DMSO at 50 °C. We are pleased to isolate 2f in 95% yield,
resulting from the dehydrogenation of 1f. When the amount of
PPh3·HBr was decreased to 1.0 equiv, the corresponding isolated
yield decreased to 79% after 13 h. The yield was further lowered
(13 h, 51%) with a catalytic amount of PPh3·HBr (0.5 equiv).
Besides, in both cases (1 equiv and 0.5 equiv PPh3·HBr), 10−
25% starting materials were isolated even after the reaction was
conducted for several hours. Further, the use of 2.5 equiv of
PPh3·HBr failed to improve the yield (6.5 h, 81%) of the reaction
significantly (see also Table 2 for optimization studies, vide
infra). Consequently, we decided to carry out all of the reactions
with 2.0 equiv of PPh3·HBr in DMSO at 50 °C. As shown in
Table 1, several substituted flavanones (1a−f) and 4-
thiochromanones (1h−i) underwent smooth dehydrogenation
to produce the corresponding flavones (2a−f) and 4H-
thiochromen-4-ones (2h,i) in good to excellent yields,2a,b,e but
under the standard reaction conditions, 4-chromanone was
converted to only 3-bromochroman-4-one (2ga), and raising the
temperature to 100 °C produced the corresponding 3-bromo-
4H-chromen-4-one (2g).2c,d Flavones and (thio)chromones,
being biologically active molecules, remain enthralling targets for
synthetic chemists, and the methods developed so far mostly
utilize expensive metal catalysts.2a−k
product 2 or further bromination to II, which upon elimination
of HBr produces 2g (Scheme 2).
Inspired by the above results, we investigated the substrate
scope and generality for this transformation using a broad range
of compounds containing α-methylene and α-methine ketones.
To optimize the reaction conditions, we initiated a systematic
study of 3d with PPh3·HBr in DMSO under different reaction
conditions. As shown in Table 2, we observed that a catalytic
amount of PPh3·HBr proved insufficient to drive the reaction to
completion (entry 1). The use of PPh3·HBr in stoichiometric
ratios (entries 2−4) accelerated the transformation. We isolated
a
Table 2. Optimization of the Reaction Conditions
PPh3·HBr
(equiv)
t
recovered (%) yield (%) of yield (%) of
entry
(h)
3d
4d
5d
1
2
3
4
5
6
0.5
1.0
1.5
2.0
3.0
5.0
2.0
2.0
2.0
2.0
2.0
2.0
50
48
30
23
21
18
30
36
40
3
10
73
trace
trace
trace
9
Based on the results obtained in Table 1, we propose a
plausible mechanism as in Scheme 2. We presume that PPh3·HBr
in the presence of DMSO would generate Br2, Ph3PO, (CH3)2S,
and H2O through an oxidation−reduction cycle.1t The initial
oxidative bromination of 1 could then lead to the intermediate I,
followed by either immediate elimination of HBr to generate
8
18
78
77
90
65
65
trace
28
32
b
7
100
14
c
8
d
80
trace
67
trace
Scheme 2. Proposed Reaction Mechanism
9
92
e
10
20
17
f
11
8
67
g
12
36
14
56
trace
a
By stirring a mixture of 3d (0.05 g, 0.215 mmol, 1.0 equiv) and PPh3·
HBr (equiv) in dry DMSO (2 mL) under an Ar atmosphere at room
temperature (30−35 °C), with times as noted. Yields are of isolated
b
c
products. 0.050 g of 3 Å molecular sieves was used. 10.0 equiv of
d
e
H2O was used. 100.0 equiv of H2O was used. Reaction was
performed at 50 °C. Reaction was conducted at 50 °C with 10.0 equiv
of H2O. DMSO was used without drying.
f
g
B
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4d in excellent yield (90%, entry 4) when 2 equiv of PPh3·HBr
was used, along with a minor amount of 5d (9%). Moreover, the
yield of 4d was further lowered when an excess of reagents was
used (entries 5 and 6) or the reaction was conducted either at 50
°C (entry 10) or with DMSO that hadn’t been dried (entry 12).
In all cases (entries 5, 6, and 10), 5d was also isolated in 20−32%
yields. Furthermore, in order to rationalize the influence of water
that was expected to be generated in situ through the “oxidation−
reduction cycle”, we conducted the experiment with 3 Å
molecular sieves. In this case, only starting material was
recovered (entry 7), as 3 Å molecular sieves are known to
remove the water from the reaction medium. On the other hand,
conducting the experiment with 10.0 equiv of H2O at room
temperature (entry 8) or at 50 °C (entry 11) produced 4d in 67−
80% yields; however, the use of 100.0 equiv of H2O completely
prevented the formation of product, and the starting material was
recovered (entry 9). The exact role of water in the proposed
reaction mechanism is not very clear at the moment (Scheme 3).
reaction conditions. Pleasingly, this led to the formation of
vitamin K3 or menadione (7a, Table 4).4a The reaction is
believed to proceed through the initial oxidative bromination of
6a to produce intermediate I followed by elimination of HBr to
generate alkene (II), which undergoes rapid isomerization to
give substituted 1-naphthol (II-A). Subsequent oxidative
bromination at the 4-position (more active and less hindered
side) would furnish III, which through Kornblum oxidation (IV)
yields 7a (Scheme 4). Similarly, when we used other substituted
α-methyl (6b,c), α-bromo-α′-methyl (6d), and α-unsubstituted
(6e) 1-tetralones, respective substituted 1,4-naphthoquinones
(7b−e, Table 4) were isolated.4b,c It is noteworthy that syntheses
of such 1,4-naphthoquinones, which serve as scaffolds for
therapeutic compounds, mainly rely on selective oxidation of
hydroxylated aromatics and substituted naphthalenes.4d,e
Next, we examined the scope and viability of the PPh3·HBr−
DMSO system with substituted 1-indanones (Table 5) since
functionalized indanones and indenones exhibit diverse arrays of
pharmacological applications.5a,b Interestingly, under the stand-
ard reaction conditions, 3-phenyl/3-methyl-1-indanones (8a,b)
underwent smooth conversion to 2-bromo-3- phenyl/3-methyl-
1H-inden-1-ones (9a,b),5c whereas 5-Br/6-OMe-1-indanones
without any substitution at C-3 (8c−d) produced the
corresponding 2-methylsulfanyl-1H-inden-1-ones (10a,b),
along with minor amounts of monobromo- and dibromo-1-
indanone derivatives (see the Experimental Section for details)
and other unidentified compounds.5d−f The lower yields (10a,b)
obtained in these reactions were thought to be due to the
formation of substituted indan-1,2-diones (IV) from the
corresponding α-bromo (I) intermediates through DMSO-
based Kornblum oxidation (Scheme 5). However, no such
derivatives (IV) were isolated. The structure of 10a was
established by single-crystal X-ray diffraction analysis (Table
5).5g The distinct behavior exhibited by substituted 1-indanones
could be explained on the basis of consecutive oxidative
bromination of 8 to yield II, followed either by elimination of
HBr to produce 9 or by displacement of the bromine atom by
dimethylsulfide (to form III), and final dehydrobromination to
generate 10 (Scheme 5). It must be mentioned here, after the
formation of α,α′-dibromo intermediates II, if the oxygen atom
in DMSO acts as a nucleophile to some extent rather than
dimethyl sulfide, the corresponding indan-1,2-diones (IV)
should be formed. As discussed previously, we have not isolated
any such derivatives.
To observe the effect of the PPh3·HBr−DMSO reagent system
on conjugated ketomethylene groups, we conducted the
experiment with α,β-alkenyl ketones (11) as substrates.
Interestingly, this yielded α-oxo-β,γ-unsaturated ketomethyl
derivatives (12a,b, Scheme 6) in moderate yields.6a Subse-
quently, we examined the reaction of α,β-alkynyl ketones (13)
with PPh3·HBr−DMSO, which afforded the substituted
ynedione (14, Scheme 6) in good yield.6b These dramatic
selectivity changes for unsaturated ketomethylene groups
(Scheme 6) in contrast to the saturated ketomethylene groups
(Table 3 and Scheme 3, vide supra) may be explained by the
presence of extended conjugation in 11 and 13, which makes the
α-H of intermediate bromo derivative (II, Scheme 7) more acidic
and resulting in rapid abstraction of proton by bromide anion to
produce α-diketones as the predominant products 12/14
(Scheme 7) rather than hydrolyzed products. It is interesting
to note that syntheses of such derivatives (enedione and
ynedione) are very rare in the literature, though they are useful
as medicinally active compounds.6c−h On the other hand, an
Scheme 3. Proposed Reaction Mechanism
We presume that, initially, it could help to enolize the ketomethyl
group and subsequent oxidative bromination to generate the
corresponding α-bromo derivative (I, Scheme 3). In addition,
water might help to regenerate HBr from bromide ion in the
proposed reaction mechanism. As shown in Table 3, the
reactions proceeded smoothly to afford the corresponding
unsymmetrical α-hydroxy ketones in moderate to excellent yields
(4a−r).3a−m
To expand the realm of this methodology, acyclic β-diketones
were treated under the standard reaction conditions, and the
product was isolated as a mixture of vicinal triketones and its
hydrated form (4t,u, Table 3),3o,p whereas a β-diketone with a
methine in between produced only the corresponding α-bromo
derivative (4s, Table 3).3n Besides, in few cases, the
corresponding 1,2-diketo derivatives (5, see the Experimental
Section for details), through Kornblum oxidation of intermediate
II, were isolated in minor quantities along with α-hydroxy
ketones as the major components.3q However, we observed the
change in selectivity for unsaturated ketomethylene groups
leading to the predominant formation of unsaturated 1,2-
diketones compared to their hydroxy ketones (Schemes 6 and 7).
On the basis of the above investigations and the reported
literature,1q,r,3r a plausible mechanism for α-hydroxylation is
outlined in Scheme 3. We believe that initial oxidative
bromination of 3 could generate I, which undergoes SN2
displacement by DMSO to produce II, and afterward formation
of II-A. Subsequently, intermediate II-A could be hydrolyzed
either by pathway a or pathway b to yield 4.3s,t
Consequently, the scope of 2-methyl-1-tetralone (6a) as a
substrate was explored under the standard PPh3−HBr−DMSO
C
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a
Table 3. α-Hydroxylation Using PPh3·HBr−DMSO
a
Unless otherwise noted, reactions were carried out at rt (30−35 °C) under the reaction conditions in Table 1, isolated yield. Minor amounts of
b
c
diketo derivatives were isolated in a few cases; see the Experimental Section. The reaction was carried out at 50 °C. Isolated as a mixture of vicinal
tricarbonyl and its hydrated form.
a
Table 4. Synthesis of 1,4-Naphthoquinones by PPh3·HBr−DMSO
a
Unless otherwise noted, reactions were carried out at 50 °C under the conditions in Table 1, isolated yield.
Scheme 4. Proposed Reaction Mechanism
isopropyl derivative (15a) produced merely the corresponding
α′-Br derivative (16, Scheme 6) due to the lack of α-H for further
oxidation,6i and trans-chalcone (15b) gave no conversion due to
the lack of enolizable proton.
D
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Table 5. Synthesis of Substituted 1H-Inden-1-ones by PPh3·
Scheme 6. Synthesis of Enediones and Ynedione by PPh3·
a
a
HBr−DMSO
HBr−DMSO
a
Unless otherwise noted, reactions were carried under the reaction
b
conditions in Table 1, isolated yield. Minor amounts of monobromo-
and dibromo-1-indanone derivatives were isolated; see the Exper-
c
imental Section. The thermal ellipsoids are shown in 50% probability
level (X-ray structure; 10a).
To demonstrate the potential utility of the developed
intermediates, we undertook the synthesis of substituted 2-
alkynylated 1H-inden-1-ones (17a,b) from 9a under Pd-
(PPh3)2Cl2/CuI-catalyzed standard Sonogashira coupling re-
action conditions (Scheme 8).5b Moreover, when we treated 14
with AuCl3 (2 mol %) and BnOH in CH2Cl2 at room
temperature, the corresponding substituted 3(2H)-furanone
18, a key structural unit in many biologically active natural
products, was isolated (Scheme 8).6c,j
a
Unless otherwise noted, reactions were carried out at 50 °C under
b
the reaction conditions in Table 1, isolated yield. Small amount of
hydroxyketo derviative was formed, see the Experimental Section.
CONCLUSION
hood; as the volatile byproduct, dimethyl sulfide (Me2S) having an
obnoxious odor formed in the reaction medium.
■
In conclusion, we have demonstrated PPh3·HBr−DMSO-
mediated efficient and chemoselective transformations of
ketomethylene derivatives into flavones, 4H-thiochromen-4-
ones, α-hydroxy ketones, 1,4-naphthoquinones, substituted-1H-
1-indenones, ynedione, and enediones. The operationally simple
reaction conditions and ready availability of reactants make these
transformations more practical than the reported ones. Addi-
tionally, AuCl3-catalyzed efficient access to 3(2H)-furanone and
Pd(PPh3)2Cl2/CuI-catalyzed Sonogashira coupling to produce
highly substituted 2-alkynylated 1H-inden-1-ones is described.
Further applications of this reagent system are in progress.
General Procedure for the Synthesis of 2a−i, 4a−u, 7a−e,
9a,b, 10a,b, 12a,b, 14, and 16. PPh3·HBr (2 equiv/mmol) was taken
in a 25 mL two-necked round-bottom flask under Ar atmosphere with
condenser. Dry DMSO (2 mL) was added dropwise. The corresponding
starting materials 1, 3, 6, 8, 11, 13, and 15a (0.05 g, 1 equiv) were
introduced separately into the reaction mixtures at room temperature,
and the mixtures were stirred at the same temperature or heated with
stirring for the time indicated. After completion of the reaction (TLC),
saturated ammonium chloride solution was added, and the product was
extracted with EtOAc. The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated under
reduced pressure to get a residue. The crude residue was purified over
silica gel column chromatography [230−400; eluent: ethyl acetate/n-
hexane] to obtain 2a−i, 4a−u, 5b−p, 7a−e, 9a,b, 10a,b, 12a,b, 14, and
16.
EXPERIMENTAL SECTION
■
General Information. Melting points were determined in open-
end-capillary tubes and are uncorrected. TLC was performed on silica
gel plates (Merck silica gel 60, f254), and the spots were visualized with
UV light (254 and 365 nm) or by charring the plate dipped in 5%
H2SO4−MeOH or vanillin charring solution. 1H and 13C NMR spectra
were recorded in CDCl3 or DMSO-d6 solvent using TMS as the internal
standard. HRMS (m/z) were measured using EI (magnetic sector,
positive ion) and ESI (Q-TOF, positive ion) techniques. Infrared (IR)
spectra were recorded on Fourier transform infrared spectroscopy; only
intense peaks were reported. All of the PPh3·HBr−DMSO-mediated
reactions and the workup were performed in a well-ventilated fume
4-(4-Oxo-4H-chromen-2-yl)phenyl Trifluoromethanesulfonate
(2a). Prepared according to the general procedure discussed above:
eluent, EtOAc/n-hexane (25%); isolated yield = 0.0467 g, 94%; white
solid; mp 95−97 °C; 1H NMR (300 MHz, CDCl3) δ = 8.25 (dd, J = 1.5,
8.1 Hz, 1 H), 8.04 (d, J = 9.0 Hz, 2 H), 7.72−7.77 (m, 1 H), 7.59 (d, J =
8.4 Hz, 1 H), 7.26−7.48 (m, 3 H), 6.83 ppm (s, 1 H); 13C NMR (75
MHz, CDCl3) δ = 178.0, 161.2, 156.1, 151.3, 134.1, 132.1, 128.3 (2
CH), 125.8, 125.5, 123.8, 122.1 (2 CH), 112.3−125.1 (m, 1 C, CF3),
118.0, 108.4 ppm; IR (KBr, cm−1) νCO
̃
= 1642, νCC
̃
̃
= 1502, νmax =
1422, 1376, 1217, 1138, 880, 754, 618; HRMS (EI) m/z calcd for
Scheme 5. Proposed Reaction Mechanism
E
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Scheme 7. Proposed Reaction Mechanism
H), 7.44−7.51 ppm (m, 2 H); 13C NMR (75 MHz, CDCl3) δ = 172.1,
156.0, 153.7, 134.0, 126.4, 125.8, 123.1, 118.0, 110.6 ppm. (Analytical
data are consistent with previously reported values.)
Scheme 8. Synthetic Applicationsa
3-Bromochroman-4-one (2ga).2d Prepared according to the general
procedure discussed above: eluent, EtOAc/n-hexane (3%); isolated
yield = 0.064 g, 83%; white solid; 1H NMR (300 MHz, CDCl3) δ = 7.96
(dd, J = 1.8, 8.1 Hz, 1 H), 7.53−7.58 (m, 1 H), 7.09 (dd, J = 7.2, 14.4 Hz,
1 H), 7.05 (d, J = 8.4 Hz, 1 H), 4.57−4.71 ppm (m, 3 H); 13C NMR (75
MHz, CDCl3) δ = 185.2, 160.6, 136.7, 128.2, 122.3, 118.7, 117.9, 71.2
(CH2), 45.4 ppm. (Analytical data are consistent with previously
reported values.)
C16H9F3O5S [M]+ 370.0123, found 370.0097. Anal. Calcd for
C16H9F3O5S: C, 51.90; H, 2.45. Found: C, 51.83; H, 2.72.
6-Chloro-4H-thiochromen-4-one (2h).2e Prepared according to the
general procedure discussed above: eluent, EtOAc/n-hexane (10%);
isolated yield = 0.044 g, 89%; white solid; 1H NMR (300 MHz, CDCl3)
δ = 8.53 (s, 1 H), 7.84 (d, J = 10.5 Hz, 1 H), 7.58 (s, 2 H), 7.03 ppm (d, J
= 10.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3) δ = 178.4, 137.8, 135.6,
134.3, 133.3, 131.8, 128.2, 128.1, 125.6 ppm. (Analytical data are
consistent with previously reported values.)
2-(3-Hydroxyphenyl)-4H-chromen-4-one (2b).2a Prepared accord-
ing to the general procedure discussed above: eluent, EtOAc/n-hexane
(30%); isolated yield = 0.042 g, 85%; white solid; 1H NMR (600 MHz,
DMSO-d6) δ = 9.90 (br. s., 1 H), 8.04 (dd, J = 1.8, 7.8 Hz, 1 H), 7.81−
7.84 (m, 1 H), 7.75−7.76 (m, 1 H), 7.48−7.52 (m, 2 H), 7.43 (t, J = 2.4
Hz, 1 H), 7.36 (t, J = 8.4 Hz, 1 H), 6.99 (dd, J = 1.8, 8.4 Hz, 1 H), 6.91−
6.92 ppm (m, 1 H); 13C NMR (150 MHz, DMSO-d6) δ = 178.5, 164.2,
159.3, 157.1, 135.8, 133.9, 131.7, 127.0, 126.2, 124.8, 120.3, 120.0, 118.7,
114.3, 108.4 ppm. (Analytical data are consistent with previously
reported values.)
6-Bromo-4H-thiochromen-4-one (2i).2e Prepared according to the
general procedure discussed above: eluent, EtOAc/n-hexane (10%);
isolated yield = 0.046 g, 93%; white solid; 1H NMR (300 MHz, CDCl3)
δ = 8.69 (d, J = 2.4 Hz, 1 H), 7.85 (d, J = 10.8 Hz, 1 H), 7.72 (dd, J = 2.1,
8.4 Hz, 1 H), 7.51 (d, J = 8.7 Hz, 1 H), 7.04 ppm (d, J = 10.5 Hz, 1 H);
13C NMR (75 MHz, CDCl3) δ = 178.3, 137.9, 136.2, 134.5, 133.5, 131.3,
2-(4-Methoxyphenyl)-4H-chromen-4-one (2c).2b Prepared accord-
ing to the general procedure discussed above: eluent, EtOAc/n-hexane
(25%); isolated yield = 0.036 g, 73%; white solid; 1H NMR (600 MHz,
CDCl3) δ = 8.22 (dd, J = 1.8, 8.4 Hz, 1 H), 7.88−7.90 (m, 2 H), 7.68
(ddd, J = 1.8, 7.2, 8.6 Hz, 1 H), 7.54−7.56 (m, 1 H), 7.39−7.42 (m, 1 H),
7.01−7.04 (m, 2 H), 6.75 (s, 1 H), 3.89 ppm (s, 3 H); 13C NMR (150
MHz, CDCl3) δ = 179.4, 164.4, 163.4, 157.2, 134.6, 129.0 (2 CH),
126.7, 126.1, 125.0, 124.9, 119.0, 115.5 (2 CH), 107.2, 56.5 ppm.
(Analytical data are consistent with previously reported values.)
6-Methoxy-2-phenyl-4H-chromen-4-one (2d).2b Prepared accord-
ing to the general procedure discussed above: eluent, EtOAc/n-hexane
(20%); isolated yield = 0.042 g, 85%; white solid; 1H NMR (600 MHz,
CDCl3) δ = 7.91−7.93 (m, 2 H), 7.60 (d, J = 3.0 Hz, 1 H), 7.50−7.55
(m, 4 H), 7.29 (dd, J = 3.0, 9.0 Hz, 1 H), 6.82 (s, 1 H), 3.91 ppm (s, 3 H);
13C NMR (150 MHz, CDCl3) δ = 179.3, 164.2, 158.0, 152.1, 132.9,
132.5, 130.0 (2 CH), 127.2 (2 CH), 125.6, 124.8, 120.5, 107.9, 105.8,
57.0 ppm. (Analytical data are consistent with previously reported
values.)
128.3, 125.8, 122.2 ppm. (Analytical data are consistent with previously
reported values.)
2-(5-Chlorobenzo[b]thiophene-3-yl)-2-hydroxy-1-(4-methoxy-
3,5-dimethylphenyl)ethanone (4a). Prepared according to the general
procedure discussed above: eluent, EtOAc/n-hexane (20%); 0.051 g,
97%; white solid; mp 112−113 °C; 1H NMR (600 MHz, CDCl3) δ =
7.95 (d, J = 1.8 Hz, 1 H), 7.74 (d, J = 8.4 Hz, 1 H), 7.62 (s, 2 H), 7.33 (dd,
J = 1.8, 8.4 Hz, 2 H), 6.21 (d, J = 6.0 Hz, 1 H), 4.44 (d, J = 6.0 Hz, 1 H),
3.71 (s, 3 H), 2.23 ppm (s, 6 H); 13C NMR (150 MHz, CDCl3) δ =
197.5, 162.3, 138.8, 138.6, 133.9, 131.7, 131.1, 130.1 (2 CH), 128.9,
128.1, 125.4, 123.8 (2 C), 122.1, 70.3, 59.6, 16.3 ppm (2 CH3); IR (KBr,
cm−1) νOH
̃
= 3414, νCO
̃
= 1671, νCC
̃
̃
= 1598, νmax = 1320, 1306, 1213,
1158, 1106, 1009, 832, 815, 804; HRMS (EI) m/z calcd for
C19H17ClO3S [M]+ 360.0587, found 360.0585. Anal. Calcd for
C19H17ClO3S: C, 63.24; H, 4.75. Found: C, 63.58; H, 5.05;
1-(5-Chlorobenzo[b]thiophene-3-yl)-1-hydroxybutan-2-one (4b)
and 1-(5-Chlorobenzo[b]thiophene-3-yl)butane-1,2-dione (5b). Pre-
pared according to the general procedure discussed above. 4b: eluent,
EtOAc/n-hexane (20%); 0.040 g, 75%; yellow gum. 5b: EtOAc/n-
hexane (5%); 0.008 g, 15%; yellow solid; mp 85−86 °C. 4b: 1H NMR
(300 MHz, DMSO-d6) δ = 8.03 (d, J = 8.7 Hz, 1 H), 7.92 (d, J = 1.8 Hz, 1
H), 7.86 (s, 1 H), 7.40 (dd, J = 2.1, 8.7 Hz, 1 H), 6.19 (d, J = 4.5 Hz, 1 H),
5.50 (d, J = 4.2 Hz, 1 H), 2.45−2.58 (m, 2 H), 0.86 ppm (t, J = 7.2 Hz, 3
H); 13C NMR (75 MHz, DMSO-d6) δ = 210.3, 138.6, 138.5, 134.2,
129.4, 127.8, 124.6, 124.6, 122.4, 74.7, 30.3 (CH2), 7.6 ppm; IR (KBr,
7-Methoxy-2-phenyl-4H-chromen-4-one (2e).2b Prepared accord-
ing to the general procedure discussed above: eluent, EtOAc/n-hexane
(25%); isolated yield = 0.0444 g, 89%; white solid; 1H NMR (600 MHz,
CDCl3) δ = 8.14 (d, J = 9.0 Hz, 1 H), 7.90−7.91 (m, 2 H), 7.51−7.53
(m, 3 H), 6.97−6.99 (m, 2 H), 6.76 (s, 1 H), 3.93 ppm (s, 3 H); 13C
NMR (150 MHz, CDCl3) δ = 178.9, 165.2, 164.0, 159.0, 132.9, 132.4,
130.0 (2 CH), 128.1, 127.2 (2 CH), 118.9, 115.4, 108.6, 101.4, 56.8
ppm. (Analytical data are consistent with previously reported values.)
2-Phenyl-4H-chromen-4-one (2f).2b Prepared according to the
general procedure discussed above: eluent, EtOAc/n-hexane (20%);
isolated yield = 0.047 g, 95%; white solid; 1H NMR (600 MHz, CDCl3)
δ = 8.24 (d, J = 7.8 Hz, 1 H), 7.93−7.95 (m, 2 H), 7.69−7.72 (m, 1 H),
7.51−7.58 (m, 4 H), 7.41−7.44 (m, 1 H), 6.83−6.84 ppm (m, 1 H); 13C
NMR (150 MHz, CDCl3) δ = 179.5, 164.4, 157.3, 134.8, 132.8, 132.6,
130.1 (2 CH), 127.3 (2 CH), 126.7, 126.2, 125.0, 119.1, 108.6 ppm.
(Analytical data are consistent with previously reported values.)
3-Bromo-4H-chromen-4-one (2g).2c Prepared according to the
general procedure discussed above: eluent, EtOAc/n-hexane (4%);
isolated yield = 0.025 g, 33%; light yellow solid; 1H NMR (300 MHz,
CDCl3) δ = 8.28 (dd, J = 1.2, 7.8 Hz, 1 H), 8.24 (s, 1 H), 7.69−7.75 (m, 1
cm−1) νOH
̃
= 3421, νCO
̃
= 1719, νCC
̃
̃
= 1643, νmax = 1384, 1077, 970,
832, 796; HRMS (ESI) m/z calcd for C12H11ClO2SNa [M + Na]+
277.0066, found 277.0050. Anal. Calcd for C12H11ClO2S: C, 56.58; H,
4.35. Found: C, 56.92; H, 4.42. 5b: 1H NMR (600 MHz, DMSO-d6) δ =
9.10 (s, 1 H), 8.56 (d, J = 1.8 Hz, 1 H), 8.19 (d, J = 8.4 Hz, 1 H), 7.55 (dd,
J = 1.8, 8.4 Hz, 1 H), 2.96 (q, J = 6.6, 14.4 Hz, 2 H), 1.06 ppm (t, J = 6.6
Hz, 3 H); 13C NMR (150 MHz, DMSO-d6) δ = 202.6, 185.7, 147.8,
138.3, 138.2, 131.9, 128.1, 126.3, 125.4, 123.9, 31.1, 7.3 ppm; IR (KBr,
cm−1) νCO
̃
= 1713, νCC
̃
̃
= 1642, νmax = 1420, 1096, 1076, 1023, 800;
HRMS (ESI) m/z calcd for C12H9ClO2SNa [M + Na]+ 274.9910, found
274.9912.
F
DOI: 10.1021/acs.joc.5b00846
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1-Benzo[b]thiophene-3-yl-1-hydroxypropan-2-one (4c) and 1-
Benzo[b]thiophene-3-ylpropane-1,2-dione (5c). Prepared according
to the general procedure discussed above. 4c: eluent, EtOAc/n-hexane
(15%); 0.044 g, 81%; yellow gum. 5c: EtOAc/n-hexane (3%); 0.008 g,
15%; yellow gum. 4c: 1H NMR (300 MHz, CDCl3) δ = 7.87−7.90 (m, 1
H), 7.71−7.74 (m, 1 H), 7.52 (s, 1 H), 7.37−7.41 (m, 2 H), 5.46 (s, 1
H), 4.26 (br s, 1 H), 2.11 ppm (s, 3 H); 1H NMR (300 MHz, DMSO-d6)
δ = 7.97−8.00 (m, 1 H), 7.85−7.88 (m, 1 H), 7.77 (s, 1 H), 7.37−7.39
(m, 2 H), 6.16 (d, J = 4.5 Hz, 1 H), 5.44 (d, J = 4.5 Hz, 1 H), 2.10 ppm (s,
3 H); 13C NMR (75 MHz, DMSO-d6) δ = 207.8, 140.0, 137.1, 134.4,
Hz, 1 C), 127.2, 126.1, 124.8 (d, JC−F = 1.5 Hz, 1 C), 124.3, 121.1 (d,
JC−F = 21.0 Hz, 1 C), 115.8 (d, JC−F = 22.5 Hz, 1 C), 71.6 ppm; IR (KBr,
cm−1) νOH
̃
= 3456, νCO
̃
= 1684, νCC
̃
̃
= 1586, νmax = 1486, 1433, 1266,
1075, 990, 898, 792, 680; HRMS (ESI) m/z calcd for C12H9FO2SNa [M
+ Na]+ 259.0205, found 259.0185. 5f: 1H NMR (600 MHz, CDCl3) δ =
8.24 (dd, J = 1.2, 3.0 Hz, 1 H), 7.79 (dt, J = 1.2, 7.8 Hz, 1 H), 7.72−7.74
(m, 1 H), 7.68 (dd, J = 1.2, 5.4 Hz, 1 H), 7.50 (td, J = 5.4, 7.8 Hz, 1 H),
7.42 (dd, J = 3.0, 5.4 Hz, 1 H), 7.36 ppm (tdd, J = 1.2, 2.4, 8.4 Hz, 1 H);
13C NMR (150 MHz, CDCl3) δ = 191.7, 186.3, 162.8 (d, J = 247.5 Hz, 1
C), 137.7, 137.3, 134.7 (d, J = 6.0 Hz, 1 C), 130.7 (d, J = 7.5 Hz, 1 C),
127.3, 127.2, 126.2 (d, J = 3.0 Hz, 1 C), 121.9 (d, J = 21.0 Hz, 1 C), 116.4
125.4, 124.5, 124.2, 123.0, 122.9, 75.3, 25.1 ppm; IR (KBr, cm−1) νOH
=
̃
(d, J = 22.5 Hz, 1 C) ppm; IR (KBr, cm−1) νCO
νmax = 1442, 1237, 1143, 730, 661; HRMS (EI) m/z calcd for
C12H7FO2S [M]+ 234.0151, found 234.0149.
̃
= 1658, νCC
̃
= 1585,
3439, νCO
̃
̃
= 1717, νmax = 1428, 1356, 1102, 763, 735; HRMS (EI) m/z
calcd for C11H10O2S [M]+: 206.0402; found: 206.0404. 5c: H NMR
(600 MHz, DMSO-d6) δ = 9.01 (s, 1 H), 8.57−8.58 (m, 1 H), 8.12−8.14
(m, 1 H), 7.54−7.56 (m, 1 H), 7.49 (td, J = 1.8, 8.4 Hz, 1 H), 2.49 ppm
(s, 3 H); 13C NMR (150 MHz, DMSO-d6) δ = 200.3, 185.5, 145.9,
139.5, 137.0, 128.6, 126.6, 126.2, 124.7, 123.6, 26.1 ppm; IR (KBr,
1
̃
2-Hydroxy-1-(4-methoxyphenyl)-2-(thiophene-2-yl)ethanone
(4g) and 1-(4-Methoxyphenyl)-2-(thiophene-2-yl)ethane-1,2-dione
(5g). Prepared according to the general procedure discussed above. 4g:
eluent, EtOAc/n-hexane (20%); 0.043 g, 80%; yellow gum. 5g: EtOAc/
n-hexane (7%); 0.010 g, 19%; yellow solid; mp 52−53 °C. 4g: 1H NMR
(300 MHz, CDCl3) δ = 7.97 (d, J = 9.0 Hz, 2 H), 7.25−7.26 (m, 1 H),
6.90−6.98 (m, 4 H), 6.16 (d, J = 6.6 Hz, 1 H), 4.55 (d, J = 6.9 Hz, 1 H),
3.86 ppm (s, 3 H); 13C NMR (75 MHz, CDCl3) δ = 195.6, 164.3, 142.6,
131.6 (2 CH), 127.2, 126.3 (2 CH), 126.0, 114.0 (2 CH), 70.2, 55.5
cm−1) νCO
̃
̃
= 1627, νmax = 1422, 1056, 750; HRMS (ESI) m/z calcd for
C11H8O2SNa [M + Na]+ 227.0143, found 227.0150.
2-Hydroxy-1-(4-methoxyphenyl)-2-(thiophene-3-yl)ethanone
(4d) and 1-(4-Methoxyphenyl)-2-(thiophene-3-yl)ethane-1,2-dione
(5d). Prepared according to the general procedure discussed above. 4d:
eluent, EtOAc/n-hexane (20%); 0.048 g, 90%; white solid; mp 119−122
°C. 5d: EtOAc/n-hexane (7%); 0.005 g, 9%; yellow solid; mp 65−67 °C.
4d: 1H NMR (300 MHz, CDCl3) δ = 7.93 (d, J = 9.0 Hz, 2 H), 7.25−
7.27 (m, 2 H), 6.99−7.00 (m, 1 H), 6.90 (d, J = 8.7 Hz, 2 H), 6.02 (d, J =
6.6 Hz, 1 H), 4.47 (d, J = 6.6 Hz, 1 H), 3.85 ppm (s, 3 H); 13C NMR (75
MHz, CDCl3) δ = 196.7, 164.2, 140.3, 131.5 (2 CH), 126.7, 126.3,
ppm; IR (KBr, cm−1) νOH
̃
= 3447, νCO
̃
= 1671, νCC
̃
̃
= 1599, νmax =
1262, 1172, 1073, 1028, 969, 838, 709, 607; HRMS (EI) m/z calcd for
C13H12O3S [M]+ 248.0507, found 248.0504. Anal. Calcd for
C13H12O3S: C, 62.89; H, 4.87. Found: C, 63.21; H, 4.98. 5g: 1H
NMR (300 MHz, CDCl3) δ = 8.03 (d, J = 9.0 Hz, 2 H), 7.80−7.83 (m, 2
H), 7.18 (t, J = 4.2 Hz, 1 H), 6.98 (d, J = 9.0 Hz, 2 H), 3.90 ppm (s, 3 H);
13C NMR (75 MHz, CDCl3) δ = 190.6, 186.0, 165.0, 140.1, 136.6 (2
CH), 132.7 (2 CH), 128.7, 125.6, 114.3 (2 CH), 55.6 ppm; IR (KBr,
123.8, 114.0 (2 CH), 70.9, 55.5 ppm; IR (KBr, cm−1) νOH
= 1603, νmax = 1266, 1231, 1192, 1091, 975, 864, 777;
̃
= 3443, νCO
̃
= 1667, νCC
̃
̃
HRMS (ESI) m/z calcd for C13H12O3SNa [M + Na]+ 271.0405, found
271.0439. Anal. Calcd for C13H12O3S: C, 62.89; H, 4.87. Found: C,
62.94; H, 4.59. 5d: 1H NMR (600 MHz, CDCl3) δ = 8.21 (dd, J = 1.2,
3.0 Hz, 1 H), 7.99 (dt, J = 3.0, 9.0 Hz, 2 H), 7.66 (dd, J = 1.2, 5.4 Hz, 1
H), 7.39 (dd, J = 3.0, 5.4 Hz, 1 H), 6.98 (dt, J = 3.0, 9.0 Hz, 2 H), 3.89
ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ = 192.9, 188.7, 166.0,
139.3, 137.9, 133.6 (2 CH), 128.2, 128.0, 126.7, 115.3 (2 CH), 56.6
cm−1) νCO
̃
= 1650, νCC
̃
̃
= 1596, νmax = 1411, 1169, 1265, 1226, 1169,
1025, 729, 605; HRMS (EI) m/z calcd for C13H10O3S [M]+ 246.0351,
found 246.0341.
1-(4-Fluorophenyl)-2-hydroxy-2-(thiophene-2-yl)ethanone (4h)
and 1-(4-Fluorophenyl)-2-(thiophene-2-yl)ethane-1,2-dione (5h).
Prepared according to the general procedure discussed above. 4h:
eluent, EtOAc/n-hexane (20%); 0.036 g, 67%; yellow solid; mp 80−81
°C. 5h: EtOAc/n-hexane (5%); 0.014 g, 26%; yellow solid; mp 55−57
°C. 4h: 1H NMR (300 MHz, CDCl3) δ = 7.99−8.03 (m, 2 H), 7.26−
7.29 (m, 1 H), 7.12 (t, J = 8.4 Hz, 2 H), 6.92−6.98 (m, 2 H), 6.17 (d, J =
6.6 Hz, 1 H), 4.43 ppm (d, J = 6.6 Hz, 1 H); 13C NMR (75 MHz, CDCl3)
δ = 195.8, 166.2 (d, JC−F = 255.7 Hz, 1 C), 141.7, 131.9 (d, JC−F = 9.7 Hz,
ppm; IR (KBr, cm−1) νCO
̃
= 1651, νCC
̃
̃
= 1601, νmax = 1508, 1166,
1262, 1232, 834, 738, 609; HRMS (ESI) m/z calcd for C13H10O3SNa
[M + Na]+ 269.0249, found 269.0247.
1-(4-Chlorophenyl)-2-hydroxy-2-(thiophene-3-yl)ethanone (4e)
and 1-(4-Chlorophenyl)-2-(thiophene-3-yl)ethane-1,2-dione (5e).
Prepared according to the general procedure discussed above. 4e:
eluent, EtOAc/n-hexane (20%); 0.045 g, 84%; white solid; mp 97−99
°C. 5e: EtOAc/n-hexane (4%); 0.008 g, 15%; yellow solid; mp 85−87
°C. 4e: 1H NMR (300 MHz, CDCl3) δ = 7.87 (d, J = 8.4 Hz, 2 H), 7.40
(d, J = 8.4 Hz, 2 H), 7.26−7.29 (m, 2 H), 6.96−6.98 (m, 1 H), 6.03 (d, J
= 6.0 Hz, 1 H), 4.32 ppm (d, J = 6.3 Hz, 1 H); 13C NMR (75 MHz,
CDCl3) δ = 197.3, 140.6, 139.4, 131.8, 130.4 (2 CH), 129.1 (2 CH),
2 C), 129.6 (d, JC−F = 3.0 Hz, 1 C), 127.3, 126.7, 126.6, 116.1 (d, JC−F
21.7 Hz, 2 C), 70.6 ppm; IR (KBr, cm−1) νOH
= 3427, νCO = 1681,
νCC = 1598, νmax = 1508, 1269, 1235, 1154, 1066, 970, 840, 705, 636;
=
̃
̃
̃
̃
Anal. Calcd for C12H9FO2S: C, 61.01; H, 3.84. Found: C, 60.90; H, 4.02;
HRMS (EI) m/z calcd for C12H9FO2S [M]+ 236.0307, found 236.0287.
5h: 1H NMR (300 MHz, CDCl3) δ = 8.08−8.13 (m, 2 H), 7.83−7.86
(m, 2 H), 7.17−7.26 ppm (m, 3 H); 13C NMR (75 MHz, CDCl3) δ =
190.2, 185.0, 166.8 (d, JC−F = 257.2 Hz, 1 C), 139.7, 136.9 (d, JC−F = 19.5
Hz, 2 C), 133.2, 133.1, 129.1, 128.8, 116.3 (d, JC−F = 21.7 Hz, 2 C) ppm;
127.1, 126.1, 124.2, 71.4 ppm; IR (KBr, cm−1) νOH
= 1590, νmax
̃
= 3451, νCO
̃
=
1682, νCC
̃
̃
= 1266, 1226, 1088, 976, 865, 826, 782, 673;
HRMS (ESI) m/z calcd for C12H9ClO2SNa [M + Na]+ 274.9910, found
274.9941. Anal. Calcd for C12H9ClO2S: C, 57.03; H, 3.59. Found: C,
57.25; H, 3.60. 5e: 1H NMR (600 MHz, CDCl3) δ = 8.24 (dd, J = 1.8, 3.0
Hz, 1 H), 7.97 (dt, J = 2.4, 8.4 Hz, 2 H), 7.67 (dd, J = 1.2, 5.4 Hz, 1 H),
7.49 (dt, J = 2.4, 9.0 Hz, 2 H), 7.42 ppm (dd, J = 3.0, 5.4 Hz, 1 H); 13C
NMR (150 MHz, CDCl3) δ = 191.7, 186.5, 141.5, 137.8, 137.3, 131.5 (2
IR (KBr, cm−1) νCO
̃
= 1670, 1644, νCC
̃
̃
= 1596, νmax = 1505, 1409,
1233, 1161, 843, 723, 603; HRMS (EI) m/z calcd for C12H7FO2S [M]+
234.0151, found 234.0138.
1-Hydroxy-1-(thiophene-2-yl)propan-2-one (4i)3a and 1-(Thio-
phene-2-yl)propane-1,2-dione (5i).3b Prepared according to the
general procedure discussed above. 4i: eluent, EtOAc/n-hexane
(20%); 0.0275 g, 50%; yellow liquid. 5i: EtOAc/n-hexane (8%);
0.0119 g, 21%; yellow solid. 4i: 1H NMR (600 MHz, CDCl3) δ = 7.33
(d, J = 4.8 Hz, 1 H), 7.10 (d, J = 3.0 Hz, 1 H), 7.02 (dd, J = 3.6, 5.4 Hz, 1
H), 5.37 (s, 1 H), 4.24 (br s, 1 H), 2.18 ppm (s, 3 H); 13C NMR (150
MHz, CDCl3) δ = 206.7, 141.8, 128.2, 127.6, 127.5, 76.4, 26.0 ppm. 5i:
1H NMR (600 MHz, CDCl3) δ = 8.11 (dd, J = 1.2, 4.2 Hz, 1 H), 7.80
CH), 131.1, 129.3 (2 CH), 127.3, 127.2 ppm; IR (KBr, cm−1) νCO
̃
=
1657, νCC
̃
̃
= 1583, νmax = 1403, 1225, 1168, 1087, 821, 701; HRMS
(EI) m/z calcd for C12H7ClO2S [M]+ 249.9855, found 249.9849.
1-(3-Fluorophenyl)-2-hydroxy-2-(thiophene-3-yl)ethanone (4f)
and 1-(3-Fluorophenyl)-2-(thiophene-3-yl)ethane-1,2-dione (5f).
Prepared according to the general procedure discussed above. 4f:
eluent, EtOAc/n-hexane (20%); 0.044 g, 82%; white solid; mp 102−104
°C. 5f: EtOAc/n-hexane (5%); 0.008 g, 15%; yellowish white solid; mp
82−84 °C. 4f: 1H NMR (600 MHz, CDCl3) δ = 7.70 (dt, J = 1.2, 7.8 Hz,
1 H), 7.61−7.63 (m, 1 H), 7.41 (td, J = 5.4, 7.8 Hz, 1 H), 7.24−7.29 (m,
3 H), 6.97−6.99 (m, 1 H), 6.04 (d, J = 6.6 Hz, 1 H), 4.29 ppm (d, J = 6.6
(dd, J = 1.2, 4.8 Hz, 1 H), 7.18 (dd, J = 3.6, 4.8 Hz, 1 H), 2.52 ppm (s, 3
H); 13C NMR (150 MHz, CDCl3) δ = 199.5, 181.7, 138.6, 138.3, 138.0,
129.6, 26.3 ppm. (Analytical data are consistent with previously reported
values.)
2-(Benzofuran-3-yl)-2-hydroxy-1-(4-methoxy-3,5-
dimethylphenyl)ethan-1-one (4j). Prepared according to the general
Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ = 197.4, 162.7 (d, JC−F
=
246.0 Hz, 1 C), 139.2, 135.5 (d, JC−F = 6.0 Hz, 1 C), 130.5 (d, JC−F = 7.5
G
DOI: 10.1021/acs.joc.5b00846
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
procedure discussed above: eluent, EtOAc/n-hexane (15%); 0.025 g,
48%; colorless gum; H NMR (300 MHz, CDCl3) δ = 7.67 (s, 2 H),
1-(3-Fluorophenyl)-1-hydroxypropan-2-one (4o)3f and 1-(3-
Fluorophenyl)propane-1,2-dione (5o).3g Prepared according to the
general procedure discussed above: 4o: eluent, EtOAc/n-hexane (15%);
0.035 g, 63%; yellow liquid. 5o: EtOAc/n-hexane (5%); 0.01 g, 18%;
yellow liquid. 4o: 1H NMR (600 MHz, CDCl3) δ = 7.34−7.38 (m, 1 H),
7.13 (d, J = 7.2 Hz, 1 H), 7.04−7.05 (m, 2 H), 5.08 (br s, 1 H), 4.32 (br s,
1 H), 2.10 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ = 207.3, 164.1
1
7.61−7.64 (m, 1 H), 7.58 (s, 1 H), 7.45 (d, J = 7.5 Hz, 1 H),7.22−7.32
(m, 2 H), 6.18 (d, J = 6.0 Hz, 1 H), 4.43 (d, J = 6.3 Hz, 1 H), 3.71 (s, 3
H), 2.25 ppm (s, 6 H); 13C NMR (75 MHz, CDCl3) δ = 197.4, 162.3,
155.5, 143.4, 131.6 (2 × C), 130.0 (2 × CH), 128.7, 125.5, 124.9, 123.1,
120.3, 119.6, 111.6, 67.5, 59.6, 16.3 ppm (2 CH3); IR (KBr, cm−1) νOH
=
̃
(d, JC−F = 246.0 Hz, 1 C), 141.3 (d, JC−F = 7.5 Hz, 1 C), 131.6 (d, JC−F
=
3419, νCO
̃
= 1677, νCC
̃
̃
= 1595, νmax = 1452, 1312, 1156, 1084, 1009,
750; HRMS (ESI) m/z calcd for C19H18O4Na [M + Na]+ 333.1103,
found 333.1114.
7.5 Hz, 1 C), 124.0 (d, JC−F = 3.0 Hz, 1 C), 116.8 (d, JC−F = 21.0 Hz, 1
C), 115.2 (d, JC−F = 21.0 Hz, 1 C), 80.5, 26.2 ppm. 5o: 1H NMR (600
MHz, CDCl3) δ = 7.82−7.83 (m, 1 H), 7.74 (ddd, J = 1.2, 2.4, 9.3 Hz, 1
H), 7.48 (td, J = 6.0, 8.1 Hz, 1 H), 7.34 (tdd, J = 1.2, 2.4, 8.1 Hz, 1 H),
2.53 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ = 199.6, 189.5 (d,
JC−F = 3.0 Hz, 1 C), 162.7 (d, JC−F = 247.5 Hz, 1 C), 133.8 (d, JC−F = 6.0
Hz, 1 C), 130.5 (d, JC−F = 7.5 Hz, 1 C), 126.3 (d, JC−F = 3.0 Hz, 1 C),
121.7 (d, JC−F = 21.0 Hz, 1 C), 116.8 (d, JC−F = 22.5 Hz, 1 C), 26.2 ppm.
(Analytical data are consistent with previously reported values.)
1-Hydroxy-1-naphthalen-2-ylpropan-2-one (4p)3a and 1-Naph-
thalen-2-ylpropane-1,2-dione (5p).3e Prepared according to the
general procedure discussed above. 4p: eluent, EtOAc/n-hexane
(15%); 0.041 g, 75%; white solid. 5p: EtOAc/n-hexane (6%); 0.009 g,
17%; yellow gum. 4p: 1H NMR (600 MHz, CDCl3) δ = 7.84−7.88 (m, 4
H), 7.50−7.53 (m, 2 H), 7.37 (dd, J = 1.8, 8.4 Hz, 1 H), 5.27 (s, 1 H),
4.41 (br s, 1 H), 2.11 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ =
208.1, 136.3, 134.4, 134.3, 130.1, 129.0, 128.8, 128.2, 127.6, 127.6, 125.3,
81.3, 26.4 ppm. 5p: 1H NMR (600 MHz, CDCl3) δ = 8.57 (s, 1 H), 8.05
(dd, J = 1.8, 9.0 Hz, 1 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.93 (d, J = 8.4 Hz, 1
H), 7.89 (d, J = 8.4 Hz, 1 H), 7.65 (ddd, J = 1.2, 6.8, 8.1 Hz, 1 H), 7.58
(ddd, J = 1.2, 6.8, 8.1 Hz, 1 H), 2.59 ppm (s, 3 H); 13C NMR (150 MHz,
CDCl3) δ = 200.8, 191.4, 136.2, 133.8, 132.3 (2 C), 130.0, 129.4, 129.0,
127.9, 127.1, 124.3, 26.6 ppm. (Analytical data are consistent with
previously reported values.)
3-(2-Hydroxybutanoyl)-2H-chromen-2-one (4k) and 1-(2-Oxo-
2H-chromen-3-yl)butane-1,2-dione (5k). Prepared according to the
general procedure discussed above. 4k: eluent, EtOAc/n-hexane (10%);
0.033 g, 61%; white solid; mp 110−112 °C. 5k: EtOAc/n-hexane (20%);
0.005g, 9%; light yellow solid; mp 98−100 °C. 4k: 1H NMR (300 MHz,
CDCl3) δ = 8.63 (s, 1 H), 7.68−7.74 (m, 2 H), 7.36−7.43 (m, 2H),
5.23−5.26 (m, 1 H), 3.53 (d, J = 6.6 Hz, 1 H), 1.93−2.00 (m, 1 H),
1.51−1.60 (m, 1 H), 1.01 ppm (t, J = 7.5 Hz, 3 H); 13C NMR (75 MHz,
CDCl3) δ = 199.7, 158.7, 155.4, 149.3, 135.0, 130.3, 125.3, 122.3, 118.1,
116.8, 76.8, 26.8 (CH2), 9.4 ppm; IR (KBr, cm−1) νOH
= 1608, νmax
̃
= 3491, νCO
̃
=
1733, νCC
̃
̃
= 1561, 1453, 1297, 1188, 1129, 1056, 971, 760;
HRMS (EI) m/z calcd for C13H12O4 [M]+ 232.0736, found 232.0737.
Anal. Calcd for C13H12O4: C, 67.23; H, 5.21. Found: C, 67.33; H, 5.26.
5k: 1H NMR (600 MHz, CDCl3) δ = 8.47 (s, 1 H), 7.68−7.72 (m, 2 H),
7.37−7.42 (m, 2 H), 2.90 (q, J = 7.2, 14.4 Hz, 2 H), 1.25 ppm (t, J = 7.2
Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ = 203.6, 192.6, 160.2, 156.5,
149.2, 136.1, 131.4, 126.4, 123.5, 119.1, 118.2, 32.0 (CH2), 7.6 ppm; IR
(KBr, cm−1) νCO
̃
= 1719, 1684, νCC
̃
̃
= 1608, νmax = 1562, 1452, 1136,
766; HRMS (ESI) m/z calcd for C13H10O4Na [M + Na]+ 253.0477,
found 253.0473.
6-Bromo-3-(2-hydroxybutanoyl)-2H-chromen-2-one (4l). Pre-
pared according to the general procedure discussed above: eluent,
EtOAc/n-hexane (20%); 0.034 g, 64%; light yellow solid; mp 110−112
°C; 1H NMR (600 MHz, CDCl3) δ = 8.52 (s, 1 H), 7.82 (d, J = 2.4 Hz, 1
H), 7.77 (dd, J = 2.4, 9.0 Hz, 1 H), 7.29 (d, J = 9.0 Hz, 1 H), 5.22 (td, J =
4.2, 6.0 Hz, 1 H), 3.48 (d, J = 6.0 Hz, 1 H), 1.95 (dqd, J = 4.2, 7.2, 11.4
Hz, 1 H), 1.50−1.57 (m, 1 H), 1.00 ppm (t, J = 7.8 Hz, 3 H); 13C NMR
(150 MHz, CDCl3) δ = 200.4, 159.0, 155.1, 148.7, 138.6, 133.3, 124.4,
2-Hydroxy-2-methyl-2,3-dihydro-1H-inden-1-one (4q).3h Prepared
according to the general procedure discussed above: EtOAc/n-hexane
(20%); 0.049 g, 88%; light yellow liquid; 1H NMR (400 MHz, CDCl3) δ
= 7.77 (d, J = 6.4 Hz, 1 H), 7.62 (t, J = 6.0 Hz, 1 H), 7.37−7.43 (m, 2 H),
3.27 (d, J = 10.2 HZ, 1 H), 3.21 (d, J = 9.9 Hz, 1 H), 3.01 (br. s., 1 H),
1.44 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3) δ = 208.1, 151.3,
135.9, 133.7, 128.0, 126.9, 125.1, 77.2, 42.4, 25.8 ppm. (Analytical data
are consistent with previously reported values.)
120.5, 119.6, 118.8, 77.8, 27.8 (CH2), 10.4 ppm; IR (KBr, cm−1) νOH
=
̃
3506, νCO
̃
= 1714, 1686, νCC
̃
̃
= 1605, νmax = 1552, 1197, 984, 834;
HRMS (ESI) m/z calcd for C13H11BrO4Na [M + Na]+ 332.9739, found
332.9747. Anal. Calcd for C13H11BrO4: C, 50.19; H, 3.56. Found: C,
50.39; H, 3.71;
2-Hydroxy-6-methoxy-2-methyl-2,3-dihydro-1H-inden-1-one
(4r). Prepared according to the general procedure discussed above:
1
EtOAc/n-hexane (20%); 0.040 g, 73%; light yellow liquid; H NMR
1-(3,4-Dimethoxyphenyl)-1-hydroxy-propan-2-one (4m)3c and 1-
(3,4-Dimethoxyphenyl)propane-1,2-dione (5m).3b Prepared accord-
ing to the general procedure discussed above. 4m: eluent, EtOAc/n-
hexane (30%); 0.042 g, 78%; yellow gum. 5m: EtOAc/n-hexane (20%);
0.006 g, 11%; yellow solid. 4m: 1H NMR (300 MHz, CDCl3) δ = 6.86−
6.93 (m, 2 H), 6.76 (d, J = 1.8 Hz, 1 H), 5.04 (d, J = 4.2 Hz, 1 H), 4.25 (d,
J = 3.9 Hz, 1 H), 3.89 (s, 3 H), 3.88 (s, 3 H), 2.09 (s, 3 H) ppm; 13C
NMR (75 MHz, CDCl3) δ = 207.4, 149.5, 149.4, 130.4, 120.3, 111.2,
109.6, 79.8, 55.9, 55.9, 25.2 ppm. 5m: 1H NMR (600 MHz, CDCl3) δ =
7.66 (dd, J = 1.8, 7.8 Hz, 1 H), 7.57 (d, J = 1.8 Hz, 1 H), 6.91 (d, J = 8.4
Hz, 1 H), 3.97 (s, 3 H), 3.94 (s, 3 H), 2.51 ppm (s, 3 H); 13C NMR (150
MHz, CDCl3) δ = 202.1, 191.2, 155.8, 150.4, 127.4, 125.7, 112.1, 111.3,
57.2, 57.0, 27.6 ppm. (Analytical data are consistent with previously
reported values.)
(300 MHz, CDCl3) δ = 7.34 (d, J = 8.1 Hz, 1 H), 7.25−7.26 (m, 1 H),
7.22 (d, J = 3.0 Hz, 1 H), 3.85 (s, 3 H), 3.17 (s, 2 H), 2.55 (br. s., 1 H),
1.45 ppm (s, 3 H); 13C NMR (75 MHz, CDCl3) δ = 208.1, 159.6, 144.0,
134.5, 127.5, 125.2, 105.9, 78.1, 55.6, 41.5 (CH2), 25.8 ppm; IR (KBr,
cm−1) νOH
̃
= 3426, νCO
̃
= 1713, νCC
̃
̃
= 1614, νmax = 1492, 1281, 1239,
1026, 836, 771; HRMS (EI) m/z calcd for C11H12O3 [M]+ 192.0786,
found 192.0787.
Ethyl 1-Bromo-2-oxocyclohexane-1-carboxylate (4s).3n Prepared
according to the general procedure discussed above: EtOAc/n-hexane
(2%); overall yield 0.068 g, 93%; yellow liquid; inseparable mixture of
1
major and minor diastereomers. Major diastereomers: H NMR (300
MHz, CDCl3) δ = 4.31 (q, J = 7.2, 14.1 Hz, 2 H), 2.84−2.98 (m, 2 H),
2.42−2.51 (m, 1 H), 2.19−2.28 (m, 1 H), 1.70−1.99 (m, 4 H), 1.32 ppm
(t, J = 6.9 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ = 199.1, 167.4, 67.5,
62.9 (CH2), 40.5 (CH2), 38.8 (CH2), 26.7 (CH2), 23.1 (CH2), 13.8
ppm. (Analytical data are consistent with previously reported values.)
2,2-Dihydroxy-1-phenylbutane-1,3-dione and 1-Phenylbutane-
1,2,3-trione (4t).3o Prepared according to the general procedure
discussed above: EtOAc/n-hexane (20%); overall yield 0.052 g, 87%;
yellow gummy liquid. According to NMR analyses, the compound was
observed mostly in hydrated form in DMSO-d6, whereas in CDCl3, as a
1-Hydroxy-1-(4-methoxyphenyl)propan-2-one (4n)3d and 1-(4-
Methoxyphenyl)propane-1,2-dione (5n).3e Prepared according to the
general procedure discussed above. 4n: eluent, EtOAc/n-hexane (20%);
0.04 g, 73%; yellow gum. 5n: EtOAc/n-hexane (10%); 0.007 g, 13%;
yellowish white solid. 4n: 1H NMR (300 MHz, CDCl3) δ = 7.23 (d, J =
8.7 Hz, 2 H), 6.91 (d, J = 8.4 Hz, 2 H), 5.04 (s, 1 H), 4.23 (d, J = 3.3 Hz, 1
H), 3.81 (s, 3 H), 2.07 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ =
208.4, 160.9, 131.0, 129.6 (2 CH), 115.4 (2 CH), 80.6, 56.3, 26.2 ppm.
5n: 1H NMR (600 MHz, CDCl3) δ = 8.02 (t, J = 2.4 Hz, 1 H), 8.00 (t, J =
1.8 Hz, 1 H), 6.97 (t, J = 3.0 Hz, 1 H), 6.95 (t, J = 1.8 Hz, 1 H), 3.89 (s, 3
H), 2.50 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ = 201.2, 190.0,
164.8, 132.8 (2 CH), 124.6, 114.2 (2 CH), 55.6, 26.5 ppm. (Analytical
data are consistent with previously reported values.)
1
mixtures of two (hydrated: keto form ∼2.5:1): H NMR (300 MHz,
DMSO-d6) δ = 8.02 (d, J = 7.2 Hz, 2 H), 7.63 (t, J = 7.5, 14.7 Hz, 1 H),
7.50 (t, J = 7.8, 15.3 Hz, 2 H), 7.41 (s, 2 H), 2.23 ppm (s, 3 H); 1H NMR
(300 MHz, CDCl3) δ = 8.02 (d, J = 7.5 Hz, 2 H), 7.89−7.91 (m, 1 H)
7.62−7.72 (m, 2 H), 7.45−7.56 (m, 4 H), 5.53 (br. s., 2 H), 2.56 (s, 3 H),
2.15 ppm (s, 3 H); 13C NMR (75 MHz, DMSO-d6) δ = 205.8, 196.2,
H
DOI: 10.1021/acs.joc.5b00846
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
133.4, 133.2, 130.0, 128.4, 96.7, 24.4 ppm. (Analytical data are
consistent with previously reported values.)
5-Bromo-2-(methylsulfanyl)inden-1-one (10a), 2,2,5-Tribromoin-
dan-1-one (10aa),5d and 2,5-Dibromoindan-1-one (10ab).5e Pre-
pared according to the general procedure discussed above. 10a: eluent,
EtOAc/n-hexane (5%); 0.012 g, 20%; red solid; mp 130−131 °C;
solvent of crystallization: dichloromethane/acetone. 10aa: EtOAc/n-
hexane (5%); 0.006 g, 7%; light brown solid. 10ab: EtOAc/n-hexane
(5%); 0.004 g, 6%; white solid; mixture of two isomers. 10a: 1H NMR
(600 MHz, CDCl3) δ = 7.20−7.24 (m, 2 H), 7.04 (d, J = 1.2 Hz, 1 H),
6.72 (s, 1 H), 2.43 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ =
192.4, 147.7, 141.8, 132.8, 129.6, 129.5, 129.5, 124.4, 123.6, 14.0 ppm;
Ethyl 2,2-Dihydroxy-3-(4-nitrophenyl)-3-oxopropanoate and
Ethyl 3-(4-Nitrophenyl)-2,3-dioxopropanoate (4u).3p Prepared ac-
cording to the general procedure discussed above: EtOAc/n-hexane
(25%); overall yield 0.0436 g, 77%; light yellow solid. According to
NMR analyses, the compound was observed in CDCl3 as a mixtures of
1
two (hydrated: keto form ∼3.6:1): H NMR (300 MHz, CDCl3) δ =
8.25−8.34 (m, 4 H), 5.19 (br. s., 2 H), 4.24 (q, J = 7.2, 14.4 Hz, 2 H),
1.12 ppm (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ = 190.6,
169.0, 150.9, 136.1, 131.2 (2 CH), 123.8 (2 CH), 92.0, 63.6 (CH2), 13.7
ppm. (Analytical data are consistent with previously reported values.)
2-Methylnaphthalene-1,4-dione (7a).4a Prepared according to the
general procedure discussed above: EtOAc/n-hexane (5%); 0.026 g,
48%; red solid; 1H NMR (400 MHz, CDCl3) δ = 8.03−8.09 (m, 2 H),
7.70−7.72 (m, 2 H), 6.82 (d, J = 1.6 Hz, 1 H), 2.18 ppm (s, 3 H); 13C
NMR (100 MHz, CDCl3) δ = 185.5, 184.9, 148.2, 135.7, 133.6, 133.6,
132.3, 132.2, 126.5, 126.1, 16.4 ppm. (Analytical data are consistent with
previously reported values.)
IR (KBr, cm−1) νCO
̃
= 1706, νCC
̃
̃
= 1591, νmax = 1443, 1257, 1046,
886, 823, 698; HRMS (EI) m/z calcd for C10H7BrOS [M]+ 253.9401,
found 253.9400. 10aa: 1H NMR (600 MHz, CDCl3) δ = 7.80 (d, J = 8.4
Hz, 1 H), 7.65 (dd, J = 0.6, 8.4 Hz, 1 H), 7.60 (s, 1 H), 4.26 ppm (s, 2 H);
13C NMR (150 MHz, CDCl3) δ = 191.6, 148.5, 132.7, 132.5, 129.3,
127.9, 127.7, 55.8, 51.9 (CH2) ppm. 10ab: NMR of mixtures: 1H NMR
(600 MHz, CDCl3) δ = 7.68−7.71 (m, 1 H), 7.64−7.65 (m, 1 H), 7.58−
7.60 (m, 1 H), 4.64 (dd, J = 3.6, 7.8 Hz, 1 H; major isomer), 4.55 (dd, J =
4.2, 7.8, Hz, 1 H; minor isomer), 3.82 (dd, J = 7.2, 18.0 Hz, 1 H; major
isomer), 3.77 (dd, J = 8.4, 18.0 Hz, 1 H; minor isomer), 3.41 (dd, J = 3.0,
18.0 Hz, 1 H; major isomer), 3.29 ppm (dd, J = 4.2, 18.0 Hz, 1 H; minor
isomer); 13C NMR (150 MHz, CDCl3) δ = 198.3, 152.5, 132.4, 132.0,
131.5, 129.7, 126.2, 43.4, 37.6 (CH2) ppm. (Analytical data are
consistent with previously reported values.)
6-Methoxy-2-methylnaphthalene-1,4-dione (7b).4b Prepared ac-
cording to the general procedure discussed above: EtOAc/n-hexane
(5%); 0.024 g, 45%; yellow solid; 1H NMR (600 MHz, CDCl3) δ = 8.03
(d, J = 9.0 Hz, 1 H), 7.47 (d, J = 3.0 Hz, 1 H), 7.17 (dd, J = 3.0, 9.0 Hz, 1
H), 6.79 (q, J = 1.8, 3.0 Hz, 1 H), 3.93 (s, 3 H), 2.17 ppm (d, J = 1.8 Hz, 3
H); 13C NMR (150 MHz, CDCl3) δ = 186.1, 185.6, 164.9, 149.5, 136.2,
135.3, 130.0, 126.7, 121.2, 110.3, 56.9, 17.5 ppm. (Analytical data are
consistent with previously reported values.)
6-Methoxy-2-(methylsulfanyl)inden-1-one (10b), 2,2-Dibromo-6-
methoxyindan-1-one (10ba),5f and 2-Bromo-6-methoxyindan-1-
one (10bb).5f Prepared according to the general procedure discussed
above. 10b: eluent, EtOAc/n-hexane (7%); 0.008 g, 12%; dark red solid;
mp 41−43 °C. 10ba: EtOAc/n-hexane (7%); 0.006 g, 6%; light brown
solid. 10bb: EtOAc/n-hexane (7%); 0.005 g, 7%; white solid; mixture of
two isomers. 10b: 1H NMR (600 MHz, CDCl3) δ = 7.01 (d, J = 2.4 Hz, 1
H), 6.78−6.79 (m, 2 H), 6.71 (dd, J = 2.4, 7.8 Hz, 1 H), 3.79 (s, 3 H),
2.41 ppm (s, 3 H); 13C NMR (150 MHz, CDCl3) δ = 193.8, 159.5,
137.7, 137.6, 136.6, 132.8, 120.9, 117.1, 111.5, 55.7, 14.2 ppm; IR (KBr,
7-Methoxy-2-methylnaphthalene-1,4-dione (7c).4b Prepared ac-
cording to the general procedure discussed above: EtOAc/n-hexane
1
(5%); 0.0261 g, 49%; yellow solid; H NMR (600 MHz, CDCl3) δ =
7.99 (d, J = 8.4 Hz, 1 H), 7.52 (d, J = 3.0 Hz, 1 H), 7.18 (dd, J = 3.0, 8.4
Hz, 1 H), 6.77 (q, J = 1.2, 3.0 Hz, 1 H), 3.94 (s, 3 H), 2.17 ppm (d, J = 1.2
Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ = 186.7, 185.2, 164.9, 148.6,
136.9, 135.1, 129.5, 126.8, 121.1, 110.9, 56.9, 17.4 ppm. (Analytical data
are consistent with previously reported values.)
cm−1) νCO
̃
= 1715, νCC
̃
̃
= 1608, νmax = 1477, 1424, 1282, 1226, 1015,
839, 768; HRMS (EI) m/z calcd for C11H10O2S [M]+ 206.0402, found
206.0395. 10ba: 1H NMR (600 MHz, CDCl3) δ = 7.35 (d, J = 2.4 Hz, 1
H), 7.28−7.33 (m, 2 H), 4.22 (s, 2 H), 3.87 ppm (s, 3 H); 13C NMR
(150 MHz, CDCl3) δ = 192.8, 160.4, 139.7, 130.2, 126.8, 126.4, 107.4,
57.2, 55.8, 51.9 (CH2) ppm. 10bb: (major isomer) 1H NMR (600 MHz,
CDCl3) δ = 7.33−7.35 (m, 1 H), 7.25−7.27 (m, 2 H), 4.67 (dd, J = 3.6,
7.8 Hz, 1 H), 3.85 (s, 3 H), 3.77 (dd, J = 7.2, 17.2 Hz, 1 H), 3.35 ppm
(dd, J = 3.0, 17.4 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ = 199.6,
160.0, 143.9, 134.7, 127.1, 125.5, 106.0, 55.7, 44.7, 37.4 (CH2) ppm.
(Analytical data are consistent with previously reported values.)
(E)-5-Phenylpent-4-ene-2,3-dione (12a).6a Prepared according to
the general procedure discussed above: EtOAc/n-hexane (1%); 0.03 g,
55%; yellow solid; 1H NMR (600 MHz, CDCl3) δ = 7.85 (d, J = 16.2 Hz,
1 H), 7.64 (dd, J = 1.8, 7.8 Hz, 2 H), 7.46−7.41 (m, 4 H), 2.46 ppm (s, 3
H); 13C NMR (150 MHz, CDCl3) δ = 198.9, 186.8, 147.8, 134.4, 131.4,
129.1 (2 CH), 129.0 (2 CH), 117.9, 24.4 ppm. (Analytical data are
consistent with previously reported values.)
8-Bromo-7-methoxy-2-methylnaphthalene-1,4-dione (7d). 2,8-
Dibromo-7-methoxy-2-methyl-3,4-dihydronaphthalen-1(2H)-one was
converted to 7d according to the general procedure discussed above:
EtOAc/n-hexane (20%); 0.012 g, 30%; yellow solid; mp 110−111 °C;
1H NMR (600 MHz, CDCl3) δ = 8.12 (d, J = 9.0 Hz, 1 H), 7.18 (d, J =
8.4 Hz, 1 H), 6.77 (d, J = 1.8 Hz, 1 H), 4.02 (s, 3 H), 2.20 ppm (d, J = 1.8
Hz, 3 H); 13C NMR (150 MHz, CDCl3) δ = 185.7, 184.0, 161.9, 150.6,
135.1, 132.1, 129.1, 128.7, 115.5, 113.5, 58.0, 18.1 ppm; IR (KBr, cm−1)
νCO
̃
= 1666, νCC
̃
̃
= 1631, 1571, νmax = 1329, 1270, 969, 718; HRMS
(EI) m/z calcd for C12H9BrO3 [M]+ 279.9735, found 279.9740.
6-Bromonaphthalene-1,4-dione (7e).4c Prepared according to the
general procedure discussed above: EtOAc/n-hexane (20%); 0.010 g,
19%; brick red solid; 1H NMR (600 MHz, CDCl3) δ = 8.22 (d, J = 1.8
Hz, 1 H), 7.79 (dd, J = 1.8, 7.8 Hz, 1 H), 7.41 (d, J = 10.2 Hz, 1 H), 7.25
(d, J = 9.0 Hz, 1 H), 6.47 ppm (d, J = 9.6 Hz, 1 H); 13C NMR (150 MHz,
CDCl3) δ = 180.9, 178.8, 145.3, 139.6, 134.4, 134.1, 133.7, 132.1, 129.2,
126.8 ppm. (Analytical data are consistent with previously reported
values.)
(E)-5-(4-Methoxyphenyl)pent-4-ene-2,3-dione (12b). Prepared
2-Bromo-3-phenyl-1H-inden-1-one (9a).5c Prepared according to
the general procedure discussed above: EtOAc/n-hexane (1%); 0.058 g,
85%; red solid; 1H NMR (600 MHz, CDCl3) δ = 7.65−7.67 (m, 2 H),
7.51−7.57 (m, 4 H), 7.36 (td, J = 1.2, 7.8 Hz, 1 H), 7.25−7.28 (m, 1 H),
7.15 ppm (d, J = 7.2 Hz, 1 H); 13C NMR (150 MHz, CDCl3) δ = 190.9,
157.9, 145.5, 134.8, 132.1, 131.3, 130.9, 129.9, 129.7 (2 CH), 129.2 (2
CH), 124.7, 122.3, 119.0 ppm. (Analytical data are consistent with
previously reported values.)
according to the general procedure discussed above: EtOAc/n-hexane
1
(6%); 0.027 g, 50%; light yellow solid; mp 61−63 °C. H NMR (600
MHz, CDCl3) δ = 7.81 (d, J = 16.2 Hz, 1 H), 7.60 (d, J = 9.0 Hz, 2 H),
7.31 (d, J = 15.6 Hz, 1 H), 6.93 (d, J = 8.4 Hz, 2 H), 3.86 (s, 3 H), 2.45 (s,
3 H); 13C NMR (150 MHz, CDCl3) δ = 199.4, 186.8, 162.4, 147.7, 130.9
(2 CH), 127.3, 115.6, 114.5 (2 CH), 55.5, 24.5 ppm; IR (KBr, cm−1)
νCO
̃
= 1711, 1677, νCC
̃
̃
= 1595, 1510, νmax = 1257, 1171, 1062, 1025,
824; HRMS (EI) m/z calcd for C12H12O3 [M]+ 204.0786, found
204.0784.
2-Bromo-3-methyl-1H-inden-1-one (9b). Prepared according to the
general procedure discussed above: EtOAc/n-hexane (2%); 0.040 g,
52%; red solid; mp 77−79 °C; 1H NMR (400 MHz, CDCl3) δ = 7.43 (d,
J = 7.2 Hz, 1 H), 7.35−7.38 (m, 1 H), 7.21 (t, J = 7.6 Hz, 1 H), 7.08 (d, J
= 7.2 Hz, 1 H), 2.23 ppm (s, 3 H); 13C NMR (100 MHz, CDCl3) δ =
189.7, 157.6, 144.9, 134.0, 129.8, 129.0, 122.8, 119.3, 119.1, 13.4 ppm;
1,4-Diphenylbut-3-yne-1,2-dione (14)6b and 1-Hydroxy-1,4-di-
phenylbut-3-yn-2-one (14a).6b Prepared according to the general
procedure discussed above. 14: EtOAc/n-hexane (5%); 0.043 g, 81%;
yellow liquid. 14a: EtOAc/n-hexane (15%); 0.006 g, 11%; light yellow
solid. 14: 1H NMR (600 MHz, CDCl3) δ = 8.09−8.10 (m, 1 H), 8.08
(m, 1 H), 7.65−7.69 (m, 3 H), 7.50−7.55 (m, 3 H), 7.40−7.43 ppm (m,
2 H); 13C NMR (150 MHz, CDCl3) δ = 188.5, 178.5, 134.9, 133.7 (2
CH), 131.7, 131.6, 130.5 (2 CH), 128.9 (2 CH), 128.8 (2 CH), 119.2,
IR (KBr, cm−1) νCO
̃
= 1718, νCC
̃
̃
= 1606, 1575, νmax = 1453, 1425,
1376, 1267, 1121, 1037, 832, 748, 696, 662; HRMS (EI) m/z calcd for
C10H7BrO [M]+ 221.9680, found 221.9664.
I
DOI: 10.1021/acs.joc.5b00846
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
99.2, 87.0 ppm. 14a: 1H NMR (600 MHz, CDCl3) δ = 7.47−7.49 (m, 2
H), 7.40−7.46 (m, 5 H), 7.35−7.38 (m, 3 H), 5.34 (s, 1 H), 4.17 ppm
(br. s., 1 H); 13C NMR (150 MHz, CDCl3) δ = 186.4, 137.0, 133.1 (2
CH), 131.4, 128.9, 128.8 (2 CH), 128.7 (2 CH), 127.6 (2 CH), 119.2,
98.6, 85.1, 81.1 ppm. (Analytical data are consistent with previously
reported values.)
free of charge on the ACS Publications website at DOI: 10.1021/
acs.joc.5b00846.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+91) 33 2473 5197. E-mail: id@csiriicb.in.
■
(E)-4-Bromo-4-methyl-1-phenylpent-1-en-3-one (16).6i Prepared
according to the general procedure discussed above: EtOAc/n-hexane
(1%); 0.055 g, 76%; white solid; 1H NMR (600 MHz, CDCl3) δ = 7.78
(d, J = 15.6 Hz, 1 H), 7.62−7.61 (m, 2 H), 7.42−7.39 (m, 4 H), 1.95 (s, 6
H); 13C NMR (75 MHz, CDCl3) δ = 194.3, 144.8, 134.4, 130.7, 128.9 (2
CH), 128.5 (2 CH), 120.2, 63.7, 29.7 ppm (2 CH3). (Analytical data are
consistent with previously reported values.)
Author Contributions
‡K.M. and A.K. contributed equally.
Notes
The authors declare no competing financial interest.
General Procedure for the Synthesis of 17a,b. Compound 9a
(0.05 g, 0.175 mmol, 1 equiv) in dry DMF (2 mL) was placed separately
into a flame-dried, two-necked, round-bottomed flask equipped with a
magnetic stir bar and rubber septa. [PdCl2(PPh3)2] (0.06 equiv),
terminal alkyne (1.2 equiv), and CuI (0.2 equiv) were added into the
flask at 0 °C, and then N,N-diisopropylethylamine (DIPEA; 1.5 equiv)
was added dropwise to the resulting mixtures and allowed to stir at room
temperature for the required times (3−8 h). After completion of the
reaction (TLC), saturated NH4Cl solution was added, and the product
was extracted with EtOAc. The combined organic layers were dried over
anhydrous Na2SO4 and filtered, and the filtrate was concentrated under
reduced pressure to obtain a residue. The crude residue was purified by
using silica gel column chromatography (230−400 mesh particle size;
eluent: ethyl acetate/n-hexane) to obtain 17a,b.
ACKNOWLEDGMENTS
■
I.D. thanks CSIR−New Delhi (Network Project ORIGIN-
CSC0108) for financial support and Drs. Ramalingam Natarajan
and Basudeb Achari for valuable discussions. K.M., A.K., and F.H.
thank CSIR−India, NIPER−Kolkata, and UGC−India for their
fellowships, respectively. We thank Mr. Santu Paul for his
cooperation in carrying out the combustion analysis.
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(5%); 0.042 g, 78%; brick red solid; mp 144−146 °C; H NMR (600
1
MHz, CDCl3) δ = 7.89−7.91 (m, 2 H), 7.52−7.60 (m, 4 H), 7.48−7.51
(m, 2 H), 7.40−7.43 (m, 1 H), 7.35−7.37 (m, 1 H), 7.32−7.33 ppm (m,
4 H); 13C NMR (150 MHz, CDCl3) δ = 194.4, 161.2, 145.2, 134.7,
133.2, 132.9 (2 CH), 131.8, 131.6, 130.6, 129.7, 129.6 (2 CH), 129.4 (2
CH), 129.3 (2 CH), 124.5, 123.9, 123.1, 118.8, 100.8, 83.1 ppm; IR
(KBr, cm−1) νCC
̃
= 2211, νCO
̃
= 1710, νCC
̃
̃
= 1599, νmax = 1487,
1449, 1360, 1185, 1125, 777, 752, 712; HRMS (EI) m/z calcd for
C23H14O [M]+ 306.1045, found 306.1013.
2-(Cyclopentylethynyl)-3-phenyl-1H-inden-1-one (17b). Prepared
according to the general procedure discussed above: EtOAc/n-hexane
(1%); 0.021 g, 40%; gummy red liquid; 1H NMR (300 MHz, CDCl3) δ
= 7.82−7.85 (m, 2 H), 7.50−7.55 (m, 4 H), 7.29−7.40 (m, 3 H), 2.87−
2.92 (m, 1 H), 1.91−1.97 (m, 2 H), 1.61−1.73 ppm (m, 6 H); 13C NMR
(75 MHz, CDCl3) δ = 194.0, 159.0, 144.3, 133.5, 132.3, 130.6, 130.2,
129.2, 128.4 (2 CH), 128.3 (2 CH), 123.3, 121.7, 118.6, 106.2, 72.4, 33.7
(2 CH2), 31.4, 25.0 ppm (2 CH2); IR (KBr, cm−1) νCC
̃
= 2211, νCO
̃
=
1710, νCC
̃
̃
= 1634, 1602, νmax = 1450, 1358, 1077, 774, 710; HRMS
(EI) m/z calcd for C22H18O [M]+ 298.1358, found 298.1343.
2-(Benzyloxy)-2,5-diphenylfuran-3(2H)-one (18). To a well-stirred
solution of 14 (0.05 g, 0.21 mmol) in CH2Cl2 (4 mL) were added 2 mol
% of AuCl3 and benzyl alcohol (0.04 mL, 0.42 mmol) under Ar
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61%; yellow gum; 1H NMR (300 MHz, CDCl3) δ = 7.94 (d, J = 7.2 Hz, 2
H), 7.62−7.68 (m, 3 H), 7.53−7.58 (m, 2 H), 7.30−7.40 (m, 8 H), 6.10
(s, 1 H), 4.78 (d, J = 10.8 Hz, 1 H), 4.68 ppm (d, J = 11.1 Hz, 1 H); 13C
NMR (75 MHz, CDCl3) δ = 198.9, 184.4, 137.0, 134.6, 133.4, 129.5,
129.1, 128.6, 128.3, 127.9, 127.4, 126.0, 107.3, 99.3, 67.7 ppm (CH2); IR
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C NMR spectra for all new compounds;
ORTEP diagram of 10a. The Supporting Information is available
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